i brazilian guidelines on cardiovascular prevention

Transcription

www.arquivosonline.com.br
Sociedade Brasileira de Cardiologia • ISSN-0066-782X • Volume 101, Nº 6, Suppl. 2, December 2013
I BRAZILIAN GUIDELINES ON
CARDIOVASCULAR PREVENTION
I Brazilian Guidelines on
Cardiovascular Prevention
This guideline shall be referred as:
Simão AF, Precoma DB, Andrade JP, Correa Filho H, Saraiva JFK, Oliveira GMM, Murro ALB, Campos A,
Alessi A, Avezum Junior A, Achutti AC, Miguel ACMG, Sousa ACS, Lotemberg AMP, Lins AP, Falud AA,
Brandão AA, Sanjuliani AF, Sbissa AS, Alencar Filho AC, Herdy AH, Polanczyk CA, Lantieri CJ, Machado
CA, Scherr C, Stoll C, Amodeo C, Araújo CGS, Saraiva D, Moriguchi EH, Mesquita ET, Fonseca FAH,
Campos GP, Soares GP, Feitosa GS, Xavier HT, Castro I, Giuliano ICB, Rivera IV, Guimaraes ICB, Issa JS,
Souza JRM, Faria Neto JR, Cunha LBN, Pellanda LC, Bortolotto LA, Bertolami MC, Miname MH, Gomes
MAM, Tambascia M, Malachias MVB, Silva MAM, Izar MC, Magalhães MEC, Bacellar MSC, Milani M,
Wajngarten M, Ghorayeb N, Coelho OR, Villela PB, Jardim PCBV, Santos Filho RD, Stein R, Cassani
RSL, D’Avila RL, Ferreira RM, Barbosa RB, Povoa RMS, Kaiser SE, Ismael SC, Carvalho T, Giraldez VZR,
Coutinho W, Souza WKSB.
Scientific Director
A JOURNAL OF BRAZILIAN SOCIETY OF CARDIOLOGY - Published since 1948
Interventionist Cardiology
Luiz Alberto Piva e Mattos
Pedro A. Lemos
Chief Editor
Luiz Felipe P. Moreira
Pediatric/Congenital Cardiology
Antonio Augusto Lopes
Associated Editors
Arrhythmias/Pacemaker
Clinical Cardiology
Non-Invasive Diagnostic Methods
José Augusto Barreto-Filho
Surgical Cardiology
Paulo Roberto B. Evora
Mauricio Scanavacca
Epidemiology/Statistics
Lucia Campos Pellanda
Arterial Hypertension
Paulo Cesar B. V. Jardim
Ergometrics, Exercise
and Cardiac Rehabilitation
Carlos E. Rochitte
Ricardo Stein
Basic or Experimental Research
First Editor (1948-1953)
Leonardo A. M. Zornoff
† Jairo Ramos
Editorial Board
Brazil
Adib D. Jatene (SP)
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Enio Buffolo (SP)
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Mario S. S. de Azeredo Coutinho (SC)
Maurício I. Scanavacca (SP)
Mauricio Wajngarten (SP)
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Exterior
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Brazilian Society of Cardiology
President
Jadelson Pinheiro de Andrade
Vice-President
Dalton Bertolim Précoma
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Moreira
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Andrade
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Filho (AM)
BSC/PA - Claudine Maria Alves Feio
BSC/PB - Alexandre Jorge de Andrade Negri
BSC/PE - Silvia Marinho Martins
Cardiovascular Prevention Committee
Antonio Delduque de Araujo Travessa
Sergio Baiocchi Carneiro
Regina Coeli Marques de Carvalho
BSC/PI - Ricardo Lobo Furtado
Strategic Planning Committee
Fabio Sândoli de Brito
José Carlos Moura Jorge
Walter José Gomes
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Member Assistance Committee
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BSC/RJ - Glaucia Maria Moraes Oliveira
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BSC/TO - Adalgele Rodrigues Blois
Presidents of the Specialized Departaments and Study Groups
BSC/DA - Hermes Toros Xavier (SP)
BSC/DCC - Evandro Tinoco Mesquita (RJ)
BSC/DCM - Orlando Otavio de
Medeiros (PE)
BSC/DFCVR - José Carlos Dorsa Vieira
Pontes (MS)
BSC/DCC/GECETI - João Fernando
Monteiro Ferreira (SP)
BSC/DHA - Weimar Kunz Sebba Barroso de
Souza (GO)
BSC/DCC/GEECABE - Luis Claudio Lemos
Correia (BA)
BSC/DIC - Jorge Eduardo Assef (SP)
BSC/DCC/GEECG - Carlos Alberto Pastore (SP)
BSC/DCC/CP - Estela Suzana Kleiman
Horowitz (RS)
BSC/SBCCV - Walter José Gomes (SP)
BSC/DECAGE - Abrahão Afiune Neto (GO)
BSC/SBHCI - Marcelo Antonio Cartaxo
Queiroga Lopes (PB)
BSC/DEIC - João David de Souza Neto (CE)
BSC/DERC - Pedro Ferreira de
Albuquerque (AL)
BSC/SOBRAC - Adalberto Menezes Lorga
Filho (SP)
BSC/DCC/GAPO - Daniela Calderaro (SP)
BSC/DCP/GECIP - Angela Maria Pontes
Bandeira de Oliveira (PE)
BSC/DERC/GECESP - Daniel Jogaib
Daher (SP)
BSC/DERC/GECN - José Roberto Nolasco
de Araújo (AL)
Arquivos Brasileiros de Cardiologia
Volume 101, Number 6, Supplement 2, December 2013
Indexing: ISI (Thomson Scientific), Cumulated Index Medicus (NLM), SCOPUS,
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SUPPORT
Summary
Foreword...............................................................................................................................................page 1
Introduction.........................................................................................................................................page 1
1. Risk stratification.........................................................................................................................page 2
Cardiovascular risk stratification for atherosclerosis prevention and treatment..........................................page 2
Risk stratification in stages........................................................................................................................page 2
Phase 1 - Presence of significant atherosclerosis or its equivalent...........................................................page 2
Phase 2 - Risk score...................................................................................................................................page 2
Phase 3 - Aggravating Factors...................................................................................................................page 5
Phase 4 - Risk stratification by lifetime.....................................................................................................page 5
2. Smoking...........................................................................................................................................page 7
Smoking Prevention...................................................................................................................................page 7
Primordial smoking prevention..................................................................................................................page 7
Factors contributing to the initiation of smoking........................................................................................page 7
Strategies to fight smoking initiation..........................................................................................................page 8
How to treat the psychological dependence on smoking............................................................................page 8
Tools that help to evaluate and understand patient profile:........................................................................page 9
Pharmacological Treatment of Smoking....................................................................................................page 9
Nicotine replacement therapy....................................................................................................................page 10
Transdermal nicotine.................................................................................................................................page 10
Oral use nicotine - nicotine gum or lozenges...........................................................................................page 10
Bupropion chloride...................................................................................................................................page 10
Varenicline tartrate....................................................................................................................................page 10
Second-line medications...........................................................................................................................page 11
Nortriptyline..............................................................................................................................................page 11
Associations of anti-tobacco drugs.............................................................................................................page 11
3. Diet, supplements and vitamins...........................................................................................page 11
Introduction................................................................................................................................................page 11
Carotenoids................................................................................................................................................page 11
Vitamin E....................................................................................................................................................page 12
Vitamin C...................................................................................................................................................page 12
Vitamin D...................................................................................................................................................page 12
Vitamins B and folate.................................................................................................................................page 13
Omega-3 polyunsaturated fatty acids of marine origin (Docosahexaenoic (DHA) and
Eicosapentaenoic (EPA)...............................................................................................................page 13
Omega-3 polyunsaturated fatty acids of vegetable origin...........................................................................page 13
4. Obesity and overweight.............................................................................................................page 14
Primary Prevention.....................................................................................................................................page 14
Secondary Prevention................................................................................................................................page 14
Drug therapy.............................................................................................................................................page 15
Bariatric surgery........................................................................................................................................page 15
5. Arterial Hypertension.................................................................................................................page 15
Definition and classification (VI DBH).........................................................................................................page 16
Blood pressure measurements...................................................................................................................page 16
Routine initial evaluation of the hypertensive patient.................................................................................page 16
Identification of subclinical target-organs injuries...................................................................................page 16
Prevention.................................................................................................................................................page 17
Primary prevention of SAH........................................................................................................................page 18
Non-pharmacological measures.................................................................................................................page 18
Diets..........................................................................................................................................................page 18
Sodium......................................................................................................................................................page 18
Alcohol......................................................................................................................................................page 18
Physical activity.........................................................................................................................................page 18
Weight Control..........................................................................................................................................page 19
Control of psychosocial stress...................................................................................................................page 19
Multidisciplinary team..............................................................................................................................page 19
Other non-pharmacological strategies for blood pressure control..........................................................page 19
Drug measures for hypertension prevention...............................................................................................page 19
Treatment decision-making and risk category............................................................................................page 19
Pharmacological treatment........................................................................................................................page 19
Therapeutic targets....................................................................................................................................page 20
6. Dyslipidemia..................................................................................................................................page 20
Non-pharmacological treatment of dyslipidemia........................................................................................page 21
Pharmacological treatment of dyslipidemia...............................................................................................page 22
Statins........................................................................................................................................................page 22
Ezetimibe...................................................................................................................................................page 23
Resins........................................................................................................................................................page 23
Niacin........................................................................................................................................................page 23
Fibrates......................................................................................................................................................page 23
Omega 3 Fatty Acids.................................................................................................................................page 24
7. Diabetes...........................................................................................................................................page 24
Prevention..................................................................................................................................................page 24
8. Metabolic Syndrome..................................................................................................................page 25
Metabolic Syndrome definition...................................................................................................................page 25
Prevalence of metabolic syndrome in different population groups.............................................................page 25
Cardiovascular and Metabolic Risks Associated with MS............................................................................page 25
Risk Factors for Metabolic Syndrome.........................................................................................................page 26
Prevention of Metabolic Syndrome.............................................................................................................page 26
Weight reduction.......................................................................................................................................page 26
Abdominal obesity....................................................................................................................................page 27
Healthy diet...............................................................................................................................................page 27
Physical Exercise........................................................................................................................................page 27
Changes in life style versus drug therapy....................................................................................................page 27
9. Physical activity, exercises and sports................................................................................page 27
Concepts and most relevant expressions....................................................................................................page 27
Major Acute and Chronic Effects of Exercise...............................................................................................page 27
Epidemiological Rationale of Physical Activity Benefits .............................................................................page 27
Risks of Physical Activity, Physical Exercise and Sports Practice................................................................page 29
Physical Exercise Prescription ...................................................................................................................page 29
Formal and Informal Physical Activity: Strategies to Encourage Referral, Implementation
and Adherence.................................................................................................................................page 30
10. Psychosocial risk factors.......................................................................................................page 30
Definitions and Impact...............................................................................................................................page 30
Assessment of psychosocial risk factors....................................................................................................page 31
Significance of Interventions on the Psychosocial Risk Factors..................................................................page 31
“Ten strategic steps” to improve counseling for behavioral change.............................................................page 31
Future Directions........................................................................................................................................page 32
Adherence to cardiovascular disease prevention strategies: life style and medication................................page 32
Definition..................................................................................................................................................page 32
Impact.......................................................................................................................................................page 32
Causes.......................................................................................................................................................page 32
Evaluation..................................................................................................................................................page 33
Interventions.............................................................................................................................................page 33
11. Childhood and adolescence.................................................................................................page 34
Dyslipidemia..............................................................................................................................................page 34
Epidemiology in Brazil..............................................................................................................................page 34
Screening...................................................................................................................................................page 34
Reference values.......................................................................................................................................page 34
Treatment..................................................................................................................................................page 34
Change in life style....................................................................................................................................page 34
Drug therapy.............................................................................................................................................page 35
Obesity.......................................................................................................................................................page 38
Definition and Epidemiology....................................................................................................................page 38
Prognosis...................................................................................................................................................page 38
Diagnosis...................................................................................................................................................page 38
Prevention and Treatment.........................................................................................................................page 38
Systemic Arterial Hypertension..................................................................................................................page 38
Physical activity..........................................................................................................................................page 40
12. Legislation and prevention of risk factors for cardiovascular diseases............page 42
13. Topics in prevention.................................................................................................................page 45
Autoimmune diseases and cardiovascular disease....................................................................................page 45
Influenza and cardiovascular disease.........................................................................................................page 46
Chronic Kidney Disease..............................................................................................................................page 47
Obstructive Artery Disease.........................................................................................................................page 48
Socioeconomic Factors..............................................................................................................................page 48
Obstructive sleep apnea.............................................................................................................................page 49
Erectile dysfunction....................................................................................................................................page 50
Periodontitis...............................................................................................................................................page 50
References...........................................................................................................................................page 51
I Brazilian Guidelines on Cardiovascular
Prevention
Development
Sociedade Brasileira de Cardiologia (Brazilian Society of Cardiology)
Board
of
Standardizations
and
Guidelines
Antônio Carlos Sobral Sousa, Harry Correa Filho, Iran Castro, Marcus Vinícius Bolivar Malachias, Mário Sérgio de Carvalho Bacellar
Coordinator
of the
Board
of
Standardizations
and
Guidelines
Harry Correa Filho
Coordinator
Antônio Felipe Simão
President
Brazilian Society
(2012-2013 term)
of the
of
Cardiology
Jadelson Pinheiro de Andrade
Editorial Board
Harry Correa Filho, Antônio Felipe Simão, Dalton Bertolim Précoma, Gláucia Maria Moraes de Oliveira
Editors
Jadelson Pinheiro de Andrade, Andrei de Carvalho Sposito, Dalton Bertolim Précoma, Jose Francisco Kerr Saraiva,
Oscar Pereira Dutra e Gláucia Maria Moraes de Oliveira
The guideline should be cited as:
Simão AF, Précoma DB, Andrade JP, Correa Filho H, Saraiva JFK, Oliveira GMM et al. Sociedade Brasileira de
Cardiologia. I Diretriz Brasileira de Prevenção Cardiovascular.
Arq Bras Cardiol. 2013: 101 (6Supl.2): 1-63
Correspondence to:
Sociedade Brasileira de Cardiologia
Av. Marechal Câmara, 360/330 – Centro – Rio de Janeiro – CEP: 20020-907
e-mail: [email protected]
DOI: 10.5935/abc.2013S012
Work Groups
Group 1 - Risk Stratification
Coordinator: Francisco Antonio Helfenstein Fonseca. Participants: Sergio Emanuel Kaiser, Marcelo Chiara Bertolami,
Maria Cristina O Izar e Emilio H Moriguchi.
Group 2 - Smoking
Coordinator: Aristoteles Comte de Alencar Filho. Participants: Aloyzio Achutti, Carla Janice Lantieri, Jaqueline Scholz Issa,
Silvia Cury Ismael.
Group 3 - Diet, Supplements and Vitamins
Coordinator: Raul Dias dos Santos Filho. Participants: Ana Maria Pita Lotemberg, Ana Carolina Moron Gagliardi,
Roberta Lara Cassani, Marcio Hihoshi Miname.
Group 4 - Obesity and Overweight
Coordinator: Carlos Scherr. Participants: Walmir Coutinho, Adriana Campos, Ana Paula Lins.
Group 5 - Arterial Hypertension
Coordinator: Marcus Vinícius Bolivar Malachias. Participants: Weimar Kunz Sebba Barroso de Souza, Celso Amodeo,
Paulo Cesar Brandão Veiga Jardim, Luiz Aparecido Bortolotto, Rui Manuel dos Santos Povoa.
Group 6 - Dyslipidemia
Coordinator: Jose Rocha Faria Neto. Participants: Andre Arpad Faludi, Carolina Stoll, Hermes Toros Xavier, Marcelo Chiara Bertolimi,
Viviane Z. Rocha.
Group 7 - Diabetes
Coordinator: Otávio Rizzi Coelho. Participants: Jose Roberto Matos de Souza.
Group 8 - Metabolic Syndrome
Coordinator: Andréa Araujo Brandão. Participants: Emilia Moriguchi, Maria Eliane Campos Magalhães, Walmir Coutinho,
Alexandre Alessi, Antonio Felipe Sanjuliani.
Group 9 - Physical Activity
Coordinator: Artur Haddad Herdy. Participants: Claudio Gil Soares de Araujo, Mauricio Milani, Nabil Ghorayeb,
Ricardo Stein, Tales de Carvalho
Group 10 - Psychosocial Factors
Coordinator: Mauricio Wajngarten. Participants: Alvaro Avezum Junior, Carise Anne Polanczyk, Evandro Tinoco Mesquita,
Gilson Soares Feitosa.
Group 11 - Childhood and Adolescence
Coordinatora: Isabela de Carlos Back Giuliano. Participants: Lucia Campos Pellanda, Ivan Romero Rivera, Maria Alayde
Mendonça R.Rivera.
Group 12 - Legislation
Coordinator: Carlos Alberto Machado. Participants: Antonio Silveira Sbissa, Marco Antonio Mota Gomes, Geniberto Paiva Campos,
Lucelia Batista N. Cunha, Lenildo de Moura and Romero Bezerra Barbosa.
Group 13 - Topics in Prevention
Coordinator: Glaucia Maria Moraes de Oliveira. Participants: Roberto Muniz Ferreira, Paolo Branco Vilela and Gabriel Porto Soares.
Participated in clinical
studies and / or
experimental trials
supported by
pharmaceutical or
equipment related to the
guideline in question
Has spoken
at events
or activities
sponsored
by industry
related to the
guideline in
question
It was (is)
advisory board
member or
director of a
pharmaceutical
or equipment
Committees
participated
in completion
of research
sponsored by
industry
Personal or
institutional aid
received from
industry
Adriana Campos
Junqueira de Souza
No
No
No
No
No
No
No
Alexandre Alessi
No
No
No
No
No
No
No
Álvaro Avezum Junior
No
No
No
Population Health
Research Institute,
McMaster University,
Hamilton, Canada
No
No
No
Aloyzio Cechella Achutti
No
No
No
No
No
No
No
Ana Carolina Moron
Gagliardi
No
No
No
No
No
No
No
Ana Maria Pita
Lotemberg
No
No
No
No
No
No
No
Ana Paula Machado Lins
No
No
No
No
No
No
No
Andre Arpad Falud
No
No
No
No
No
No
No
Andrea Araújo Brandão
No
Servier, Biolab, Astra
Zeneca, Novartis,
Chiesi, Daiichi
Sankyo
Biolab, Servier
No
Servier, Daiichi
Sankyo, Biolab
Medley, Biolab,
Servier, Astra
Zeneca, Novartis,
Daiichi Sankyo
No
Antônio Felipe Simão
No
No
No
No
No
No
No
Names Members
Produced
scientific
It shares
papers
the
in journals
industry
sponsored by
industry
Antônio Felipe Sanjuliani
No
No
No
No
No
No
No
Antônio Silveira Sbissa
No
No
No
No
No
No
No
Aristóteles Comte
Alencar Filho
No
No
No
No
Biolab, Pfizer, Bayer
No
No
Artur Haddad Herdy
No
No
No
No
No
No
No
Carise Anne Polanczyk
No
No
No
No
No
No
No
Carla Janice Lantieri
No
No
No
No
No
No
No
Carlos Alberto Machado
No
No
No
No
No
No
No
Carlos Scherr
No
Coca-Cola, Unilever
No
No
Carolina Stoll
No
No
No
No
Celso Amodeo
No
Dalton Bertolim Precoma
No
No
Denise Saraiva
No
No
Pfizer
Biolab, DaiichiSankyo, MSD
No
No
Evandro Tinoco
Mesquita
Francisco Antônio
Helfenstein Fonseca
No
No
astra zeneca,
astra zeneca,
astra zeneca, Biolab, astra zeneca, Biolab, astra zeneca, Biolab,
astra zeneca, Biolab, ache,
Biolab, ache,
Biolab, ache,
ache, novartis,
ache, novartis,
ache, novartis,
novartis, Sankyo, Takeda
novartis, Sankyo, novartis, Sankyo,
Sankyo, Takeda
Sankyo, Takeda
Sankyo, Takeda
Takeda
Takeda
Cláudio Gil Soares de
Araújo
Emílio H. Moriguchi
Novartis, Biolab,
Astrazeneca,
MSD, Nycomed
Bayer, Ache,MSD,
Boehringer
Novartis, Aché, Libbs, MSD,
AstraZeneca, Torrent, Novartis
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
No
Merck, Daiichi-Sankyo
No
Merck, DaiichiSankyo, Biolab
Biolab
No
No
No
No
No
No
No
AstraZeneca,
Novartis, Biolab,
Aché, Pfizer,
BMS, Libbs,
MSD, Nestlé,
Hypermarcas
No
No
Novartis
No
No
No
Continuation
Geniberto Paiva Campos
No
No
No
No
No
No
No
Gabriel Porto Soares
No
No
No
No
Novartis
Aché, Bristol
No
Gilson Soares Feitosa
No
No
No
No
No
No
No
Gláucia Maria Moraes
de Oliveira
No
No
No
No
No
No
No
Harry Correa Filho
No
No
No
No
No
No
No
No
Amgen, MSD,
Torrent
Aché, Amgen,
AstraZeneca,
Biolab, Chiesi,
MSD, Novartis,
Pfizer, Torrent.
No
Aché, Amgen,
AstraZeneca,
Biolab, Chiesi, MSD, Amgen, MSD, Torrent
Novartis, Pfizer,
Torrent
Hermes Toros Xavier
Pfizer, AstraZeneca
Isabela de Carlo Back
Giuliano
No
No
No
No
No
No
No
Ivan Romero Rivera
No
No
No
No
No
No
No
Isabel Cristina Britto
Guimaraes
No
No
No
No
No
No
No
Jadelson Pinheiro de
Andrade
No
No
No
No
No
No
No
Jaqueline Scholz Issa
Pfizer
Pfizer,
Johnson&Johnson,
Glaxo-Smith Kline
No
No
No
No
No
AstraZeneca
No
Novartis, Nova
Quimica,
Boheringer
No
No
No
No
No
No
No
No
No
MSD
No
Jose Francisco Kerr
Saraiva
José Roberto Matos de
Souza
José Rocha Faria Neto
AstraZeneca, Daichii Sankyo
No
AstraZeneca,
Boheringer, Pfizer, Boheringer, Pfizer,
BMS, Chiesi, Daichii BMS, NovoNordisk
Sankyo
No
Astra Zeneca, Daichi
Astra Zeneca, Daichi Sankyo Sankyo, Boehringer
Ingelheim, MSD
Lucelia Batista N. Cunha
No
No
No
No
No
No
No
Lucia Campos Pellanda
No
No
No
No
No
No
No
Luiz Aparecido Bortolotto
No
No
No
No
No
No
No
No
No
No
MSD, Pfizer,
Novaquímica,
Aché
No
Marcelo Chiara
Bertolami
MSD, Astrazeneca,
Biolab, Pfizer,
MSD, Astrazeneca, ScheringNovartis, Aché,
Plough, Pfizer, Novartis
Novaquímica,
Novonordisk, Bayer,
Libbs
Márcio Hihoshi Miname
No
No
No
No
No
No
No
Marco Antônio Mota
Gomes
No
No
Biolab, Servier, Omron
Torrent
Biolab, Daiichi
Sankyo, Novartis,
Takeda
Biolab, Torrent,
Novartis
No
Marcus Vinícius Bolivar
Malachias
No
Servier, BoehringerIngelheim, Torrent,
AstraZeneca, Pfizer,
Novartis
No
No
No
Servier, Nova
Química, Libbs,
Bayer
No
Maria Alayde Mendonça
da Silva
No
No
No
No
No
No
No
Amgen, Genzyme, Novartis,
MSD, Aché,
Aché, MSD, Aegerion,
Aegerion, UNILEVER
Unilever, Libbs
No
No
Aegerion
Torrent,
Genzyme, Libbs
No
Maria Cristina de
Oliveira Izar
Maria Eliane Campos
Magalhães
No
AstraZeneca, Pfizer,
MSD
No
No
Maurício Milani
No
No
No
No
No
No
No
Maurício Wajngarten
No
No
No
No
No
No
No
Nabil Ghorayeb
No
No
No
No
No
No
No
Pfizer, AstraZeneca Nova Química
No
Continuation
Otávio Rizzi Coelho
Improve
Paolo Blanco Villela
Pfizer e Bayer
Pfizer, Novo Nordisk
e Biolab
No
Takeda, Bayer e
Pfizer
No
No
No
No
Paulo César Brandão
Veiga Jardim
Servier
Novartis, Biolab,
Aché
Raul Dias dos Santos
Filho
Pfizer, Astra Zeneca, ISIS,
MSD, Roche
No
Pfizer, Astra Zeneca, Pfizer,Astra Zeneca,
biolab, BMS,
BMS, Biolab,
Aegerion, Novartis, Aegerion, Genzyme,
MSD
Boehringer
No
nao
AstraZeneca
No
No
No
No
No
Novartis, Biolab,
Aché
No
Genzyme, Aegerion,
Biolab, MSD
Biolab, Sanofi, MSD
No
Ricardo Stein
No
No
No
No
No
No
No
Roberta Soares Lara
Cassani
No
Gomes da Costa
No
No
No
No
No
Roberto Luiz D'Avila
No
No
No
No
No
No
No
Roberto Muniz Ferreira
No
No
No
No
No
No
No
Romero Bezerra
Barbosa
No
No
No
No
No
No
No
Rui Manuel dos Santos
Povoa
No
No
No
No
No
No
No
Sérgio Emanuel Kaiser
No
MSD, Abbott,
Farmasa
No
No
No
Novaquimica,
Medley
No
Silvia Cury Ismael
No
No
No
No
No
No
No
Tales de Carvalho
No
No
No
No
No
No
No
Viviane Zorzanelli Rocha
Giraldez
No
No
No
No
No
No
No
Walmir Coutinho
No
No
No
No
No
No
No
Weimar Kunz Sebba
Barroso de Souza
No
No
No
No
No
No
No
Definitions for grade of recommendation and level of evidence:
Grade of recommendation
Class I: Conditions for which there is conclusive evidence, or in its absence, general agreement that the procedure is safe and
useful / effective.
Class II: Conditions for which there is conflicting evidence and/or divergence of opinion about safety and usefulness/efficacy
of the procedure.
Class IIa: Weight or evidence/opinion in favor of the procedure. Approved by most professionals.
Class IIB: safety and usefulness/efficacy less well established, with no predominance of opinions in favor of the procedure.
Class III: Conditions for which there is evidence and / or consensus that the procedure is not useful / effective and in some
cases may be harmful.
Level of Evidence
Level A: Data obtained from multiple consistent randomized trials of good size, and/or robust meta-analysis of randomized
clinical trials.
Level B: Data obtained from less robust meta-analysis, from a single randomized trial or nonrandomized trials (observational studies).
Level C: Data obtained from consensual experts’ opinion.
It is noteworthy that levels of evidence classified as B or C cannot be interpreted as weak recommendations. There are many
consensus recommendations; therefore, with a degree of recommendation I, level of evidence C (experts’ opinions). On the
other hand, some indications considered controversial (recommendation grade II) may be supported by randomized controlled
trials (Level of evidence A).
I Brazilian Guidelines on Cardiovascular Prevention
Guidelines
Foreword
Introduction
When we analyze the epidemiology of Cardiovascular
Diseases, we observe it has the same behavior in the beginning
of this century that major epidemics had in the past centuries.
Ever since the Brazilian Society of Cardiology (SBC)
established as its goal, following the example of the World
Health Organization (WHO), to reduce cardiovascular mortality
by 25% by the year 2025, it became clear the need to create
the I Brazilian Guideline of Cardiovascular Prevention9.
This becomes clear when we look at the data from the World
Health Organization (WHO) in recent decades, showing that,
of 50 million deaths, Cardiovascular Diseases (CVD) accounted
for 30% of this mortality, i.e., 17 million individuals1,2.
The identification of risk factors with higher population
prevalence allowed well-conducted cardiovascular prevention
programs in several countries such the United States, Canada,
Finland, United Kingdom, Australia and Japan, to be able to
significantly reduce mortality from cardiovascular diseases3.
Based on this epidemiological profile, the identification of
risk factors and the outcome of these programs application,
the World Health Organization established as its goal decrease
by 25% the Noncommunicable Chronic Diseases (NCDs),
among them the CVDs, by the year of 20254.
In line with this global proposal and considering that the
epidemiological reality in Brazil also discloses alarming rates
of 30% of deaths from CVDs, among all other related causes,
the Board of Directors of the Brazilian Society of Cardiology
(SBC), during its current term, decided to draft the “National
Cardiovascular Prevention Program” and implement it in the
country aiming to modify this epidemiological reality.
Several arms of the National Cardiovascular Prevention
Program are already being applied in Brazil, with international
effects, such as the “Carta do Rio”5, created and signed jointly
by SBC and the main Cardiology Societies in the world and
published on their sites and Cardiology journals. The “SBC goes
to school” program, the Brazilians Cardiovascular Registries6,
the Agreement on Cooperation between the SBC/OPAS/MS
for the application of the TECA A and TECA B program7, the
Agreement on Cooperation with State and Municipal Health
Secretariats for the training of Public Health8 physicians and the
Agreement on Cooperation between SBC/CNBB/Ministry of
Health, are some of these examples that have already started
to show impact of results, being disseminated in Brazil and in
international forums.
The proposal of creating the I Brazilian Guideline for
Cardiovascular Prevention of the Brazilian Society of
Cardiology is another important step in this program.
With this document, SBC offers to Brazilian Cardiology an
important tool for the standardization of procedures regarding
Cardiovascular Prevention in Brazil.
Our acknowledgments to all those who contributed
for the creation of this guideline, which will certainly be a
relevant milestone in the National Cardiovascular Prevention
Program of SBC.
Jadelson P. Andrade
President SBC - 2012/2013 Term
1
Arq Bras Cardiol. 2013; 101(6Supl.2): 1-63
The first step taken in this direction was the “Carta do Rio”
(Letter from Rio), a document prepared during the course of
Brazil III Prevent & I Latin America Prevent, held in the city
of Rio de Janeiro in December 20125.
CVDs will increase the disability-adjusted life years (DALYs)
of 85 million patients to 150 million worldwide by 2020,
leading to a noticeable decrease in global productivity10,11.
The WHO estimates that three quarters of cardiovascular
mortality can be reduced with appropriate changes in
life style, and that is the great challenge of all existing CV
prevention guidelines9.
Therefore, we need to adopt governmental measures
associated with institutional measures and of the organs
responsible for health prevention in our country at all levels.
SBC is doing its part in this process.
The I Brazilian CV Prevention Guideline has this goal: to
discuss the necessary measures to be adopted as a practical
guide for the routine practice of the Brazilian cardiologist.
The bases of prevention have their roots in CV
epidemiology and evidence-based Medicine. Based on that,
the team of editors and contributors of the I Brazilian CV
Prevention Guideline elected 13 items as the foundation
of this guideline, which will be proposed and discussed
throughout the document.
Antonio Felipe Simão - Coordinator
Guidelines
1. Risk stratification
Cardiovascular risk stratification for atherosclerosis
prevention and treatment
An acute coronary event is the first manifestation of
atherosclerotic disease in at least half the individuals with
this complication. Thus, the identification of asymptomatic
individuals that are more susceptible is crucial for effective
prevention, with the correct definition of therapeutic goals11.
To estimate the severity of cardiovascular disease (CVD),
the so-called risk scores and algorithms based on regression
analyses of population studies were created, through which
the overall risk identification is substantially improved.
Among the existing algorithms, the Framingham risk score
(FRS)12, the Reynolds Risk Score (RRS)13-14, the Global Risk
Score (GRS)15 and the Lifetime Risk (LRS)16-18, are options that
will be discussed later.
The FRS estimates the probability of occurrence of
myocardium infarction or death from coronary heart disease
in a 10-year period in individuals with no prior diagnosis of
clinical atherosclerosis12. Although this risk estimate is subject
to corrections according to epidemiological indicators of the
studied population, the FRS appropriately identifies individuals
with high and low risks, the RRS includes C-reactive protein
(CRP) and family history of premature coronary heart disease
and estimates the probability of myocardial infarction, stroke,
death and revascularization in 10 years13,14. The GRS estimates
the risk of myocardial infarction, cerebrovascular accident
(CVA), peripheral vascular insufficiency and heart failure in
10 years15. The LRS assesses the probability of an individual
to have an ischemic event after 45 years of age16-18. The
calculation of the LRS considers that the individual belongs
exclusively to one of the following categories: a) those with no
risk factors, or all optimal risk factors at age 45; b) those that
have one or more non-optimal risk factors; c) those with one
or more high risk factors; d) those with one of the main risk
factors; e) those with two or more of the main risk factors16-18.
The combination of these various scores allows a better
risk estimate. The justification for the use of a short-term
score and another long-term one is the fact that most
women and young adult men are at the range of low
predicted short-term risk; however, part of these will
remain low risk, while others will have predicted high risk
throughout life. Thus, the risk approach through lifetime
can be used to improve the motivation of individuals with
low predicted short-term risk, but with predicted high
risk in the long term to intensify changes in life style and
control risk factors.
This guideline recommends the use of the GRS15 for
risk assessment in 10 years and the LRS16-18 to estimate risk
throughout life in individuals over 45 years.
Note: All other scores can be used as risk stratification tools.
Risk stratification in stages
The risk stratification proposed by this Guideline proposes
four stages:
Phase 1 - Presence of significant atherosclerosis or
its equivalent
The risk of atherosclerotic disease is estimated based on the
joint analysis of characteristics that increase the individual’s
likelihood of developing the disease. Therefore, the most
evident risk identification factor is the previous manifestation
of the disease itself. Thus, the first phase in risk stratification is
the identification of clinical manifestations of atherosclerotic
disease or its equivalent (such as diabetes mellitus type 1
or 2, or significant chronic kidney disease, even in primary
prevention) (Chart 1.1). Individuals thus identified, both men
and women, have a higher than 20% risk in 10 years to have
new cardiovascular events19 or a first cardiovascular event19.
The patient that falls into one of these categories does
not require additional steps for risk stratification and is
automatically considered to be high risk.
High-risk conditions are those shown in Table 1.120.
Phase 2 - Risk score
The Global Risk Score (GRS)15 (http://www.zunis.org/
FHS_CVD_Risk_Calc_2008.htm ) must be used in the initial
evaluation in individuals that were not included in the high-risk
conditions (Tables 1.2 , 1.3 , 1.4 , 1.5).
Individuals considered LOW RISK by this Guideline are
those with probability < 5% to have major cardiovascular
events (coronary artery disease - CAD, stroke, peripheral
obstructive arterial disease or heart failure) in 10 years. Patients
classified in this category with family history of premature
cardiovascular disease will be reclassified to intermediate risk.
Individuals considered INTERMEDIATE risk are men
with calculated risk ≥ 5% and ≤ 20% and women with
calculated risk ≥ 5 % and ≤ 10% occurrence of any of the
aforementioned events12,20,21.
Individuals are considered HIGH risk are those with
calculated risk > 20% for men and > 10% for women in a
10-year period21.
Table 1.1 – Criteria for identification of patients with high risk of coronary events (Phase 1)20
•
Coronary artery atherosclerotic disease, peripheral arterial, cerebrovascular or peripheral obstructive disease, with clinical manifestations (cardiovascular events), and
also in the subclinical form documented by diagnostic methodology.
•
Revascularization procedures.
•
Diabetes mellitus type 1 and type 2.
•
Chronic Kidney Disease.
2
Guidelines
Table 1.2 – Scoring according to overall risk for women19,20
Points
Age (years)
HDL-C
TC
-3
SBP (untreated)
SBP (treated)
Smoking
Diabetes
No
No
< 120
-2
60+
-1
50-59
0
30-34
1
2
35-39
< 120
45-49
< 160
120-129
35-44
160-199
130-139
< 35
140-149
3
120-129
200-239
130-139
4
40-44
240-279
150-159
5
45-49
280+
160+
Yes
Yes
140-149
6
150-159
7
50-54
8
55-59
9
60-64
10
65-69
11
70-74
12
75+
160+
Points
Total
HDL-C: high-density lipoprotein cholesterol; TC: total cholesterol; SBP: systolic blood pressure.
Table 1.3 – Overall cardiovascular risk in 10 years for women19,20
Points
3
Risk (%)
Points
Risk (%)
≤ -2
<1
13
10.0
-1
1.0
14
11.7
0
1.2
15
13.7
1
1.5
16
15.9
2
1.7
17
18.5
3
2.0
18
21.6
4
2.4
19
24.8
5
2.8
20
28.5
6
3.3
21+
> 30
7
3.9
8
4.5
9
5.3
10
6.3
11
7.3
12
8.6
Guidelines
Table 1.4 – Scoring according to overall risk for men19,20
Points
Age (years)
-2
HDL-C
TC
60+
-1
SBP (untreated)
SBP (treated)
50-59
0
30-34
< 160
120-129
35-44
160-199
130-139
< 35
200-239
140-159
120-129
3
240-279
160+
130-139
4
280+
2
35-39
5
40-44
6
45-49
Diabetes
No
No
< 120
45-49
1
Smoking
< 120
140-159
Yes
Yes
160+
7
8
50-54
9
10
55-59
11
60-64
12
65-69
13
14
70-74
15
75+
Points
Total
HDL-C: high-density lipoprotein cholesterol; TC: total cholesterol; SBP: systolic blood pressure.
Table 1.5 – Overall cardiovascular risk in 10 years for men19,20
Points
Risk (%)
Points
Risk (%)
≤ -3 ou menos
<1
13
15.6
-2
1.1
14
18.4
-1
1.4
15
21.6
0
1.6
16
25.3
1
1.9
17
29.4
2
2.3
18+
>30
3
2.8
4
3.3
5
3.9
6
4.7
7
5.6
8
6.7
9
7.9
10
9.4
11
11.2
12
13.2
4
Guidelines
Phase 3 - Aggravating Factors
For intermediate-risk individuals, aggravating factors
should be used, which, when present (at least one) reclassify
the individual for high-risk condition. (Chart 1.1)22 and the
criteria for metabolic syndrome according to the International
Diabetes Federation (IDF) (Chart 1.2)23,24.
The diagnosis of metabolic syndrome requires the presence
of abdominal obesity as an essential condition and two or
more of the criteria shown out in Chart 1.223,24.
Phase 4 - Risk Stratification by Lifetime
Aiming to reduce the burden of cardiovascular
disease, the overall risk calculation in 10 years has been
emphasized. However, it has been observed that many
individuals considered low risk in 10 years, are actually
high risk throughout the lifetime. The cardiovascular
disease estimation using the lifetime risk stratification
allows stratifying more comprehensively the burden of
cardiovascular disease in the general population at the
present time and in the future, as it takes into account
the risk of cardiovascular disease as the individual ages.
This tool can assist in public health policies, allowing
projections of global cardiovascular disease burden of in
the population. This guideline recommends the use of the
Lifetime Risk Score in individuals at low to intermediate
risk after 45 years of age.
Table 1.6 classifies risk factors, according to the control and/
or their importance as optimal, non-optimal, high and main.
Table 1.7 and Table 1.8 show the calculation of LRS for men
and women, respectively, after 45 years of age, based on the
exposure to these factors throughout the lifetime.
The risk predicted by the lifetime > 39% in men and
> 20.2% in women characterizes a high-risk condition for
the lifetime25,26.
The algorithm in Figure 1 summarizes and aids in
cardiovascular risk stratification.
Chart 1.1 – Aggravating risk factors12
•
•
•
•
•
•
Family history of early coronary artery disease (male first-degree relative < 55 years-old or female first-degree relative < 65 years-old).
Criteria of metabolic syndrome according to the International Diabetes Federation24,25 .
Microalbuminuria (30-300 mg/min) or macroalbuminuria (> 300 mg/min).
Left ventricular hypertrophy.
High-sensitivity C-reactive protein > 3 mg/L.
Evidence of subclinical atherosclerotic disease:
–
carotid stenosis/thickening > 1mm26;
–
coronary calcium score > 100 or > 75th percentile for ageo or sex27;
–
ankle-brachial test < 0.9.
Chart 1.2 – Diagnostic criteria for metabolic syndrome23,24
Criteria
•
Abdominal obesity
•
Men
•
•
Caucasian of European origin and African descendants
•
≥94
•
South Asians, Native Americans and Chinese
•
≥90
•
Japanese
•
≥85 cm
Women
•
Caucasian of European origin, African descendants, South Asians, Native Americans and Chinese
•
≥80 cm
•
Japanese
•
≥90 cm
•
≥150 mg/dL
•
Triglycerides
•
HDL-cholesterol
•
•
5
Definition
•
Men
•
<40 mg/dL
•
Women
•
<50 mg/dL
Blood pressure
•
Systolic
•
≥ 130 mmHg or treatment for arterial hypertension
•
Diastolic
•
•
Fasting ≥100 mg/dL
Glycemia
Guidelines
Table 1.6 – Classification of risk factors, according to their control and/or importance19,20
Risk factor
Optimal risk factors
Total Cholesterol
1 Non-optimal risk factors
High risk factors
Main risk factors
<180 mg/dl
180-190 mg/dl
200-239 mg/dl
> 240 mg/dl
Systolic blood pressure
Non-treated <120 mmHg
Non-treated 120-139 mmHg
Treatment for SAH or non-treated SBP ≥ 160 mmHg
Diastolic blood pressure
Non-treated <80 mmHg
Treatment for SAH or Non-treated DBP≥ 100 mmHg
Smoking
No
No
No
Yes
Diabetes
No
No
No
Yes
SBP: systolic blood pressure; DBP: diastolic blood pressure; SAH: systemic arterial hypertension.
Table 1.7 – Risk of fatal and nonfatal cardiovascular events by Lifetime in men, according to the exposure to risk factors throughout life19,20
Variable
Situation according to risk factors
All optimal risk factors
≥ 1 non-optimal
Risk factor
≥ 2 High risk factors
1 Main risk factor
≥ 2 Main risk factors
Percentage risk (95% CI)
Risk after 45 years
Fatal CAD or non-fatal AMI
1.7 (0-4.3)
27.5 (15.7-39.3)
32.7 (24.5-41.0)
34.0 (30.4-37.6)
42.0 (37.6-46.5)
6.7 (1.4-11.9)
7.7 (5.0-10.4)
8.5 (6.9-15.6)
8.4 (7.5-9.4)
10.3 (9.0-11.7)
Death from cardiovascular disease
9.1 (0-18.6)
13.1 (9.9-16.3)
15.3 (13.3-17.3)
20.7 (19.4-22.2)
32.5 (30.5-34.5)
Total of events related to
atherosclerotic CVD
1.4 (0-3.4)
31.2 (17.6-44.7)
35.0 (26.8-43.2)
39.6 (35.7-43.6)
49.5 (45.0-53.9)
Fatal or nonfatal stroke
CAD: coronary artery disease; AMI: acute myocardial infarction; CVD: cardiovascular disease.
Table 1.8 – Risk of fatal and nonfatal cardiovascular events by Lifetime in women, according to exposure to risk factors throughout life19,20
Variable
Situation according to risk factors
All optimal risk
factors
≥ 1 non-optimal risk
factors
≥ 2 high-risk factors
1 main risk factor
≥ 2 main risk
factors
Percentage risk (95% CI)
Risk after 45 years
Fatal CAD or non-fatal AMI
1.6 (0-4.3)
9.3 (3.0-15.6)
9.3 (5.0-13.7)
12.7 (10.3-15.0)
21.5 (17.5-25.5)
Fatal or nonfatal stroke
8.3 (3.8-12.8)
8.9 (6.5-11.3)
9.1 (7.5-10.9)
9.1 (7.9-15.9)
11.5 (9.5-13.5)
Death from cardiovascular disease
4.8 (0.8-8.7)
4.9 (3.1-6.7)
6.9 (5.4-8.3)
11.2 (9.9-12.5)
21.9 (19.4-24.5)
4.1 (0-8.2)
12.2 (4.6-19.7)
15.6 (10.3-20.9)
20.2 (17.2-23.2)
30.7 (26.3-35.0)
Total of events related to
atherosclerotic CVD
Table 1.9 – Classification of recommendation and level of evidence for risk stratification in cardiovascular prevention
Recommendation
Class
Level of
evidence
I
A
IIa
B
•
Clinical manifestations of atherosclerotic disease or equivalents (type 1 or 2 diabetes mellitus and significant chronic kidney disease),
even in primary prevention, have a risk > 20% in 10 years of new cardiovascular events or of the first cardiovascular event
•
Patients classified as intermediate-risk with a family history of early cardiovascular disease will be reclassified as high-risk
•
Men with a calculated risk for any of the events cited ≥5% and ≤20% and women with that calculated risk ≥5% and ≤10% are
considered intermediate-risk
I
A
•
Men with a calculated risk >20% and women with that calculated risk >10% are considered high-risk
I
A
•
For individuals at intermediate risk, aggravating factors should be used, and when present (at least one) reclassify the individual
as high-risk (Class IIa recommendation, level of evidence B)
IIa
B
•
Use of risk according to lifespan for low- and intermediate-risk individuals aged >45 years
IIa
B
6
Guidelines
ORS < 5% in men and women
ORS ≥ 5% and ≤20% in men or
≤ 10% in women
LOW RISK
INTERMEDIATE
RISK
If family history of early CAD, reclassify
Use aggravating: if an aggravating factor
is present
INTERMEDIATE
RISK
HIGH RISK
High-risk condition present or
ORS > 20% in men and > 10%
in women
Risk based on lifespan
Ifrisk based on lifespan
•
>39% for men or
•
> 20.2 % for women,
•
High risk of CV events
HIGH RISK
Figure 1 – Algorithm for cardiovascular risk stratification19,20
ORS: overall risk stratification; CAD: coronary artery disease; CV: cardiovascular
2. Smoking
There are over 1 billion smokers worldwide and 80% of
them live in low-and middle-income countries, where the
burden of tobacco-related diseases and death is heavier.
It is estimated that current smokers consume about 6 trillion
cigarettes every year27.
Approximately 50% of avoidable deaths among smokers
could be prevented if the addiction was abolished, with most
of these deaths being caused by CVD. The relative risk of
myocardial infarction is two-fold higher among smokers aged
> 60 years and five-fold higher among those aged < 50 years,
when compared with nonsmokers. Tobacco consumption has
declined in the general population, but showed an increase
among individuals of low socioeconomic status and among
women. In women, its deleterious effects appear to be
stronger, being related to accelerated nicotine metabolism,
with greater relevance in women that make concurrent use
of oral contraceptives28.
Smoking prevention
The Framework Convention on Tobacco Control (FCTC)
was the first international public health treaty in the history of
the World Health Organization and represented a response
instrument of the 192 countries members of the World Health
Assembly to the growing smoking epidemic worldwide27.
In 1989, approximately 32% of the population aged 15
and older were smokers, according to the National Survey on
Health and Nutrition/IBGE. Data from the household survey
called Special Smoking Survey (PeTab) disclosed that in Brazil
in 2008 there were around 25 million smokers and 26 million
former smokers. The prevalence of smokers was 17.2% of
the population aged 15 or older in 2008, demonstrating the
decline occurred during these 20 years. However, data from
7
the Surveillance of Risk Factors and Protection against Chronic
Diseases Telephone Survey (VIGITEL) released in April 2012,
showed a further decline to 14.8% of smokers in Brazil, aged
> 18 years. Among men, the percentage of smokers was
18.1% and among women, 12 %. Among those who smoked
20 or more cigarettes a day, 5.4% were men and 3.3% women.
Men, in contrast, stop smoking more frequently: 25% said
they were former smokers, while 19% of women said they
were smokers in the past. The capital cities with the most
smokers are Porto Alegre (23%), Curitiba (20%) and São Paulo
(19%). The Northeast region has the capital cities with lowest
incidence of smoking among their residents: Maceió (8%),
João Pessoa, Aracaju and Salvador (all 9%)29.
Primordial smoking prevention
Primordial prevention of smoking is understood as
preventing the initiation of smoking. The earlier an individual
starts smoking, the more likely he or she will become an adult
smoker. After one year, children inhale the same amount of
nicotine per cigarette as adults; they also experience symptoms
of dependence and abstinence30; such dependence can
develop very rapidly in children. Approximately 80% of all
individuals who start smoking in adolescence will continue to
do so into adulthood, and a third of these will die prematurely
because of smoking-related diseases31,32.
Factors that contribute to the initiation of smoking
1. Attitudes and beliefs - a study with adolescents33 showed
that 40% of those who had never smoked became
experimenters and 8% had the habit of smoking for
4 consecutive years. The firm decision of not smoking
was the strongest predictor to prevent smoking. Attitudes
that lead to smoking are influenced by several factors:
Guidelines
the influence of friends and family, social pressure among
adolescents, age, false conception (adolescents tend to
overestimate the frequency of smoking of adults and
underestimate their own); advertising33.
2. Nicotine addiction - Nicotine is a highly addictive
substance and many individuals develop dependence
within days or weeks of exposure. Young individuals are
more vulnerable to nicotine addiction than adults34,35.
3. Depression: most studies show an association between
the presence of depression and initiation of smoking,
although it is unclear whether the association is causal36.
4. Inadequate school performance: truancy and poor
school performance are associated with the initiation and
continuity of smoking34,35.
5. Adverse experiences: parental separation or divorce,
physical emotions, emotional, physical or sexual abuse;
growing up with an addicted, mentally ill or convict
family member36.
6. Substance abuse: there is a high frequency of current
smoking among adolescents who use illicit drugs 38.
Thus, every adolescent that smokes should be seen as,
potentially, engaged in other risky behaviors37.
Strategies to fight smoking initiation38
One way to address the primordial prevention is by age
groups, observing, for each group, the top five items (5 As):
Group 0-4 years: ask parents and other family members
about their smoking habits; advise them to keep the
environment free of tobacco smoke; the message should
include information about the risks to parents and children,
as well as the importance of the parental role model for the
children; assess the willingness to cooperate among the
parents and other family members; assist parents in their
attempt to stop smoking, by providing your own assistance
material and/or referring them to their own physicians;
arrange a visit within 3 months if a family member is a
smoker; check on the progress of the parents in each
subsequent pediatric visit.
Group 5-12 years: ask children about how it feels
when someone nearby is smoking and what they do
about it; also, if they consider it dangerous to smoke
and if they think they will smoke when they are older,
and moreover, if they have tried smoking or if they have
friends who smoke, advise children not to try smoking,
praise them for remaining a non-smoker and/or free of
exposure to cigarette smoke; remind them about the
negative effects of tobacco in the short term, such as a
reduction of smell and athletic capacity, as well as risks
to personal health (e.g., asthma exacerbation); advise
parents to stop smoking and provide clear anti-smoking
information to their children; assess the risk factors for
smoking initiation or progression of smoking regularly,
including the level of experimentation, smoking among
friends, depressive symptoms, school performance and
adverse experiences; assist parents in their attempts
to quit smoking, help the children to develop skills to
refuse smoking and tobacco exposure; assist parents in
their efforts to prevent smoking in their children through
parental style and firm antismoking messages; arrange visit
within 1-2 months for any child who has tried smoking or
has clear risk factors to do so, referring them as required
in cases of social or learning difficulties, as well as mental
disorder cases.
Group of adolescents and young adults: ask the adolescents
about their smoking behavior, confidentially, about friends who
are smokers and about light cigarettes; advise adolescences
to quit smoking, reinforcing the risks to personal health and
danger of addiction; praise adolescences that are not smoking
and remind them about the health risks; assess the motivation
and symptoms of tobacco dependence among adolescents
who are smoking; assess the risk factors for smoking initiation
among those that are not smoking; assist teenagers who are
smoking in their attempt to quit smoking, including nicotine
replacement and by referring if necessary; assist parents in their
efforts to prevent the initiation of smoking in their children
through parenting style and firm antismoking information;
arrange a visit within a month for each adolescent that is
smoking, supporting their attempt to stop smoking or assessing
the motivation and barriers to stop smoking; refer them as
necessary, if risk factors such as social or learning difficulties
or signs of mental disorders are identified.
Primordial cardiovascular prevention includes avoiding
the establishment of modifiable cardiovascular risk factors
including smoking and building effective strategies in
order to promote cardiovascular health of individual
and the population. For this purpose, the joint action of
multidisciplinary teams (doctors, nurses, psychologists,
physical educators, educators, nutritionists, social workers,
communicators, managers) is necessary, as well as of
intersectorial actions (family, school, government, society
experts, university), continuously and simultaneously.
How to treat the psychological dependence on smoking
There are two types of approach:
Basic Approach (AAAPA) where the goal is to ask if the
individuals smoke, assess the profile of smokers, advise them
to quit, prepare them for smoking cessation and arrange
follow-up for smoking cessation. This approach should always
be performed by the doctor during a routine consultation,
lasting at least 3 minutes and a maximum of 5 minutes, on
average, at each visit that the patient does. The patient should
be questioned and asked systematically at every consultation
and return visit on the evolution of the cessation process.
This approach is indicated for all smokers. A meta-analysis
involving 29 studies showed that cessation rates were 19.9%
for those who were submitted to medical intervention39.
Specific intensive approach: is carried out by
health professionals available and trained to perform
a more detailed follow-up with the patient, including
the physician. In this case, the professional should
have a structured program available to the patient with
scheduled sessions (eight sessions in group/individual) and
national reference medication will be used for treatment
of smoking, as well as cognitive-behavioral approach. If
possible, patients should be followed up to one year of
8
Guidelines
treatment. Cognitive behavior is a psychological approach
based on dealing with the automatic thoughts that smokers
have and that lead them to seek cigarette smoking39.
In cognitive-behavioral approach, the most often used
behavioral techniques are: self-observation, control of stimuli
or triggers that lead to smoking (phone, computer, alcoholic
beverages, bathroom, car), identification and learning of
functional thought patterns, relaxation and deep breathing
techniques, deferral and pattern interruption, assertiveness
training (so that patients may face situations where they feel
tempted to smoke), self-instruction (in which participants
are taught to argue with themselves about the situation that
tries to trick them into smoking) and troubleshooting, so that
the patients are taught about appropriate ways to solve a
problematic situation39.
Tools that help in evaluating and understanding patient profile:
•
9
Prochaska and DiClemente Scale for change in behavior:
this scale brings a model that allows assessing what
stage of change in behavior the patient is, clearly and
objectively. Smoking cessation is a dynamic process
that is repeated over time and has different stages.
At each stage, the individual uses different cognitive
and behavioral processes40. The authors propose five
different stages in this process: precontemplation,
characterized by the absence of intention to change
behavior, i.e., the individual does not perceive, in this
case, the act of smoking as a problem; contemplation
implies some awareness of the problem. It is perceived,
there is intention to change, but there is no concept of
when, or commitment to do it; preparation is a stage
prior to the action. There is a clear intention to change;
the individual has already taken some initiatives towards
change, but the action is not yet effective; action is
a change of behavior to try to resolve the problem.
The individual spends time looking for treatments
and promotes changes that should be long-lasting
and maintenance is the stage at which such changes
should be consolidated, encompassing everything that
was gained at the stage of action. The stages occur
non‑linearly, i.e., spirally, which means that each stage
that is not maintained leads to the initial stage.
•
Motivational Interviewing: It is a viable alternative
for the treatment of addictive behaviors, within brief
interventions, as the initial impact seems to influence
the motivation for change in behavior. Strategies for
motivational interviewing: provide advice, remove
barriers/ help with obstacles, provide alternative choices
to smoking, decrease the undesirable aspect of the
behavior, practice empathy, give feedback, clarify goals
and actively help and provide care for relapse prevention
- abstinence coping41.
•
Fagerström Scale: it is an assessment scale that
allows checking the degree of physical dependence
on nicotine. It should be used in the initial evaluation
of smokers when they come for treatment. In case
of need for medication, it helps define the best
medication and how much of it should be taken 42.
In this case, it is noteworthy that one should not
consider using the medication only in cases where
Fagerström score is > 5. It is now known by scientific
studies that a very low Fargeström score means that
the psychological addiction is very high and in this
case, the medication helps by reducing abstinence
symptoms 42.
•
Reasons for Smoking Scale: is a scale that allows
assessing in which situations the smoker uses cigarettes.
Is related to physical, psychological dependence
and conditioning and helps clarify the risk situations
in everyday life for the smoker. This scale assesses:
stimulation, handling (ritual), pleasure derived from
smoking , tension reduction/relaxation, physical
addiction, habit/automatism and social smoking. These
items must be worked throughout the intensive process
of smokers’ approach43,44.
Pharmacological Treatment of Smoking
There is consistent evidence that anti-tobacco drugs
increase the success rate in smoking cessation37. Their use
doubles or even quadruples the possibilities of abstinence37.
Nicotine replacement therapy (NRT), bupropion and
varenicline are considered first-line treatment for smoking
and are recommended for prescription in national45 and
international37 guidelines. Other drugs such as Nortriptyline,
despite their proven efficacy, have side effects and
contraindications that may limit their use37, and are therefore
considered second-line treatment.
Some drugs appear as promising agents for smoking
cessation because somehow, they have an effect on
different brain circuits involved in nicotine dependence46.
However, systematic reviews have not demonstrated the
expected efficacy. These include the lack of consistency
regarding results with the use of clonidine47, Naltrexone48,
serotonin reuptake inhibitors49 and anxiolytics50. That is a
quite different situation when compared to the first-line
drugs, of which efficacy has been by acting primarily on
the dopaminergic system, known to be related to the
mesolimbic and reward systems50, crucial in the withdrawal
and dependence process.
There are no defined criteria to choose among them. In
clinical practice, prescription is made considering

specific drug
contraindications, product availability in the public healthcare
system, patients’ financial availability for drug acquisition,
professional clinical experience, among others, with no
well-structured technical selection criteria. In some services,
assessment of nicotine dependence and previous attempts at
medication use are part of an algorithm used to define the
choice of the first-line drug for the start of treatment, but this
is limited to local experience52,53 and, therefore, there are no
subsidies to support the standardized choice of drug.
The prescription of anti-smoking drugs is critical to
improving the effectiveness of smoking cessation treatment, as
also are key consultations of accompanying and encouraging
the promotion of changes in habits and behavior of patients53,54.
The main characteristics of anti-tobacco first-line drugs are
described below.
Guidelines
Nicotine replacement therapy
•Contraindications:
Nicotine is primarily responsible for the dependence
attributed to cigarettes and nicotine replacement therapies
have used since 1984 in the treatment of smoking cessation.
Forms of nicotine replacement therapy (NRT) currently used
and available in Brazil are transdermal and oral (tablets and
gum). They are both effective in smoking cessation, are often
used in association and can double the success rate when
compared to placebo55.
– Nicotine gum - Incapacity to chew, active peptic
ulcer, 15 days after AMI.
– Nicotine lozenges - active peptic ulcer, 15 days
after AMI.
–
Overdose (toxicity): nausea, dizziness, tachycardia
and hypertensive crisis.
Bupropion hydrochloride
Transdermal nicotine
•
Effectiveness compared with placebo: (RR: 1.9; 95% CI:
1.7-2.2).
• Rate of abstinence at 6 months (RR: 23.4; 95%
CI: 21.3 - 25.8).
•
Dose: 21 mg, 14 mg, 7 mg.
•
Presentation: transdermal adhesive patches.
• Route (s) of administration: transdermal use with
daily replacement.
• Treatment regimen: use of each presentation for
4 weeks on average, with progressive dose reduction.
Example: (21, then 14, then 7 mg/day).
•
Care in the administration: application on the upper chest,
or anterior, posterior and lateral superior arm regions.
•
Adverse reactions: itching and redness at the application
site, nausea, dizziness and tachycardia with overdose.
• Contraindications: dermatological diseases that prevent
adhesive application, 15-day period after acute myocardial
infarction episode, pregnancy and breastfeeding.
Bupropion is an inhibitor of dopamine and norepinephrine
reuptake that has shown to be effective in smoking cessation37,56,57
by reducing nicotine withdrawal symptoms. Being an
antidepressant, it helps in controlling depressive symptoms that
may arise during the process of smoking cessation.
•
•
Presentation: Extended Release Tablets 150 mg.
•
Route of administration: Oral.
•
Dose schedule: 1 tablet daily for 4 days, then increase to
1 tablet twice daily with a minimum interval of 8 hours
between doses.
• Care in the administration: avoid nightly administration
to minimize the risk of insomnia.
• Adverse effects: dry mouth, insomnia (discontinued
sleep), constipation, abdominal pain, dizziness.
•Contraindications:
–
• Overdose (toxicity): nausea, dizziness, tachycardia and
hypertensive crisis.
Oral use nicotine - nicotine gum or lozenges
• Efficacy when compared with placebo: (RR: 2.2; 95%
CI: 1.5 -3.2).
Efficacy compared to placebo (RR: 2.0; 95% CI: 1.8 -2.2).
• Rate of abstinence at 6 months - (RR: 24.2; 95%
CI: 22.2-26.4).
Absolute: risk of seizure (history of seizures, epilepsy,
febrile seizures in childhood, known abnormalities
in the electroencephalogram (EEG); alcoholism, use
of monoamine oxidase inhibitor (MAOI) in the last
14 days, cerebrovascular disease, central nervous
system (CNS) tumor and head trauma.
• Rate of abstinence at 6 months: (RR: 26.1; 95%
CI: 9.7-33.6).
• Warnings/Precautions: The combination of bupropion
and nicotine replacement, mainly in the form of adhesive
patches, can raise blood pressure and its concomitant use
with alcohol use may predispose to seizures.
•
Doses: 2 and 4 mg.
•
•
Presentation: chewing gum or lozenges.
•
Route of administration: Oral.
•
Treatment regimen: when there is intense desire to smoke,
replacing cigarettes (1-15 gums/day).
•
Care in the administration: drinking a glass of water before
use to neutralize the oral pH, due to the alteration caused
by the consumption of food and removal of food waste,
which may decrease absorption through the oral mucosa.
• Adverse reactions: nicotine gum may cause pain in
the temporomandibular joint, when chewed fast and
incessantly, as well as oropharyngeal irritation and nausea
when chewed quickly and often. Nicotine lozenges can
cause irritation of the oropharynx and nausea when
chewed, rather than dissolved in the mouth, or when
there is excessive use.
Overdose (toxicity): convulsions.
Varenicline tartrate
Varenicline 37,58 is a partial agonist of the nicotinic
receptor in the central nervous system. Among the first-line
drugs for the treatment of smoking, varenicline is the most
effective medication59,60.
•
Efficacy compared to placebo (RR: 3.1; 95% CI: 2.5-3.8).
• Rate of abstinence at 6 months (RR: 33.2; 95%
CI: 28.9-37.8).
•
Dose: 0.5 and 1 mg tablets of varenicline tartrate.
•
Route of administration: oral.
• Treatment regimen: Start with 0.5 mg once a day. On
the 4th day prescribe 0.5 mg twice a day. On the 7th day,
prescribe 1 mg twice a day. Prescribe for 12 to 24 weeks.
10
Guidelines
Table 2.1 – Degree of recommendation and level of evidence for the treatment of smoking on cardiovascular prevention
Class
Level of Evidence
•
Recommendation
Smoking is an independent risk factor for cardiovascular disease and, therefore, should be avoided
I
B
•
•
Passive exposure to tobacco smoke increases the risk of cardiovascular disease and should be avoided
I
B
Pharmacological treatment of smoking
Nicotine replacement therapy
Bupropion hydrochloride
Varenicline tartrate
I
I
I
I
A
A
A
A
Varenicline therapy does not require immediate smoking
cessation. Smoking cessation is recommended after the
14th day of the start of medication.
•
Adverse reactions: The most expected side effect with the
use of this substance is nausea (30% of patients), which is
minimized by ingesting the medication after meals and
with a glass of water. Less than 6% of patients stop the
medication for this reason.
• Contraindications: Absolute - patients with end-stage
renal failure, pregnant and breastfeeding women. Dose
adjustment is necessary in patients with severe renal
failure (see table of adjustment).
• Care in the administration: One must be cautious when
prescribing it to patients with a history of psychiatric illnesses
such as severe depression, bipolar disorder and panic
disorder. Although no causal association has been shown
and considering that smokers have higher risk of depression
and suicidal thoughts61, the Food and Drug Administration
(FDA) in 200962, warned against the possibility of mood
alterations, agitation and suicidal thoughts among varenicline
users and therefore, it is not recommended for patients with
nonstabilized psychiatric disorders63.
In 2011, Sigh63 carried out a meta-analysis with some
studies on varenicline use, warning of a possible risk of
cardiovascular events among users. After careful analysis of the
study, it was concluded that a significant number of patients
using varenicline in randomized studies were not included in
the meta-analysis and showed no cardiovascular event. A more
comprehensive meta-analysis was performed64 including all
studies with varenicline and no increased risk of cardiovascular
events was observed in the varenicline versus placebo group.
The safety and efficacy of varenicline were evaluated and
demonstrated by Rigotti et al.65, in a randomized and placebocontrolled trial in patients with cardiovascular disease.
•
Associations of anti-tobacco drugs
The effectiveness of first-line anti-tobacco drugs is
between 20% and 25% for nicotine replacement therapy
and Bupropion, not exceeding 35% with varenicline37. Some
studies on the combination of adhesive nicotine patches and
oral nicotine have shown improved results. A meta-analysis
of nine studies56 that combined a nicotine patch with a rapid
nicotine-release agent (gum, spray, lozenges) showed that the
combination was more effective than a single type of NRT
(RR: 1.34; 95% CI: 1:18-1:51).
The combination of NRT and bupropion was more effective
than bupropion alone in the meta-analysis of four studies53
(RR: 1.24; 95% CI: 1.06 -1.45).
The association between varenicline and bupropion
seems to be the most effective of all66; however, randomized
studies67 of greater consistency are in progress to demonstrate
such indication.
3. Diet, supplements and vitamins
Introduction
Second-line medications
Although they can modulate a number of physiopathological
mechanisms associated with atherosclerosis, prospective
studies failed to show any benefits in the intake of vitamins
and omega 3 fatty acids in the form of supplementation in
cardiovascular disease (CVD) prevention. More information
is needed about vitamin D and alpha-linoleic acids, but in
the light of current knowledge, one cannot recommend the
use of these supplements to prevent CVDs. Summaries of
recommendations for the intake of these supplements can
be found in Tables 3.1 to 3.3.
Nortriptyline
Carotenoids
Overdose (toxicity): nausea, dizziness, vomiting.
Nortriptyline is a tricyclic antidepressant that blocks
noradrenaline reuptake in the central nervous system. It is a
second-line drug in the treatment of smoking. The FDA has
not yet approved its use for this purpose because, although
its efficacy is similar to that obtained with NRT or bupropion,
there is greater risk of side effects37,56. The recommended
11
dose is 25 mg/day as a single dose, with gradual increase
up to 75 to 100 mg/day. The use is not recommended in
patients with structural heart disease of any kind, due to the
risk of inducing arrhythmias and conduction disturbances.
Carotenoids are a class of over 600 compounds, responsible
for the yellow, red and orange pigments in plants, with
α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and
zeaxanthin being the ones most often found in foods. Known
mainly as precursors of vitamin A, carotenoids are also important
suppressors of free radicals and act as potent antioxidants68.
Guidelines
Table 3.1 – Summary of recommendations for non-consumption of vitamin supplements in cardiovascular disease prevention
Class
Level of Evidence
There is no evidence of benefit of vitamin A or beta-carotene supplementation in the primary or secondary prevention
of cardiovascular disease
Indication
III
A
Vitamin B and folic acid supplementation is not effective in primary or secondary cardiovascular disease prevention
III
A
There is no evidence of vitamin C supplementation benefit for prevention, progression or death from cardiovascular disease
II
A
Vitamin D supplementation is not recommended for cardiovascular disease prevention in individuals with normal
blood levels of this vitamin. Likewise, there is no evidence that supplementation in individuals with vitamin D
deficiency will prevent CVD
III
C
Class
Level of Evidence
Supplementation with omega-3 of marine origin (2-4 g/day) or even higher doses should be recommended for severe
hypertriglyceridemia (> 500 mg/dL), with risk of pancreatitis, refractory to non-pharmacological measures and drug therapy
I
A
At least 2 fish meals a week as part of a healthy diet should be recommended to reduce cardiovascular risk. This
recommendation is particularly directed to high-risk individuals such as those who have already had myocardial infarction
I
B
EPA + DHA supplementation is not recommended for individuals at risk of cardiovascular disease using preventive
evidence-based treatments
III
A
Table 3.2 – Recommendations for consumption of products rich in omega-3 fatty acid
Indication
Evidence for a role of carotenoids in CVD came from studies
that showed that increased consumption of fruits and vegetables
was associated with lower risk of cardiovascular disease69.
A series of retrospective longitudinal and prospective
studies identified an inverse association between intake of
carotenoids and the risk of CVD69. However the effect of
carotenoids is complex and probably not due to a single
compound alone.
In contrast, prospective randomized trials showed no
benefit of supplementation with carotenoids for CVD70,71.
Therefore, the use of supplements with carotenoids,
beta-carotene or others is not recommended. Instead of
that, efforts should be directed at the increased consumption
of fruits and vegetables rich in this nutrient.
Vitamin E
Vitamin E is the main fat-soluble antioxidant in the
human body and is present in a complex of four isomers
(α, β, γ, δ - tocopherol). Interest in the potential benefit of
vitamin E on the risk of CVD was related to its antioxidant
capacity and the possibility of modifying the oxidized
low-density lipoprotein (oxLDL), particularly involved in
atherogenesis72. However, prospective randomized trials
such as the ATBC, CHAOS, GISSI, and HOPE showed
no benefits of vitamin E supplementation on CVD70,71,73.
Despite a solid theory of the molecular basis of oxidative
stress and its role in atherosclerosis, these trials do
not support the use of supplemental vitamin E in the
prevention of CVD, with its consumption being more
effective and safe when obtained from foods. Therefore,
vitamin E supplementation is not recommended for the
cardiovascular disease prevention.
Vitamin C
Vitamin C or ascorbic acid is soluble in water and a very
effective antioxidant, as it easily loses electrons. The theory
of free radicals in the aging process elucidates its role in the
progression of chronic diseases74.
Although supported by observational studies, randomized
controlled trials do not support a role of vitamin C
supplementation in primary or secondary prevention of
cardiovascular diseases74. Thus, vitamin C supplementation
for the prevention of cardiovascular disease is not
recommended.
Vitamin D
Vitamin D is a fat-soluble nutrient that has several
functions in the body, with the main one being bone
metabolism. However, vitamin D has many other functions
and the use of vitamin D supplements for the prevention
and treatment of a wide range of diseases has increased
considerably in the last decade76.
Its two main forms are vitamins D2 (ergocalciferol) and D3
(cholecalciferol). Vitamin D3 can be synthesized by humans by
the skin cells after exposure to UV-B radiation from sunlight.
In the absence of sunlight, vitamin D intake is crucial. Vitamin
D and dietary supplements are absorbed by the intestine and
then converted into 25-hydroxyvitamin D3 [25 (OH) D] in
the liver, and 1,25 dihydroxyvitamin D3 [1,25 (OH) 2D3],
the active form of vitamin D, in the kidney.
Zittermann et al.76 summarized the underlying mechanisms
for a possible role of vitamin D in the prevention of coronary
disease. These include inhibiting the proliferation of vascular
smooth muscle, suppression of vascular calcification, the
downregulation of proinflammatory cytokines, increased
12
Guidelines
regulation of anti‑inflammatory cytokines and the effect
of the vitamin D as an endocrine downregulator of the
renin‑angiotensin system.
Low concentrations of circulating vitamin D have been
associated with hypertension, obesity, diabetes mellitus and
metabolic syndrome; additionally, vitamin D deficiency
has been associated with risk of cardiovascular disease in
recent studies76,77.
There is evidence of a role of vitamin D in CVD in ecological
studies, with an increase in heart disease events with the
geographical latitude, i.e., associated with less exposure
to sunlight, considering that vitamin D concentrations
decrease with the latitude. Several prospective studies have
investigated the serum concentration of 25-hydroxy (OH)
vitamin D in relation to cardiovascular diseases, showing
biased results for the association of low concentrations of
this marker and increased risk for cardiovascular disease77-78.
While the protective effect of vitamin D in cardiovascular
events is supported by epidemiological evidence, there is
insufficient evidence to date to recommend supplementation
for the prevention of cardiovascular disease. Thus, vitamin
D supplementation for cardiovascular disease prevention
is not recommended.
Vitamins B and Folate
Evidence of an association between CVD and vitamin B
were demonstrated by the effect of these vitamins on the
reduction of homocysteine79,80. Homocysteine, an amino acid
that contains sulfur, is a metabolite indirectly produced during
the demethylation of methionine. Prospective studies have
shown an independent association, albeit of modest intensity,
between serum homocysteine levels

and CVD risk80. A number
of factors have been identified as being associated with elevated
homocysteine levels.

These include inadequate intake of folic
acid, vitamins B6 and/or B12, preexisting atherosclerotic disease,
drinking coffee, smoking, alcohol consumption, diabetes, use of
antiepileptic drugs or methotrexate, renal failure, rheumatoid
arthritis, hypothyroidism and cystathionine beta-synthase and
methylenetetrahydrofolate reductase mutations.
Randomized prospective studies with large number of
cardiovascular events failed to show any benefit of folate and
B complex supplementation in reducing homocysteine levels
and CVD prevention80.
The discrepancy between the results of epidemiological
studies and clinical trials may be due in part to the inclusion
of different populations and the use of foods fortified with
folic acid in some countries.
The supplementation of folic acid or B complex is not
recommended for cardiovascular disease prevention.
Omega-3 polyunsaturated fatty acids of marine origin
(docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)
The omega-3 fatty acids of marine origin, docosahexaenoic
acid (DHA) and eicosapentaenoic acid (EPA), have several
effects on different physiological and metabolism aspects
that may influence the chance of developing cardiovascular
diseases 81,82. While it is generally agreed that the regular
13
consumption of fish rich in omega-3 fatty acids is part of a
healthy diet, the recommendation of supplementing the diet
with fish oil capsules is surrounded by controversy, generated
by the conflicting results of clinical trials83-86.
Clinical trials have show that supplementation with 2 g
to 4 g of EPA/DHA a day can lower the levels of triglycerides
(TG) by 25% to 30%, slightly increase HDL-C levels (1% to
3%) and increase LDL-C by 5% to 10%86. The capacity to
reduce the levels of TG is dose-dependent, with a reduction of
approximately 5% to 10% for each 1 g of EPA/DHA consumed
daily, being higher in individuals with higher baseline TG levels .
In a meta-analysis of 36 randomized clinical trials,
supplementation with fish oil (median dose of 3.7 g/day) was
shown to reduce systolic blood pressure by 3.5 mmHg and
diastolic by 2.4 mmHg87. The reduction of adrenergic tone
and systemic vascular resistance is a proposed mechanism.
Despite early evidence suggesting a protective effect
of fish and omega-3 fatty acids of marine origin on
cardiovascular events 87, especially in individuals that
already had cardiovascular disease, recent studies have
shown no benefit of supplementation with omega-3 in
individuals who had already shown or not manifestations of
atherosclerotic disease83,84. One possible reason is related to
the population profile, especially regarding the more frequent
use of medications known to be protective (e.g., statins,
beta‑blockers, angiotensin-converting enzyme inhibitors),
the more aggressive control of traditional risk factors and
the higher number of revascularization procedures in more
contemporary studies. Thus, it is debatable whether omega-3
fatty acids can bring real added benefits when the patient is
managed according to current recommendations.
As most studies evaluated EPA and DHA in combination,
currently there is not enough evidence to support separate
recommendations for each of these fatty acids.
EPA and DHA supplementation is not recommended for
cardiovascular disease prevention.
Omega-3 polyunsaturated fatty acids of vegetable origin
The alpha-linolenic fatty acid (ALA) has shown inconsistent
effects on lipid levels 88,89. In a systematic review and
meta-analysis of 14 randomized controlled trials with ALA
supplementation, no significant effect was observed on total
cholesterol, LDL-C or triglycerides, showing a minimal effect
on HDL-C (reduction of 0.4 mg/dL)90.
Specifically, the effects of flaxseed in experimental animals
varied from nil to slight lipid decrease and a review suggested
a triglyceride-lowering effect of the consumption of large
amounts of flaxseed oil in humans90. Observational studies
suggest a modest reduction in the risk of CVD with ALA
consumption90. Data from the alpha-omega study showed
no benefits of ALA supplementation for CVD prevention in
individuals who had experienced previous cardiovascular
disease85. However, further studies on ALA supplementation
for CVD prevention are needed90. ALA supplementation is
not recommended for cardiovascular disease prevention.
Recommendations for consumption and supplementation
of ALA are shown in Table 3.3.
Guidelines
Table 3.3 – Recommendation for consumption of products rich in omega-3 fatty acids of vegetable origin
Recommendation
Class
Level of Evidence
Encourage the consumption of omega-3 polyunsaturated fatty acids of vegetable origin as part of a healthy diet can
be recommended to reduce cardiovascular risk, although the real benefit of this recommendation is debatable and the
evidence is not conclusive
IIb
B
ALA supplementation is not recommended for cardiovascular disease prevention
III
B
4. Obesity and overweight
Introduction
In recent decades, Brazil has gone through a process called
nutritional transition91, a concept that refers to secular changes in
the patterns of nutrition and nutritional status, major alterations
in food intake and physical activity patterns as a result of
economic, social, demographic and sanitary changes92.
In Brazil, the prevalence of overweight and obesity has
increased continuously from 1974 to the present day among
adults of both genders. However, from 2002-2003 the
prevalence of overweight, which was higher among women,
became higher among men, increasing from 18.5% to 50.1%
in all regions except the Northeast, while it increased from
28.7% to 48% among women93.
During a 34-year period, the prevalence of obesity
increased more than four-fold for men (from 2.8% to 12.4%)
and more than two-fold for women (8% to 16.9 %)94,95. Brazil
currently ranks fourth among countries with the highest
prevalence of obesity96 and for the first time the number
of overweight adults will exceed the number of low weight
ones96. In children and adolescents, there is a significant
increase in overweight and obesity, regardless of gender and
social class, and a significant proportion of obese children will
become obese adults.
Obesity, with its multifactorial characteristic, is one of
the prevalent factors to explain the increased burden of
noncommunicable chronic diseases (NCDs), as it is often
associated with cardiovascular diseases such as hypertension,
dyslipidemia, type 2 diabetes, osteoarthritis and certain types
of cancer, and it is also considered an important condition that
predisposes to mortality96,97.
Primary prevention
It is important to identify at which biological time it is
possible to prevent weight gain. For women, the time of
greatest risk of weight gain appears to be the reproductive
age, specifically pregnancy and the first two years after
delivery97,98. Among children and adolescents, excessive
weight gain prevention was expected, precisely because it is a
growth phase that requires extra energy, while the possibility of
energy expenditure is higher compared to other stages of life.
However, these potential facilitators do not seem to outweigh
factors associated with obesity and that are responsible for
the growth of this epidemic also in these age groups and
stages of life99.
In this sense, it is important to highlight the so-called
“obesogenic environment”, i.e.: the role of the food industry,
fast food chains, advertising and TV programs, movies, video
games, in conclusion, situations that make children more
sedentary and exposed to excessive consumption. The most
appropriate interventions should combine environmental and
behavioral changes100-102.
Children and adolescents: see specific chapter.
Adults
Among adults, several studies have shown the decline
in the consumption of rice and beans, increased intake of
processed products (mainly cookies and soft drinks), excessive
consumption of sugar, the systematic increase in fat and low
intake of fruit and vegetables (FV), a situation of unfavorable
trends for a healthy eating pattern and directly associated
with the increase in NCDs, in which obesity is one of the
most important, a situation similar to that observed in the
preceding age groups103,104.
The recommendations are as follows:
•
Three meals (breakfast, lunch and dinner) and two healthy
snacks a day. Do not skip meals. Avoid snacking between
meals.
•
Pay attention to food labels and choose those with lower
amounts of trans fats.
• Avoid soft drinks and processed juices, cakes, pastries
and cookies, sweet desserts and other sugared foods.
•
Give preference to water consumption between meals.
•
Do at least 30 minutes of physical activity every day.
•
However, those with a tendency to obesity or family profile
should do 45-60 minutes of moderate-intensity physical
activity a day; those who were obese and lost weight should
do 60-90 minutes to prevent regaining weight.
• Even in the elderly physical activity and exercise can
prevent weight gain and obesity105.
•
Avoid excessive consumption of alcoholic beverages106.
Secondary Prevention
The proposed intervention at this level aims at modifications
in life style and other actions, for children as well and for
adolescents and adults.
It is often considered an acceptable strategy to achieve
weight reduction necessary at the beginning of the process.
This daily reduction may promote reduction of approximately
500 g a week107.
Intensification of physical exercising such as walking,
cycling, swimming, aerobics, 30 to 45 minutes 3-5 times a
week can contribute to the reduction of cardiovascular risk
14
Guidelines
Table 4.1 – Summary of recommendations for obesity and overweight in the primary prevention of cardiovascular disease
Indication
Class
Level of Evidence
Three meals (breakfast, lunch and dinner) and two healthy snacks a day.
II
A
Pay attention to food labels and choose those with lower amounts of trans fats.
II
A
Avoid soft drinks and processed juices, cakes, pastries and cookies, sweet desserts and other sugared foods.
I
A
Give preference to water consumption between meals.
II
A
Do at least 30 minutes of physical activity every day.
I
A
Those with a tendency to obesity or family profile should do 45-60 minutes of moderate-intensity physical activity a
day; those who were obese and lost weight should do 60-90 minutes to prevent regaining weight.
I
A
Avoid excessive consumption of alcoholic beverages.
I
A
Table 4.2 – Summary of recommendations for obesity and overweight in the secondary prevention of cardiovascular disease
Indication
Class
Level of Evidence
Diet with a caloric reduction of about 500 kcal/day
I
A
Intensification of physical exercises such as walking, cycling, swimming, aerobics, 30-45 minutes 3-5 times a week
I
A
Minimize sedentary activities such as sitting for long periods watching television, playing at computer or video games
I
B
Encourage healthy eating habits for children and adolescents
I
B
Use of sibutramine for weight loss in patients with cardiovascular disease
III
B
Bariatric surgery for selected patients
I
B
factors. It is important to increase the lean mass, thus the
combination of aerobic exercise with the isometric/static
ones is crucial.
Sedentary activities, such as sitting for long periods watching
television, at the computer or playing video games should
be minimized. In addition, one should have physical activity
during the work period, for instance, take the stairs instead of
the elevator, take a walk at lunchtime, and encourage healthy
eating habits for children and adolescents.
Thus, the recommended amount of weight loss and the
schedule to determine this loss may vary depending on the
degree of obesity and the characteristics and severity of the
complications and other features related to individuals and
their life style.
Drug therapy
There are two drugs approved for the treatment of obesity
in Brazil: Orlistat and Sibutramine. Sibutramine, although
approved in Brazil, should not be used in patients with CVD107.
Both promote modest weight loss, in a sustainable manner,
and are indicated for the long-term treatment of obesity in
conjunction with a reduced-calorie eating plan and regular
physical activity.
Bariatric surgery
Comorbidities associated with obesity showed improvement
after bariatric surgery. The Adelaide study showed that 60% of
15
patients who initially had comorbidities related to obesity were
able to stay drug-free for three years after the surgery108, 109.
Surgical intervention is an option for carefully selected
patients with clinically severe obesity (body mass index
[BMI] ≥ 40 kg/m² without comorbidities or 35 kg/m² with
comorbidities) when clinical treatments have failed.
Multidisciplinary follow-up of the patient due to possible
nutritional changes is required.
5. Arterial hypertension
Systemic arterial hypertension (SAH) is the most important
risk factor for the development of coronary artery disease,
heart failure, cerebrovascular disease, chronic kidney disease
and atrial fibrillation110,111 and has been associated with the
development of cognitive deficit and dementia112.
Mortality from CVD increases progressively with increasing
levels of blood pressure (BP) from 115/75 mmHg, in a linear,
independent and continuous manner113.
In a decade, approximately 7.6 million deaths worldwide
were attributed to hypertension (54 % from stroke and 47%
from ischemic heart disease [IHD]), mostly in low and medium
economic development and more than 50% in individuals
aged between 45 and 69 years114.
Considering BP values ≥ 140/90 mmHg, 22 studies found
hypertension prevalence in the adult population between
22.3% and 43.9% (mean 32.5%), with more than 50%
between 60 and 69 years and 75% > 70 years115-118.
Guidelines
Definition and classification (VI DBH119)
Table 5.1 – Classification of blood pressure according to the casual office measurements (> 18 years)
Classification
Systolic pressure (mmHg)
Diastolic pressure (mmHg)
Optimal
< 120
< 80
Normal
< 130
< 85
Borderline*
130-139
85-89
Stage 1 hypertension
140-159
90-99
160-179
100-109
≥ 180
≥ 110
Isolated systolic hypertension
≥ 140
< 90
When the systolic and diastolic pressures are at different categories, the higher one should be used to classify blood pressure.
* Normal-high pressure or pre-hypertension are equivalent terms in the literature.
Blood pressure measurements
At the first assessment, the measures must be taken in
both arms and in case of different results, the arm with the
higher value should be used as reference in subsequent
measurements. Individuals should be investigated for arterial
disease in the presence of pressure differences between the
upper limbs > 20/10 mmHg for systolic/diastolic pressures,
respectively120.
At least three measurements should be carried out
at each visit and a one-minute interval between them
is suggested 121,122. The mean of the last two should be
considered the actual BP. If the systolic and/or diastolic
pressures obtained show a greater than 4 mmHg difference,
new measurements should be performed until a smaller
difference is obtained.
The recommended manner to measure blood pressure
is in the sitting position. Measurements in the supine and
orthostatic positions must be made at least in the first
assessment in all individuals and in all assessments in the
elderly, diabetics, patients with dysautonomia, alcoholics
and/or those using antihypertensive medication (Table 5.1).
The ABMP (ambulatory blood pressure monitoring), HBPM
(home blood pressure monitoring) and SMBP (self-measured
blood pressure) are important tools in the investigation of
patients with suspected hypertension or for treatment control.
It is recommended, whenever possible, to measure BP
outside the office to confirm a diagnosis, identify white-coat
hypertension and masked hypertension, in addition to the
anti-hypertensive treatment control123,124.
Routine initial evaluation of the hypertensive patient
Basic routine complementary tests for hypertension should
include: urinalysis; serum potassium; serum creatinine and
estimated glomerular filtration rate using formulas126,127; fasting
glucose, total cholesterol, HDL-C, triglycerides, serum uric acid
and conventional electrocardiogram (ECG)119.
The supplementary assessment for hypertensive patients
may include119:
a) Chest radiography: recommended for patients with
suspected heart failure when other tests are not available
and to assess pulmonary and aortic involvement.
b) Echocardiogram: hypertensive patients stages 1 and 2, without
left ventricular hypertrophy on ECG, but with two or more risk
factors; hypertensive patients with suspected heart failure.
c) Microalbuminuria in a single urine sample (by urinary
albumin/creatinine ratio): hypertensive diabetic patients,
hypertensive patients with metabolic syndrome and
hypertensive patients with two or more risk factors.
d) Ultrasound of the carotid arteries: patients with carotid
murmur, with signs of cerebrovascular disease, or
atherosclerotic disease in other territories.
e) Exercise testing: suspected stable coronary heart disease,
patient with diabetes, or family history of coronary disease
in patients with controlled blood pressure.
f) Glycated hemoglobin: in patients with metabolic
syndrome, diabetic or glucose intolerant individuals.
When it is not possible to assess glycated hemoglobin,
we suggest the oral glucose tolerance test in patients with
fasting glucose between 100 and 126 mg/dL.
g) ABPM, HBPM and SMBP, according to the conventional
indications for the methods.
h) Evaluation of arterial stiffness by pulse wave velocity or
other methods, if available.
i)
Investigation of secondary hypertension, as indicated
by history, physical examination or by the initial
laboratory assessment.
Identification of subclinical target-organ injuries
a) ECG with LVH (Sokolow-Lyon > 35 mm; Cornell > 28 mm
-0 for males (M); > 20 mm – for females [F]);
b) Echocardiogram with LVH (LV mass > 134 g/m2 in M or
110 g/m2 in F);
c) intima-media thickness of the carotid artery > 0.9 mm
or presence of atheroma plaque;
16
Guidelines
Table 5.2 – Initial routine assessment of the hypertensive patient119
Recommendation
Class
Level of Evidence
Urinalysis
I
C
Serum potassium
I
C
Serum creatinine
I
B
Estimated glomerular filtration rate
I
B
Fasting glucose
I
C
Total cholesterol, HDL-C, serum triglycerides
I
C
Serum uric acid
I
C
Conventional ECG
I
B
Recommendation
Class
Level of evidence
Chest radiography
IIa
C
Echocardiogram - hypertensive patients stages 1 and 2 without LVH on the ECG
IIa
C
HDL-C- colesterol da lipoproteína de alta densidade por High-density lipoprotein cholesterol
Table 5.3 – Supplementary assessment for hypertensive patients119
I
C
Microalbuminuria - hypertensive and diabetic patients
- hypertensive patients with suspected HF
I
A
- Hypertensive patients with metabolic syndrome
I
C
- Hypertensive patients with two or more risk factors
I
C
Carotid ultrasound
IIa
B
Exercise test for suspected coronary artery disease
IIa
C
Glycated hemoglobin
IIa
B
Pulse wave velocity
IIb
C
LVH, left ventricular hypertrophy, ECG, electrocardiogram, HF-heart failure
Chart 5.1 – Calculation of creatinine clearance and glomerular filtration rate and interpretation of values for classification of chronic kidney
disease according to NKF121
•
•
•
Estimated glomerular filtration rate (eGFR) by the Cockcroft-Gault formula122: eGFR (mL/ min) = [140 - age] x weight (kg)/serum creatinine (mg/dL) x 72 for men; for
women, multiply the result by 0.85.
Glomerular filtration rate by the MDRD formula123 at www.kidney.org/professional / KDOQI / guidelines_ckd.
Interpretation124:
–
Normal kidney function: > 90 mL/ min with no other changes in urinalysis;
–
Kidney disease Stage 1: > 90 mL/min with changes in urinalysis;
–
Kidney disease Stage 2: 60-90 mL/min;
–
Kidney disease Stage 3: 30-60 mL/min;
–
Kidney disease stage 4-5: < 30 mL/min.
d) ankle-brachial index < 0.9;
Prevention
e) estimated creatinine clearance < 60 mL/min/1.72 m ;
2
f) low glomerular filtration rate or creatinine clearance
(< 60 mL/min);
g) microalbuminuria 30-300 mg/24 hours or albumin/
creatinine ratio > 30 mg per g;
h) assessment of arterial stiffness by pulse wave velocity
> 12 m/s125, 126.
17
Clinical studies demonstrated that the detection,
treatment and control of hypertension are crucial to
reducing cardiovascular events. A meta-analysis of
354 clinical trials showed that the reduction in morbidity
and mortality is proportional to the decrease in blood
pressure, both systolic and diastolic, and may reduce
decrease by 46% the occurrence of myocardial infarction
and by 63% the number of strokes 127 . In Brazil,
Guidelines
14 population studies performed in the last fifteen years,
with 14,783 individuals (BP < 140/90 mmHg) showed low
rates of BP control (19.6%)116-118.
Primary prevention of SAH
Hypertension can be prevented or postponed. Changes
in life style are enthusiastically recommended for primary
prevention of SAH, notably in individuals with borderline
BP levels. Such life style adjustments reduce BP, as well as
cardiovascular mortality128.
Healthy life style habits should be adopted since
childhood and adolescence, respecting the regional,
cultural, social and economic characteristics of individuals.
The main non-pharmacological recommendations for
primary prevention of hypertension are: healthy diet, low
sodium and alcohol intake, adequate intake of potassium,
fight against sedentary life style and smoking and maintain
body weight control. Such recommendations are indicated
for the prevention of hypertension as adjuvants to drug
treatment for hypertension129.
Vegetarian diets are inversely associated with the
incidence of cardiovascular diseases. This is explained
by the lower amount of nutrients consumed, such as
saturated fat and cholesterol. However, these diets are
deficient in micronutrients such as iron, vitamin B12 and
calcium and supplementation is needed to meet current
recommendations. Micronutrient deficiencies often
seen in lactovegetarians have been identified as factors
predisposing to SAH in adults following this type of diet.
A relevant fact is the observation that vegetarians have, in
general, lower BMI, which, regardless of the type of diet,
is associated with lower BP134,135.
Sodium
The maximum amount considered to be healthy for daily
ingestion of sodium chloride (table salt) is 5 g (corresponding
to 2 g of Sodium)136,137. In practice, it is recommended the
consumption of no more than 3 shallow teaspoons of salt
(3 g), which added to 2 g of salt already present in foods,
would come to a total of 5 g.
Alcohol
Non-pharmacological measures
Diets
The DASH (Dietary Approaches to Stop Hypertension)
dietary pattern, rich in fruits, vegetables, fiber, minerals and
low-fat dairy products, has a significant impact in BP reduction.
A high degree of adherence to this type of diet reduced by 14%
the development of hypertension. The benefits on the BP have
been associated with high intake of potassium, magnesium
and calcium in this nutritional pattern. The DASH diet also
enhances the effect of dietary guidelines for weight loss, also
reducing cardiovascular risk biomarkers130,131.
The Mediterranean diet is also associated with BP
reduction. High consumption of fruits and vegetables was
found to be inversely proportional to the BP levels, even
with a higher percentage of fat. Replacement of excess
carbohydrates in this diet by unsaturated fat induces a more
significant BP reduction132,133.
In hypertensive subjects, alcohol intake, acutely and
dose-dependently, reduces BP, but elevation occurs a few
hours after alcohol consumption. Given the controversy
regarding the safety and cardiovascular benefit of low
doses, as well as the harmful use of alcohol in society, it
should be recommended to those who have the habit of
drinking alcoholic beverages not to exceed 30 g of ethanol
per day, for men, preferably non-habitually, with half of that
amount being indicated to women138,139. The maximum
daily amounts suggested for the most common types of
alcoholic drinks are two cans (350 x 2 = 700 mL) or 1 bottle
(650 mL) of beer; 2 150 mL glasses or 1 300 mL glass of
wine, two 50 mL doses of whiskey, vodka or distilled liquor.
Physical activity
The regular practice of aerobic physical activity such as
walking for at least 30 minutes a day, 3 times/week, is indicated
Table 5.4 – Non-pharmacological treatment of hypertensive patients119
Recommendation
Class
Level of Evidence
Diet -DASH
I
A
-Mediterranean
I
B
-Vegetarian
IIa
B
Sodium - daily intake of 2 g
I
A
Alcohol - no more than 30 g of alcohol a day
I
B
Physical activity - 30 minutes/day/3 times a week (minimum)
I
A
Weight control - BMI between 18.5 and 24.9 kg/m
I
A
IIa
B
I
B
2
Psychosocial stress control
Multidisciplinary team
DASH = Dietary Approaches to Stop Hypertension BMI- body mass index.
18
Guidelines
for the prevention, whereas, for treatment, daily supervised
exercise is recommended140. Resistance exercises may be
associated with aerobics141.
The therapeutic decision-making should be based on risk
stratification, as shown in Chart 5.2 below:
Pharmacological treatment
Weight control
Individuals should maintain body weight within the normal
range (BMI between 18.5 and 24.9 kg/m2) and abdominal
circumference measures below 102 cm for men and 90 cm
for women142,143.
Control of psychosocial stress
Different techniques of stress management have been
assessed, but with conflicting results. Meditation, music
therapy, biofeedback, yoga, and other stress management
techniques, were able to slightly reduce BP in hypertensive
individuals144.
Multidisciplinary team
Considering that hypertension is a multifactorial clinical
syndrome, rely on the support of the multidisciplinary
support team for hypertensive patients is a desirable conduct,
whenever possible145.
Other non-pharmacological strategies for blood
pressure control
Specific strategies, such as using slow-breathing
techniques146, the use of CPAP (continuous positive airway
pressure) in case of obstructive sleep apnea syndrome147 and
bariatric surgery for advanced obesity148 have shown significant
impact in reducing blood pressure.
Drug measures for hypertension prevention
The TROPHY149 and PHARAO150 studies evaluated the
efficacy and safety of antihypertensive drugs in hypertension
prevention. The drug strategy based on the blocking of the
renin-angiotensin system was well tolerated and prevented
the development of hypertension in young high-risk
populations. However, to date, no previously performed
study showed enough power to determine the indication
of drug treatment for individuals with borderline BP with
no evidence of cardiovascular disease.
Treatment decision-making and risk category
Hypertensive patients must be classified based on their
mean level of blood pressure and presence or not of associated
risk factors, target-organ lesions and established cardiovascular
or renal disease.
Drug treatment of hypertension significantly alters the
prognosis, regardless of the antihypertensive drugs used both
in monotherapy and in combination. Several randomized
trials and meta-analyses have demonstrated the benefits of
reducing blood pressure levels on cardiovascular morbidity
and mortality. Several clinical trials showed reduction of
relevant outcomes in studies with diuretics, beta-blockers
(BB), angiotensin-converting enzyme inhibitors (ACEIs),
angiotensin-receptor blockers (ARBs) AT1 receptor and
calcium-channel antagonists (CCAs) 151. As monotherapy
controls BP in less than 1/3 of hypertensive individuals, most
clinical trials used associations of drugs for blood pressure
control, demonstrating that the benefits achieved do not
depend on the drug classes used.
According to the VI Brazilian Guidelines on Hypertension,
treatment should be started with monotherapy in stage 1
patients with low or moderate risk and drug combinations in
stages 2 or 3, or stage 1 with high or very high risk (Figure 5.1)119.
Regarding the recommended drug associations, one should
always take into account the patients’ comorbidities; however,
in general, the best associations in terms of effectiveness are
drugs that inhibit the renin-angiotensin-aldosterone system
(ACEIs or ARBs) with calcium channel antagonists or diuretics152.
1. Diuretics: are effective in lowering blood pressure levels,
showing evidence in reducing morbidity and mortality.
Thiazide diuretics (hydrochlorothiazide, chlorthalidone,
indapamide) are indicated. Potassium‑sparing diuretics
(amiloride and triamterene) have low diuretic
effect, but when combined with thiazides or loop
diuretics, they are useful in preventing hypokalemia153.
Spironolactone has greater antihypertensive effect than
the other potassium‑sparing diuretics, being especially
indicated for resistant hypertension cases.
2. Calcium-channel antagonists: are effective in reducing
morbidity and mortality. Sustained release drugs are
indicated due to the reduction of events and even superiority
in reducing stroke154. Dihydropyridines are the most often
indicated, as they have greater antihypertensive effect.
3. Beta-blockers: are effective in reducing blood
pressure; however, in some meta-analyses, the first and
second‑generation drugs, when used alone, promoted
less protection against stroke in individuals older than
55 years. They are well indicated in special situations
such as arrhythmias, coronary artery disease and heart
failure. Clinical trials with carvedilol, metoprolol,
Chart 5.2 – Treatment decision-making
Risk category
No additional risk
Isolated non-medical treatment
Low additional risk
Isolated non-medical treatment for up to 6 months. If goal is not reached, associate medical treatment
Medium, high and very high additional risk
19
Consider
Non-drug + drug treatment
Guidelines
Stage 1 Hypertension
Low and moderate CV risk
Stage 2 and 3 Hypertension
High and very high CV risk
Monotherapy
All classes of antihypertensive drugs,
except for direct vasodilators
Combinations
Two antihypertensive drugs of different classes and at low doses
Inadequate response or intolerable adverse events
Increase the
monotherapy dose
Change monotherapy
Increase association
dose
Add 2nd drug
Change drug
association
Add 3rd drug
Inadequate response
Add other antihypertensive drugs
Figure 5.1 – Hypertension treatment algorithm according to the VI Brazilian Guidelines on Hypertension119.
Chart 5.3 – BP goals to be achieved according to individual characteristics
Category
Consider
•
Hypertensive patients stages 1 and 2 with low and medium cardiovascular risk
•
Hypertensive patients and borderline behavior with high and very high cardiovascular risk, or 3 or
more risk factors, DM, MS or TOL
130/80 mmHg
•
Hypertensive patients with renal failure and proteinuria > 1.0 g/L
130/80 mmHg
< 140/90 mmHg
DM - diabetes melito; SM - síndrome metabólica; LOA - lesões em órgãos-alvo por DM - Diabetes Mellitus, MS - metabolic syndrome; TOI – target-organ injuries
bisoprolol and nebivolol have shown significant
reduction in cardiovascular mortality and morbidity
in patients with heart failure, regardless of age155.
4. ACEIs or ARBs: Both classes are very useful in the
treatment of most hypertensive patients, especially
in populations with high cardiovascular risk or with
comorbidities. Several clinical trials demonstrated
beneficial effects in heart failure, in the prevention of
cerebrovascular accidents and in patients with diabetes
mellitus with renal impairment. ARBs are equivalent to
ACE inhibitors in relation to coronary events, but superior
in cerebrovascular protection156,157.
5. Other agents: a) aliskiren, a direct inhibitor of renin,
showed to be effective in reducing blood pressure
levels and useful in combination with diuretics or
calcium-channel blockers. However, the association
with other ACEIs or ARBs proved deleterious; b) central
action agents and alpha-adrenergic blockers are more
useful in multiple combinations158.
Blood pressure goals that are recommended according to
the “2013 ESH/ESC Guidelines for the management of arterial
hypertension” are < 140 mmHg for systolic blood pressure (SBP)
and < 90 mmHg for diastolic blood pressure (DBP). An exception
is made for diabetic patients, for which DBP < 85 mmHg is
recommended. The SBP recommendation for patients with
nephropathy and proteinuria is < 130 mmHg159.
Therapeutic targets
Blood pressure goals to be achieved, according to the
VI Brazilian Guidelines on Hypertension, are shown in
the Chart 5.3119.
6. Dyslipidemia
High cholesterol can be considered a major modifiable
risk factor for coronary artery disease (CAD) 160,161
and its control, mainly of the low-density lipoprotein
cholesterol (LDL-C) levels, brings great benefit in reducing
cardiovascular outcomes such as infarction and death from
coronary heart disease160.
After patient risk stratification (previously discussed), the
primary and secondary therapeutic goals to be achieved in
the treatment of dyslipidemia are established, according to
the overall risk (low, intermediate or high). The primary goal
to be achieved is the recommended LDL-C level and the
secondary one, the recommended non-HDL (high-density
lipoprotein) cholesterol level, calculated by subtracting HDL-C
from total cholesterol, representing the serum concentration
of atherogenic lipoproteins (Table 6.1). Specific goals are
determined for patients at high and intermediate risk. Patients
at low cardiovascular risk should have individualized goals
according to clinical decision and the reference values of the
lipid profile (Table 6.2).
20
Guidelines
Table 6.1 – Lipid Goals according to cardiovascular risk19
Risk level
Primary goal (mg/dL)
Secondary goal (mg/dL)
HIGH
LDL-C < 70
Non-HDL-C < 100
INTERMEDIATE
LDL-C < 100
Non-HDL-C < 130
Individualized goal
Individualized goal
LOW
* Patients at low CV risk should receive individualized advice, with goals established by reference values of the lipid profile (shown in Table 6.2), with focus on the
prevention and control of other CV risk factors.
Table 6.2. – Reference values of
lipid profile for adults19
Lipids
Values (mg/dl)
Category
LDL-C
< 100
100 – 129
130 – 159
160 – 189
≥ 190
Optimal
Desirable
Limítrofe
High
Very high
Non-HDL-Cholesterol
< 130
130 − 159
160 − 189
≥ 190
Optimal
Desirable
High
Very high
Table 6.3 – Recommendations for the nonpharmacological treatment of dyslipidemia in cardiovascular prevention19
Class
Level of
evidence
Control LDL-C
I
A
Meet the recommended LDL-C level (primary goal)
I
A
No goals proposed for HDL-C
I
A
Reduce the intake of saturated fatty acids and trans fatty acids, and consume phytosterols (2-3 g/day) and soluble fibers
I
A
Increase physical activity
I
A
Reduce body weight and increase the ingestion of soy proteins; replace saturated fatty acids with mono- and polyunsaturated fatty acids
I
B
Meet the recommended non-HDL-cholesterol level (secondary goal)
II
A
Use proper therapy when triglyceride levels > 500 mg/dL to reduce the risk of pancreatitis, and use individualized therapy when
triglyceride levels are between 150 and 499 mg/dL
II
A
No goals proposed for apolipoproteins or lipoprotein(a)
II
A
Indication
In relation to hypertriglyceridemia, patients with triglyceride
levels > 500 mg/dL should receive drug therapy to reduce
the risk of pancreatitis. Those with levels between 150 and
499 mg/dL should receive individualized treatment according
to the clinical decision, based on cardiovascular risk and
associated conditions. There are no proposed goals for HDL-C,
for apolipoproteins or lipoprotein (a) [Lp (a)] (Table 6.3).
21
Non-pharmacological treatment of dyslipidemia
food selection, preparation, the amount to be consumed and
possible substitutions. Dietary recommendations are shown
in Chart 6.1. In the treatment of hypercholesterolemia, the
reduction in the intake of saturated fatty acids and trans fatty
acids and intake of phytosterols (2-3 g/day) have a major impact.
Soluble fiber intake has less impact than the previous measures,
but has also shown to be effective in reducing cholesterol. Less
impressive results are obtained with the increase in physical
activity, weight reduction and soy protein intake160,161.
Nutrition therapy, weight loss and physical activity should
be recommended to all patients. Taking into account that the
serum levels of cholesterol and triglycerides are correlated with
increased consumption of cholesterol, carbohydrates, saturated
fatty acids and trans fatty acids, patients should be advised on
In the treatment of hypertriglyceridemia, the reduction of
weight, alcohol, simple sugars and carbohydrate intake has a
great impact. Increased physical activity and the replacement
of saturated fatty acids by mono- and polyunsaturated ones
have a moderate impact on serum levels of triglycerides160,161.
Guidelines
Table 6.4 – Recommendations for the drug treatment of dyslipidemias19
Indication
Class
Level of Evidence
Statins as a first-choice drug in primary and secondary prevention
I
A
Use of fibrates alone or in combination with statins for prevention of microvascular disease in type 2 diabetics
I
A
Association of ezetimibe or resins to statins when LDL-C goal is not achieved
IIa
C
Association of niacin to statins
III
A
Use of omega 3 fatty acids for cardiovascular prevention
III
A
Chart 6.1 – Dietary Recommendations for reducing hypercholesterolemia19
Prefer
•
Refined bread, rice and pasta,
cookies, sugary cereals
•
Grains
•
Whole grains
•
Vegetables
•
Raw or cooked vegetables
•
Legumes
•
All, including soy and soy protein
•
Fruit
•
Fresh or frozen fruit
•
Dried fruit, jelly, jam, ice cream
•
Sweets and sweeteners
•
Non-caloric sweeteners
•
Honey, chocolate, sweets
•
Lean and oily fish, chicken
without the skin
•
Meat and fish
•
Dairy products and eggs
•
Nonfat milk and yogurt and egg whites
•
Sauces for cooking and
seasoning
•
Vinegar, ketchup, mustard,
nonfat sauces
•
Nuts and seeds
•
Food preparation
•
Grilled, cooked or steamed foods
Pharmacological treatment of dyslipidemia
The drugs available for the treatment of dyslipidemias
are statins (inhibitors of hydroxy-methyl-glutaryl coenzyme
A [HMG-CoA] reductase), ezetimibe, resins or bile acid
sequestrants, niacin, fibrates and omega-3 fatty acids.
Lomitapide and mipomersen are drugs that have been
approved for use in some countries in the treatment of the
homozygous form of familial hypercholesterolemia, but not
yet in Brazil. New drugs such as PCSK9 inhibitors are currently
undergoing phase III clinical trials.
Statins
Statins should be used as the first-choice drug in primary and
secondary prevention, as they constitute the most clinical‑trial
validated therapy in reducing cardiovascular events. There is a
reduction in the risk of death from all causes by 10% and CAD
mortality by 20% for each 40 mg/dL reduction in LDL-C with
statins19,162-165.
The reduction in LDL-C varies greatly between types of statins
used and this difference has been primarily related to the initial
dose (Figure 6.1). Every time the dose of any of the statins is
doubled, the additional mean reduction in LDL-C will be 6% to 7%.
Consume occasionally at low
amounts
Consume moderately
•
Sweet breads, cakes, pies,
croissants
•
Vegetables prepared with
butter or cream
•
Cakes and ice-cream
•
Frankfurters, salami, bacon,
ribs, tripe
•
Yellow, creamy cheeses,
egg yolks, full-fat milk and
dairy products
•
Lean beef cuts, pork, seafood
•
Semi-skimmed milk, white
cheese and skim dairy products
•
Vegetable oils, light margarines,
salad dressing and mayonnaise
•
Butter, shortening, pork fat,
trans fats, coconut oil
•
All
•
Coconut
•
Roast and stir-fried foods
•
Fried foods
Adverse effects with statins are rare164,165. Myalgia with
or without increase in creatine kinase (CK) levels occurs in
approximately 10% of patients and may occur weeks or years
and after the start of the treatment. CK alterations are observed
in approximately 3% of patients and rabdomyolysis is extremely
rare164,165. The risk of myopathy can be reduced by avoiding
interactions with niacin, fibrates (particularly gemfibrozil),
calcium-channel blockers (diltiazem, verapamil), macrolides
(azithromycin, clarithromycin, erythromycin), azole antifungals
(fluconazole, itraconazole, ketoconazole), anti-retroviral
protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir,
saquinavir), immunosuppressors (cyclosporine, tacrolimus),
nefazodone, sildenafil and digoxin166,167. CK levels up to
5 times the upper limit of normal are considered acceptable.
One should consider treatment discontinuation when levels
are above this acceptable limit (5 to 10 times the upper limit),
as well as in the presence of persistence of muscle symptoms.
In these situations, lower doses or other statins may be tried.
A significant increase in liver enzymes (more than 3 times
the reference value ) occurs in about 1% of patients, but it
is usually reversible, even without therapy interruption167.
Regarding liver toxicity, temporary discontinuation is advised
with increases higher than three times the reference value
22
Guidelines
0
-15
-30
-45
-60
20
40
80
Fluvastatina
Fluvastatin
10
20
40
80
Pravastatina
Pravastatin
10
20
40
80
Sinvastatina
Simvastatin
10
20
40
Atorvastatina
Atorvastatin
80
5
10
20
Rosuvastatina
Rosuvastatin
40
1
2
4
Pitavastatina
Pitavastatin
Figure 6.1. – Mean reduction of LDL-C with statins19,161-163.
of transaminases and permanent suspension in cases with
active liver disease or severe hepatic dysfunction. The stable
transaminase increases in patients with no evidence of acute
illness and no complaints, as frequently observed in hepatic
steatosis, are not contraindications for the start of statin therapy.
Due to the previously stated reasons, CK and liver
transaminases (especially Alanine transaminase [ALT]) must be
measured before starting the treatment and after 6-12 weeks.
New measurements can be performed after statin dose
modifications, after combination with other drugs with interaction
potential or according to clinical criteria.
Ezetimibe
The addition of ezetimibe is recommended when
the LDL-C goal is not achieved with statin therapy,
remembering that statins should be used at the highest
tolerated dose to achieve target LDL-C before choosing
combination therapy. Ezetimibe reduces serum levels
of LDL-C by 10% to 25% and associated with statins,
it decreased cardiovascular events in patients with
degenerative aortic stenosis and chronic kidney disease
when compared with placebo168,169. Compared with statin
monotherapy, a study is currently testing the added benefit
of ezetimibe associated with statin.
Resins
Resins can be associated with statins when the LDL-C
goal is not achieved despite the use of potent statins
at effective doses. However, there is no study that has
demonstrated clinical benefit of this measure. The reduction
in LDL-C is dose-dependent, ranging from 5% to 30%
at doses of 4-24 g/day, which may cause an increase in
triglycerides in individuals with severe hypertriglyceridemia
23
(> 400 mg/dL). In Brazil only cholestyramine is available,
tested against placebo, with a 19% reduction in the primary
combined endpoint of death from coronary heart disease
and myocardial infarction170.
Niacin
Niacin is used to reduce triglycerides and increase
HDL-C levels, but no cardiovascular benefits of niacin in
combination with statins have been observed in patients
within the recommended LDL goal. The Coronary Drug
Project170,171,172, performed in the 1970s, demonstrated that
treatment with niacin in its crystalline form can reduce the
incidence of cardiovascular events172. Treatment with more
tolerable formulations, such as the niacin extended-release
formulations, reduced medio-intimal thickness even in
patients using statins.
However, two recent clinical trials have not demonstrated
the benefit of adding niacin to effective statin therapy with or
without ezetimibe171,172.
Fibrates
Fibrates are also used to reduce triglycerides and
increase HDL-C. There is evidence of microvascular
disease prevention (retinopathy and nephropathy) in type
2 diabetic patients with the use of fibrates, either alone or
in association with statins173,174.
Regarding cardiovascular events, monotherapy with
fibrates has shown inconsistent results in clinical trials and
association of fibrate and statins has not demonstrated any
benefits. In patients with hypertriglyceridemia, particularly
those with low HDL-C, some macrovascular benefit is
possible, as suggested in the subgroup analysis, but this
possibility requires confirmation.
Guidelines
The risk of myopathy increases with the combination
of fibrates and statins and simvastatin and other drugs
metabolized by cytochrome P450 should be avoided; use
gemfibrozil should not be used due to the marked increase
in the risk of rhabdomyolysis.
Omega 3 Fatty Acids
Omega-3 (ω-3) fatty acids are polyunsaturated fats
obtained from fish oil and certain plants and nut oils.
Fish oil contains both docosahexaenoic acid (DHA) and
eicosapentaenoic acid (EPA), but vegetable oils contain
predominantly alpha-linoleic acid (ALA). At higher doses
(4 to 10 g per day) they slightly reduce triglycerides
and increase HDL-C levels, but they may also increase
LDL-C and meta-analyses have shown no benefit in the
reduction of clinical events175, and, therefore, they are not
recommended for cardiovascular prevention.
7. Diabetes
The projection of 300 million adults with diabetes
mellitus (DM) in the world in 2030, with the current range
of more than 180 million diagnosed individuals, arouses the
urgent need to act on prevention at global level. Developing
countries have the highest incidences, which account
for two thirds of cases worldwide176. In Brazil, regional
data indicate high rates of DM prevalence in the adult
population, reaching 13.5% in some cities177. The 2010
census indicated 128 million adults, which may represent
a current population of up to 17 million individuals with
DM. These numbers are increasing due to factors such as
population growth and aging, urbanization, sedentary life
style and increasing obesity.
U.S. figures in 2012 point to a total of 245 billion dollars
in costs, including direct medical costs of 176 billion and
69 billion with the decrease in the productivity of affected
individuals178. The cost of treating an individual with diabetes
was 2.3 higher than in those without diabetes in the healthcare
service. Compared to 2007, total expenditures were 47%
higher, according to the same survey.
The metabolic control in individuals with the disease is
becoming one of the biggest challenges for public health
services 179, so the development of effective and viable
public health service programs for the primary prevention
of type 2 diabetes in the population at risk is necessary to
control both the incidence of type 2 diabetes, as well as
for secondary prevention of its metabolic complications.
Prevention
Changes in life style, such as diet adjustments 180
and aerobic exercises 181 have shown benefits in the
management of blood glucose and weight. The indisputable
association of obesity and overweight with increased
prevalence of diabetes puts weight control as the primary
target for the control of the diabetes epidemic 182 .
Weight loss is independently associated with the restoration
of normal glucose regulation in pre-diabetic individuals, as
demonstrated in the Diabetes Prevention Program (DPP)
study183. Simple measures such as reducing fat intake to
less than 30% of total daily calories and total daily calories
with regular physical activity can lead to a decrease of 5-7%
of the weight in the long term. The diet should result in
a deficit of daily calories from 500 to 1,000 Kcal, which
usually results in a weekly loss of 450-900 grams, reaching
a total of 8% weight loss in 6 months184.
The recommended physical activity is at least 150 minutes
of moderate to intense aerobic activity per week or 90 minutes
divided into at least three times a week, avoiding more than
two days without physical activity185.
It is worth mentioning that weight loss is recommended
for all overweight or obese individuals who are at risk of
developing diabetes. Changes in life style are the primary
means of reducing the risk, through weight decrease and
regular physical activities. Regular physical activity is an
important mechanism to maintain the ideal weight and
improve insulin sensitivity and glycemic control, favorably
affecting complicating factors such as hypertension and
dyslipidemia and increased aerobic capacity.
Table 7.1 outlines interventions on diet and physical activity.
Table 7.1 – Interventions on diet and physical activity in diabetes for cardiovascular disease prevention
Class
Level of Evidence
At least 150 minutes of moderate exercise associated with moderate diet and energy restriction to prevent DM in
individuals at risk
Indication
I
A
Due to the effects of insulin resistance in obesity, weight loss is an important therapeutic goal in individuals at risk of
developing DM.
I
A
Reducing fats to less than 30% of the energy intake and decrease energy intake in overweight individuals
I
A
24
Guidelines
8. Metabolic syndrome
Metabolic syndrome definition
The metabolic syndrome (MS) has received increasing
attention not only by the impact of each of its diagnostic
components, but mainly because the presence of cardiovascular
risk factors has been increasingly prevalent.
There are several versions of the definition of MS, but
adopts the criterion of this Policy will set the positioning of
several international organizations about tema186.
The diagnosis of MS requires the presence of three or more
of the criteria set out in Chart 8.1.
Prevalence of metabolic syndrome in different
population groups
Information on the prevalence of MS is still limited
and incomplete187 and depend on the criteria used for its
definition, justifying the implementation of treatment and
especially, prevention strategies188,189,190.
In the U.S., analysis of data from the National Health
and Nutrition Examination Survey (NHANES, 1988-1994) of
8,814 individuals of both genders older than 20 years showed
a prevalence of MS (non-adjusted and adjusted for age) of
21.8% and 23.7%, respectively, according to the criteria of the
National Cholesterol Education Program - Adults Treatment
Panel III (NCEP - ATP III). An increase in prevalence was
observed with age: 6.7% (20-29 years) and 43.5% and 42%
(60-69 years and 70 years), with little difference between
the genders (24% M and 23.4% F, respectively)189. Data from
NHANES of 2003-2006 showed even higher non-readjusted
prevalence rates (34%) when compared with 1988-1994:
29.2% in individuals ≥ 20 years. Among adults (20-39 years),
the prevalence of MS increased from 10.8% (1988-1994) to
15.6% (2003-2006) in women and 15.7% (1998-1994) to
20.3 % (2003-2006) in men189.
A Finnish study of 1,025 individuals aged 65 to 74 years
followed for 13 years assessed the prevalence of MS by six
Chart 8.1 – Diagnostic criteria for metabolic syndrome
Criteria
•
Definition
Abdominal obesity
•
Men
•
≥94 cm
•
Women
•
≥80 cm
•
≥150 mg/dL
•
Triglycerides
•
HDL-cholesterol
•
•
Men
•
<40 mg/dL
•
Women
•
<50 mg/dL
Blood pressure
•
Systolic
•
≥ 130 mmHg or treatment for arterial
hypertension
•
Diastolic
•
•
Fasting glycemia ≥ 100 mg/dL
•Glycemia
25
different diagnostic criteria and found rates ranging from
22.5% (European Group for the Study of Insulin Resistance
[EGIR]) to 66.4% (American College of Endocrinology [ACE])191,
while a Swedish study in nondiabetic individuals found rates
of 21.9%, 20.7% and 18.8% according to the criteria of the
International Diabetes Federation (IDF), NCEP-ATPIII and
EGIR, respectively192.
In Japan, Nanri et al. 192 found that MS prevalence
in adult men and women in 2007 of 26.9 % and 9.9%,
respectively, while Sakurai et al.194, in cohort studies with
812 participants and using three different diagnostic criteria
(IDF, Japanese Society of Internal Medicine [JSIM] and
American Heart Association and the National Heart, Lung
and Blood Institute [AHA/ NHLBI]), obtained values of
44%,
37.1% and 67.7%, respectively194.
The Transition and Health Impact in North Africa
(TAHINA) Project, with 4,654 individuals (1,840 men and
2,814 women) aged 35 to 74 years described an overall
MS prevalence of 30 % with the NCEP-ATP III criteria
(36.1% in women and 20.6% in men). In both genders, the
prevalence increased with age and was higher in residents
of urban areas195.
The Bogalusa study assessed young adults aged 19 to
39 years from a semi-rural community in America, with
61% females and 39% males (80% whites and 20% blacks)
and found an overall prevalence of MS of 12.2% (14.9%
in men and 10.4% in women), with no difference between
the several ethnic groups (12.8% in whites and 9.6% in
blacks). However, black men had higher prevalence than
white women (15.4% vs. 5.8%)190.
In Brazil, the data are still scarce, particularly on
young individuals. Literature review of eight studies with
adolescents (10-19 years) using the MS criteria of the World
Health Organization (WHO) or the NCEP-ATPIII described
MS prevalence of 4.2% to 15.4% (NCEP-ATPIII) and from
4.5% to 38.7% (WHO), with triglyceride elevation being
the most frequently altered component (4% to 75%), while
glucose alterations were less frequently observed196. In the
Rio de Janeiro study, the presence of aggregation of several
cardiovascular risk factors and MS was also observed and
strongly correlated with blood pressure197.
Cardiovascular and Metabolic Risks Associated with MS
The evaluation of patients according to their metabolic
profile, with early recognition of associated risk factors,
is desirable to identify and treat patients at high
cardiovascular and metabolic risk. In general, MS is
associated with a two-fold higher risk of cardiovascular
diseases such as myocardial infarction, cerebrovascular
accident (stroke) and cardiovascular mortality, and one
and a half-fold higher risk of death from any cause198.
The risk of developing cardiovascular disease associated
with MS has been demonstrated in meta-analyses, with relative
risk ranging from 1.53 to 2.18199-201.
The physiopathological mechanism by which MS increases
cardiovascular risk is still under debate; however, there is
strong evidence that insulin resistance is the main factor.
The progression of insulin resistance to hyperinsulinemia
Guidelines
and hyperglycemia triggers peripheral vasoconstriction and
sodium retention. There is a higher production of liver
levels of triglycerides, low density lipoprotein cholesterol
(LDL-C), apolipoprotein B and dense and concentrated
LDL-C, a situation that predisposes to atherosclerosis.
This unfavorable situation in relation to lipids leads to a
systemic prothrombotic and proinflammatory state. With
central obesity, adipocytes secrete mediators such as
tumor necrosis factor alpha (TNF‑alpha) and leptin, and,
independently, obesity leads to hypertension, dyslipidemia
and increased insulin resistance186.
There is a strong association between MS and the
development of diabetes, which intensifies as the number
of MS components increases. The relative risk of developing
diabetes is 2.1 according to the definition of the ATPIII and
3.6 using the WHO definition, in which insulin resistance
should be present202-206.
Risk Factors for Metabolic Syndrome
Several risk factors for the development of MS have been
identified by cross-sectional, prospective and case-control
studies, with important differences being found according to
the definition used in the diagnosis207.
Some factors are associated with the prevention of a
component of MS, without necessarily preventing the other
components or reducing the incidence of the syndrome as a
whole. The frequency of pre-school activities, for instance,
was associated with a lower incidence of hypertension in adult
life, but did not protect against the other MS components207.
Some studies identified multiple determinants of MS,
including age, male gender, low educational level, physical
inactivity, family history of diabetes and hypertension and
inadequate protein intake208.
Poor physical fitness and excess adiposity during adolescence
also correlated with increased risk for MS in the adult life209.
Many studies correlated sedentary behavior with MS risk210.
Nutritional factors seem to be related to MS. The frequent
consumption of dairy products, such as milk and yogurt,
appears to protect against the development of the syndrome211.
Excessive consumption of fructose as an artificial sweetener is
related to the development of MS in humans and animals212.
Soft drink consumption, even the sugar-free type, has also
been associated with increased risk of MS213. However, fruit
consumption seems to protect against MS212.
Several ethnic and environmental factors appear to
modulate the impact of some of the risk factors for MS.
In the Tunisian population, the prevalence was higher
among women than among men. In both genders the
prevalence increased with age, but the impact of this factor
was higher among women. The urban population had a
higher prevalence than the rural one, with greater risk
among individuals with higher educational level214.
Filipino women living in the United States showed a
greater impact of waist circumference as a component
of MS. Women of the same ethnic group living in the
Philippines showed low levels of HDL cholesterol as the
factor of greatest impact on MS216.
Several psychological disorders also appear to contribute
to MS. Depressive symptoms in North Americans police
officers were correlated with higher prevalence of MS217.
In a case‑control study performed in India, it was also
demonstrated a higher prevalence of MS among patients with
schizophrenia than among controls218.
Prevention of Metabolic Syndrome
There are scarce data in the literature regarding
the prevention of MS through pharmacological or
non‑pharmacological measures in the same theoretically
healthy population. The experts’ recommendations pointed
out that prevention strategies for MS must be the same used
in the non-pharmacological treatment of the syndrome.
For individuals without MS or type 2 diabetes mellitus
(DM2) or cardiovascular disease, but with glucose tolerance
impairment or the presence of some components of MS
(individuals with metabolic risk) there is evidence that changes
in life style may prevent MS and/or DM2 (Table 8.1).
Weight reduction
For those with metabolic risk that are overweight or
have abdominal obesity, a reduction of 5% to 10% of total
weight in one year followed by weight loss maintenance
is recommended. Those who are not overweight should
maintain their weight. Weight reduction should be achieved
Table 8.1 – Interventions in metabolic syndrome for cardiovascular disease prevention
Indication
Class
Level of Evidence
The reduction of 5% to 10% of weight in one year is recommended, followed by weight loss maintenance
I
B
Diet low in total and saturated fats, as well as trans-fats, which includes adequate amounts of fiber
I
B
Physical activity for a period of no less than 30 min/day, preferably 45-60 min/day, 5 days/week
I
B
Individuals with impaired glucose tolerance undergoing drug therapy may show more significant reduction in
the incidence of MS or DM2
I
B
For individuals with metabolic risk and waist circumference higher than the recommended limits, a reduction of 5%
to 10% of weight in one year is recommended
IIa
B
The ingestion of less than 7% of total calories from saturated fat and less 200 mg/day of cholesterol in the daily
diet is suggested
IIa
B
26
Guidelines
by means of a formal program changes life style and physical
activity must understand and caloric intake adequate219-222.
Abdominal obesity
Individuals with metabolic risk and abdominal
circumference higher than the recommended limits should
follow the recommendations of the previous item223-225.
Healthy diet
It is recommended that all individuals, with and without
metabolic risk, have a diet that is low in total and saturated
fat, as well as trans-fat, which includes adequate amounts
of fiber. The intake of less than 7% of total calories from
saturated fat and less than 200 mg/day of cholesterol in the
daily diet is suggested225-227.
There is no consensus on the optimal amount of
carbohydrates that the diet should contain. It is recommended
that individuals with metabolic risk substantially increase the
amount of fibers, unprocessed grains and unsaturated fats in
their diets and avoid foods with a high glycemic index225 -227.
Physical exercise
A regular program of moderate physical activity is
recommended for patients with metabolic risk, which should be
performed for a period of no less than 30 min/day, but preferably
45-60 min/day, for at least five days / week. These activities can
be brisk walks or more extenuating exercises223 -227.
Changes in life style versus drug therapy
Individuals with impaired glucose tolerance may have more
significant reduction in the incidence of MS or DM2 using
an adequate diet and exercise program, when compared
to the ones that use pharmacological therapy (metformin or
glitazones). The main reasons for choosing changes in life style
rather than the use of drugs in these patients with glucose
intolerance include: changes in life style are at least as effective
in reducing the incidence of metabolic syndrome or type 2
diabetes as drugs; there are few data in the literature about
the long-term safety of the use of these drugs in this group
of individuals, the cost-effectiveness of drug therapy in this
population has not been adequately evaluated223-227.
9. Physical activity, exercise and sports
Physically active individuals tend to be healthier, have
higher quality of life and life expectancy 228. Physical activity,
physical exercise and sports integrate the medical approach
for the prevention of cardiovascular diseases (CVDs).
Concepts and most relevant expressions
Physical activity, exercise and sports are correlated, but
distinct terms. Physical activity can be defined as any bodily
movements produced by skeletal muscles that result in
energy expenditure229. In practical terms, it can be classified
into occupational or work-related (including housework),
transportation or leisure. The leisure physical activity
27
encompasses those eminently recreational or sports-related
(sports practice), with rules, scores, winners, losers and activities
focused on physical fitness and health promotion. This last
subgroup of physical activity, more structured and with a clearly
defined purpose of performance and/or health improvement, is
conventionally called “exercise” (for sub-classifications or types
of exercise, consult other specific guidelines of the Brazilian
Society of Cardiology [SBC])230. According to this concept,
the cardiologist will very likely prescribe exercise, and not just
physical activity to their patients.
Some degree of physical activity is necessary for the
individual’s survival and autonomy. While there is a clear trend
of young individuals to move more than the elderly, levels of
physical activity, specifically exercise, vary from person to person
and this variability increases with advancing age. Thus, regular
physical exercises begin gradually, from immobility to higher
levels, with longer and more frequent durations231.
Individuals are classified into five options: sedentary
(or very little active or inactive), somewhat active, moderately
active (or simply active), more or very active and very active
(or exceptionally active). Tables 9.1 and 9.2 show the recommended
levels of weekly physical exercise for health promotion and
illustrate examples of how to classify the patterns of exercise and
sports for a child or adolescent, the latter incorporating the matter
of the need to define separate criteria according to different age
ranges and the estimated average energy expenditure per hour
(MET/h) in several examples of physical activity, exercise and sports
situations. Further details and suggestions for a more objective
quantification of the patterns of exercise and sports in a given
patient can be found in another SBC publication232.
Physical fitness is characterized by a series of conditions that
allow the individual to perform their daily activities and have
sufficient physical capacity to exercise or be physically active229.
Physical fitness comprises five components: aerobic status, muscle
strength/power, flexibility, balance and body composition.
Major Acute and Chronic Effects of Exercise
For a more objective analysis of the beneficial effects of
physical exercise for health, they can be divided into acute
(or responses) and chronic (or training)235. The acute effect
is one that dissipates quickly and can be an immediate
action after a single session or last for up to 24 hours (thus
being classified as subacute). The improvement in the
flow‑mediated response regarding the endothelial function
is an example of a single acute effect of the exercise session.
The chronic effect is achieved through repeated acute/
subacute effects. It can be evaluated at rest, even some time
after the last exercise session. The bradycardia observed
in athletes that practice predominantly aerobic modalities
is an example of a chronic effect. On the other hand, the
repetition of responses may generate a chronic effect, such
as the decrease in blood pressure levels.
Epidemiological Rationale of Physical Activity Benefits
There is consistent epidemiological evidence on the
relevance of aerobic physical fitness for health233-239, indicating
that the components of aerobic fitness, together or separately,
may be associated with clinical prognosis and life expectancy
Guidelines
Table 9.1 – Recommended levels of physical activity for health promotion and maintenance (adapted from Powell KE et al.228)
Characteristics of the exercise
Health benefits
< 150 min/week of mild to moderate intensity
Comment
Some
Some exercise is certainly preferable to a sedentary life style
150-300 min/week of moderate intensity
Substantial
Longer duration and / or higher intensity exercise confers greater benefits
> 300 min/week of moderate to high intensity
Additional
Current scientific information does not clearly defines an upper limit for the
benefits or to become harmful for an apparently healthy given individual
Table 9.2 – Examples of Physical Exercise Profile Classification in childhood (adapted from Balassiano DH et al.232)
Score
Definition
Childhood/Adolescence
0
Sedentary or very little active
Eventual cycling, frequent absenteeism from school physical education
1
Somewhat active
Normal attendance at physical education classes and short and intermittent periods of sports or dancing practice
2
Active or moderately active
Regular participation, most of the time, in small gyms or dance or fighting classes in gyms and fitness centers
3
More or very active
Regular and frequent participation in several sporting activities on most days of the week
4
Very active and competitive
Participation, during most of the time, in trainings and/or competitions or regular and frequent practice of
predominantly aerobic exercises
Chart 9.1 – Main effects of exercise
Acute
Endothelial fucntion
Cardiac output
Muscle blood flow
Coronary blood flow
Proteção enzimática antioxidativa
Insulin sensitivity
Baroreceptor sensitivity
Lipolysis
Chronic
Endothelial fucntion
Maximum VO2
Telomere length
Antioxidant enzymatic protection
Insulin sensitivity
Baroreceptor sensitivity
Joint flexibility and mobility
Muscle mass, strength and power
Resting metabolic rate
Vasoactive substances (bradykinin, NO)
Growth hormone
Protein synthesis
Better control of body weight
Bone mass
Trabecular bone structure
Nitrogen economy (protein-sparing effect)
Glycemia
Autonomic system
Arterial hypertension
Inflammatory markers
Postprandial hyperlipemia
Pulse wave velocity
Hormones ghrelin and NP γ (appetite regulators)
Glycated hemoglobin
Resting and submaximal exercise heart rate
Pulse pressure in exercise
Autonomic system
Arterial stiffness
Lipemia
Risk of degenerative cognitive diseases (dementia, Alzheimer’s)
Anxiety and symptoms associated with depression
Risk of falls in elderly
VO: Oxygen consumption; NO: nitric oxide.
of middle-aged and elderly individuals240,241,242. This ratifies
the recommendations of national243 and international244
guidelines, contemplating the regular practice of aerobic
exercises combined with muscle strength ones, such as weight
lifting. Additionally, stretching and flexibility exercises should
be part of a more complete and comprehensive program245.
of aerobic physical fitness are compared in an increasing scale,
one can observe the decreased risk of cardiac death and
death from all causes. The higher the level of aerobic fitness,
the lower the risk of overall and cardiovascular mortality and
morbidity in both healthy individuals and in patients with
CVD233,234,236,238,243.
Regarding the regular practice of physical exercises,
the greatest benefit occurs when sedentary individuals are
compared with those that perform no or only very little
exercise, as the positive impact of abandoning the sedentary
life style is very significant. However, when the varying degrees
Several studies have identified the effectiveness of regular
exercise on the prevention of hypertension and on blood pressure
levels246 in patients with systemic hypertension247, probably due
to a more favorable autonomic modulation and local vasodilator
effect on the smooth muscle of the arterial wall. These beneficial
28
Guidelines
effects occur and are added to those of the antihypertensive drugs,
often resulting in a reduction of the medication dose. The effects
of reducing blood pressure through exercise occur immediately
after and last up to several hours after it. Thus, similar to what
occurs with the drugs, this action on the cardiovascular system
needs to be repeated periodically for the benefit to be maintained
chronically. In recent years, in opposition to past dogmas,
performing muscle strengthening exercises also became accepted
and even recommended within the broader approach of physical
exercise for CVD prevention248. Recent evidence suggests that
dyslipidemic individuals with higher cardiorespiratory fitness,
even without the use of statins, have a lower risk than those with
lower fitness using the medication. Those with higher aerobic
fitness that used statins showed less mortality from all causes249.
Recently, the hypothesis that the concomitant use of statins would
have the potential to reduce some of the benefits resulting from
physical training has emerged250.
Risks of Physical Activity, Physical Exercise and Sports Practice
Healthy individuals have an extremely low risk of dying
as a result of regular exercise practice. A study of more
than 20,000 physicians carried out for a mean time of
12 years found that the risk of a fatal event in asymptomatic
individuals between 40 and 84 years of age was
approximately 1/1.5 million exposures to exercise (during
and within 30 minutes immediately post-exercise)251. Thus,
the recommendation to be physically active is very safe.
However, only 30% of our population exercises regularly
as recommended252. The use of the joint guidelines of the
Brazilian Societies of Cardiology and Exercise Medicine
and Sports 253 is recommended, which establish objective
and detailed criteria for pre-participation assessment in
exercise programs or in sports activities appropriate for
different age groups and for the presence or absence of
coronary risk factors and/or CVD.
Recent reviews and some observational studies253,254 have
identified increases in biochemical indicators and alterations
in cardiac images, suggesting the presence of myocardial
dysfunction induced by long training periods and repeated
competitions in long-lasting aerobic events (usually more
than 4 hours) in a small portion of these individuals255,256.
Clinical and/or demographic characteristics should be
identified that can indicate a higher probability of developing
these alterations and whether there is a safe limit regarding
the amount and intensity of exercise253,254.
Physical Exercise Prescription
Exercises may be prescribed concerning their characteristics
such as type (aerobic, muscular strength, flexibility), modality
(walking, running, biking, dancing), duration (performance
time), weekly frequency and intensity adjustment.
Aerobic exercises should be performed at least five times a
week, for at least 30 minutes, continuously or with intervals,
in order to significantly reduce cardiovascular events and
contribute to risk factor control253.
In general, the intensity should be moderate, which
can be prescribed using the methods listed in Table 9.1.
Previously sedentary patients can start exercising at the
lower limit of the prescribed intensity and increase it
with regular practice253. As for physically active patients,
according to individual assessment, they can perform
exercises at more intense levels, with a minimum duration
of 20 minutes, three times a week, being a safe activity and
one that brings additional benefits.
The muscular resistance or strength training exercises
are also beneficial for cardiovascular and musculoskeletal
health. They should be performed at least twice a week,
at moderate intensity, involving large muscle groups of the
upper limbs, trunk and lower limbs. Their performance can
be carried out with free weights, ankle weights, resistance
bands and weight machines. The intensity of the load can
be adjusted so that one is able to perform the exercises with
8 to 15 repetitions per series253.
Stretching and flexibility exercises can result in musculoskeletal
benefits, quality of life improvement and prevention of falls in
elderly individuals and may even be performed with these
purposes. In these exercises, one attempts to achieve maximum
range of motion, to the point of mild discomfort and statically
maintaining the position for 10 to 30 seconds. The types of
stretching can be general or individualized, based on specific
assessments such as the Flexitest25.
Table 9.3 – Methods of prescription of moderate-intensity aerobic physical exercises253
Method
Subjective sensation of effort (Borg)
Speech Testing
Description
Performing the exercises with self-perceived exertion as “medium/moderate, or somewhat heavy.”
2 to 4 in the Borg scale 0-10 or 10-13 in the scale 6-20.
Performing the exercises at an intensity where one feels somewhat breathless, but controlled, so that one can complete a
sentence without pausing.
Using the HR peak percentage
Performing the exercises at an intensity that reaches 60% to 85% of peak HR*
Target HR=peak HR x percentage
Use of HR reserve (Karvonen)
Performing the exercises at an intensity that reaches 50% to 80% of HR reserve (HR peak * - HR rest)
Target HR = HR rest + (HR peak* - resting HR) x percentage
Use of ventilatory thresholds in
Cardiopulmonary Testing
Performing the exercises at an intensity between the ventilatory thresholds 1 and 2 (anaerobic threshold and
respiratory compensation point)
* It is preferable to use the HR peak obtained at a maximal exercise test, as there may be individual variations that can lead to errors in predicting HR by age, especially in
patients using medications with negative chronotropic effect4,6.
29
Guidelines
Chart 9.2 – Time required for a 70-kg individual to achieve weekly caloric expenditure of 2,000 kcal in some activities (approximate values)
Activity
Walking on level surfaces
Time per week
Time per day (7x week)
Time per day (5x week)
6h
50min
1h10min
Bike riding
7h30min
1h05min
1h30min
Jogging
3h30min
30min
40min
Running
2h
20min
25min
Gardening
4h40min
40min
1h
Dancing
9h20min
1h20min
1h50min
Shopping
8h
1h10min
1h35min
Swimming (slow crawl)
3h40min
30min
45min
Swimming (fast crawl)
3h
30min
35min
Cleaning carpet or rug
10h30min
1h30min
2h10min
The performance of aerobic and non-aerobic fitness
evaluations allows a better prescription of physical exercise
to attain the best results and, through risk stratification and
search for occult heart disease, minimize the risks of greater
intensity exercises257.
The initial assessment consists of clinical history, physical
examination and electrocardiogram (ECG). More detailed
assessments should be individualized, with exercise stress test,
cardiopulmonary test, anthropometric, muscle strength and
flexibility assessment253. At the initial assessment, we can quantify
the functional deficit against the desirable level and establish
goals to be reached257,258. It is essential for the patient to undergo
re-evaluation, in order to encourage their dedication, as well
as measure their evolution during the period. The benefits are
proportional to the achieved gains257-259.
Formal and Informal Physical Activity: Strategies to
Encourage Referral, Implementation and Adherence
Although health benefits occur with relatively low-intensity
activities, resulting from informal everyday actions such as
walking, climbing stairs, cycling and dancing, ideally they
should also occur with the regular practice of physical exercises
(formal activities), which makes it easier to achieve the optimal
amount of physical activity, equal to or more than 2,000 kcal
per week (Chart 9.2)260.
The referral to structured services of physical activity and
cardiac rehabilitation is very important and can significantly
impact the health of the population261.
It is necessary to implement comprehensive strategies
established through simultaneous actions, such as, for instance,
increased physical activity in school programs; transportation
policies and systems that favor displacements through walking,
cycling and public transportation; public education, including
educational campaigns for the population; sports organization
at several levels (school, work, community, etc.), with proposals
that encourage and enable the practice of sports throughout
life, from childhood to old age261.
10. Psychosocial risk factors
Definitions and impact
Low socioeconomic status, lack of social support, stress at
work and in family life, depression, anxiety, hostility and Type
D personality are psychosocial risk factors for cardiovascular
diseases (CVDs) that hinders adherence to a healthy life
style, guidelines and treatments. Often, several psychosocial
risk factors coexist. Thus, subjects or populations of low
socioeconomic status and/or with chronic stress are more
likely to experience depression, hostility and social isolation.
Furthermore, CVDs can weaken patients and trigger disorders
such as depression and anxiety, creating a pernicious cycle.
Among the mechanisms connecting psychosocial factors with
CVDs are inappropriate behaviors (inappropriate life style and
poor treatment adherence), barriers to health care access and
biological alterations (on endocrine, autonomic, hemostatic,
inflammatory, endothelial activity, etc.)262.
Socioeconomic status: several prospective studies and
systematic reviews have shown that men and women with low
socioeconomic status, low educational level, low income, low
social status jobs, low social support or living in poor residential
areas have increased cardiovascular risk263.
Depression: several systematic reviews and meta-analyses
have shown that the clinical symptoms of depression and
depressive mood increase the incidence and worsen the
prognosis of coronary artery disease. Perceived social support
seems to reduce, and the lack of it, to increase the negative
influence of depression264,265.
Anxiety: large epidemiological studies indicate that panic
attacks increase the risk of cardiovascular event incidence,
whereas anxiety, generalized phobia and panic attacks can
worsen the evolution of established CVDs. In spite of some
contradictory data, two recent meta-analyses have confirmed that
anxiety is an independent risk factor for the incidence of coronary
artery disease and adverse events after myocardial infarction266.
30
Guidelines
Hostility and anger: hostility is a trait of personality
characterized by distrust, anger and tendency to engage in
aggressive and maladaptive social relationships. A recent metaanalysis confirmed that hostility and anger are associated with
increased risk of cardiovascular events in both healthy subjects
and patients with CVDs. Patients with CVD who suppress
anger have an increased risk of adverse cardiac events267.
behavioral interventions and appropriate, simple and
understandable communication.
Type D personality: type D personality (“distressed”)
involves a permanent tendency to show negative emotions
(negative affectivity) and social inhibition. The Type D
personality is associated with worse prognosis in patients with
CVD, regardless of depressive symptoms, stress and anger268.
Social support can help people adhere to healthy habits
and medical advice, and are particularly important to explore
each patient’s experiences, thoughts and concerns, prior
knowledge and everyday life circumstances. Individualized
counseling is the basis to obtain motivation and commitment
on the part of the patient.
Assessment of psychosocial risk factors269
As previously seen, psychosocial factors increase the
vulnerability to diseases and thus, their evaluation is essential
in planning prevention according to the individual’s risk
profile270. Yet, there is scant evidence on the benefits of
including this assessment into routine care. Standardized tools
and questionnaires to assess anxiety, depression, hostility,
socioeconomic status, social support, psychosocial stress and
Type D personality that have been validated in our country are
available. As a practical option, a simplified evaluation can be
carried out by asking a few questions, as follows.
Low socioeconomic status
What is your educational level?
Are you a blue-collar worker?
Cognitive-behavioral methods: are recommended as they
are effective in providing support to people wishing to adopt
a healthy life style. However, there is limited evidence to
determine the most effective interventions for specific groups
regarding age, gender and socioeconomic level, for instance.
Decision-making should be shared with patients and
caregivers. A crucial step is to help the individual set realistic
goals that can be further expanded.
For individuals at high risk of CVD multimodal interventions
are indicated, integrating education about a healthy life style
and medical resources, physical activity, stress management
and counseling about psychosocial risk factors. Individuals of
low socioeconomic status, the elderly or females may need
individualized programs to meet their specific needs for
information and emotional support.
Whenever possible, the multimodal treatment must be
carried out with doctors, nurses, psychologists and experts in
nutrition, cardiac rehabilitation and sports Medicine.
Work and family stress
Adequate communication: it must follow some principles
such as:
Can’t you accomplish your tasks at work?
•
Is the reward for your efforts inadequate?
• acknowledge the individual’s view of the disease and
contributing factors;
Do you have serious problems with your spouse?
Social isolation
•
Do you live alone?
Do you miss having a close partner?
encourage the expression about worries and anxiety,
self‑assessment and motivation for successful behavior
change;
Depression
• use the patient’s language and be supportive of each
improvement in life style;
Do you feel down, depressed or hopeless?
•
check whether the individual understood the guidelines
and have all the support needed to follow them;
•
recognize the difficulty to change lifelong habits and that
sustainable gradual change can be more efficient than
rapid changes;
Have you lost your interest and pleasure in life?
Anxiety
Do you frequently feel nervous, anxious or on edge?
Do you often feel unable to stop or control your worries?
Hostility
Do you often feel angry over small things?
Do you often feel uncomfortable with other people’s habits?
Type D personality
Do you often feel anxious, angry or depressed?
Do you avoid sharing your thoughts and feelings with others?
Significance of Interventions on the Psychosocial Risk
Factors269
Changing behaviors is a complex matter, as it involves
individual, cultural and environmental aspects, among
others. Thus, it is essential to adopt simple and effective
strategies and, especially among them, the multimodal
31
allow enough time to create a good relationship;
• accept the need for long-term support and repeated
efforts to encourage and maintain life changes;
•
make sure that all health professionals involved provide
consistent information.
The European guidelines recommend 10 practical strategic
steps to increase the efficiency of counseling for behavioral
changes, as follows.
“Ten strategic steps” to improve counseling for behavioral
change
1. Develop a therapeutic alliance.
2. Advise all individuals at risk or with CVD.
3. Help individuals understand the association between
health and behavior.
Guidelines
Table 10.1 – Class of recommendation and level of evidence when addressing psychosocial factors in the primary prevention
Recommendation
Class
Level of Evidence
Behavioral change with cognitive-behavioral strategy (motivational)
I
A
Integration of education and motivational strategies with multidisciplinary team whenever possible
I
A
Psychiatric or psychological consultation for cases of more significant disorder
I
C
Assessment of psychosocial risk factors
IIa
B
Pharmacological and psychotherapeutic treatment in patients with depression, anxiety,
hostility of great impact aiming at better quality of life, despite the lack of evidence
IIb
B
4. Help individuals assess the barriers to behavior change.
5. Obtain commitments from individuals to promote
behavior change.
6. Get individuals involved in the identification and selection
of risk factors to be modified.
7. Match strategies, including strengthening individual
capacity for change.
8. Design a life style modification plan.
9. Involve the healthcare team whenever possible.
10. Monitor progress during follow-up.
Interventions on depression, anxiety and distress: the
treatment of these conditions improves quality of life and
should always be considered, as they are safe in cardiac
patients. However, conclusive evidence is still lacking
about their influence on cardiovascular outcomes, even for
depression, which has been the most extensively studied271,272.
Stress management programs improve the well-being, risk
factors and CVD outcomes. Interventions to control hostility in
coronary patients may lead to decreased levels of behavioral
hostility and depression, improves physiological parameters
(autonomic response, reactivity to mental stress), strengthening
the social support and life satisfaction273. Recently, a program
of stress reduction for women prolonged life regardless of
other prognostic factors274.
Programs in the workplace aimed to improving autonomy
and increase control can reduce stress for workers of all
hierarchical levels273.
as the overall duration of treatment during which patients
continue to take the prescribed medications274. Persistence is
particularly important for the control of chronic (such as heart
failure) and/or asymptomatic conditions (such as hypertension
and dyslipidemia).
Impact
Several studies have shown that adherence to the medication
by high-risk individuals with CVD is low, with worse outcomes
and higher healthcare costs. For instance, months after the acute
myocardial infarction (AMI), 25%-30% of patients stop taking at
least one medication, with a progressive decline in adherence
over time. After one year, only 50% of patients report the use
of statins, beta-blockers (BBs) and antihypertensive drugs.
The PURE study275 showed that the use of antiplatelet agents,
BBs, angiotensin-converting enzyme (ACE) inhibitors, angiotensin
receptor blockers and statins in individuals with a history of
coronary artery disease (CAD) or cerebrovascular accident (CVA)
is low worldwide, especially in low-income and rural areas.
Causes
Adherence and persistence are dynamic and multifactorial
processes that require continuous attention and long-term
interventions. The World Health Organization (WHO)
classifies them into five major groups of factors that influence
poor adherence276.
•
Health system - low quality of care; little knowledge about
the medication and/or low acceptance of counseling;
lack of appropriate communication (e.g., complex or
confusing instructions), lack of access to health care and
lack of care continuity.
•
Patient’s condition - chronic asymptomatic disease, mental
(such as depression or cognitive impairment) or physical
comorbidities that cause dependence (such as problems
with vision or mobility), psychological/behavioral factors
(lack of awareness and motivation about treatment,
impulsivity), younger age group.
Future Directions
Despite the lack of definitive evidence, everything suggests
that psychological interventions to address psychosocial
stress and promote healthy behaviors can contribute to the
prevention and control of CVDs. Therefore, they should be
implemented and properly assessed to produce data that
allow the development of more effective treatment strategies.
Adherence to cardiovascular disease prevention strategies:
life style and medication
Definition
Permanent adherence is defined as the measure the
behavior of an individual in terms of taking the medication as
the recommended by the health care provider and persistence
• Treatment - complexity of the therapeutic regimen,
adverse effects.
• Socioeconomic factors - low literacy level; costs of
medication, lack of social support.
• The causes of poor adherence were also classified as
predictable (low literacy level, lack of compliance with the
first prescription, lack of response to treatment, irregular
32
Guidelines
acquisition of drugs, costs) and unpredictable (severe
mental illness, severe adverse effects)276.
These factors tend to agglutinate and bring difficulties.
For instance, complex medication regimens are often
necessary in patients with asymptomatic chronic disease
or multiple risk factors, unmotivated patients and those
that lack proper perception about treatment reasons and
regimens. Another complicating factor is the association
between disease/cardiovascular risk factors and cognitive
alterations277, as well as between depression and cognitive
decline278.
Evaluation
The identification of patients with poor adherence is
difficult. The measurement of adherence and/or persistence
has obstacles. It is based on self-report, use of questionnaires or
tools such as the Morisky scale (Chart 10.1)279, medical reports
for the Monitoring System, “smart” packaging, pill counting
records, pharmacy records and serum concentrations of drugs.
In most studies adherence and/or persistence were measured
by self-report, with obvious limitations.
It is known that adherence depends on the time of
evaluation. It is higher in the period within five days before
and after contact with the healthcare provider (“white coat
adherence”), but it usually decreases significantly within 30
days. This knowledge influences intervention strategies to
improve adherence.
The European Prevention Guidelines strongly recommend
“that physicians assess adherence and identify the reasons
for non-adherence, to adopt additional individualized
interventions”.
Recently, a careful review of community interventions
used in patients with hypertension, dyslipidemia, congestive
heart failure or ischemic heart disease found that behavioral
interventions show greater success in relation to educational
strategies 282. Behavioral strategies include motivational
counselling, self-monitoring (using daily records, drug packages
with calendars, electronic reminders and alerts), positive
reinforcement (e.g., digital feedback mechanisms, trends,
incentives and rewards) and partnerships with providers and
support groups on the web. It is worth mentioning that this
review mentioned only one study carried out in our country280.
In addition to the relative scarcity of available data, important
differences should be considered between research and the real
world (such as type of patient, physician profile, motivation,
monitoring, and follow-up), which can promote, in clinical
practice, inferior results than those obtained in researches.
The implementation of clinical strategies to improve
adherence (Chart 10.2) should employ evidence-based
strategies in an integrated manner and consider the
peculiarities in each case. Their goal should be shared and
involve all members of the healthcare team, the patient, family
members, providers, community contacts and health policy
makers. Local strategic actions, even if restricted, can bring
results and knowledge276.
Low compliance/persistence requires a multifaceted
solution. Many interventions could, if effectively implemented,
have an impact on public health improvement. An initial step
is to search for solutions to some of the key issues involving
representatives of the government, industry (pharmaceutical,
Chart 10.2 – Clinical strategy to improve adherence276
Interventions
Many interventions have been developed and evaluated,
but most have produced only modest results280,281.
•
A recent systematic review of interventions to improve
adherence in CVDs and diabetes, focused on the mechanism of
transferring information to patients, concluded that the highest
success rates were obtained with the following: electronic
interventions; personal intervention made by
pharmacists in a
place of drug distribution, and personal intervention directed
at patients at the time of hospital discharge283.
•
•
Chart 10.1 – Morisky medication adherence scale279
1.
2.
3.
4.
5.
6.
7.
8.
33
Do you sometimes forget to take your medicine?
In the past 2 weeks, were there any days when you did not take your medicine?
Have you ever cut back or stopped taking your medicine without telling your
doctor because you felt worse when you took it?
When you travel or leave home, do you sometimes forget to bring along
your medicine?
Did you take all your medicines yesterday?
When you feel like your symptoms are under control, do you sometimes stop
taking your medicine?
Do you ever feel hassled about sticking to your treatment plan?
Do you often have difficulty remembering to take all your medicine?
•
Estratégias para melhorar a adesão
Simplify the dosage
•
Decrease the number of tablets and the
daily doses
Decrease costs
•
Lower-cost drugs
•
Generic Drugs
•
Government subsidies and low-cost
programs
Adequate
•
Provide clear information on treatment
communication
benefits, possible adverse effects and
duration
•
Evaluate, without judging or criticizing,
the presence of poor adherence
•
Actively check for possible side effects
(e.g., sexual dysfunction, cough,
bleeding)
•
Avoid using technical terms and
overwhelming the patient with too much
information
Behavioral strategies
•
Incorporate the use of medications to
patients’ routines, adjusting the dosage
to activities, mealtimes and time when
patients usually go to sleep
•
Use pill-boxes, daily alert electronic
devices, packaging with calendars
•
Internet support groups
•
Positive reinforcement (incentives,
rewards)
•
Give instructions on self-monitoring
•
Motivational counseling
Guidelines
Table 10.2 – Classification of recommendation and level of evidence of adherence to strategy in cardiovascular prevention, lifestyle and medication
Recommendation
Assess and identify the causes of lack of adherence to define the proper orientation
Use behavioral and motivational strategies for patients with persistent lack of adherence
packaging), insurers, employers, service providers and patients.
The main shortcoming has been the incapacity to measure
and monitor adherence in routine care276.
The technology that allows continuous exchange of
information between patients and providers can be an
important tool. Incentives, including financial ones, to patients
and providers should be considered.
11. Childhood and Adolescence
Dyslipidemia
Epidemiology in Brazil
Brazilian population studies have demonstrated, according
to region and criteria, prevalence of 10% to 35% of
dyslipidemia in children and adolescents283.
Screening
The measurement of serum lipid profile in children should
occur after 2 years old, as until this age, a higher intake of fat is
necessary for myelination. Before that, cases must be analyzed
individually, according to concomitant diseases, therapeutic
measures and family history284.
The lipid profile should be screened in children between
2 and 10 years when:
•
they have male family members (parents or grandparents)
with a history of ischemic heart disease before 55 years
and females before 65 years;
•
they have parents with total cholesterol levels higher than
240 mg/dL;
•
they have other risk factors such as hypertension, obesity,
smoking, diabetes mellitus (DM), were born small for
gestational age;
• have diseases that course with dyslipidemia (human
immunodeficiency syndrome, chronic cholestasis,
hypothyroidism, nephrotic syndrome, obesity, chronic
inflammatory diseases);
class
level of evidence
I
A
IIa
A
After 10 years of age, every child should have total
cholesterol levels measured at least once, regardless of the
presence of risk factors.
Reference values
The reference values for lipids and lipoproteins in children
and adolescents are described in Table 11.1285.
Treatment
In most cases, dyslipidemia is caused by poor life habits:
poor diet (high in saturated or trans-fats) and sedentary
life style. Obesity also has an adverse metabolic effect,
with increase in levels of triglycerides and low-density
lipoprotein cholesterol (LDL-C) and decrease in high-density
lipoprotein cholesterol (HDL-C), in addition to altering
the lipid subfractions, increasing the concentration of the
pro‑atherogenic fractions286.
Changes in life style286
A healthy diet, of adequate quality and quantity for age,
is the basis of dyslipidemia prevention in children, except
in cases of familial hypercholesterolemia, which require
specific approach. It consists in the most varied, balanced
diet possible regarding amounts of proteins, carbohydrates
and fats. One should give preference to natural vegetable
fats, monounsaturated or polyunsaturated (vegetable oils
and almonds) plant. It is recommended to avoid fried
foods, processed foods rich in trans-fats and visible fat
from meat and skin from poultry. It is also very important
to prefer foods rich in insoluble (fruits, vegetables and
whole grains) and soluble fibers (legumes, fruits rich in
pectin and whole grains). To facilitate the nutritional
advice given to the population, it is suggested to use,
whenever possible, whole grains and five servings of fruits
or vegetables a day.
In the treatment of dyslipidemia, there are two phases
of the diet according to the concentration of lipids and
lipoproteins in the blood.
use drugs that alter the lipid profile (valproic acid, betablockers, smoking, oral contraceptives, corticosteroids,
parenteral nutrition, amiodarone);
• Type I Diet: up to 30% of calories from fat, up to 10%
of saturated fat and 100 mg/1,000 cal of cholesterol
(maximum 300 mg/d).
• have clinical manifestations of dyslipidemia (xanthoma,
xanthelasma, corneal arcus, recurrent abdominal pain,
pancreatitis).
• Type II Diet: up to 20% of calories from fat, up to
7% saturated fat and 60 mg/1,000 cal of cholesterol
(maximum 200 mg/d).
•
34
Guidelines
When it is necessary to prescribe this diet, the child or
adolescent should ideally be accompanied by a nutritionist,
due to risk of impaired growth or development. Recent studies
have shown benefits of a vegetarian diet at any age, as long
as it is balanced, to foster proper growth and development
and lower the risk of developing noncommunicable chronic
diseases, including atherosclerosis287.
in children and adolescents, and Figure 11.2 shows the
algorithm of statin treatment in cases when drug therapy
is necessary288,289.
The most commonly used medications are290:
Physical activity should be encouraged, as an active daily
routine, as well as with scheduled or supervised activities.
Every child or adolescent must practice at least 30 minutes
daily of moderate activity. At the population level, the practice
of unstructured recreational activity should be recommended.
The more varied and playful is this physical activity, the
greater the chance that this practice will continue throughout
adolescence and adulthood286.
•
Statins: is the most frequently used drug, recommended
for children aged > 8 years. There are not enough
consensuses regarding when to start statins in childhood
or what the target is in children290. The doses of statins
commonly used in children and adolescents are
described in Chart 11.1.
•
Cholesterol absorption inhibitors (ezetimibe): its use
is recommended as monotherapy starting at 5 years and
in combination with statins, after 8 years old, reducing
the side effects of these drugs.
•
Bile acid sequestrants: they can be used at any age,
associated with statins, at different times. Due to risk of
malnutrition associated with fat-soluble vitamins, nutritional
monitoring and supplementation are recommended
according to objective criteria of deficiency.
•
Supplements: Supplementation of 1.2 g to 1.5 g of
phytosterols can lower total cholesterol and LDL-C290.
Drug therapy
The lipid-lowering therapy may be initiated after 8 years
of age, except in very severe cases, after individualized
assessment. Figure 11.1 illustrates the ideal flow of
conduct in the screening and treatment of dyslipidemia
Table 11.1 – Reference values for lipids and lipoproteins in children and adolescents.
Parameter
Acceptable
Borderline
High (p95)
TC
< 170
170-199
> 200
LDL-C
< 110
110-129
> 130
n-HDL-C
123
123-143
> 144
TG (0-9a)
< 75
75-99
> 100
TG (10-19a)
< 90
90-129
> 130
HDL-C
> 45
35-45
Apo A1
> 120
110-120
Apo B
< 90
90-109
Low (p5)
< 35
< 110
> 110
TC: total cholesterol; LDL-C: low-density-lipoprotein cholesterol; n-HDL-C: non-high-density-lipoprotein cholesterol; TG: triglycerides; HDL-C: high-density-lipoprotein
cholesterol; Apo A1: apolipoprotein A1; Apo B: apolipoprotein B.
35
Guidelines
Child at risk aged < 10 years or child aged
> 10 years regardless of risk
TC < 170
170 - 199
> 199
Repeat TC
Child with FH+ for early
cardiovascular disease
TC < 170
170 - 199
Healthy lifestyle
Onaverage, 2
lipidprofiles
LDL-C < 100
LDL-C 100-129
LDL-C ≥ 130*
Healthy LS – measure
in 5 years
Type I diet*** measure
in 1 year
Secondary DLP*****?
Type II diet****
LDL-C
> 160 and
early COI or + 1
RF**
LDL-C > 190
Type II diet and lipid-lowering drugs
Therapeutic target
Figure 11.1 – Algorithm for the diagnosis and management of dyslipidemia in children based on risk factors and lipid levels (mg/dL). Adapted from Giuliano I. and
Caramelli B.290.
Legend: TC: total cholesterol; FH: family history; LDL-C: low-density-lipoprotein cholesterol; COI: coronary insufficiency; DLP: dyslipidemia; LS: lifestyle; RF: risk factor.
Notes:
*In the presence of DM, HIV infection, Kawasaki disease, nephrotic syndrome and systemic lupus erythematosus, pharmacological treatment should be started if LDL-C
levels > 130 mg/dL, after lifestyle changes
**Some authors consider the presence of emerging risk factors (high levels of lipoprotein(a), homocysteine and C-reactive protein) a determinant of the use of lipid-lowering
drugs in children with LDL-C levels > 160 mg/dL.
***Type I diet: up to 30% of calories from fat, up to 10% of saturated fat, up to 100 mg/1000 Cal of cholesterol, maximum of 300 mg/dL.
****Type II diet: up to 20% of calories from fat, up to 7% of saturated fat, up to 60 mg/1000 Cal of cholesterol, maximum of 200 mg/dL.
*****For every child diagnosed with hypercholesterolemia, a secondary cause of dyslipidemia should be ruled out and/or their first-degree relatives should undergo lipid screening.
36
Guidelines
Statin use criteria
Age of start depends on
the number and magnitude of
other RF or xanthomas
Observe interaction with
cyclosporine, fibrates, niacin,
erythromycin, antifungal drugs,
protease inhibitors
Ideally, over 8 years
Begin with < dose, 1x/day;
measure CK, AST and ALT
Instructions on risk for
teratogenesis
Myalgia?CK?
Stop using
Resume use after solution
4 weeks
Risk
CK > 10x/baseline
AST/ALT >3x/baseline
Lipids, AST, ALT, CK
Minimum LDL-C < 130
Ideal LDL-C < 100
Enzyme alteration*
Goal met
Goal not met
Reduce dose orchangestatin;
reassess in 2 weeks
Monitor
8 weeksand 3/3 months
Double the dose and
tests in 4 weeks
Figure 11.2 – Algorithm to monitor the use of statins in children and adolescents. Adapted from Giuliano I. and Caramelli B.290.
Legend: RF: risk factor; CK: creatine kinase; AST: aspartate transaminase; ALT: alanine transaminase; *CK: symptomatic + 3 to 10x; asymptomatic: > 10x
37
Guidelines
Chart 11.1 – Doses of hypolipidemic used in children and adolescents
Drug
Doses (mg/d)
Lovastatin
10-40
Pravastatin
10-40
Simvastatin
10-40
Rosuvastatin
5-40
Atorvastatin
10-40
Cholestyramine
4-16
Ezetimibe
10-
Obesity
Definition and Epidemiology
The change of life style habits, such as inadequate eating
patterns associated with sedentary habits, has contributed
to the increased prevalence of obesity in recent decades,
leading the World Health Organization (WHO) to declare
obesity a global epidemic291. A review of 450 prevalence
studies in 144 countries showed that 43 million children
were overweight in the world in 2010, with 35 million
in developing countries. In 2020, it is estimated that
approximately 9% of children worldwide will be obese, i.e., a
total of 60 million children292. In Brazil, approximately a third
(33.5%) of the children aged 5-9 years are overweight293.
Prognosis
Children and adolescents who are overweight have an
increased risk for obesity in adulthood, a phenomenon known
as “tracking phenomenon”. The proportion of overweight
adolescents who become overweight adults can vary from
22% to 58%294.
Furthermore, several studies have shown that children/
adolescents who are overweight or obese have a greater risk
of having DM, cerebrovascular accident (CVA), dyslipidemia,
coronary artery disease and hypertension and early mortality
in adulthood295.
Diagnosis
The diagnosis of obesity or overweight in children is a
clinical one, established by history and physical examination,
followed by the comparison of anthropometric data with
population parameters through curves of body mass index
(BMI) for age. The curves used earlier, by the National
Center for Health Statistics (NCHS/1977)296 and the Centers
for Disease Control and Prevention (CDC/2000) were based
on populations of North-American children who received
artificial feeding and, therefore, they tended to underestimate
the prevalence of obesity and overestimate malnutrition,
significantly changing clinical management. The WHO
developed a multicenter study and in 2006 published the
new curves for assessing nutritional status of children aged
zero to five years (WHO Multicentre Growth Reference Study
Group. WHO Child Growth Standards based on length/height,
weight and age)297. These curves are based on data from six
countries, including Brazil, and they are prescriptive, i.e.,
they are based on children who were breastfed and received
proper nutrition in infancy298. In 2007, the WHO published
the reference curves for children older than 5 years299. The use
of this standard was recommended by the Brazilian Ministry
of Health in 2007 and the growth curves were included in
the Child Health Handbook.
After weight and height measurement, BMI is calculated
(weight (kg)/height (m2). Overweight is considered when values
are > the 85th percentile or z score +2, and severe obesity
when values are > the 97th percentile or z score +3 of BMI.
For calculations it is also possible to use the free software
available on the WHO page300 or on the telehealth page301.
Additional examinations may be used for more detailed
evaluation of body composition, to investigate secondary
causes and to identify consequences of obesity, such as
changes in metabolic and inflammatory profiles, orthopedic
and sleep disorders.
Prevention and Treatment
From a lifetime perspective, prevention begins before birth,
which is called primordial prevention, i.e., preventing the child
from developing a risk profile. Thus, prevention includes proper
nutrition during pregnancy, breastfeeding promotion302 and
identification of family risk factors, in addition to monitoring
the growth and development of the child303.
Similarly, treatment of obesity in children and adolescents
(primary prevention) is mainly based on changing habits,
especially adopting a healthy diet and increasing physical
activity overall. It is important to involve the children’s entire
family, parents, teachers and health professionals, as well as
a multidisciplinary team303-307.
Systemic Arterial Hypertension
The prevalence of systemic arterial hypertension (SAH) in
children and adolescents ranges from 0.8 % to 8.2 %308-312.
Some studies indicate a mean prevalence of 3.5% when the
diagnosis is attained through repeated measures, both for the
diagnosis of hypertension and for the pre-hypertension, but
others report a prehypertension prevalence of 12% to 17%
through isolated measures, particularly in overweight and
obese adolescents308-313.
Although secondary hypertension with defined etiology
is the most common type in children, primary hypertension
is being increasingly diagnosed, especially in older children
and adolescents, when other risk factors are associated, with
overweight and obesity being the most common.
The consequences of hypertension are usually evident
after the fifth decade of life, but there is evidence that primary
hypertension originates in childhood and that high blood
pressure levels in this phase of life are strong predictors of
hypertension in adult life. It is also known that left ventricular
hypertrophy detected by echocardiography, considered the
greatest marker of target-organ injury from hypertension
in children and adolescents, is present in 34 % to 38% of
38
Guidelines
individuals in this age group that have moderate hypertension
and are not receiving treatment. In addition, primary
hypertension in children and adolescents is often associated
with excess weight and both are present in metabolic
syndrome (MS), which also includes elevated triglycerides,
low HDL - C, central obesity and hyperinsulinemia, known
risk factors for the development of atherosclerosis. Autopsy
studies in children, adolescents and young adults have shown
that as the number of risk factors for atherosclerosis increases,
the number and extent of fatty streaks and fibrous plaques
also increase in the aorta and coronary arteries of these
individuals313-315.
Blood pressure (BP) measurement is considered mandatory
after 3 years of age, annually or before that age when children
have neonatal history of morbidities, kidney disease or
family risk factors 316-318. Arterial hypertension is defined as
the percentile of BP in relation to age, gender and height.
Tables with age and height percentiles can be obtained from
the CDC growth charts available at http://www.cdc.gov/
growthcharts/2000growthchart-us.pdf. Once defined the height
percentile for age and sex, it should be correlated with the 90th,
95th or 99th percentile regarding the obtained BP level318-319.
Table 11.2 shows the levels of BP in normal and hypertensive
children and adolescents. The diagnosis of SAH should be
attained after three measurements on different occasions.
Studies suggest that there is a progression rate of
approximately 7% per year from pre-hypertension to
hypertension and that this persists in approximately one third
of boys and a quarter of girls in a longitudinal follow-up of
two years318-319.
For all children and adolescents with BP persistently at or
above the 95th percentile, the initial evaluation should attempt
to identify the etiology, if any, through data on sleep habits,
family history, risk factors, diet, smoking and alcohol intake.
The initial complementary study should include complete
blood count, serum urea, creatinine, sodium, potassium,
calcium, uric acid, urinalysis, urine culture and kidney
ultrasound. Levels of fasting glucose, total cholesterol, LDL-C,
HDL-C and triglycerides should be measured in all children
with hypertension and also in those with borderline BP that
are overweight, have chronic kidney disease or a family history
of cardiovascular disease (CVD).
C h e s t r a d i o g r a p h y, e l e c t r o c a r d i o g r a p h y a n d
echocardiography: Echocardiography should be requested
to assess left ventricular hypertrophy or other cardiac
abnormalities in all children and adolescents with hypertension
and those with borderline BP that have comorbidities
(including DM and kidney disease). Other tests that investigate
in target-organs damage from SAH, such as the assessment
of intima-media carotid thickness and microalbuminuria
measurement, still have no recommendation for routine use.
Ambulatory blood pressure monitoring (ABPM) is indicated
in children and adolescents to investigate white coat
hypertension, to assess therapeutic efficacy in hypertensive
individuals or hypotension-related symptoms during the
use of antihypertensive drugs, to investigate episodic BP
elevations and to assess BP patterns throughout the day in
individuals with diabetes, chronic kidney disease or autonomic
dysfunction. Additional examinations are necessary when
a disease that courses with elevated BP is suspected and
include: polysomnography, measurement of renin or plasma
renin activity, renal scintigraphy with captopril administration,
measurement of plasma and urinary catecholamines, serum
steroids in plasma and urine, nuclear magnetic resonance,
digital angiography and renal arteriography318-319.
Obesity is probably the most important associated condition
for primary hypertension in children and adolescents,
accounting for more than 50% of the risk of developing
SAH320,321,322. Thus, dieting, exercise and weight loss are
mentioned as important factors in changing the life style317.
Observational and intervention studies have shown beneficial
effects of weight reduction in pediatric patients321,322 and
weight loss improves not only BP but also other cardiovascular
risk factors associated with obesity, such as insulin resistance
and dyslipidemia. Some recommendations can be mentioned
in relation to changes in life style317: moderate aerobic physical
activity (see separate chapter); avoid excessive intake of sugar,
soft drinks, saturated fat and salt and eat more fruits, vegetables
and grains; implement changes in behavior (physical activity
and diet) adapted to the individual and family characteristics;
get relatives and family to be part of the process and provide
educational support material; set realistic goals; develop a
reward system for health promotion; the competitive sports
should be limited in the presence of uncontrolled stage
2 hypertension. The goals are appropriate to BMI, and
when BMI is below the 85th percentile, the weight should
be maintained; when between percentiles 85th and 89th, it is
indicated for children to maintain weight or gradual weight
loss in adolescents to reduce BMI to a percentile < 85th.
When the BMI is above the 95th percentile, gradual weight
loss is indicated (1-2 kg/month) until values below the 85th
percentile are attained316,317.
The decrease in body weight may make the drug treatment
unnecessary, but it should not delay its start when indicated316,
Table 11.2 – Blood pressure classification in children and adolescents318-319
Class
Percentile of systolic or diastolic blood pressure
Normal
< 90
Pre-hypertension
Normal high
39
90 to < 95 or BP ≥ 120 x 80 mmHg
Stage 1 SAH
95 to 99 plus 5 mmHg
Stage 2 SAH
> 99 plus 5 mmHg
Guidelines
as well as the reduction of sodium intake to 1.2 g/day for
children aged 4-8 years and 1.5 g/day for those older than
8 years and adolescents seems to be an effective measure312,316.
Changes in life style are the initial therapeutic
recommendation of primary SAH in children and adolescents.
Drug treatment is indicated for individuals with symptomatic
hypertension, secondary hypertension, target-organ injury
from SAH, diabetes types 1 and 2 and persistent SAH despite
the adoption of non-drug measures, situations in which these
measures are complementary to the drug treatment317,322.
Physical activity
The current strategy for the reduction in cardiovascular
mortality in developed and developing countries is the
prevention of its most important risk factors, by adopting
healthy habits (especially those related to physical activity
and diet), beginning as early as possible in the lives of
individuals323,324. As the performance of physical activity (PA) by
young individuals is the greatest predictor of its maintenance in
adult life, this is a strong argument to encourage its continuous
performance in children and adolescents324.
Children and adolescents are more physically active than
adults325; however, it is believed that currently, a progressive
and significant reduction in daily PA is occurring in individuals
of all ages as a result of several changes occurring in society,
among which stands out the abundant means of transportation
to different places (cars, buses, subways), eliminating the need
to walk or ride bikes, for instance. The reduction of PA in
leisure is favored by urban violence, lack of safe play areas in
large cities and the working hours of both parents, who end up
confining children at home, in addition to greater propensity
to habits that do not require energy expenditure (watch TV/
video, computer and phone use). There have been reports
that physical inactivity in Brazilian cities can reach 93.5 % of
its young population310.
This growing inactivity among individuals at a stage of life
that is naturally and biologically of great activity can generate
immediate and negative consequences for children’s health
(such as overweight and its comorbidities)326-329 and lead them
(tracking) to a habit (non-propensity toward PA) that can
extend to the rest of the individual’s life330,331, thus contributing
in the long-term, to the occurrence of chronic- degenerative
diseases in adults, including cardiovascular atherosclerotic
disease 332.
Thus, PA should be encouraged in children and adolescents
so that they acquire an active habit that will remain throughout
life and for PA to acts as an agent:
a) to assist growth (strengthening muscles, bones and
joints); b) therapeutic (in those who have other cardiovascular
risk factors such as obesity, hypertension, diabetes mellitus,
dyslipidemia, metabolic syndrome (MS), anxiety and
depression); c) prevention, including CVDs in adults332-335. A
systematic review of 18 studies involving 12,742 participants
aged 0-4 years has shown that high levels of physical activity
are associated with better parameters of adiposity, bone
and muscle health, motor and cognitive development and
cardiovascular health, even at this range early age range336.
Therefore, children and adolescents should be encouraged
to engage in physical activities that are pleasurable to them
at home, at school and at play, through physical education
classes, sports, games, play, actively commuting to school
(walking, cycling) among others337-340. For that, a joint action
is required: a) by the family (that must be active together and
not just encourage the children to practice PA); b) by the
health professionals (investigating the level of PA carried out
by the children and their parents; by encouraging an active
life style; by investigating morbid conditions that limit the
practice of PA or require special care); c) school (by offering
regular physical education classes, sports, health education
promotion; inclusion of parents in PA programs, opening
the school for the community; d) community (requesting PA
programs in schools and recreational areas in the cities, as well
as a health promotion policy that includes PA in education,
sports and health care)332-335.
In general, it is recommended that children and adolescents
participate in moderate to severe PA (“that will make them
sweat, become breathless or with tired legs”), lasting at least
60 minutes, preferably on every day of the week332-335. This
recommendation includes intense activity at least three days
a week and activities that promote muscle and bone strength
at least three days a week337. A higher level of daily physical
activity promotes more health benefits337.
When structuring an active life style for children and
adolescents, it is also extremely important to reduce the
number of daily hours spent in sedentary activities (TV,
video games, computer, phone)332-335. A study carried out in
a Brazilian capital showed that children aged 7 to 17 years
spent around three hours (median) in front of the TV343. There
is evidence that the time spent watching television during
childhood and adolescence is greater than the time spent at
school and that the prevalence of obesity increases by 2%
for each additional hour watching TV; that 4 or more hours
watching TV is associated to higher frequency of smoking,
hostile behavior, depression and alcohol consumption and
that a high number of hours watching TV in childhood and
adolescence is associated with obesity, low physical fitness,
smoking, and hypercholesterolemia in adulthood332-335. Thus,
it is suggested that the daily time spent in sedentary activities
is limited to a maximum of 2 hours.
A systematic review of studies on the effectiveness
of interventions to promote PA in pediatric patients
(particularly adolescents) showed better results when
associated with actions at school involving the family
or the community and educational activities involving
environmental and health policies338.
Therefore it is recommended that when planning
PA for children and adolescents, it should be based
on the identification of cognitive-behavioral mediators
(self‑awareness, self-esteem, knowledge, intention to
become active, pleasurable activities, favorite activities)
and social support (family, friends)338 that may be used to
evaluate the effectiveness of the chosen strategies, so that
the best can continue to be used in future programs aimed
at this population337-339.
40
Guidelines
Table 11.3 – Classification of recommendation and level of evidence for the presence of cardiovascular diseases (CVD) in children and adolescents.
Recommendation
class
level of evidence
•
•
Obesity screening by use of BMI in children ≥ 6 years, providing or indicating intensive behavioral interventions directed to
achieving a healthy weight
Ask about early CAD family history to identify children at risk
In the presence of positive family history, assess all family members, especially the parents
I
B
•
•
•
In children aged > 2 years with BMI ≥ 85th percentile:
Reinforce preventive instructions (see below)
Identify complications and RF: SBP, gallbladder disease symptoms, diabetes, sleep apnea, hypothyroidism, orthopedic disorders, lipid profile
I
C
In children aged > 2 years with BMI ≥ 85th– 94th percentile,
• all measures above plus:
• control of weight gain and fat ingestion, focusing on nutrition and development
• treatment of RF and complications
• multidisciplinary approach of moderate to high intensity
• measure aspartate transaminase (AST), alanine transaminase (ALT) and blood sugar in children ≥ 10 years of age
I
C
In children aged > 2 years with BMI ≥ 95th percentile,
• all measures above plus:
• Long-term objective: maintain BMI < 85
I
B
I
A
Exclusive maternal breastfeeding for the first 6 months
I
B
From the 12th to the 24th month, transition to non-aromatic low-fat milk (2% or skim)
I
B
From 2 to 21 years of age, non-aromatic skim milk should be the major beverage
I
A
Avoid sugar beverages, encourage water ingestion
I
B
Fat ingestion by infants should not be restricted without medical indication
I
C
From the 12th to the 24th month, transition to family meals with fat corresponding to 30% of the total caloric ingestion, 8%-10% of
which of saturated fat
I
B
From 2 to 21 years of age, fat should correspond to 25%-30% of the total caloric ingestion, 8%-10% of which of saturated fat
I
A
Avoid trans fat
I
B
Cholesterol < 300 mg/dL
I
A
I
B
Parents should create an environment that promotes physical activity and limit sedentary activities, and be role models
I
C
Limit sedentary activities, especially TV/video
I
B
Moderate to vigorous physical activity every day
I
A
Obesity screening
•
•
•
Consider more aggressive approaches if conservative strategies fail
Check urea and creatinine every 2 years
Nutrition – Milk/other beverages
Dietary fat
Others
From 2 to 21 years of age, encourage fiber ingestion, limit sodium ingestion and encourage healthy life habits: family meals, breakfast,
limit fast snacks
Physical activity
BMI: body mass index; CAD: coronary artery disease; RF: risk factors; SBP: systolic blood pressure
41
Guidelines
12. Legislation and prevention of risk
factors for cardiovascular disease
Introduction
Some considerations should be made regarding the
association between legislation and prevention of risk factors
(RFs) for cardiovascular disease (CVD), starting with simple
matters such as: can specific health laws fulfill an effective
role in health promotion and CVD prevention?
In principle, the answer is yes. Knowledge of the RFs for the
development of CVDs is the first step to change the lifestyle
of the population, supporting their prevention. Encouraging
CVD prevention and control, promoting and creating healthy
environments requires that both the population and the
health managers be well informed about the importance
of surveillance, prevention, care, rehabilitation and health
promotion.
For that purpose, the creation of public policies that
have the support of the population, consolidating the
actions of the community and redirecting health services is
essential. Thus, it is necessary to develop actions for health
promotion and disease prevention that integrate individual
actions and assistance to population actions of collective
comprehensiveness, positively intervening with RFs for
CVDs through legislation and regulatory actions, as well as
educational, information and community mobilization ones.
The last two decades have shown evidence of legal
restrictions concerning:
1. Cigarette advertising in the media;
2. The content of nicotine and substances that potentiate
its action;
3. Smoking in enclosed public places;
and risks are relevant strategies that contribute to reducing the
impact of CVDs. The appropriation of knowledge about the
RFs, scientifically recognized as those involved in the genesis
of CVDs, has provided new and more effective measures
related to their prevention.
Epidemiological researches carried out in the American
town of Framingham (Framingham Heart Study) at the end
of the 1940s constitute the starting point and one of the
most important scientific advances that established the base
of knowledge capable of unequivocally correlating RFs and
CVDs. Moreover, very importantly, allowed the capacity to
strategically intervene effectively on the FRs and reduce the
prevalence of CVD morbidity and mortality344.345.
Two important aspects must be considered from the
strategic point of view, regarding the RFs related to CVDs and
the expected response to control actions - rules, regulations
and legislation - issued by authorities in the area of health:
potential of response to interventions and possibility that
the regulatory measures and legislation will induce effective
changes in the epidemiological profile of the population.
Regarding the potential response to interventions,
there is an accumulation of knowledge indicating that
preventive actions are effective in reducing the prevalence
of CVDs, as it was observed with smoking reduction, for
instance. After the first decade of changes in habits of the
population, it was already possible to see the effects of the
phenomenon on morbimortality statistics340.
With the development of knowledge in the medical area
in recent years, mainly through Evidence-based Medicine
(EBM), it is now possible to quantify or categorize responses
to interventions according to the degree of evidence observed.
Based on the concepts of EBM, four hierarchical categories
of response to interventions were established:
4. The sale of cigarettes to minors, among others - and of utmost
importance - in association with educational measures.
a) those that prove a decrease in the risk of CVD;
These restrictions resulted in a significant reduction
(of approximately 50%) in the population of smokers in
the country340.
c) those that can reduce the risk;
As smoking is one of the biggest RFs for the group of CVDs,
morbimortality statistics were expected to stabilize or decrease
during this period, in the group of smoking-related diseases.
This was indeed observed, according to several scientific
studies published in recent years and the data released by the
mortality information system of the country341,342.
The first group - which have proven to reduce – include
the following risk factors: smoking, LDL - C, diets high in fat/
cholesterol, high blood pressure (hypertension), left ventricular
hypertrophy, thrombogenic factors.
Therefore, one can infer that legislative and regulatory
actions can play an effective role in the prevention of
tobacco‑related diseases, such as coronary artery disease (CAD)
and cerebrovascular accident (CVA) and in the group of CVDs
and respiratory diseases, such as emphysema, chronic obstructive
pulmonary disease (COPD) and lung cancer343,344.
Developing a system of health communication using local
resources (radio, local and broad-circulation newspapers,
television programs, the web), developing and maintaining
educational campaigns with clear and accessible information
to help individuals in changing habits, formulating strategies
for drug treatment adherence, building the individuals’
empowerment to promote self-management of their diseases
b) those that clearly reduce the risk;
d) those that are associated with increase in CVDs, but are
not modifiable.
In the second – which obviously reduce - are: diabetes,
sedentary lifestyle, HDL - C, triglycerides, LDL, obesity,
postmenopausal period.
In the third group – which can reduce - are: psychosocial
factors, lipoprotein (a), homocysteine, oxidative stress, nonalcohol consumption.
In the four – non-modifiable – are age, male gender, low
socioeconomic status, history of early CVD345.
The World Health Organization (WHO) released in 2011,
the most cost-effective interventions, some of which are still
considered the “best buy” (actions that must be performed
immediately to produce accelerated results in terms of
lives saved, diseases prevented and avoided high costs).
The WHO also disclosed cost-effective interventions at the
42
Guidelines
population level (health promotion) and in relation to primary
and secondary prevention and treatment. There are other
promising measures, because the studies are still in progress.
Chart 12.1 details the measures proposed by the WHO that
may be effective for reducing CVDs346.
Regarding the “possibilities of normative actions and
legislation on reduction and control of CVDs” one can expect
the effectiveness of these interventions provided that they
preceded/accompanied by educational measures and that
laws and health standards originate from broad discussions
with the community. After all, it is a difficult task, that of
interfering with the freedom of individual citizens in relation
to their habits of life: poor diet x healthy eating; sedentary
life x correct practice exercises; free and exaggerated use of
alcohol x moderate use.
Going back to the example of smoking, it is worth
remembering that the antismoking campaign of the Ministry
of Health at the end of the 1980s was planned and executed
with the effective participation of social sectors, including
universities, representatives of health professional - mainly
in the areas of oncology, cardiology and pulmonology community representatives and leaders, representatives of the
political class, all with the collaboration of the individuals that
have historically been at the front of the anti-tobacco fight.
Starting with educational actions, with appeals and
messages that were quite different from previous campaigns,
it was possible to gradually initiate the legal actions and
restrictive rules, which were well assimilated by the general
population and smokers, with positive results.
Finally, one needs to analyze what the state of the art is
on the topic “legislation and control of CVDs”, by assessing:
• What place regulatory measures and legislation occupy
in CVD control strategies and in health agencies at the
three levels of the government.
•
How this regulatory apparatus interacts with educational
activities and society.
• What are the laws and regulations at the federal level,
general and specific ones, aimed at the control of CVDs.
• What is still missing regarding the regulatory apparatus
that could constitute into a gap to be filled by new laws,
rules and regulations.
•
•
Which measures seem more appropriate to make strategic
use of the available Legislation and which need to be
created, eventually, to obtain effective control of RFs
involved in CVDs.
What RFs are the priority and need to be addressed, of
which reduction and / or control will result in effective
impact on morbidity and mortality from CVD.
Let us consider, collectively, the questions listed in the
previous item.
•
43
It can be argued that, in general, there is a great positive
expectation on the part of the population and health
officials in relation to the coercive/normative strength of
laws and regulations. If these laws and regulations are
being effectively obeyed is a detail which, in most cases,
is not taken into account. What is important is the mere
existence of legislation.
Chart 12.1 – Evidence of interventions in CVD
1. Population interventions considered the “best buy” by the WHO:
• Increase taxes and prices on tobacco products.
• Protect individuals from tobacco smoke, prohibit smoking in public places
and warn about the dangers of tobacco consumption.
• Enforce the prohibition of advertisement, sponsorship and promotion of
tobacco.
• Restrict alcohol sales at retail.
• Reduce salt intake and salt content in foods.
• Replace trans-fats in foods by polyunsaturated fats.
• Promote public understanding of nutrition and physical activity, including the
mass media.
2. Other population-based cost-effective and low-cost interventions:
• Promotion of breastfeeding and appropriate complementary feeding.
• Apply laws against drinking and driving.
• Restrict the advertising of foods and beverages high in salt, fats and sugars,
especially for children.
• Taxes on foods and subsidies for healthy foods.
3. Interventions with promising evidence and studies still in progress:
• Healthy nutrition environments in schools.
• Nutrition information and counseling in health care.
• National guidelines for physical activity.
• School-based physical activity programs for children.
• Programs of physical activity and healthy eating in the workplace.
• Community programs of physical activity and healthy eating.
• Construction of environments that promote physical activity.
4. Interventions for the health care of specific groups:
• Therapy with acetylsalicylic acid (ASA), statins and antihypertensive drugs
for prevention of acute myocardial infarction and other cardiovascular
diseases.
• Counselling and multidrug therapy, including glycemic control for
diabetes, for individuals older than 30 years, preventing fatal or nonfatal
cardiovascular event.
• Treatment of nicotine dependence.
• Financing and strengthening health systems to provide cost-effective
individual interventions through primary care approach.
• Hence the problem of effective significance of the
legislation as a strategic element or component of
preventive health actions. Using examples to clarify
this argument, let us take the content of salt (sodium
chloride) in processed foods for human consumption.
The importance of salt intake control in primary and
secondary prevention of hypertension is well-known.
It is, therefore, essential to monitor, through the official
organs, the sodium content of foods and if there is real
consistency between this content and what is stated on
the labels of these foods. This is a preventive health action.
• If the legal apparatus does not interact with society
through continuous educational activities, the trend is
that there is a gradual loosening of its standards, putting
the population under its responsibility at unnecessary risk.
It should be taken into account that the users/consumers
are also agents responsible for verifying compliance with
the laws, as long as they are warned and fully educated
to pursue that task.
•
There is a whole set of federal laws and regulations aimed
at the control of CVDs. They originate from food and
nutrition security surveillance organs aimed at children,
adults and senior citizens, and, theoretically, can fulfill
an important role in the prevention and control of
non-transmissible chronic diseases. Other standards
Guidelines
originate from specific government organs, which focus
on detection and control of CVDs. The most significant
part of this normative framework is listed in the Annexes
of this Guideline.
Regarding RFs that, at first, should be considered as
priority, the ones that will be considered strategic will be
chosen. As such, those which interventions have - unarguably
- demonstrated decreases in cardiovascular risks will be listed.
Intervention is proposed for three RFs with high potential
of response to interventions through educational measures
- change of lifestyle - and drug interventions: smoking,
hypertension and dyslipidemia. These factors will be addressed
in a specific way, demonstrating that this strategic indication of
priority is not done at the expense of other RFs, also important
for the control of CVDs.
After establishing a close correlation between lifestyle x
CVD, arterial hypertension x CVD and diabetes mellitus (DM) x
CVD, it is essential to identify the common point of interaction
between these factors. The evidence points to obesity and
overweight as factors clearly associated with hypertension,
dyslipidemia, diabetes and atherosclerosis.
Based on the changes observed in some important social
determinants of health, obesity has become epidemic in
many countries and is independent from the degree of
economic and technological development achieved by them.
Obesity and overweight currently constitute a severe public
health problem. It affects millions of people, has severe
repercussions on the health care services and impacts the
quality of life and productive capacity of men and women,
usually at the top of their functional capacity.
Changes in life style, such as using motor vehicles as a
way of getting from home to work and vice versa, leading to
a sedentary lifestyle; abuse of fast food and processed foods;
introduction of sugar and carbohydrates in the diet; excessive
stress of the urban life and abusive consumption of alcohol
have combined to produce overweight individuals with risk
aggregation, whose metabolism allows the development of
the so-called diseases of modern life. And all this was caused
by the rapid urbanization process.
From the physiopathological point of view, obesity is
definitely related with diabetes and insulin resistance, with
dyslipidemia and arterial hypertension, resulting, as the final
outcome of this pathological cycle, in atherosclerosis.
It is known that in the obese individual: to insulin resistance
develops by blocking the receptors of this hormone in tissues;
there is an increase in total cholesterol and LDL-C due to
increased production of fatty acids; due to insulin resistance,
there is a gradual increase in these hormone levels, resulting
in chronic activation of the sympathetic system and SAH.
It can be concluded, therefore, that the control of obesity /
overweight, through laws, rules and regulations, conceptually
becomes a measure capable of producing a significant
epidemiological impact on CVD morbimortality statistics.
However there are two variables that hinder the full
implementation of this measure.
The first is related to difficulties in attaining adherence
of the several population age groups to changes in their
eating habits and cultural/behavioral patterns. Permanent
educational campaigns are needed, with a priority strategic
focus on the school environment, aiming at raising adults
capable of keeping healthy life habits. As for children and
adolescents, educational measures must be shared at the
home level, aimed primarily at the parents. The content of
salt, fats and trans-fats and the consumption of healthy foods
in school cafeterias deserve special attention from educators
and health authorities. Legal and regulatory measures are
perfectly reasonable in this context.
The second variable, perhaps more complex and one
that brings many difficulties and challenges to governmental
authorities in the area of health, consists in the attitude of the
food producing industry, which is repeating what cigarette
manufacturers did in the past, when they decided to put into
their products additive substances that were strongly inducers
of tobacco addiction: they are adding substances capable of
creating addiction in the consumer of foods that are harmful
to their health, making them cheaper and more attractive.
Studies on the behavior of consumers, including children and
young adults, show how to alienate them from healthy foods,
making them prefer food products with high sugar content
and low in nutrients347.
In this context we show in Chart 12.2, the main
regulatory actions and legislation related to strategies of
health surveillance, prevention, care, rehabilitation and
promotion in Brazil.
It is noteworthy that Brazil has been committed to the
prevention and care of the NCDs and launched the Strategic
Action Plan for the Fight against Noncommunicable Chronic
Diseases (NCDs), 2011-2022, which defines and prioritizes
actions and investments required to prepare the country
to face and stop NCDs and their risk factors in the next 10
years. The plan addresses the four main groups of diseases
(cardiovascular, cancer, diabetes and chronic respiratory
diseases) and the modifiable risk factors they have in common
(smoking, alcohol, physical inactivity, poor nutrition and
obesity) and defines three strategic directions: a) surveillance,
information, assessment and monitoring; b) health promotion;
c) full care. The plan establishes goals and commitments made
by Brazil in relation to NCDs340,348,349.
CVD is a multifaceted disease in relation to its RFs and
its control demands articulated promotional and preventive
actions that have an impact, such as the fight against sedentary
life style and obesity and tobacco control, and integrated
health services for the diagnosis and monitoring of detected
and treated cases. The laws and decrees currently being
enforced in the country are subsidies for managing NCDs,
particularly CVD, requiring articulated efforts from the health
area together with the other governmental, non-governmental
and private sectors, both in the design, development and
implementation of specific policies that coordinate and
integrate health surveillance, prevention, care, rehabilitation
and promotion, producing quality of life and citizenship.
Thus, the approach to public policymakers will imply in the
adoption and development of integrated and comprehensive
public health actions and policies, supported by intersectorial
actions, taking into account the several cycles of life, local
conditions and needs.
44
Guidelines
Table 12.2 – Main legislation and regulatory actions related to strategies for health surveillance, prevention, care, rehabilitation and
promotion in Brazil
Decree/Law
Content
•
Decree n 687/GM/MS, March 30, 2006
•
Health Promotion Policy
•
Decree n 971/GM/MS, May 3, 2006
•
National Policy on Integrative and Complementary Practices (PNPIC) in the Unified Health System (SUS)
•
Provides for the distribution of free medications and materials needed to implement and monitor
capillary blood glucose for patients with diabetes enrolled in education programs for diabetics
•
Defines list of medications and supplies available through SUS, pursuant to Law No. 11,347, 2006, for
users with diabetes mellitus
•
Law N. 11.347, Sept. 27, 2006
•
Decree n 2.583, Oct. 10,2007
•
Decree n. 1.559/GM/MS, Aug. 1, 2008
•
National Policy for SUS Regulation
•
Decree n. 992/GM/MS, May 13, 2009
•
National Policy for Integrated Health of the Black Population;
•
Decree n. 4.279/GM/MS, Dec. 30,2010
•
Establishes guidelines for the organization of the health Care Network in SUS
•
Decree n. 4.217, Dec. 28, 2010
•
Basic component in Pharmaceutical Assistance
•
Decree n. 1.600/GM/MS, July 7, 2011
•
Reformulates the National Policy for Emergency Health Care and establishes the Emergency Care
Network in SUS
•
August 2011
•
Strategic Action Plan for the Fight against Noncommunicable Chronic Diseases (NCDs) in Brazil from
2011 to 2022
•
Decree n. 2.029 Aug. 24, 2011
•
Institutes Home Care in SUS
•
Approves the National Primary Care Policy, setting the review of guidelines and standards for the
organization of Primary Care for the Family Health Strategy (FHS) and Community Agent Program (PACS)
•
Decree n. 2.488, Oct. 21, 2011
•
Decree n. 2.715/GM/MS, Nov. 17,2011
•
Updates the National Food and Nutrition Policy (PNAN)
•
Decree nº 971, May 15, 2012
•
Popular Pharmacy Program in Brazil
•
Decree nº 252, Feb. 19, 2013
•
Institutes the Health Care Network for Patients with Chronic Diseases in SUS
•
Decree nº XX, March 19, 2013
•
Creates a Priority Care Line of Treatment for Overweight and Obesity in SUS
13. Topics in Prevention
Autoimmune diseases and cardiovascular disease
Several autoimmune diseases can affect the heart through
several manifestations including arrhythmias, pericardial
diseases, cardiomyopathies and coronary diseases. Regarding
the latter, advances and research in the field of atherosclerosis
have increasingly supported the participation of the immune
system in its physiopathology. The presence of lymphocytes
and macrophages inside the atherosclerotic plaques suggests
that inflammation is an important factor in the cascade of
disease evolution. In patients with rheumatic autoimmune
diseases, this inflammatory process is exacerbated and the
result may be the occurrence of accelerated atherosclerosis350.
The use of certain immunosuppressive drugs such as
corticosteroids, may also contribute to this worsening of
the cardiovascular risk profile. Accelerated atherosclerosis
Table 13.1 – Recommended approach for autoimmune diseases in
the prevention of cardiovascular diseases
Recommendations
In the context of the prevention of cardiovascular
events, the benefit of using more stringent therapeutic
targets, specifically due to the presence of autoimmune
diseases, is uncertain.
45
Class
Level of
Evidence
IIb
C
may be the main explanation for the high percentages of
cardiovascular morbidity and mortality of these patients350,352.
Among the diseases that can occur together with this
physiopathological characteristic, the following are worth
mentioning: rheumatoid arthritis (RA), systemic lupus
erythematosus (SLE), psoriasis and certain primary vasculitis
such as Wegener’s granulomatosis166,350,352.
RA is associated with a reduction of up to three-fold in survival,
with ischemic heart disease as the primary cause of death353.
Furthermore, the risk of acute myocardial infarction (AMI) is
about two-fold higher than in the general population, and the
prognosis after the event tends to be worse166. This profile starts its
development early in the course of the disease and independently
from other factors classically associated with atherosclerosis354.
The use of methotrexate may also contribute to this scenario,
perhaps by concomitant elevation of homocysteine during

its
use. In such cases, folate supplementation seems to reduce this
risk, including evidence of cardiovascular mortality reduction355.
Still, the functional limitation and consequent inactivity imposed
by the disease can also increase the likelihood of developing
other risk factors such as obesity, hypertension and diabetes.
Dyslipidemia is another condition often found in these patients,
with a prevalence of up to 65%356.
Just like RA, SLE also behaves as an independent risk
factor for cardiovascular disease (CVD), with a prevalence
of coronary disease of up to 10% and a risk up to eight times
that found in the general population351,357. Some studies
suggest that AMI may be the cause of death in up to 25% of
Guidelines
cases, mainly in patients with a longer time of the disease358.
The risk of this complication can be 52-fold higher than
that of the population without the disease, when the time
of evolution exceeds five years351. At the same time, the
prevalence of major cardiovascular risk factors such as
SAH, diabetes, obesity, physical inactivity and dyslipidemia
is also higher in individuals with SLE352. The frequent use of
corticosteroids for disease management is another condition
that helps worsen the metabolic profile, although lower
daily doses of 10 mg of prednisone appear to be safe in this
respect, as well as antimalarial drugs352,359. Nevertheless,
the fact that coronary artery disease associated with SLE is
most often associated with atherosclerosis than to vasculitis
further reinforces the importance of these factors in this
context. On the other hand, the association between
anti‑phospholipid antibody syndrome, often associated with
SLE and accelerated atherosclerosis is less clear, although it
is known to increase the risk of thrombotic events350.
Accelerated atherosclerosis associated with psoriasis also
gives this disease a definitively higher risk of AMI. However,
unlike with LES, this complication tends to occur more
often in younger individuals and in those with more severe
disease. This characteristic could be a consequence of a more
exuberant inflammatory condition, which would be associated
with greater activation of the immune system166.
The primary vasculites are another group of diseases
that are relevant in this context, occurring together with
systemic inflammation of autoimmune etiology that affects
the vascular bed in different ways. The inflammatory
process inherent to these diseases makes up an important
aspect of the physiopathology, mainly when vessels of
medium and large sizes are affected, thus increasing the
risk of cardiovascular events. However, what has been
increasingly recognized is the association of this group of
diseases with atherosclerosis, although still less evident than
in rheumatologic diseases 350. Vascular remodeling with
endothelial dysfunction, increased formation of oxidized
low-density lipoprotein cholesterol (LDL-C) and prolonged
treatment with corticosteroids are important factors involved
in this process352. However, clinical studies are scarce in
this area, with only a few studies evaluating intermediate
outcomes, such as the increase in carotid medial‑intimal
thickness in Wegener’s granulomatosis350. Still, it must be
remembered that other diseases of this group, such as
Takayasu arteritis, polyarteritis nodosa and Kawasaki disease
can potentially affect coronary circulation, even though most
of the time it occurs independently of atherosclerosis.
Most autoimmune diseases are more common among
women, of which prevalence can be nine-fold higher,
as in LES352. This is particularly relevant to the detailed
cardiovascular risk stratification in the female gender in the
presence of these diseases, even at an age group in which
coronary disease is usually rarer (< 65 years). Nevertheless,
the key issue is the lack of clinical studies demonstrating
the benefits of aggressively treating this group of patients.
To date, there is no evidence that the therapeutic targets
for blood pressure, blood glucose, LDL-C, or any other
risk factor should be modified due to the presence of an
autoimmune disease.
The studies performed in this area focused mostly
on surrogate outcomes such as the reduction of carotid
medial‑intimal thickness in SLE patients treated with
atorvastatin. But it is noteworthy that the same study showed
an increase in the occurrence of liver and muscle adverse
effects in patients treated with the drug360. This suggests that
this approach should be taken with caution, as it exposes the
patient to a higher risk of adverse effects without necessarily
providing a clinical benefit. Moreover, this risk does not appear
to be restricted to SLE, as approximately 80% of patients with
rheumatoid arthritis have at least one risk factor for myopathy
associated with statins 361. The use of anti-inflammatory drugs
or corticosteroids could also increase the risk of bleeding when
associated with aspirin, often used in the setting of primary and
secondary prevention of cardiovascular events362. However, the
relatively low prevalence of these diseases in the population is
the main factor limiting the performance of good quality studies
to answer these questions. Possibly, the treatment itself directed
to the underlying disease could reduce cardiovascular risk by
controlling the inflammatory process, although this hypothesis
also needs to be studied. The complexity becomes even greater
when the medication used in the disease management is known
to worsen the metabolic profile, as in the case of corticosteroids.
Therefore, it is essential that each case be individualized, with
constant reassessment throughout disease evolution, of potential
risks and benefits of treatment.
The recommendations of this guideline for autoimmune
diseases and cardiovascular diseases can be seen in Table 13.1.
Influenza and cardiovascular disease
The possible association between the influenza virus and
disease cardiovascular was first suggested in the early twentieth
century, especially after the Spanish flu pandemic of 1918363.
Since then, several observational studies have reinforced this
association, with increasingly strong evidence that this is not
a chance finding. In this context, it was observed over the last
100 years, the influenza epidemics tend to be accompanied by
a significant increase in cardiovascular deaths and events364,365.
Even during the 2009 pandemic of the H1N1 virus, it was
observed in Brazil that chronic cardiovascular disease was
the most prevalent comorbidity (23.8%) among patients who
died366. Furthermore, it is currently acknowledged that most
cardiovascular events affecting these patients occur in winter
months, following the virus seasonal trend365.
The mechanisms involved in this association are not
yet completely understood, but it is speculated that the
virus may act directly on the destabilization of vulnerable
atherosclerotic plaques, which makes its infection particularly
relevant in individuals known to have coronary and/or
cerebrovascular disease. This characteristic differentiates it
from other infectious agents that have also been associated to
increased cardiovascular risk, such as Chlamydia pneumonia
and Mycoplasma pneumonia, which promote a more
systemic inflammatory process. The loss of anti-inflammatory
properties of high-density lipoprotein cholesterol (HDL-C)
and endothelial dysfunction are also factors possibly involved
in the physiopathology367,368. Nonetheless, regardless of the
46
Guidelines
mechanism, the risk of AMI seems to be higher in the first
10 days of respiratory infection evolution369. The benefits of
vaccination against influenza were investigated by several
observational studies and, although the results have not
been unanimous, a protective effect was observed in most
of them, especially in relation to cardiac outcomes 364.
The largest cohort ever studied in this context followed more
than 102,000 people older than 65 years, with or without
CVD, for 10 months. The more than 35,000 participants that
were vaccinated showed lower and statistically significant
percentage of total death, cardiac death and stroke (CVA),
when compared with the group that was not vaccinated370.
Although this result is significant, one must consider the biases
that accompany the interpretation of any observational study.
Case-control studies on this subject have also been published,
mostly with similar results and the same limitations364.
Three clinical trials have been performed to evaluate
the effect of influenza vaccination on cardiovascular event
prevention. However, all of them included only patients
with established coronary disease, using the vaccine as
a secondary prevention strategy367,371-373. Patients with or
without a past history of myocardial infarction were studied,
as well as those submitted or not to coronary interventions.
Although the number of participants varied between 200
and 658 in the different studies, all showed similar results,
with a reduction in the combined cardiovascular outcomes
(death, AMI, need for hospitalization for ischemia or
revascularization) in the vaccinated group throughout the
12 months of follow-up371-373. However, only the study
“Flu vaccination in acute coronary syndromes and planned
percutaneous coronary interventions (FLUVACS) showed a
significant reduction in cardiovascular death, particularly
among patients with a history of AMI373. A systematic review
published in 2009 also suggested this same benefit by jointly
analyzing data from the studies FLUVACS and “Influenza
vaccination in secondary prevention from coronary ischaemic
events in coronary artery disease” (FLUCAD), although the
result was clearly influenced by the findings of the first one364.
These studies also showed limitations that should be
considered when analyzing the results. Among them, we can
highlight the small number of patients and outcomes, the
lack of blinding and single-center characteristic. Moreover,
the results may not be generalizable to individuals without
established atherosclerotic disease as a primary prevention
strategy for cardiovascular events, although the protective
effect of the vaccine on respiratory infection remains.
Similarly, the impact of vaccination on the decrease of
cerebrovascular events has not been established, although
a positive result has been suggested by several observational
studies373. Still, despite the relevance of these limitations, this
evidence was vital to at least rule out the previously raised
hypothesis that the period immediately after the vaccination
could increase cardiovascular risk.
The recommendations of this guideline for influenza and
cardiovascular disease can be seen in Table 13.2.
Chronic kidney disease
The relationship between CKD and CVD is well established
and multiple interactions between them have been described.
Apart from the fact that both have risk factors in common,
CKD is an independent risk factor for coronary disease
development374,375.
In general, patients with CKD have variable increases in
the risk of developing cardiovascular events, being lower
(43%) in patients with glomerular filtration rate (GFR)
between 45-59 mL/min and higher (343%) in those with
GFR < 15 mL/min376.
Moreover, the presence of proteinuria, regardless of age,
gender, renal function and diabetes, increases the risk of
coronary heart disease and perpetuates chronic kidney injury377.
However, the discussion on considering CKD an
equivalent of coronary heart disease is extensive and
controversial. In 2003, the recommendation of the National
Kidney Foundation (USA) in fact considered CKD an
equivalent of coronary disease378. However, factors such as
the degree of reduction in GFR, presence of comorbidities,
such as albuminuria, and especially the dynamic behavior of
the disease, make that even patients with similar GFRs may
present with different cardiovascular risk. Thus, more recent
studies consider CKD an important risk factor for CVD, but
not an equivalent of this disease379.
Thus, CKD should be considered in the overall
context of the cardiovascular risk of each individual
and should not be generalized as the equivalent of CVD
for all patients. The guidelines of the Brazilian Society
of Cardiology (SBC) have been considering CKD as
such, either as target‑organ injury in the VII Systemic
Arterial Hypertension Guideline119, or as an aggravating
cardiovascular risk factor in the Dyslipidemia Guideline22.
Due to the significant association between the risk factors
Table 13.2 – Recommendation for influenza approach in
cardiovascular disease prevention
Recommendation
47
–
Indicate vaccination against influenza annually for
patients with established coronary heart disease
or cerebrovascular disease, regardless of age
–
Indicate the influenza vaccination annually for
patients at high risk for coronary events, but
without established cardiovascular disease,
regardless of age
Class
Level of
Evidence
I
B
IIa
C
Table 13.3 – Recommended approach for chronic kidney disease
(CKD) in the cardiovascular disease prevention
Recommendation
Patients with chronic kidney disease should be
considered very high risk for the approach of
cardiovascular risk factors, being necessary to
evaluate factors such as level of reduced glomerular
filtration rate (GFR) and presence of comorbidities
Class
Level of
Evidence
I
C
Guidelines
for both diseases, measures of cardiovascular prevention
in these patients resemble the therapeutic measures for
each of them separately.
Thus, smoking cessation380, aerobic physical activity381 and
weight reduction382 are part of the initial approach of these
patients and should always be encouraged.
In addition to hypertension control for levels lower than
130/80 mmHg119, diabetes control targeting a glycated
hemoglobin (HbA1c) level < 7% and anemia correction,
when indicated, should be considered targets to be achieved.
The use of statins for primary prevention in this population
has been evaluated in several studies383,384 and showed
reduction in mortality from all causes, from cardiovascular
mortality383 and number of events mediated by atherosclerotic
disease 384. Nevertheless, there is no consensus on the dose or
the targets of lipid profile to be achieved379,384 and, therefore,
an overall risk assessment of the patient is recommended
according to the SBC guideline on the treatment of
dyslipidemias22, taking into account that the presence of
GFR < 60 mL/min, serum creatinine > 1.5 mg/dL and/or
the presence of microalbuminuria are considered aggravating
cardiovascular risk factors.
When choosing to initiate statin therapy, any of the drugs
can be used, always starting with the lowest possible dose
and gradually increasing it up to the therapeutic target,
with frequent monitoring of liver enzymes and creatine
phosphokinase (CPK).
Regarding antiplatelet therapy for primary prevention in
patients with CKD, the evidence does not show a significant
reduction in overall mortality or CVA, with significant increase
in bleeding rates384,386. In a recent meta-analysis of more than
27,000 patients, the use of these drugs reduced the incidence
of fatal or nonfatal myocardial infarction (reduction of three
events per 1,000 treated patients), but at the cost of significant
increase in the incidence of major bleeding (15 events for
1,000 treated patients), with no reduction in the frequency
of CVA or mortality387.
Therefore, we recommend the evaluation of the patient’s
overall cardiovascular risk, not just the consideration of CKD
as enough to start treatment with these medications. Low-dose
aspirin is the drug of choice due to the possible reduction in
the effectiveness of clopidogrel in patients with CKD388-390.
The recommendations of this guideline for chronic kidney
disease approach in cardiovascular disease prevention can be
seen in Table 13.3.
As atherosclerosis is a systemic disease, the involvement
of an arterial bed is often associated with the involvement of
other beds, such as the carotid and coronary territories391 and
thus, the presence of established peripheral artery disease
(PAD), even in the absence of diabetes mellitus (DM), is
considered an equivalent of coronary artery disease22, thus
sharing aspects of secondary prevention of the latter392,393.
Therefore, as in KCD, the PAD shares risk factors with
CVD, so that the approach to primary prevention in these
patients is connected with the recommendations for the
treatment of CVDs.
Changes in lifestyle, such as weight control (maintaining
body mass index [BMI] ≤ 25 kg/m2), proper diet, diabetes
control (target HbA1c < 7%), smoking cessation and control
of hypertension aiming at BP levels ≤ 130/80 mmHg, are
measures that are part of the approach to these patients.
Serum lipid control should be strict, preferably with drugs
that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase
(HMG-CoA-R), as several studies have shown a reduction in
cardiovascular events when used in patients with PAD393-395.
In the Heart Protection Study (HPS)396, for instance, the use of
statins induced a reduction of 19% (relative risk) in the incidence
of major cardiovascular events at five years in patients with PAD,
even without proven CVD.
Thus, the recommendation is that the target should be the
same for patients with manifest coronary artery disease, aiming
at maintaining LDL - C levels < 100 mg/dL or, in selected cases,
such as in patients with diffuse atherosclerosis or recurring
events, < 70 mg/dL20,22,391.
Regarding the use of antiplatelet agents, low-dose aspirin
is recommended (75-100 mg/day) for PAD patients, even
without evidence of manifest coronary disease. Although the
benefits are more evident in patients with symptomatic PAD
(except in cases of carotid artery disease), its use is prescribed
even in asymptomatic patients, because clinical presentation
differences can be a confounding factor392,397-399. Clopidogrel
is an alternative to aspirin in this population400.
The recommendations of this guideline for the approach
of obstructive arterial disease in cardiovascular disease
prevention can be seen in Table 13.4.
Socioeconomic factors
Obstructive Artery Disease
The association between high rates of mortality and
low socioeconomic status has been demonstrated in Brazil
and even in developed countries. An association between
Table 13.4 – Recommendation for approaching obstructive arterial
disease in cardiovascular disease prevention
Table 13.5 – Recommendation for the approach of socioeconomic
factors in cardiovascular disease prevention
Recommendation
Patients with obstructive arterial disease should
be considered at very high risk, similarly to that of
manifest coronary artery disease, for approaching
cardiovascular risk factors.
class
level of
evidence
I
C
Recommendation
Socioeconomic indicators should be investigated in
the clinical assessment and considered in patient
management to improve quality of life and prognosis of
circulatory diseases.
Class
Level of
Evedence
IIa
B
48
Guidelines
reduction in mortality from circulatory diseases (CAD) and
improvement in socioeconomic indicators for each region are
evident401,402. Several prospective studies have shown that low
socioeconomic status, defined as low education, low income,
low employment status, or live in poorer residential areas, has
contributed to the increase in death from all causes, as well
as the risk of mortality from CAD402-405.
Between 1930 and 1980, there was great economic
development in Brazil, which despite the concentration
of income, allowed educational, health, economic and
infrastructure improvement, with a reduction in infectious
diseases and consequently, of inflammatory processes.
In developed countries, the decline in mortality from CAD
started approximately 15 years after the end of World War
II, which came after the Great Depression that occurred
in the early 1930s and the 1918 influenza pandemic.
In Brazil, this same decline began just over 40 years after the
start of the economic growth period. Exposure to infectious
agents and other unsanitary conditions in early life can
make individuals more susceptible to the development of
vascular atherothrombosis. The decline in infant mortality
preceded that of mortality from CAD. It is also possible
that a reduction in exposure to infectious diseases in the
early stages of life is related to the observed decline in
cardiovascular mortality in adults406-409.
Strong correlations have been demonstrated between the
decrease in infant mortality, increase in the gross domestic
product (GDP) per capita and increased schooling with the
reduction in mortality from cardiovascular diseases in adults,
since 1980, in the states of Rio de Janeiro, São Paulo and Rio
Grande do Sul, showing that improvements in socioeconomic
indicators preceded the reduction in cardiovascular deaths.
The significant increase in educational levels over the past
decades, which has nearly doubled in the three states, had a
major impact on mortality and is associated with a reduction
of more than 100 CAD deaths, with a one-year increase in
the mean years of schooling in adults410.
Comprehensive improvement measures of socioeconomic
indicators should be part of the paradigm for cardiovascular
disease control. Socioeconomic development programs should
be included in policies aiming at this control. Reductions in
mortality from ischemic heart disease and cerebrovascular
diseases depend not only on the health sector, but also on
social policies including access to education, employment,
reducing environmental risks and protection against evolutive
impoverishment. These associations indicate the importance of
improving life conditions of the population in order to reduce
cardiovascular mortality411,412.
The evaluation of social factors in patients and individuals
with cardiovascular risk factors is essential as a means to stratify
future preventive efforts with the risk profile of individuals413.
The recommendations of this guideline for the approach of
socioeconomic factors in the cardiovascular disease prevention
can be seen in Table 13.5.
49
Obstructive Sleep Apnea
Obstructive sleep apnea is characterized by recurrent partial
or total upper airway obstruction, with oxygen desaturation
and sleep fragmentation. The adult prevalence is increasing
due to increase in obesity and life expectancy of the world’s
population. The estimated prevalence of moderate to important
sleep disordered breathing (apnea-hypopnea index measured by
events / time ≥ 15) in adult males is 10% (95% confidence interval
[95% CI] = 7.12) in those aged 30-49 and 17% (95% CI = 15.21)
at 50-70 years. In women it is relatively lower, being 3% (95%
CI = 2.4) between 30-49 years and 9% (CI = 7.11) between
50-70 years. The estimated prevalence increased relatively from
14% to 50% over the past two decades depending on the age
group considered414.
It is represented by a variety of symptoms, of which snoring
and tiredness during the day are emphasized and was associated,
in observational studies, to increased cardiovascular risk, cognitive
alterations and mental problems. The gold standard for diagnosis
is the polysomnography performed in the laboratory during the
night. Obesity, hypertension, depression and diabetes have
been frequently found in patients with obstructive sleep apnea.
The change of lifestyle and the use of continuous positive airway
pressure (CPAP) is the initial treatment of choice415.
The increase in sympathetic activity, with effects on
blood pressure, and oxidative stress results in episodes of
hypoxemia and is described as an intermediary mechanism
associated with increased inflammatory mediators and onset
of endothelial dysfunction and atherosclerosis416.
Obstructive sleep apnea is associated with 70% increase
in the relative risk of cardiovascular morbidity and mortality
and seems to have a complex bidirectional association,
being both a cause and consequence of heart failure, arterial
hypertension, arrhythmia and coronary heart disease and may
worsen the course of these pathologies. Although the treatment
of obstructive sleep apnea reduces the aggravation of chronic
cardiovascular diseases, the reversal of treatment-related risks
is not well established and randomized-controlled multicenter
studies are required to elucidate this question417.
All patients with obstructive sleep apnea should be
considered potential candidates for primary prevention, be
submitted to cardiovascular risk stratification and be treated
according to the observed risk estimates166.
Table 13.6 – Recommendation for the approach of obstructive sleep
apnea in cardiovascular disease prevention
Recommendation
All patients with obstructive sleep apnea should be
considered potential candidates for primary prevention;
undergo cardiovascular risk stratification and treated
according to the observed risk estimates
Class
Level of
Evidence
IIa
A
Guidelines
The recommendations of this guideline for obstructive
sleep apnea approach in cardiovascular disease prevention
potential candidates for primary prevention, be submitted to
cardiovascular risk stratification and be treated according to
the observed risk estimates166.
Erectile dysfunction
The recommendations of this guideline for erectile
dysfunction approach in cardiovascular disease prevention
Erectile dysfunction (ED) is defined as the incapacity to
achieve and maintain an erection satisfactory for sexual activity.
It affects 52% of adult men aged 40-70 years and increases with
advancing age. In the U.S., it is estimated to affect 18 million
men aged 20 years or older and the projection for 2025 is to
affect approximately 300 million men worldwide. Currently,
it is believed that it could represent a sentinel marker for CVD418.
ED can result from psychological, neurological, hormonal,
arterial or local disorders in the corpus cavernosum, or even the
combination of these factors. Erectile dysfunction is associated
with established atherosclerotic disease and increased
cardiovascular risk, but the systematic research of this condition
did not improve the prediction of the risk of developing CVDs,
beyond that attributed to traditional risk factors166.
A meta-analysis of 20 prospective cohort studies involving
36,744 participants suggested that erectile dysfunction
significantly increases the risk of ischemic heart disease, stroke
and all-cause mortality and concluded that it could have an
additive role in the quantification of cardiovascular risk based
on traditional risk factors419.
A recent population-based Australian study420 carried out
with 95,038 men aged ≥ 45 years showed that the risk of
cardiovascular disease is related to the severity of erectile
dysfunction in men without and with established CVD.
In the first group, there was an increased risk of 1.60 (95%
CI = 1.31 to 1.95) for ischemic heart disease, 8 (95%
CI = 2.64 to 24.2) for heart failure and 1.92 (95% CI = 1.12
to 3.29) for peripheral vascular disease, among others. In the
group with established disease, the corresponding relative
risk was 1.70 (95% CI = 1.46 to 1.98), 4.40 (95% CI = 2.64
to 7.33) and 2.46 (1.63 to 3.70)420.
Changes in life style and drugs used for the treatment
of traditional risk factors are effective for improving sexual
dysfunction in men. All men with ED should be considered
Table 13.7 – Recommended approach for erectile dysfunction in
Recommendation
All men with ED should be considered potential
candidates for primary prevention and should undergo
cardiovascular risk stratification and treated according
to the observed risk estimate
Class
Level of
Evidence
Periodontitis
The inflammatory process plays an important role in the
pathogenesis of atherosclerosis, and systemic and chronic
inflammatory diseases, such as periodontitis, have been
associated with adverse cardiovascular outcomes.
Periodontitis is characterized by a chronic infection of
the tissue that surrounds the teeth and is associated with
an increase in biomarkers such as C-reactive protein,
inflammatory cytokines such as tumor necrosis factor
alpha (TNF-α), interleukin 1 (IL-1β), interferon gamma
(IFN-γ) and prostaglandin E2 (PGE2) as well as other
inflammation mediators. Cohort and case-control studies
have demonstrated the association between periodontitis
and endothelial dysfunction, atherosclerosis and increased
risk of AMI and CVA, although it is not possible to rule out
confounding factors such as socioeconomic factors and
smoking status, among others421.
A randomized, controlled, single-blind study with 120
patients with periodontitis showed significant improvement
in endothelial dysfunction after six months of intensive
periodontal treatment421.
More recently, the association of CKD with periodontitis
has been demonstrated and its diagnosis and treatment
is indicated to prevent kidney disease progression due to
the concomitant presence of endothelial dysfunction and
atherosclerosis385. The same was observed in association
with DM423.
Periodontitis may be considered an indicator for
cardiovascular health status, with local intensive treatment
being indicated, as well as of associated risk factors166.
The recommendations of this guideline for the periodontitis
approach in cardiovascular disease prevention can be seen
in Table 13.8.
Table 13.8 – Recommendation for periodontitis approach in
Recommendation
IIa
B
Patients with periodontitis should be considered for
cardiovascular risk stratification and local intensive treatment
Class
Level of
Evidence
IIa
B
50
Guidelines
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