Increased Risk of Myocardial Infarction and Stroke Following Exacerbation of COPD

Transcription

Increased Risk of Myocardial Infarction and
Stroke Following Exacerbation of COPD
Gavin C. Donaldson, John R. Hurst, Christopher J. Smith, Richard B.
Hubbard and Jadwiga A. Wedzicha
Chest 2010;137;1091-1097; Prepublished online December 18, 2009;
DOI 10.1378/chest.09-2029
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Supplemental material related to this article is available at:
http://chestjournal.chestpubs.org/content/suppl/2010/05/04/chest.09-202
9.DC1.html
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© 2010 American College of Chest Physicians
CHEST
Original Research
COPD
Increased Risk of Myocardial Infarction and
Stroke Following Exacerbation of COPD
Gavin C. Donaldson, PhD; John R. Hurst, PhD; Christopher J. Smith, BA;
Richard B. Hubbard, DM; and Jadwiga A. Wedzicha, MD
Objective: Patients with COPD are at risk for cardiovascular events. This is attributed to increased
systemic inflammation. The course of COPD is punctuated by exacerbations, which further
increase systemic inflammation, but the risk of vascular events in the postexacerbation period has
never been defined.
Methods: We analyzed data from 25,857 patients with COPD entered in The Health Improvement
Network database over a 2-year period. Exacerbations were defined using a health-care use definition of prescription of oral corticosteroids . 20 mg/d and/or selected oral antibiotics. The risk
of myocardial infarction (MI) and stroke in the postexacerbation period was calculated relative to
the patient’s baseline risk using the self-controlled case series approach.
Results: We identified 524 MIs in 426 patients and 633 ischemic strokes in 482 patients. The incidence rates of MI and stroke were 1.1 and 1.4 per 100 patient-years, respectively. There was a
2.27-fold (95% CI, 1.1-4.7; P 5 .03) increased risk of MI 1 to 5 days after exacerbation (defined by
prescription of both steroids and antibiotics). This relative risk diminished progressively with
time and was not significantly different from the baseline MI risk at any other postexacerbation
time interval. One in 2,513 exacerbations was associated with MI within 1 to 5 days. There was a
1.26-fold (95% CI, 1.0-1.6; P 5 .05) increased risk of stroke 1 to 49 days after exacerbation.
Conclusion: The results suggest that exacerbations of COPD increase the risk of MI and stroke.
This may have implications for therapy in both stable and exacerbated COPD.
CHEST 2010; 137(5):1091–1097
Abbreviations: GPRD 5 General Practice Research Database; IQR 5 interquartile range; IRR 5 incidence rate ratio;
MI 5 myocardial infarction; THIN 5 The Health Improvement Network
will be the third leading cause of death by
COPD
2020. People with COPD are at increased risk of
1
acute cardiovascular events,2-4 and about 30% die of
cardiovascular disease.5,6 Some of this increase in risk
Manuscript received August 27, 2009; revision accepted November
23, 2009.
Affiliations: From the Academic Unit of Respiratory Medicine
(Drs Donaldson, Hurst, and Wedzicha), University College London,
London; and the Division of Epidemiology and Public Health
(Mr Smith, Dr Hubbard), University of Nottingham, Nottingham
City Hospital, Nottingham, England.
Funding/Support: This study was funded by the British Lung
Foundation.
Correspondence to: Jadwiga A. Wedzicha, MD, Academic
Unit of Respiratory Medicine, Royal Free and University College
Medical School, University College London, Rowland Hill
Street, London, NW3 2PF, England; e-mail: j.a.wedzicha@medsch.
ucl.ac.uk
© 2010 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians (www.chestpubs.org/
site/misc/reprints.xhtml).
DOI: 10.1378/chest.09-2029
www.chestpubs.org
is likely to come from shared risk factors, such as
smoking, but the increased systemic inflammation
associated with acute exacerbations could be an
additional risk factor. If so, management of COPD
exacerbations should include strategies to reduce this
additional risk.
Exacerbations are important events in the natural
history of COPD. Patients experiencing frequent
exacerbations have a faster rate of decline in lung
function,7 impaired health-related quality of life,8
reduced daily activity,9 increased airway inflammation10,11 and greater mortality.12 Most COPD
exacerbations are due to lower respiratory tract
infections13,14 that are associated with an acute phase
response with an increase in systemic inflammatory
markers, such as fibrinogen and interleukin-6.15
Increased levels of these markers in the blood have
been associated directly or indirectly with an increased risk of thrombus formation and cardiovascular
CHEST / 137 / 5 / MAY, 2010
1091
events.16-18 Previous self- and case-controlled epidemiologic studies have found an association between
respiratory infection and cardiovascular events in the
general population.19,20 However, it is possible that
this association may differ in patients with COPD
who already have increased systemic inflammation,
and in whom respiratory infections are common and
known to cause marked morbidity and mortality.
We therefore carried out a self-controlled case series
study to assess the magnitude and timing of the risk of
myocardial infarction (MI) and ischemic cerebrovascular (stroke) events following an exacerbation of COPD.
Knowledge of these risks would inform rational drug
prescribing for prevention of cardiovascular disease,
not only at exacerbation but also in stable COPD.
Materials and Methods
We examined The Health Improvement Network (THIN) database, which contains anonymized medical records of primary care
practices in England and Wales. The database is comparable to the
General Practice Research Database (GPRD)21 and the prevalence, demographics, smoking habits, and mortality of patients
with COPD in THIN match other national data.22 The study had
approval from the Nottingham Research Ethics committee.
The main analysis used the self-controlled case series approach.
This involved comparing the incidence of MI or stroke events
during “high-risk” periods, immediately postexacerbation, against
the incidence in the remaining “low-risk” periods when the patient
was stable (exacerbation-free) (see Fig 1). Thus, each patient acts
as his or her own control, so avoiding the need for multivariate
analysis to adjust for confounders such as socioeconomic background or family history.23 The 2-year observation period was
from February 25, 2003, to February 24, 2005. No practices
stopped contributing data during this period.
Patient Selection
All patients permanently registered to a practice on February
25, 2003, with a physician diagnosis of COPD were identified
using a list of Quality and Outcomes Framework codes for COPD,
and the prevalence matched other estimates of demographics and
smoking habits of patients with COPD.22 Those with an MI were
identified by a Read code, chosen a priori, for acute or subsequent MI (see online supplement for list of codes). Read and
Quality and Outcomes Framework codes describe medical diagnoses and are well-validated for use in UK administrative databases. One patient was excluded from the analysis as the MI was
recorded as having occurred after they transferred out of the
practice and, thus, treatment prior to the MI might not have been
recorded. A second analogous set of cases were a priori selected
with the diagnosis of a stroke (cerebral infarction, cerebral thrombosis, and transient ischemic attack) (see online supplement).
Cerebral hemorrhage was excluded. The diagnosis of MI and
stroke in THIN has been validated by reproducing established
associations with other diseases and drugs.21 Approximately half
the practices contributing to THIN also supply the GPRD. Several studies have confirmed the validity of the diagnostic and prescription data in the GPRD,24,25 particularly for MI and strokes.26
Exacerbation Definitions
Exacerbations were defined, a priori, in three ways: (1) a prescription of oral steroids (except fludrocortisone), (2) a prescription of preselected oral antibiotics commonly used in treating
exacerbations (see online supplement for list), and (3) prescription of oral steroids and a preselected oral antibiotic. Courses of
oral steroids , 20 mg/d were excluded to avoid falsely identifying
exacerbations when the patient was on low-dose maintenance steroid therapy. Antibiotics had to be orally delivered and used in
treating respiratory infections. They included penicillins, cephalosporins, tetracyclines, macrolides, sulfonamides, and quinolones.
Medical diagnostic codes for acute exacerbations were not reliable
(incidence 0.22/y) reflecting the frequent use of chronic disease codes
at acute events requiring prescription of antibiotics and steroids.
Hospital Admission
Hospital admissions occurring 1 to 5 days postexacerbation
were identified by Read codes. These codes were 8H2.0.00
(emergency hospital admission), 8Hd.0.00 (admission to hospital),
and 66Ye.00 (emergency COPD admission since last appointment).
Analysis
Fixed-effects conditional Poisson regression was used to estimate the incidence rate ratios (IRRs) and performed with Stata
8.2 (StataCorp; College Station, TX). The natural logarithm of the
duration of each high-risk or low-risk period was used as the exposure time. Allowance was made for seasonality in both cardiovascular events and exacerbations, with 3-month-long seasons starting
December 1, 2002.27
We have previously reported that fibrinogen and interleukin-6
return to stable (preexacerbation) levels within 4 to 8 weeks following an exacerbation.15 We therefore conservatively defined,
a priori, the high-risk period as 7 weeks long. The period started
1 day after the exacerbation to avoid as much as practical the misdiagnosis of ischemic events as COPD exacerbations.19 We also
examined the time-course of risk by dividing the 7-week period
into days 1 to 5, 6 to 10, 11 to 15, and 16 to 49, with the short early
intervals chosen to match the first three intervals used by Meier
et al.20 High-risk periods due to exacerbations starting in the 49-day
period before the start of the study’s observation period were also
included in the analysis.
Figure 1. Hypothetical timeline for a patient with COPD experiencing two exacerbations and two myocardial infarctions (MI), the first of
which occurs in the low-risk period and the second during the high-risk 1- to 5-day period postexacerbation.
1092
Original Research
Relationship Between MI and Exacerbation Frequency
For each of the three definitions, we calculated the number of
exacerbations per year experienced by each patient. Their association
with the annual incidence of MI was tested with a Spearman rank
correlation. The data are presented in line with the recent Strengthening the Reporting of Observational Studies in Epidemiology statement on the reporting of observational studies in epidemiology.28
Results
MI and Stroke Incidence Rates
Table 1 reports the total number of patients with
COPD and the number experiencing an MI or stroke.
There were 25,857 patients with COPD in 277 practices at the start of the observation period. Over the
subsequent 2 years, these patients were alive and in
contributing practices for 16,874,379 days (average
1.79 years per patient). For all patients with COPD,
the incidence rate of MI events was 1.1 per 100 patientyears and for stroke events, 1.4 per 100 patient-years.
Number and Annual Rates of Exacerbations
Table 2 shows the number and incidence rates of
exacerbations defined by drug treatment. Exacerbation rates were significantly (all P , .005) higher in
patients experiencing MI compared with those without MI. For patients who experienced a stroke compared with those who did not, the annual rate of
exacerbations defined by courses of steroids was also
significantly higher (P , .01), but not for treatment
with antibiotics or antibiotics combined with oral steroids. Regarding exacerbation severity, in patients
with MI, 12 exacerbations (0.7% of 1,737) defined by
antibiotics were followed by hospital admission within
1 to 5 days. Hospitalization occurred in 0.7% (6 of
858) of exacerbations defined by steroids and 1.3%
(5 of 387) by steroids and antibiotics combined. For
patients with stroke, these percentages were 0.6%,
0.3%, and 0.6% for antibiotics, steroids, and antibiotics combined with steroids, respectively.
Characteristics of Patients With an MI
Of the 426 patients who had an MI during the
observation period, 346 patients had one MI and
80 patients had . 1 MI. Forty-nine of these patients
had a previous MI and 27 patients had . 1 MI prior to
the observation period. One hundred twenty-seven
of them died (29.8%) within the 2-year observation period, and 17 transferred to another practice.
The average length of follow-up was 1.698 (SD 0.53)
years. The median age was 74 years (interquartile
range [IQR], 67-80; range 43-93). Two hundred
fifty-eight were men (60.6%). It was possible to calculate the FEV1, measured during or within 1 year of the
start of the study, as a percentage of that predicted
from age, height, and sex, for 101/426 patients
(23.7%). The median FEV1% predicted was 55.9%
(IQR, 43-73).
Characteristics of Patients With a Stroke
Of the 482 patients who had a stroke, 369 patients
had one stroke and 113 had . 1 stroke. Fifty-three
patients had one stroke and 36 patients had . 1
stroke prior to the observation period. One hundred
thirty-two of them died (27.3%) within the 2-year
period, and 36 transferred to another practice. The
average follow-up was 1.674 (SD 0.55) years. The
median age was 77 years (IQR, 69-82; range 38-101).
Two hundred seventy-nine were men (57.9%). The
median FEV1% predicted was 55.8% (IQR, 44-69;
N 5 93).
Exacerbations and Risk of MI
Table 3 gives the IRRs from the Poisson regression
analysis of the high-risk period of 1 to 49 days. There
was no overall increased risk of MI with any exacerbation definition, and there was a significant association between the prescription of antibiotics and stroke
(P 5 .05).
Table 4 shows the MI IRRs on days 1 to 5, 6 to 10,
11 to 15, and 16 to 49 postexacerbation. There was a
significantly greater risk of MI in the 1- to 5-day
period when exacerbations were defined in the most
exacting manner, by prescription of both steroids and
antibiotics. The IRR was 2.27 (95% CI, 1.1-4.7;
P 5 .03). The magnitude of the rate ratio decreased
stepwise with time, although it was not significantly
different from baseline at any other time period, or
with exacerbations defined in any other way.
There were eight MI events in the 1- to 5-day
period posttreatment with oral steroids and antibiotics. Therefore, with 20,101 such exacerbations in all
Table 1—Number and Duration of Study of All Patients With COPD and Those Who Had a Myocardial Infarction or
Stroke Event
Patients, No.
Time in study, d
Events (MI or
CVA/TIA), No.
All Patients With COPD
All Patients With COPD and MI
All Patients With COPD and CVA/TIA
25,857
16,874,379
426
264,102
524
482
294,717
633
CVA 5 cerebrovascular accident; MI 5 myocardial infarction; TIA 5 transient ischemic attack.
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CHEST / 137 / 5 / MAY, 2010
1093
Table 2—Number and Incidence Rates of Exacerbations Using the Three Definitions of Exacerbation
All Patients With COPD
Exacerbation
Definition
All Patients With COPD and CVA/
TIA
All Patients With COPD and MI
Exacerbations, No.
Incidence Rate
(per y)
Exacerbations, No.
Incidence Rate
(per y)
Exacerbations, No.
Incidence Rate
(per y)
87,554
46,519
20,101
1.89
1.01
0.43
1,737
858
387
2.40a
1.19a
0.53a
1,560
1,010
346
1.93
1.25a
0.43
Antibiotics
Steroids
Antibiotics and
steroids
See Table 1 for expansion of abbreviations.
aP , .005; two-sided exact significance test.
the patients with COPD, the odds of an MI were one
in 2,513 exacerbations.
The 31 patients who experienced the 33 MI events
within 49 days were no older than the remaining
395 patients (73.2 [SD 8.1] vs 73.4 [9.6] years, P 5 .92).
There was also no difference in gender (48.4% vs
61.5% men; P 5 .15). They were, however, more
likely to transfer to another practice (12.9% vs 4.1%;
P 5 .03) during the study, possibly reflecting a move
to a care home or relatives. Over the 2 years, there
was no significant seasonality in this small group of
patients in the number of MI per month (x2 test,
P 5 .189) or in the number of exacerbations defined
by steroids and antibiotics per month (x2 test, P 5 .488),
steroids (P 5 .531), or antibiotics (P 5 .054).
Exacerbations and Risk of Stroke
Table 5 shows the IRRs for strokes associated with
the three different exacerbation definitions. Only for
exacerbations defined by treatment with antibiotics
was there a significant association, at a delay of 16 to
49 days (IRR 5 1.29; 95% CI, 1.0-1.7; P 5 .05). The
IRRs at 1 to 5 and 6 to 10 days were of similar magnitude (1.27 and 1.36, respectively), but not statistically
significant. There were no significant associations with
the other exacerbation definitions.
MI Incidence and Exacerbation Frequency
Irrespective of the definition of exacerbation, patients
with more frequent exacerbations had a higher inci-
dence rate of MI. Figure 2 illustrates this relationship
with patients grouped into one-exacerbation-per-year
intervals. When exacerbations were defined by treatment with antibiotics and steroids, the correlation (r)
over the whole population was only 0.0131 (P 5 .03;
n 5 25,857). The weak relationship maybe due to death
from MI limiting the opportunity for a relationship to
exist and because few patients experience an MI.
Discussion
This study has for the first time, to our knowledge,
shown that exacerbation of COPD is associated with a
small, but statistically significant, 2.27-fold increased
relative risk of MI during a short 5-day period and of
a stroke during the 1- to 49-day period immediately
following an exacerbation. There are a number of
strengths of our study. We examined a large population of patients with COPD. Although the diagnosis of
COPD could not be confirmed with spirometry in all
patients, we found a median FEV1% predicted of 55%
in the patients experiencing an MI or stroke for whom
data were available. Furthermore, the prevalence,
demographics, smoking habits, and mortality in our
cohort of patients appear appropriate for people with
COPD in the United Kingdom.22 Another important
strength of our work is the self-case-control method,
which avoids confounding by other cardiovascular risk
factors, such as hypertension, lipid abnormalities, and
diabetes, or noncompliance with treatment, since
each patient acts as his or her own control. Change in
Table 3—Incidence Rate Ratios for MI and Stroke Event During Days 1 to 49 Postexacerbation Compared With the
Remaining Low-Risk Periods for the Three Definitions of Exacerbation
MI
Stroke
Definition of Exacerbation
IRR (95% CI)
P Value
IRR (95% CI)
P Value
Antibiotics
Steroids
Antibiotics and steroids
0.95 (0.7-1.2)
1.12 (0.8-1.5)
1.11 (0.7-1.7)
.69
.49
.61
1.26 (1.0-1.6)
0.69 (0.5-1.0)
0.93 (0.6-1.5)
.05
.06
.75
IRR 5 incident rate ratio. See Table 1 for expansion of other abbreviations.
1094
Original Research
Table 4—IRRs for MI Event on Days 1 to 5, 6 to 10, 11 to 15, and 16 to 49 Following COPD Exacerbation for the
Three Definitions of Exacerbation
Definition of
Exacerbation
Antibiotics
Steroids
Antibiotics and
steroids
1-5 d
6-10 d
11-15 d
16-49 d
IRR (95% CI)
P Value
IRR (95% CI)
P Value
IRR (95% CI)
P Value
IRR (95% CI)
P Value
1.14 (0.7-1.8)
1.55 (0.9-2.8)
2.27 (1.1-4.7)
.57
.15
.03
0.90 (0.5-1.5)
1.37 (0.7-2.6)
1.74 (0.8-4.0)
.71
.33
.19
0.71 (0.4-1.3)
0.80 (0.3-1.8)
0.90 (0.3-2.9)
.27
.59
.86
0.97 (0.7-1.3)
1.04 (0.7-1.5)
0.83 (0.5-1.4)
.80
.83
.51
See Tables 1 and 3 for expansion of abbreviations.
these confounders over the 2-year observation period
could potentially bias the findings if exacerbations,
MI, and stroke all occurred toward the start or end of
the period, but we found no such trend over time in
the monthly incidence rate of these events.
Our finding of a transient increased MI risk postexacerbation appears insufficient to fully account for
the higher annual MI incidence in patients with more
frequent exacerbations. The relationship between
exacerbations and MI could be explained by common
risk factors, such as smoking, low socioeconomic status, and early life experiences. But there is also the
possibility that systemic inflammation remains
increased after the exacerbation is over and the
patient is clinically stable. We have previously shown
that patients with frequent exacerbations have higher
stable airway inflammatory markers10 and that plasma
fibrinogen increases faster over time in frequent than
infrequent exacerbators.11 This suggests that treatments to reduce cardiovascular events in COPD are
also needed during stable periods.29
We suggest that increased inflammation is a plausible
explanation for increased MI and strokes following an
exacerbation. Most COPD exacerbations are triggered
by airway infection that is viral or bacterial in origin.14
This results in increased airway and systemic inflammation and we have previously shown that during a
COPD exacerbation there are increases in both fibrinogen and C-reactive protein.15,30 The former is directly
thrombogenic,31 whereas the latter can upregulate
other inflammatory cytokines, promote uptake of
low-density lipoproteins by macrophages, and increase
adhesion of leukocytes to arterial endothelium.5
Another possible explanation is that exacerbations will
increase mucus production and bronchoconstriction
resulting in alveolar hypoxia, increased pulmonary
artery pressures, and an increased burden on the right
side of the heart. Additional factors could be increased
b2-agonist use by the patient32 or an increase in cardiac
afterload due to dynamic hyperinflation, either of which
will also increase the risk of adverse cardiac events in
obstructive airways disease. Indeed, the effects of
inflammation, tachycardia, and hypoxia may be synergistic but the mechanisms underlying our findings
require further elucidation.
We based our analysis on a health-care definition of
exacerbation, with our major finding present using the
most robust definition of coprescription of antibiotics
and steroids. Identification of MI and stroke was based
on Read codes, which have been validated by reproducing known associations with disease and drugs.21
One concern is that physicians may confuse symptoms
of an MI with those of a COPD exacerbation. We
believe misdiagnosis to be extremely rare given the
different clinical history of events, the increased purulent sputum, cough, and wheeze often present with an
exacerbation but not with MI, and acute and characteristic central chest pain that commonly accompanies
an MI but is rarely associated with COPD exacerbation. Furthermore, diagnosis of an MI will eventually
be confirmed by a visit to the hospital, where cardiac
enzymes or troponin levels will be measured and an
electrocardiogram performed.
One limitation of our study was that the date of
exacerbation onset could not be determined precisely.
The date of consultation cannot be taken as the date of
exacerbation onset as patients may hesitate in seeking
medical attention33 or be delayed by reluctance to
Table 5—IRRs for Stroke on Days 1 to 5, 6 to 10, 11 to 15 and 16 to 49 Following COPD Exacerbation for the Three
Definitions of Exacerbation
Definition of
Exacerbation
Antibiotics
Steroids
Antibiotics and
steroids
1-5 d
6-10 d
11-15 d
16-49 d
IRR (95% CI)
P Value
IRR (95% CI)
P Value
IRR (95% CI)
P Value
IRR (95% CI)
P Value
1.27 (0.8-2.1)
0.55 (0.2-1.3)
0.55 (0.1-2.3)
.34
.16
.41
1.36 (0.8-2.2)
0.66 (0.3-1.5)
1.40 (0.6-3.6)
.22
.31
.46
0.96 (0.5-1.7)
0.41 (0.1-1.2)
0.59 (0.1-2.4)
.90
.10
.46
1.29 (1.0-1.7)
0.78 (0.5-1.2)
0.97 (0.6-1.6)
.05
.28
.91
See Table 3 for expansion of the abbreviation.
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CHEST / 137 / 5 / MAY, 2010
1095
Figure 2. Annual rate of MI against the annual rate of exacerbation defined as prescription of steroids and antibiotics together.
r 5 0.0131; P 5 .03. See the Figure 1 legend for expansion of the
abbreviation.
access health care on weekends. Patients may also selftreat at home with prophylactically prescribed courses
of antibiotics and/or steroids, which would make it
harder to detect any significant association between
exacerbations and cardiovascular events. We also cannot rule out the possibility that treatment with oral
steroids, which can affect fibrinolysis,34 increased the
risk of a cardiovascular event. However, we found no
significant increase in MI or stroke post exacerbations
treated by oral corticosteroids alone. Another potential limitation of this study is that we have not looked
for subgroups of patients who might be at greater risk
of a cardiovascular event postexacerbation. This question is complicated by whether drug therapy indicates
increased risk (eg, presence of hypercholesterolemia)
or reduced risk of MI (because hypercholesterolemia
has been treated). Risk stratification may prove a productive area for future research.
We found that exacerbations defined by treatment
with antibiotics were associated with an increased risk
of stroke. Although the relative risk (IRR 5 1.29) was
significant only at 16 to 49 days postexacerbation, it
was similar in magnitude to those immediately after
exacerbation (IRR 5 1.27 on days 1-5 and IRR 5 1.36
on days 6-10). This suggests a somewhat different
mechanism may be involved in the pathogenesis of MI
and stroke risk. Tachycardia, hypoxia, increased cardiac work load, and thrombotic risk could all contribute to rapid occlusion at a site of existing stenosis in the
relatively narrow coronary arteries that would explain
the higher risk of an MI 1 to 5 days postexacerbation.
With ischemic cerebral events, however, the carotid
arteries are relatively larger and embolic phenomena
are more important. Events may take longer to manifest with increased levels of fibrinogen and other clotting factors in the blood. Our findings for stroke agree
1096
with a recent case-controlled study in which there was
an increased risk of a stroke at both 1 to 7 days and
8 to 28 days delay post respiratory infection.35
Our findings in patients with COPD agree with
other studies that have shown that respiratory infection in the general population increases the likelihood
of an MI. Meier et al20 report a relative risk of 2.7 in
healthy individuals at days 1 to 5 and Smeeth et al19
reported a relative risk of 4.95 over days 1 to 3. Clayton
et al35 have reported in a case-controlled study an odds
ratio of 2.10 with recent respiratory infection. The
generally lower relative risk in our study may be due to
patients with COPD seeking medical help because of
their limited respiratory capacity for milder respiratory infections than the general population. This is
consistent with our finding of no association between
MI and treatment with antibiotics or corticosteroids.
Indeed, only the most severe COPD exacerbations,
those requiring the greatest treatment and causing a
higher proportion of hospital admissions, resulted in a
demonstrable increased risk of an MI. Alternatively, as
patients with COPD are already at increased risk of
vascular disease, there may be a ceiling effect to the
additional risk at the time of exacerbation.
In conclusion, we have defined the magnitude and
timing of a small yet significantly increased risk of MI
following an exacerbation of COPD that is approximately double that present in stable disease. MI occurs
following one in 2,513 exacerbations, and the risk returns
to baseline within 5 days of treatment of the exacerbation. The data suggest that there is a good rationale for
treating both the stable and exacerbation states to
reduce cardiovascular events in patients with COPD.
Acknowledgments
Author contributions: Dr Donaldson had full access to all the
data in the study and takes responsibility for the integrity of the
data and the accuracy of the data analysis.
Dr Donaldson: contributed to the original idea for the study,
performed the statistical analysis, wrote the initial draft of the
paper, edited the paper, and approved the final version.
Dr Hurst: contributed to the original idea for the study, decided
which Read codes to use for definitions, wrote the initial draft of
the paper, edited the paper, and approved the final version.
Mr Smith: contributed to performing the initial data extraction
and provided expert advice on data interpretation, edited the
paper, and approved the final version.
Dr Hubbard: contributed to performing the initial data extraction
and provided expert advice on data interpretation, edited the
paper, and approved the final version.
Dr Wedzicha: contributed to the original idea for the study,
decided which Read codes to use for definitions, edited the paper,
and approved the final version.
Financial/nonfinancial disclosures: The authors have reported
to CHEST that no potential conflicts of interest exist with any
companies/organizations whose products or services may be
discussed in this article.
Other contributions: We thank the British Lung Foundation for
support and EPIC for funding The Health Information Network
(THIN) database. The study had approval from the Nottingham
Research Ethics Committee.
Original Research
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DP, Sin DD. C-reactive protein and mortality in mild to
moderate chronic obstructive pulmonary disease. Thorax.
2006;61(10):849-853.
3. Camilli AE, Robbins DR, Lebowitz MD. Death certificate
reporting of confirmed airways obstructive disease. Am J
Epidemiol. 1991;133(8):795-800.
4. Anthonisen NR, Connett JE, Enright PL, Manfreda J; Lung
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5. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in
COPD: role of comorbidities. Eur Respir J. 2006;28(6):12451257.
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in chronic obstructive pulmonary disease. N Engl J Med.
2007;356(8):775-789.
7. Donaldson GC, Seemungal TAR, Bhowmik A, Wedzicha JA.
Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax.
2002;57(10):847-852.
8. Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries
DJ, Wedzicha JA. Effect of exacerbation on quality of life in
patients with chronic obstructive pulmonary disease. Am J
Respir Crit Care Med. 1998;157(5 Pt 1):1418-1422.
9. Donaldson GC, Wilkinson TM, Hurst JR, Perera WR,
Wedzicha JA. Exacerbations and time spent outdoors in
chronic obstructive pulmonary disease. Am J Respir Crit Care
Med. 2005;171(5):446-452.
10. Bhowmik A, Seemungal TA, Sapsford RJ, Wedzicha JA.
Relation of sputum inflammatory markers to symptoms and
lung function changes in COPD exacerbations. Thorax.
2000;55(2):114-120.
11. Donaldson GC, Seemungal TA, Patel IS, et al. Airway and
systemic inflammation and decline in lung function in
patients with chronic obstructive pulmonary disease. Chest.
2005;128(4):1995-2004.
12. Soler-Cataluña JJ, Martínez-García MÁ, Román Sánchez P,
Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(11):925-931.
13. Seemungal TA, Harper-Owen R, Bhowmik A, Jeffries DJ,
Wedzicha JA. Detection of rhinovirus in induced sputum at
exacerbation of chronic obstructive pulmonary disease. Eur
Respir J. 2000;16(4):677-683.
14. Seemungal T, Harper-Owen R, Bhowmik A, et al. Respiratory
viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.
Am J Respir Crit Care Med. 2001;164(9):1618-1623.
15. Wedzicha JA, Seemungal TAR, MacCallum PK, et al. Acute
exacerbations of chronic obstructive pulmonary disease are
accompanied by elevations of plasma fibrinogen and serum
IL-6 levels. Thromb Haemost. 2000;84(2):210-215.
16. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with
coronary heart disease: meta-analyses of prospective studies.
JAMA. 1998;279(18):1477-1482.
17. Fisman EZ, Benderly M, Esper RJ, et al. Interleukin-6 and
the risk of future cardiovascular events in patients with angina
pectoris and/or healed myocardial infarction. Am J Cardiol.
2006;98(1):14-18.
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18. Dahl M, Vestbo J, Lange P, Bojesen SE, Tybjærg-Hansen A,
Nordestgaard BG. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. Am J Respir
Crit Care Med. 2007;175(3):250-255.
19. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P,
Vallance P. Risk of myocardial infarction and stroke after acute
infection or vaccination. N Engl J Med. 2004;351(25):26112618.
20. Meier CR, Jick SS, Derby LE, Vasilakis C, Jick H. Acute
respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet. 1998;351(9114):1467-1471.
21. Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol
Drug Saf. 2007;16(4):393-401.
22. Smith CJP, Gribbin J, Challen KB, Hubbard RB. The impact
of the 2004 NICE guideline and 2003 General Medical
Services contract on COPD in primary care in the UK. QJM.
2008;101(2):145-153.
23. Whitaker HJ, Farrington CP, Spiessens B, Musonda P.
Tutorial in biostatistics: the self-controlled case series method.
Stat Med. 2006;25(10):1768-1797.
24. Jick H, Terris BZ, Derby LE, Jick SS. Further validation of information recorded on general practitioner based
computerised data resources in the United Kingdom.
Pharmacoepidemiol Drug Saf. 1992;1(6):347-349.
25. Hollowell J. The General Practice Research Database: quality
of morbidity data. Popul Trends. 1997;87(87):36-40.
26. Soedamah-Muthu SS, Fuller JH, Mulnier HE, Raleigh VS,
Lawrenson RA, Colhoun HM. High risk of cardiovascular
disease in patients with type 1 diabetes in the U.K.: a cohort
study using the general practice research database. Diabetes
Care. 2006;29(4):798-804.
27. Donaldson GC, Seemungal T, Jeffries DJ, Wedzicha JA. Effect
of temperature on lung function and symptoms in chronic
obstructive pulmonary disease. Eur Respir J. 1999;13(4):
844-849.
28. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche
PC, Vandenbroucke JP. The Strengthening the Reporting
of Observational Studies in Epidemiology (STROBE)
Statement: guidelines for reporting observational studies.
Prev Med. 2007;45(4):247-251.
29. Fabbri LM, Rabe KF. From COPD to chronic systemic
inflammatory syndrome? Lancet. 2007;370(9589):797-799.
30. Hurst JR, Donaldson GC, Perera WR, et al. Use of plasma
biomarkers at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;174(8):
867-874.
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Fibrinolytic activity, clotting factors and long term incidence
of ischaemic heart disease in the Northwick Park Heart Study.
Lancet. 1993;342(8879):1076-1079.
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effects of beta-agonists in patients with asthma and COPD:
a meta-analysis. Chest. 2004;125(6):2309-2321.
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Wedzicha JA. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir
Crit Care Med. 2004;169(12):1298-1303.
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2008;29(1):96-103.
CHEST / 137 / 5 / MAY, 2010
1097
Read codes used to identify COPD patients.
QOL code for COPD
Read code
H3...00
H3...11
H30..00
H30..11
H30..12
H300.00
H301.00
H302.00
H30z.00
H31..00
H310.00
H310000
H310z00
H311.00
H311000
H311100
H311z00
H312.00
H312000
H312011
H312100
H312300
H312z00
H313.00
H31y.00
H31y100
H31yz00
H31z.00
H32..00
H320.00
H320000
H320100
H320200
H320300
H320311
H320z00
H321.00
H322.00
H32y.00
H32y000
Description
Chronic obstructive pulmonary disease
Chronic obstructive airways disease
Bronchitis unspecified
Chest infection - unspecified bronchitis
Recurrent wheezy bronchitis
Tracheobronchitis NOS
Laryngotracheobronchitis
Wheezy bronchitis
Bronchitis NOS
Chronic bronchitis
Simple chronic bronchitis
Chronic catarrhal bronchitis
Simple chronic bronchitis NOS
Mucopurulent chronic bronchitis
Purulent chronic bronchitis
Fetid chronic bronchitis
Mucopurulent chronic bronchitis NOS
Obstructive chronic bronchitis
Chronic asthmatic bronchitis
Chronic wheezy bronchitis
Emphysematous bronchitis
Bronchiolitis obliterans
Obstructive chronic bronchitis NOS
Mixed simple and mucopurulent chronic bronchitis
Other chronic bronchitis
Chronic tracheobronchitis
Other chronic bronchitis NOS
Chronic bronchitis NOS
Emphysema
Chronic bullous emphysema
Segmental bullous emphysema
Zonal bullous emphysema
Giant bullous emphysema
Bullous emphysema with collapse
Tension pneumatocoele
Chronic bullous emphysema NOS
Panlobular emphysema
Centrilobular emphysema
Other emphysema
Acute vesicular emphysema
QOL code for COPD
Read code
H32y100
H32y111
H32y200
H32yz00
H32yz11
H32z.00
H36..00
H37..00
H38..00
H3y..00
H3y..11
H3y0.00
H3y1.00
H3z..00
H3z..11
Description
Atrophic (senile) emphysema
Acute interstitial emphysema
MacLeod's unilateral emphysema
Other emphysema NOS
Sawyer - Jones syndrome
Emphysema NOS
Mild chronic obstructive pulmonary disease
Moderate chronic obstructive pulmonary disease
Severe chronic obstructive pulmonary disease
Other specified chronic obstructive airways disease
Other specified chronic obstructive pulmonary disease
Chronic obstruct pulmonary dis with acute lower resp infectn
Chron obstruct pulmonary dis wth acute exacerbation, unspec
Chronic obstructive airways disease NOS
Chronic obstructive pulmonary disease NOS
A Read code is a code for an item on a comprehensive list of terms used to describe the care and
treatment of patients, they enable computer systems to firstly capture and then retrieve on
demand patient information in natural clinical language.
QoF was an initiative aimed at general practices to receive addition payments if they were able to
demonstrate high levels of clinical care for people with specific diseases. QoF codes for COPD
refer to the conditions that patients need to have to be identified as a COPD patient.
Antibiotic BNF chapter code, Multilex Drug code and name
BNF code
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.01
05.01.01.02
05.01.01.02
05.01.01.03
05.01.01.03
Multilex
code
97969992
94845998
98987998
94762997
94762998
90862997
94845996
94845997
94533992
97970992
90864997
97110997
97592998
98987996
96621997
96621998
96944992
89177998
Description
PENICILLIN V (PHENOXYMETHYLPENICILLIN)
PENICILLIN V
PHENOXYMETHYLPENICILLIN
PENICILLIN V
PENICILLIN V
PENICILLIN V
PENICILLIN V
PENICILLIN V (PHENOXYMETHYLPENICILLIN)
PENICILLIN
PENICILLIN V
CLOXACILLIN
CLOXACILLIN
AMPICILLIN
AMOXICILLIN
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
93372997
93372998
93377997
93377998
93407997
93407998
94699997
94699998
94936997
97130997
97130998
97131997
97131998
98968998
99171998
99275997
99275998
99846990
99962997
99962998
99964997
99964998
93225997
95029997
96944998
99927997
97868996
98673998
95077998
95086997
95086998
96309997
96309998
97131996
96943998
96944996
93407996
93446998
94792997
94792998
97868997
91014998
93224996
93224998
93225996
93372996
93375998
97129997
98363998
98364998
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMPICILLIN+ CLOXACILLIN
AMPICILLIN
AMPICILLIN
AMOXICILLIN
AMOXICILLIN
AMPICILLIN
AMPICILLIN+ CLOXACILLIN
AMPICILLIN
AMPICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMPICILLIN
AMPICILLIN
CO-AMOXICLAV
AMOXICILLIN+ CLAVULANIC ACID
AMOXICILLIN
CO-AMOXICLAV
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
AMOXICILLIN
CO-AMOXICLAV
CO-AMOXICLAV
CO-AMOXICLAV
CO-AMOXICLAV
AMOXICILLIN
AMOXICILLIN
AMPICILLIN
CO-AMOXICLAV
CO-AMOXICLAV
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.03
05.01.01.05
05.01.01.05
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
98820998
95028998
95495997
97129998
97130996
98354998
93253992
94794997
94794998
96092992
96582992
96822992
99743992
88536998
93224997
93225998
94872998
95029998
95218998
95491998
95494997
95495998
96137990
96256996
96256997
96660998
96731990
96975990
97010990
97708997
98451998
99075998
99110998
99111998
99236998
99927998
95490997
98823998
88245998
90029998
92634998
92635998
93529997
93529998
94729998
94730996
94870998
94873998
96846997
96846998
PIVAMPICILLIN
PIVAMPICILLIN
AMPICILLIN
AMPICILLIN
AMOXICILLIN
AMOXYCILLIN S/F
AMOXICILLIN
AMOXICILLIN
AMOXYCILLIN
AMPICILLIN
AMOXYCILLIN
AMOXYCILLIN
CO-AMOXICLAV
CO-AMOXICLAV
CO-AMOXICLAV
PIVMECILLINAM+ PIVAMPICILLIN
TALAMPICILLIN
PIVAMPICILLIN+ PIVMECILLINAM
PIVAMPICILLIN
CO-AMOXICLAV
AMOXICILLIN
AMOXICILLIN
CLAVULANIC ACID+ AMOXICILLIN
CO-AMOXICLAV
CO-AMOXICLAV
CO-AMOXICLAV
CLAVULANIC ACID+ AMOXICILLIN
TALAMPICILLIN
CO-AMOXICLAV
PIVAMPICILLIN
CO-AMOXICLAV
PIVMECILLINAM
PIVMECILLINAM
CEFACLOR
CEFALEXIN
CEFTIBUTEN
CEFTIBUTEN
CEFALEXIN
CEFALEXIN
CEFALEXIN
CEFALEXIN
CEFACLOR
CEFACLOR
CEFRADINE
CEFRADINE
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
96855998
96856998
97311998
97887998
97888996
98984997
98984998
99741998
97885998
94915996
93901997
93901998
94791997
94791998
93245997
87657998
87658998
94873996
93246997
94729996
94729997
94904996
96835997
96835998
96855997
96856996
96856997
97311996
97311997
97806997
97886996
97886997
98813998
99741996
99741997
96147992
96836996
96836997
96836998
96846996
97886998
97887996
97887997
98984996
94565992
91561997
93245998
93246998
93534998
94730997
CEFADROXIL
CEFACLOR
CEFADROXIL
CEFALEXIN
CEFALEXIN
CEFRADINE
CEFRADINE
CEFACLOR
CEFALEXINPAED
CEFUROXIMEAXETIL
CEFACLOR
CEFACLOR
CEFACLOR
CEFACLOR
CEFIXIME
CEFALEXIN
CEFALEXIN
CEFACLOR
CEFIXIME
CEFALEXIN
CEFALEXIN
CEFUROXIMEAXETIL
CEFALEXIN
CEFALEXIN
CEFADROXIL
CEFACLOR
CEFACLOR
CEFADROXIL
CEFADROXIL
CEFPODOXIME
CEFALEXIN
CEFALEXIN
CEFADROXIL
CEFACLOR
CEFACLOR
CEPHRADINE
CEFALEXIN
CEFALEXIN
CEFALEXIN
CEFRADINE
CEFALEXIN
CEFALEXIN
CEFALEXIN
CEFRADINE
CEFACLOR M/R
CEFPROZIL
CEFIXIME
CEFIXIME
CEFALEXIN
CEFALEXIN
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.02.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
94730998
94904997
94904998
94915997
94915998
96837997
96837998
97806998
97888997
97888998
98940998
99700988
99101998
99101997
93484992
96781992
97246992
88431998
92613998
93923998
95196997
95644998
96304997
96305997
97753998
97892998
98341997
98969998
99055997
99056998
99060997
88030998
91630998
96305998
98969997
97842992
97153997
98969996
93276992
95369992
96485992
97843992
92481998
93938998
95192998
95801997
97153998
97154998
98341998
98456998
CEFALEXIN
CEFUROXIMEAXETIL
CEFUROXIMEAXETIL
CEFUROXIMEAXETIL
CEFUROXIMEAXETIL
CEFALEXIN
CEFALEXIN
CEFPODOXIME
CEFALEXIN
CEFALEXIN
CEFPODOXIME
CEFALEXIN
DOXYCYCLINE(AS HYCLATE)
DOXYCYCLINE
TETRACYCLINE
DOXYCYCLINE HCl
TETRACYCLINE
OXYTETRACYCLINE
TETRACYCLINE
TETRACYCLINE
TETRACYCLINE
TETRACYCLINE
OXYTETRACYCLINE
DOXYCYCLINE MONOHYDRATE
DOXYCYCLINE MONOHYDRATE
OXYTETRACYCLINE
TETRACYCLINE
CHLORTETRACYCLINE HCl/DEMECLOCYCLINE HCl
OXYTETRACYCLINE
TETRACYCLINE
OXYTETRACYCLINE
TETRACYCLINE+CHORTET&DEMECLOCYC
OXYTETRACYCLINE
MINOCYCLINE
TETRACYCLINE
OXYTETRACYCLINE
TETRACYCLINE
OXYTETRACYCLINE
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.03.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
99060998
99382997
99767998
99895998
98323998
94980992
87506998
90844998
94512998
94523998
96785998
97932998
99542998
97118996
97759990
97118997
97118998
97375992
89246998
92495998
88378998
92495997
94819998
94820998
97519998
90567998
96783996
96783997
98751996
99679996
94523997
96784996
96784997
96784998
97117996
97117997
97117998
98751998
99679998
99680998
97379992
97380992
94512996
94523996
94530996
94530998
94531996
94531998
94819997
94820997
OXYTETRACYCLINE
TETRACYCLINE+ NYSTATIN
OXYTETRACYCLINE
TETRACYCLINE
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
AZITHROMYCIN
AZITHROMYCIN
ERYTHROMYCINESTOLATE
ERYTHROMYCIN
ERYTHROMYCINESTOLATE
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
CLARITHROMYCIN
CLARITHROMYCIN
CLARITHROMYCIN
CLARITHROMYCIN
ERYTHROMYCIN ETHYLSUCCINATE
AZITHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN STEARATE
AZITHROMYCIN
AZITHROMYCIN
CLARITHROMYCIN
CLARITHROMYCIN
CLARITHROMYCIN
CLARITHROMYCIN
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.05.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.08.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
96781997
96781998
98752998
98754998
99103996
99103997
99542997
99681998
99682998
99683998
99749992
95351998
97199998
97200997
99143997
99919998
95353998
95354998
98523998
98612998
94119992
94849992
96169992
97168992
93957998
95233998
97200996
97200998
98521998
98522998
98613998
99143998
88261997
88261998
88267997
88267998
93079996
93080996
89361998
93079997
93079998
93080997
93080998
93255998
93256998
93552997
93552998
93554997
93554998
94429998
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
ERYTHROMYCIN
CO-TRIMOXAZOLE/TRIMETHOPRIM&SULPHAMETHAZ
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLEADULT
CO-TRIMOXAZOLEPAED
CO-TRIMOXAZOLEADULT
CO-TRIMOXAZOLEADULT
CO-TRIMOXAZOLE/TRIMETHOPRIM&SULPHAMETHOX
CO-TRIMOXAZOLE(SULPHAMETH/TRIMETH 160
CO-TRIMOXAZOLE
SULFAMETOPYRAZINE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
CO-TRIMOXAZOLE
LEVOFLOXACIN
LEVOFLOXACIN
LEVOFLOXACIN
LEVOFLOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
MOXIFLOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
NORFLOXACIN
NORFLOXACIN
OFLOXACIN
OFLOXACIN
OFLOXACIN
OFLOXACIN
ENOXACIN
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
05.01.12.00
94430998
94912996
94912998
94913996
94913998
95305997
95305998
96024990
ENOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
CIPROFLOXACIN
TEMAFLOXACIN
TEMAFLOXACIN
CIPROFLOXACIN
Oral corticosteroids BNF chapter code, Multilex Drug code and
name
BNF code
06.03.01.00
06.03.01.00
06.03.02.00
06.03.02.00
06.03.02.00
Multilex
code
96603997
96603998
93912998
95417996
92810997
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
92861998
93075998
92810998
95484992
95487992
95492992
95493992
96409992
96410992
96411992
96743992
96744992
97240992
97942992
97943992
93912996
95417997
95417998
95847997
95847998
95967998
96143997
96143998
96431997
96431998
97155997
97155998
Description
CORTISONE ACETATE
CORTISONE ACETATE
PREDNISOLONE
PREDNISOLONE
DEXAMETHASONE
BETAMETHASONE SODIUM
PHOSPHATE
PREDNISOLONE SODIUM PHOSPHATE
DEXAMETHASONE
PREDNISOLONE E/C
PREDNISOLONE
PREDNISOLONE
PREDNISOLONE
PREDNISOLONE
PREDNISONE
PREDNISOLONE
PREDNISONE
PREDNISOLONE
PREDNISOLONE
PREDNISONE
PREDNISONE
PREDNISOLONE
PREDNISOLONE
PREDNISOLONE
METHYLPREDNISOLONE
METHYLPREDNISOLONE
BETAMETHASONE
HYDROCORTISONE
HYDROCORTISONE
DEXAMETHASONE
DEXAMETHASONE
PREDNISOLONE
PREDNISOLONE
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
97156997
97156998
97436998
97492997
97492998
97502998
97829998
98326997
98326998
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
06.03.02.00
98394998
98562997
98562998
99226998
99228997
99228998
99781998
PREDNISONE
PREDNISONE
PREDNISOLONE
HYDROCORTISONE
HYDROCORTISONE
DEXAMETHASONE
METHYLPREDNISOLONE
TRIAMCINOLONE
TRIAMCINOLONE
BETAMETHASONE SODIUM
PHOSPHATE
PREDNISOLONE
PREDNISOLONE
PREDNISOLONE SODIUM PHOSPHATE
PREDNISOLONE
PREDNISOLONE
PREDNISONE
Myocardial Infarction Read Codes and Description
medcode
G30..00
G30..11
G30..12
G30..13
G30..14
G30..15
G30..16
G30..17
G300.00
G301.00
G301000
G301100
G301z00
G302.00
G303.00
G304.00
G305.00
G306.00
G307.00
G307000
G307100
G308.00
G309.00
G30A.00
G30B.00
G30X.00
G30X000
G30y.00
Description
Acute myocardial infarction
Attack - heart
Coronary thrombosis
Cardiac rupture following myocardial infarction (MI)
Heart attack
MI - acute myocardial infarction
Thrombosis - coronary
Silent myocardial infarction
Acute anterolateral infarction
Other specified anterior myocardial infarction
Acute anteroapical infarction
Acute anteroseptal infarction
Anterior myocardial infarction NOS
Acute inferolateral infarction
Acute inferoposterior infarction
Posterior myocardial infarction NOS
Lateral myocardial infarction NOS
True posterior myocardial infarction
Acute subendocardial infarction
Acute non-Q wave infarction
Acute non-ST segment elevation myocardial infarction
Inferior myocardial infarction NOS
Acute Q-wave infarct
Mural thrombosis
Acute posterolateral myocardial infarction
Acute transmural myocardial infarction of unspecif site
Acute ST segment elevation myocardial infarction
Other acute myocardial infarction
G30y000
G30y100
G30y200
G30yz00
G30z.00
G35..00
G350.00
G351.00
G353.00
G35X.00
Acute atrial infarction
Acute papillary muscle infarction
Acute septal infarction
Other acute myocardial infarction NOS
Acute myocardial infarction NOS
Subsequent myocardial infarction
Subsequent myocardial infarction of anterior wall
Subsequent myocardial infarction of inferior wall
Subsequent myocardial infarction of other sites
Subsequent myocardial infarction of unspecified site
Ischaemic Stroke Read Codes and Description
medcode
G63..11
G630.00
G631.00
G631.11
G631.12
G632.00
G633.00
G634.00
G63y.00
G63y000
G63y100
G63z.00
G64..00
G64..11
G64..12
G64..13
G640.00
G640000
G641.00
G641.11
G641000
G64z.00
G64z.11
G64z.12
G64z000
G64z200
G64z300
G64z400
G66..00
G66..11
G66..12
G66..13
G663.00
Description
Infarction - precerebral
Basilar artery occlusion
Carotid artery occlusion
Stenosis, carotid artery
Thrombosis, carotid artery
Vertebral artery occlusion
Multiple and bilateral precerebral arterial occlusion
Carotid artery stenosis
Other precerebral artery occlusion
Cerebral infarct due to thrombosis of precerebral
arteries
Cerebral infarction due to embolism of precerebral
arteries
Precerebral artery occlusion NOS
Cerebral arterial occlusion
CVA - cerebral artery occlusion
Infarction - cerebral
Stroke due to cerebral arterial occlusion
Cerebral thrombosis
Cerebral infarction due to thrombosis of cerebral
arteries
Cerebral embolism
Cerebral embolus
Cerebral infarction due to embolism of cerebral arteries
Cerebral infarction NOS
Brainstem infarction NOS
Cerebellar infarction
Brainstem infarction
Left sided cerebral infarction
Right sided cerebral infarction
Infarction of basal ganglia
Stroke and cerebrovascular accident unspecified
CVA unspecified
Stroke unspecified
CVA - Cerebrovascular accident unspecified
Brain stem stroke syndrome
G664.00
G665.00
G666.00
G667.00
G668.00
G670.00
G670.11
G671000
G677000
G677100
G677200
G677300
G677400
G6W..00
G6X..00
Cerebellar stroke syndrome
Pure motor lacunar syndrome
Pure sensory lacunar syndrome
Left sided CVA
Right sided CVA
Cerebral atherosclerosis
Precerebral atherosclerosis
Acute cerebrovascular insufficiency NOS
Occlusion and stenosis of middle cerebral artery
Occlusion and stenosis of anterior cerebral artery
Occlusion and stenosis of posterior cerebral artery
Occlusion and stenosis of cerebellar arteries
Occlusion+stenosis of multiple and bilat cerebral
arteries
Cereb infarct due unsp occlus/stenos precerebr
arteries
Cerebrl infarctn due/unspcf occlusn or sten/cerebrl
artrs
Increased Risk of Myocardial Infarction and Stroke Following
Exacerbation of COPD
Gavin C. Donaldson, John R. Hurst, Christopher J. Smith, Richard B.
Hubbard and Jadwiga A. Wedzicha
Chest 2010;137; 1091-1097; Prepublished online December 18, 2009;
DOI 10.1378/chest.09-2029
This information is current as of October 20, 2011
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References
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Increased Risk of Myocardial Infarction and Stroke Following Exacerbation of COPD

Transcription

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