Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity.

Abstract

Recent studies described association between chronic obstructive pulmonary disease (COPD) and increased risk of cardiovascular diseases (CVD). In their analysis none of these studies accounted for sociodemographic factors, health behaviors, and patient comorbidities simultaneously.
To study whether COPD diagnosis is an independent risk factor for CVD.
Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002 National Health Interview Survey (NHIS) were included in the analysis. Chi-squared tests and odds ratios (OR) were utilized to compare the data. Multiple logistic regression was employed to analyze the association between COPD and CVD with simultaneous control for sociodemographic factors (age, gender, race, marital status, education, income), health behaviors (tobacco use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension, high cholesterol, and obesity). The analysis employed NHIS sampling weights to generate data representative of the entire US population.
The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P < 0.0001). Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having coronary heart disease (OR = 2.0, 95% CI: 1.5-2.5), angina (OR = 2.1, 95% CI: 1.6-2.7), myocardial infarction (OR = 2.2, 95% CI: 1.7-2.8), stroke (OR = 1.5, 95% CI: 1.1-2.1), congestive heart failure (OR = 3.9, 95% CI: 2.8-5.5), poor circulation in lower extremities (OR = 2.5, 95% CI: 2.0-3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0-2.8). Overall, the presence of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3-3.2).
These findings support the conclusion that COPD is an independent risk factor for CVD.

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O R I g I n A L R e s e A R C h
Joseph Finkelstein1
eunme Cha1
steven M scharf 2
1Welch Center for Prevention,
epidemiology and Clinical Research,
Johns hopkins University, Baltimore,
MD, UsA; 2Division of Pulmonary
and Critical Care Medicine at the
Department of Medicine, University
of Maryland school of Medicine,
Baltimore, MD, UsA
Correspondence: Joseph Finkelstein
Welch Center for Prevention,
epidemiology and Clinical Research, Johns
hopkins University, 2024 e Monument st,
Rm. 2-615, Baltimore, MD 21205, UsA
Tel +1 410 558 0480
Fax +1 410 558 0470
Email jfinkel9@jhmi.edu
Rationale: Recent studies described association between chronic obstructive pulmonary disease
(COPD) and increased risk of cardiovascular diseases (CVD). In their analysis none of these
studies accounted for sociodemographic factors, health behaviors, and patient comorbidities
simultaneously.
Objective: To study whether COPD diagnosis is an independent risk factor for CVD.
Methods: Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002
National Health Interview Survey (NHIS) were included in the analysis. Chi-squared tests and
odds ratios (OR) were utilized to compare the data. Multiple logistic regression was employed
to analyze the association between COPD and CVD with simultaneous control for sociodemo-
graphic factors (age, gender, race, marital status, education, income), health behaviors (tobacco
use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension,
high cholesterol, and obesity). The analysis employed NHIS sampling weights to generate data
representative of the entire US population.
Results: The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P  0.0001).
Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having
coronary heart disease (OR = 2.0, 95% CI: 1.5–2.5), angina (OR = 2.1, 95% CI: 1.6–2.7),
myocardial infarction (OR = 2.2, 95% CI: 1.7–2.8), stroke (OR = 1.5, 95% CI: 1.1–2.1),
congestive heart failure (OR = 3.9, 95% CI: 2.8–5.5), poor circulation in lower extremities
(OR = 2.5, 95% CI: 2.0–3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0–2.8). Overall, the presence
of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3–3.2).
Conclusions: These findings support the conclusion that COPD is an independent risk factor
for CVD.
Keywords: chronic obstructive pulmonary disease, cardiovascular disease, risk factors,
population-based analysis, case-control study
Introduction
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
of adults in United States and it is projected to be the third leading cause of death
by 2020.1 Nonrespiratory diseases account for more than 50% of deaths in COPD
patients.2 A number of previous studies demonstrated an association between COPD
and cardiovascular disease.3–11 In fact, the presence of COPD may be an independent
risk factor for the development of cardiovascular disease (CVD) above that associated
with the most widespread factor these diseases have in common, namely smoking.5–9
Further, the Lung Health Study showed that age, smoking, male gender, married state,
higher diastolic blood pressure, and poor pulmonary function were the strongest
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cardiovascular risk factors in COPD, while high baseline
forced expiratory volume in one second (FEV1), alcohol use,
smoking cessation, and education were protective factors.12
Data consistent with the notion that COPD could be an
independent risk for CVD come from the population-based
studies13,14 that showed that the lower the FEV1, the higher
the risk of CVD. However, many conditions, including
heart failure and other lung diseases, can result in a reduced
FEV1. Thus these studies are not specific for COPD. In a
longitudinal health cohort study, Curkendall and colleagues
showed that the diagnosis “COPD” increased the risk for
hospitalization and deaths due to CVD.6 However, in this
study, no simultaneous adjustment for sociodemographic
and lifestyle risk factors for CVD, including physical activity,
alcohol consumption, and smoking, was performed. Thus,
while there are some indications that COPD may be a risk
factor per se, to date only suggestive data have been presented.
Further there are no US population based studies addressing
the potential that COPD is a risk factor for CVD.
The notion that COPD itself is an independent risk for
CVD has potentially important implications. As a systemic
inflammatory disease, COPD may accelerate the develop-
ment of CVD above and beyond that due to smoking alone.11
Indeed, if the risk were great enough, therapy directed at
reducing cardiovascular risk might be indicated in COPD
patients even without evidence of concomitant CVD, or the
presence of other known risk factors aside from smoking.
This study used data from the National Health Interview
Survey (NHIS), a representative sample of the civilian,
noninstitutionalized, adult US population to investigate
the association between COPD and CVD. Our aims were:
1) To measure prevalence of CVDs in COPD patients; 2) to
determine if the diagnosis of COPD is an independent risk
factor for CVD after adjusting for major sociodemographic,
lifestyle, and comorbidity risk factors, including physical
activity, alcohol consumption, and smoking; 3) to stratify
COPD as a CVD risk factor in different age and gender
groups; 4) to determine in a case-control study whether
COPD plays a role as an independent risk for cardiovascular
morbidity amplifying effect of smoking. We hypothesized
that the diagnosis of “COPD” increases the risk of having
CVD, independently of smoking history, age, gender, and
lifestyle risks known to lead to CVD.
Methods
study setting and sample
Data from the sample adult core of 2002 NHIS15 were
analyzed. The value of the NHIS data set lies in the design
of its field instrument which permits the collection of a broad
range of demographic, socioeconomic, and health behavior
data along with the prevalence of illness and disability.16 For
the sample adult core, one adult per family was randomly
selected to complete a computer-assisted personal interview.
The NHIS provides final weights accounting for a complex
sampling design and allowing population-based estimates.
Though the NHIS collected self-reported data, previous
studies have confirmed the validity and analysis of this type
of data.17–20 In this study all subjects 18 years and older were
included in analyses. Subjects with missing data who did
not ascertained, refused, or did not know responses were
excluded from analyses.
CVD status
CVD status was the primary outcome variable of interest.
Subjects were asked whether a doctor or other health
professional told them that they had congestive heart failure,
poor circulation in legs, stroke, coronary heart disease,
angina (angina pectoris), irregular heartbeats, or heart attack
(myocardial infarction). Subjects who answered yes to at least
one of these questions were considered to have CVD. Sub-
jects who answered no to all these conditions were considered
not to have CVD. Subjects who answered neither “yes” nor
“no” to these conditions were excluded from analysis. In
addition to defining “CVD” as above, we defined as outcomes
each of the individual conditions above.
COPD status
COPD status was ascertained based on the following
questions: “Have you ever been told by a doctor or other
health professional that you had emphysema?” and “During
the past 12 months, have you been told by a doctor or
other health professional that you had chronic bronchitis?”
Subjects’ reports of what they were told by physicians may
not necessarily correspond to the strict medical definition
of COPD (eg, GOLD criteria). To take this into account
we analyzed the data using three different definitions of
“COPD” of increasing strictness: 1) Subjects report having
“chronic bronchitis” and/or “emphysema”; 2) Same as #1
and are 40 years old; 3. Same as #2 and report smoking
more than 100 cigarettes in their lifetime. The last definition
we felt to be the most likely to correspond to the medical
definition of COPD and results based on this definition are
reported below. The two less stringent definitions (1 and 2)
lead to similar results and conclusions. To characterize the
study population, the COPD status was further subcatego-
rized as: not having COPD, having chronic bronchitis alone,

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having emphysema alone, or having both chronic bronchitis
and emphysema.
Risk factors
Sociodemographic variables included age, gender, race/
ethnicity, marital status, education level and family income.
Race/ethnicity was categorized into: White, Black, Hispanic,
and other. Subjects with spouse or partner living together
were considered as married. Education level was divided
into three groups: had 12 years education, graduated from
a high school, and had 12 years education. Family income
was dichotomized as family income less than $20,000 and
family income of $20,000 or more.
Lifestyle variables included: tobacco use, alcohol con-
sumption and physical activity. Tobacco use was defined
as current nonsmoker and current smoker. Alcohol use
was defined as nondrinkers, light, and current drinkers.
Exercise status was defined as never or ever exercised.
Comorbid conditions of interest included: hypertension,
diabetes, hypercholesterolemia, body mass index (BMI)
status (underweight = BMI  18.5, normal = BMI 18.5–25,
overweight = BMI  25).
statistical analysis
All statistical analyses were performed using SAS software
(version 9.1; SAS Institute, Cary, NC, USA). Sampling
weights were used where applicable to adjust for the
population-based multistage sampling design.21,22 To incor-
porate the complex sampling design of the NHIS in the
statistical analysis and to generate data representative of the
entire US population, SAS procedures SURVEYFREQ and
SURVEYLOGISTIC were utilized.23 Chi-squared tests were
employed to compare the prevalence of CVDs in COPD and
non-COPD population. In addition, the prevalence of each
individual category of CVDs in COPD, non-COPD subjects
and non-COPD smokers were also compared.
For cohort analysis, a series of multivariate logistic
regressions were performed to assess the association
between any CVD, individual CVD categories and COPD,
controlling for sociodemographic factors (age, gender,
race, marital status, education, and family income), health
behaviors (physical activity, alcohol consumption and current
tobacco use) and comorbidities (hypertension, diabetes,
hypercholesterolemia and obesity). The results were reported
as odds ratios (OR) with corresponding 95% confidence
intervals (CI). Furthermore, stratified analyses were utilized
to evaluate the impact of COPD on CVD in different age
and gender groups. Age was categorized into two adult
groups aged 40–60 and 60 years. Interactions between
age group and COPD status, and gender and COPD status
were also tested.
Smoking is a risk factor common to both CVD and
COPD. To further explore the possibility that COPD is
a risk for CVD independent of smoking, we performed a
matched case-control study drawn from the NHIS 2002 data
set in which COPD was considered as an exposure factor.
For this purpose we limited our analysis data set to only
subjects 40 years old who smoked more than 100 cigarettes
in their lifetime (smokers). Cases were defined as smokers of
age 40 years and older who had at least one CVD category
from above. Overall, 2,975 cases were identified in the
analysis data set. Each case was matched by age (±1 year),
gender and race with a control represented by a smoker
aged 40 years who did not have CVD and who was selected
randomly from the same analysis data set. The outcome of
interest was CVD, defined as having at least one of the CVD
categories above. Regression analysis for matched case-
control studies was used to estimate the association of CVD
and COPD.24 Conditional logistic regression was employed
to estimate the hazard ratio (HR) and 95% CI adjusting for
matched variables and other sociodemographic, lifestyle,
and comorbid risk factors.
Results
Table 1 shows the characteristics of our study population.
There were 18,342 subjects who were aged 40 years in our
cohort and did not have any missing data. Study subjects were
mostly white (78%), women (53%) with an average age of
57 years. Most subjects were married (69%) and had higher
education (51%). About 5% of the subjects had COPD and
over 28% of the subjects had CVD. Subjects who had CVD
and COPD were older and had lower family income, tended
to smoke and do less exercise.
Table 2 lists the prevalence of CVD in COPD, as well as
various COPD subgroups. Fifty-six percent of COPD patients
had CVD, while only 26% of the non-COPD subjects had
CVD, (P  0.0001). Subjects who reported both chronic
bronchitis and emphysema were more likely to have CVD
than subjects who reported no COPD, chronic bronchitis
alone or emphysema alone (P  0.0001).
Table 3 presents the breakdown of individual CVD
categories. Poor circulation in legs and irregular heartbeats
were two common conditions in COPD subjects (34% and
29%, respectively), as well as in non-COPD patients (12%
and 12%, respectively) and non-COPD smokers (13% and
13%, respectively). Sixteen percent of COPD patients had

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Table 1 Characteristics of the study population*
Variables

All population

N = 18,342
% (SE)
COPD

N = 958
% (SE)
Bronchitis and
emphysema
N = 139
% (SE)
Bronchitis
alone
N = 514
% (SE)
Emphysema
alone
N = 305
% (SE)
COPD and
CVD
N = 557
% (SE)
CVD

N = 5,242
% (SE)
Age (mean, se)
56.8
(0.1)
60.3
(0.4)
61.7
(0.6)
56.5
(0.5)
66.3
(0.5)
62.8
(0.5)
63.2
(0.2)
Gender
Male

Female

47.0
(0.4)
53.0
(0.4)

45.5
(1.6)
54.5
(1.6)

46.4
(1.9)
53.6
(1.9)

34.1
(1.8)
65.9
(1.8)

65.3
(2.1)
34.7
(2.1)

44.4
(1.8)
55.6
(1.8)

46.4
(0.8)
53.6
(0.8)
Race
White

Black

hispanic

Other

77.8
(0.5)
10.1
(0.3)
8.4
(0.3)
3.7
(0.2)

85.4
(1.1)
8.8
(0.8)
4.1
(0.8)
1.7
(0.4)

95.6
(0.1)
1.5
(0.04)
1.4
(0.04)
1.5
(0.04)

80.3
(1.4)
11.7
(0.9)
5.9
(1.1)
2.1
(0.7)

89.6
(1.2)
7.0
(0.9)
2.3
(0.2)
1.1
(0.6)

83.0
(1.4)
10.7
(1.0)
4.8
(1.1)
1.5
(0.4)

78.9
(0.7)
10.9
(0.5)
7.1
(0.4)
3.1
(0.3)
Marital status
spouse/partner
present
nonspouse/partner
present

68.6
(0.4)
31.4
(0.4)

57.8
(1.4)
42.2
(1.4)

52.8
(2.4)
47.2
(2.4)

60.0
(1.6)
40.0
(1.6)

56.3
(1.8)
43.7
(1.8)

54.5
(1.7)
45.5
(1.7)

62.5
(0.8)
37.5
(0.8)
Education
12 years

=12 years

12 years

15.8
(0.3)
33.5
(0.4)
50.7
(0.5)

26.6
(1.3)
36.4
(1.5)
37.0
(1.5)

42.1
(1.9)
29.8
(1.8)
28.1
(1.9)

18.1
(1.7)
37.5
(1.9)
44.4
(1.9)

34.3
(2.1)
37.5
(2.4)
28.2
(1.9)

32.9
(1.8)
35.3
(1.8)
31.8
(1.8)

24.2
(0.7)
33.8
(0.8)
42.0
(0.8)
Family income
Below 20 K

Above 20 K

19.2
(0.4)
80.8
(0.4)

34.4
(1.4)
65.6
(1.4)

47.5
(2.1)
52.5
(2.1)

28.0
(1.6)
72.0
(1.6)

39.4
(2.3)
60.6
(2.3)

41.6
(1.8)
58.4
(1.8)

29.3
(0.8)
70.7
(0.8)
BMI
Underweight
(BMI  18.5)
normal
(18.5  BMI  25)
Overweight (BMI  25)

1.4
(0.1)
33.2
(0.4)
65.4
(0.5)

3.8
(0.6)
31.9
(1.4)
64.3
(1.5)

4.6
(0.1)
33.9
(2.2)
61.5
(2.2)

1.9
(0.4)
28.0
(1.6)
70.1
(1.7)

6.8
(1.1)
37.9
(2.2)
55.3
(2.2)

3.8
(0.6)
30.4
(1.6)
65.8
(1.7)

2.0
(0.18)
29.6
(0.8)
68.4
(0.8)
Smoking status
nonsmoker currently

Current smoker

80.1
(0.4)
19.9
(0.3)

53.7
(1.7)
46.3
(1.7)
44.5
(2.4)
55.5
(2.4)

52.9
(2.0)
47.1
(2.0)

59.6
(2.5)
40.4
(2.5)
45.5
(1.7)
54.5
(1.7)

80.4
(0.6)
19.6
(0.6)
Drinking status
nondrinker

Light drinker

Drinker

22.1
(0.4)
50.3
(0.5)
27.6
(0.4)

11.7
(1.0)
52.6
(1.6)
35.7
(1.6)

10.9
(1.9)
52.9
(1.9)
36.2
(1.7)

12.5
(1.3)
57.3
(1.7)
30.2
(1.6)

10.8
(1.4)
44.0
(2.5)
45.2
(2.6)

12.6
(1.2)
50.8
(1.9)
36.6
(1.8)

24.0
(0.7)
47.2
(0.9)
28.8
(0.8)
(Continued)

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coronary heart disease, compared to 6% of non-COPD
patients and 7% of non-COPD smokers. The difference was
statistically significant (P  0.0001). In all, subjects with
COPD were more likely to report any individual CVD cat-
egory than non-COPD patients and non-COPD smokers.
Table 4 shows the association between COPD and
any CVD and individual CVD categories adjusting for
sociodemographic factors, health behavior factors and
comorbidities in multivariate regression model. Subjects
with COPD had more than twice the risk of CVD than
subjects without COPD (OR 2.7, 95% CI: 2.3–3.2). Older
age, lower family income, underweight, smoking, drinking,
diabetes, hypertension, and high cholesterol were signifi-
cantly associated with increased risk of CVD; while being
Hispanic, having higher education and exercise were asso-
ciated with significantly reduced the risk of CVD. Further-
more, COPD was significantly associated with all individual
definitions of CVD categories. Among them, COPD reveals
the strongest association with congestive heart failure
(OR 3.9, 95% CI: 2.8–5.5). As well, age, education, income,
exercise, and comorbidities including diabetes, hypertension
and high cholesterol indicated consistent relation with each
individual CVD categories.
Table 5 presents the association of COPD with any CVD
and individual CVD categories stratified by age and gender.
The adjusted OR of CVD was three times higher in subjects
with COPD compared to those without COPD among
subjects aged from 40 to 60 years, while the OR of CVD
was twice as high for subjects aged 60 years and older. The
difference is statistically significant (P = 0.0149). Moreover,
the ORs for myocardial infarction and irregular heart beat
were greater in subjects aged 40–60 years than for subjects
aged 60 years. In gender-related differences, there was no
significant difference between ORs for CVD or any CVD
category except for coronary heart disease, which was
significantly greater in females than in males.
Comparative analysis of health care utilization in COPD
and CVD subjects was performed to assess affect of concur-
rent COPD and CVD conditions on urgent care utilization,
hospital stay, doctor office visits, and days missing work.
About 45% of subjects with both COPD and CVD visited the
emergency room more than once during the past 12 months
compared to 38% of COPD patients and 32% of CVD
patients. Patients who had COPD and CVD tended to have
more doctor visits during past 12 months than subjects with
COPD alone and CVD alone. The mean number of days
missing work at a job for subjects with COPD and CVD was
22 days, compared to 13 days for subjects with COPD alone
and 10 days for subjects with CVD alone. Overall, subjects
who had COPD and CVD had higher health care utilization
Table 1 (Continued)
Variables

All population

N = 18,342
% (SE)

41.2
(0.6)
58.8
(0.6)
COPD

N = 958
% (SE)

57.0
(1.7)
43.0
(1.7)
Bronchitis and
emphysema
N = 139
% (SE)

73.3
(1.4)
26.7
(1.4)
Bronchitis
alone
N = 514
% (SE)

48.9
(2.1)
51.1
(2.1)
Emphysema
alone
N = 305
% (SE)

63.4
(2.0)
36.6
(2.0)
COPD and
CVD
N = 557
% (SE)

62.4
(1.8)
37.6
(1.8)
CVD

N = 5242
% (SE)

49.0
(0.9)
51.0
(0.9)
Exercise
never

ever
Notes: *COPD definition was based on subject reporting (1) “chronic bronchitis” and/or “emphysema”; (2) age  = 40 years old; (3) smoking more than 100 cigarettes in
their lifetime.
Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; se, standard error.
Table 2 CVD prevalence in different COPD categories
Variables

COPD

N = 958
% (SE)
Non-COPD

N = 17,384
% (SE)
Bronchitis and
emphysema
N = 139
% (SE)
Bronchitis
alone
N = 514
% (SE)
Emphysema
alone
N = 305
% (SE)
CVD56.5 25.682.3 48.358.6
(1.7)(0.4) (3.9)(2.4)(2.9)
non-CVD
43.5 74.417.7 51.741.4
(1.7)(0.4)(3.9)(2.4)(2.9)
Abbreviations: COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; se, standard error.