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Risk Factors for Congestive Heart Failure in US Men and Women
NHANES I Epidemiologic Follow-up Study
Jiang He, MD, PhD;
Lorraine G. Ogden, MS;
Lydia A. Bazzano, PhD;
Suma Vupputuri, MPH;
Catherine Loria, PhD, MS;
Paul K. Whelton, MD, MSc
Arch Intern Med. 2001;161:996-1002.
ABSTRACT
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Background The incidence of congestive heart failure (CHF) has been increasing
steadily in the United States during the past 2 decades. We studied risk factors
for CHF and their corresponding attributable risk in the First National Health
and Nutrition Examination Survey Epidemiologic Follow-up Study.
Participants and Methods A total of 13 643 men and women without a history of CHF at baseline
examination were included in this prospective cohort study. Risk factors were
measured using standard methods between 1971 and 1975. Incidence of CHF was
assessed using medical records and death certificates obtained between 1982
and 1984 and in 1986, 1987, and 1992.
Results During average follow-up of 19 years, 1382 CHF cases were documented.
Incidence of CHF was positively and significantly associated with male sex
(relative risk [RR], 1.24; 95% confidence interval [CI], 1.10-1.39; P<.001; population attributable risk [PAR], 8.9%), less
than a high school education (RR, 1.22; 95% CI, 1.04-1.42; P = .01; PAR, 8.9%), low physical activity (RR, 1.23; 95% CI, 1.09-1.38; P<.001; PAR, 9.2%), cigarette smoking (RR, 1.59; 95%
CI, 1.39-1.83; P<.001; PAR, 17.1%), overweight
(RR, 1.30; 95% CI, 1.12-1.52; P = .001; PAR, 8.0%),
hypertension (RR, 1.40; 95% CI, 1.24-1.59; P<.001;
PAR, 10.1%), diabetes (RR, 1.85; 95% CI, 1.51-2.28; P<.001;
PAR, 3.1%), valvular heart disease (RR, 1.46; 95% CI, 1.17-1.82; P = .001; PAR, 2.2%), and coronary heart disease (RR, 8.11; 95% CI,
6.95-9.46; P<.001; PAR, 61.6%).
Conclusions Male sex, less education, physical inactivity, cigarette smoking, overweight,
diabetes, hypertension, valvular heart disease, and coronary heart disease
are all independent risk factors for CHF. More than 60% of the CHF that occurs
in the US general population might be attributable to coronary heart disease.
INTRODUCTION
DURING THE past several decades, the incidence of and mortality from
coronary heart disease (CHD) and stroke have been continuously declining.
In contrast, the incidence of and mortality from congestive heart failure
(CHF) have been increasing and have become important public health and clinical
problems.1-2 Approximately 4.6
million Americans have a diagnosis of CHF, about 400 000 new cases occur
annually, and more than 43 000 individuals die of CHF in the United States
each year.1 The number of hospitalizations
for CHF increased from 377 000 in 1979 to 870 000 in 1996 (a 131%
increase), and deaths from CHF increased by approximately 120% during the
same period.1
Few population-based epidemiologic studies3-6
have examined the risk factors for CHF. In the Framingham Heart Study, CHD,
hypertension, left ventricular hypertrophy, valvular heart disease, and diabetes
were associated with an increased risk of CHF.3-4
Diabetes, CHD, elevated pulse pressure, and obesity were associated with an
increased risk of CHF in the New Haven, Conn, cohort of the Established Population
for Epidemiologic Studies of the Elderly program.5
In the East Boston Senior Health Project, elevated pulse pressure, diabetes,
valvular heart disease, atrial fibrillation, and use of antihypertensive medication,
but not CHD, were associated with an increased risk of CHF.6
The effect of socioeconomic status and lifestyle risk factors on the risk
of CHF has not been well studied. Furthermore, the contribution of each individual
risk factor to the overall incidence of CHF in the US general population has
not been established. This information is important in developing strategies
for the prevention of CHF in the US general population.
The First National Health and Nutrition Examination Survey (NHANES I)
Epidemiologic Follow-up Study provides an opportunity to examine the risk
factors for CHF in a representative sample of the US general population for
which relevant long-term outcome information has been obtained. It also permits
estimation of the population attributable risk (PAR) of CHF due to each risk
factor of interest.
PARTICIPANTS AND METHODS
STUDY POPULATION
In NHANES I, a multistage, stratified, probability sampling design was
used to select a representative sample of the US civilian noninstitutionalized
population aged 1 to 74 years. Details of the study design, sampling methods,
response rate, and data collection have been published elsewhere.7-8 Certain population subgroups, including
those with a low income, women of childbearing age (25-44 years), and elderly
persons ( 65 years), were oversampled.
The NHANES I Epidemiologic Follow-up Study is a prospective cohort study
of NHANES I participants aged 25 to 74 years when the survey was conducted
in 1971 to 1975.9-12
Of 14 407 NHANES I Epidemiologic Follow-up Study participants in this
age range, 219 with a positive history of CHF at baseline, defined as ever
having been told by a physician that they have had heart failure or having
used any medication for a "weak heart" during the 6 months before the baseline
interview, and 545 lost to follow-up (there was no subject or proxy interview
at any follow-up wave and no death certificate) were excluded from the analysis.
After these exclusions, the experience from 5545 men and 8098 women was available
for analysis.
MEASUREMENTS
Baseline data collection included demographic information, a medical
history, standardized medical examination, laboratory tests, and anthropometric
measurements.7-8 Frozen serum
samples were sent to the Centers for Disease Control and Prevention for measurement
of serum total cholesterol levels. Blood pressure, body weight, and height
were obtained using standard protocols. The baseline questionnaire detailing
medical history included queries about selected health conditions and medications
used for these conditions during the preceding 6 months. Data pertaining to
education, physical activity, and alcohol consumption were based on responses
to interviewer-administered questionnaires. Baseline information on smoking
status was obtained in a random subsample of 6913 participants who underwent
a more detailed evaluation at the time of their examination.7-8
For the remaining study participants, information on smoking status at baseline
was derived from responses to questions regarding lifetime smoking history
administered at follow-up interviews conducted between 1982 and 1984 or later.13-14 The validity of information on smoking
status obtained using this approach has been documented elsewhere.13-14
Hypertension at baseline was defined as a systolic blood pressure of
160 mm Hg or greater and/or a diastolic blood pressure of 95 mm Hg or greater
and/or use of antihypertensive medication. Hypercholesterolemia was defined
as a total serum cholesterol value of 6.21 mmol/L or greater (240 mg/dL).
Overweight was defined as a body mass index (calculated as weight in kilograms
divided by the square of height in meters) of 27.8 or greater for men and
27.3 or greater for women. Baseline diabetes was defined as the participant
ever having been told by a physician that he or she had this condition. Coronary
heart disease was defined as the participant ever having been told by a physician
that he or she had a heart attack or having a diagnosis with an International Classification of Diseases, Ninth Revision (ICD-9), code
of 410 to 414. Valvular heart disease was defined as having a diagnosis with
an ICD-9 code of 394 to 397 or 424 at the baseline
medical examination.
FOLLOW-UP PROCEDURES
Follow-up data were collected between 1982 and 1984 and in 1986, 1987,
and 1992.9-12
Each follow-up examination included tracking a participant or his or her proxy
to a current address; performing an in-depth interview; obtaining hospital
and nursing home records, including pathology reports and electrocardiograms;
and, for decedents, acquiring a death certificate. Incident cardiovascular
disease was based on documentation of an event that met prespecified study
criteria and occurred between the participant's baseline examination and last
follow-up interview. Mortality from cardiovascular disease was based on death
certificate reports. Validity of study outcome data from both sources has
been documented elsewhere.15
Incident CHF was based on 1 or more hospital or nursing home stays in
which the participant had a discharge diagnosis with an ICD-9 code of 428.0 to 428.9 or a death certificate report in which
the underlying cause of death was recorded using an ICD-9 code of 428.0 to 428.9. Incident CHD was based on 1 or more hospital
or nursing home stays in which the participant had a discharge diagnosis with
an ICD-9 code of 410 to 414 or a death certificate
report in which the underlying cause of death was coded as ICD-9 410 to 414. The date of record for incident events was identified
as the date of the participant's first hospital admission with an established
study event or the date of death from a study event in the absence of hospital
or nursing home documentation of such an event.
STATISTICAL ANALYSIS
The cumulative incidence of CHF by status was calculated for each risk
factor using the Kaplan-Meier method,16 and
differences in cumulative rates were examined using the log-rank test for
trend.17 Cox proportional hazards models were
used to explore the relation between baseline risk factors and CHF incidence.18 History of CHD was modeled as a time-dependent variable
in Cox proportional hazards models. Age was used as the time scale for all
time-to-event analyses.19 Cox proportional
hazards models were stratified by birth cohort using 10-year intervals to
control for calendar period and cohort effects.19
Methods to estimate variance that take into account sample clustering and
stratification of the NHANES I sample were used in Cox proportional hazards
models.19
Population attributable risk (PAR) was calculated by standard methods
as follows20:
where P is the proportion of the population
with a risk factor at baseline or the cumulative proportion exposed during
follow-up and RR is the relative risk of CHF in persons with vs without the
risk factor from the Cox proportional hazards model. The PAR estimates the
proportion of cases that could be prevented if the risk factor could be eliminated
from the total population.
RESULTS
BASELINE RISK FACTORS
The mean age of study participants was 52.2 years in men and 48.1 years
in women (Table 1). Approximately
13.6% of men and 15.6% of women were black. Among men, 47.9% had less than
a high school education, 40.7% smoked cigarettes, 37.5% drank alcohol at least
twice per week, and 37.0% did not participate in regular physical activity;
the corresponding percentages for women were 42.1%, 31.1%, 16.0%, and 49.0%.
The prevalence of hypertension, hypercholesterolemia, overweight, diabetes,
valvular heart disease, and CHD was 30.1%, 30.6%, 25.7%, 3.7%, 4.5%, and 7.3%,
respectively, in men and 26.9%, 32.8%, 31.2%, 3.9%, 5.2%, and 3.3%, respectively,
in women.
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Table 1. Baseline Characterisitics of 13 643 Participants in the
NHANES I Epidemiologic Follow-up Study*
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CUMULATIVE INCIDENCE OF CHF
During average follow-up of 19 years, 1382 participants developed CHF
(741 men and 641 women). The sex-specific cumulative incidence at age 85 years
was significantly higher in men (38.1%) than in women (31.0%) (P<.001). In men and women, the cumulative incidence of CHF at age
85 years was significantly greater in those who were less educated, less physically
active, currently smoking cigarettes, overweight, or hypertensive or had a
history of diabetes, valvular heart disease, or CHD (Table 2). In addition, black women had a higher incidence of CHF
than white women. Hypercholesterolemia was associated with an increased incidence
of CHF in men but not in women, and regular alcohol consumption was associated
with a significantly lower incidence of CHF in women but not in men.
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Table 2. Cumulative Incidence of Congestive Heart Failure at Age 85
Years in 13 643 Participants in the NHANES I Epidemiologic Follow-up
Study*
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RELATIVE RISKS
After adjustment for age, race, and time-dependent history of CHD, there
was a positive and significant association between less than a high school
education, lower level of physical activity, current cigarette smoking, overweight,
hypertension, and a history of diabetes or valvular heart disease and increased
risk of subsequently developing CHF in men and women (Table 3). Regular alcohol consumption was associated with a lower
risk of CHF in women only. In a combined analysis, less than a high school
education (RR, 1.35; 95% CI, 1.16-1.57; P<.001),
lower level of physical activity (RR, 1.33; 95% CI, 1.19-1.49; P<.001), current cigarette smoking (RR, 1.49; 95% CI, 1.30-1.70; P<.001), overweight (RR, 1.35; 95% CI, 1.17–1.55; P<.001), history of hypertension (RR, 1.50; 95% CI,
1.34-1.68; P<.001), history of diabetes (RR, 1.98;
95% CI, 1.63-2.41; P<.001), and history of valvular
heart disease (RR, 1.47; 95% CI, 1.17-1.84; P = .001)
at the baseline examination were positively and significantly associated with
an increased risk of CHF.
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Table 3. Relative Risk of Congestive Heart Failure in 13 643 Partcipants
in the NHANES I Epidemiologic Follow-up Study by Socioeconomic and Health
Characteristics*
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In a multivariate model that simultaneously included all the significant
risk factors identified in the previous model, current cigarette smoking,
overweight, hypertension, history of diabetes, history of valvular heart disease,
and history of CHD were significantly associated with an increased risk of
CHF in men and women (Table 4). There was a borderline significant association between less than a high school
education and increased risk of CHF in men and women. Lower physical activity
was positively associated, whereas regular alcohol consumption was inversely
associated with risk of CHF in women but not in men (Table 4). In the combined analysis, male sex (RR, 1.24; 95% CI,
1.10-1.39; P<.001), less than a high school education
(RR, 1.22; 95% CI, 1.04-1.42; P = .01), lower physical
activity (RR, 1.23; 95% CI, 1.09-1.38; P<.001),
cigarette smoking (RR, 1.59; 95% CI, 1.39-1.83; P<.001),
overweight (RR, 1.30; 95% CI, 1.12-1.52; P = .001),
hypertension (RR, 1.40; 95% CI, 1.24-1.59; P<.001),
diabetes (RR,1.85; 95% CI, 1.51-2.28; P<.001),
valvular heart disease (RR, 1.46; 95% CI, 1.17-1.82; P
= .001), and CHD (RR, 8.11; 95% CI, 6.95-9.46; P<.001)
were all positively and significantly associated with an increased risk of
CHF.
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Table 4. Multivariate Relative Risk of Congestive Heart Failure in
13 643 Participants in the NHANES I Epidemiologic Follow-up Study by
Socioeconomic and Health Characteristics*
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POPULATION ATTRIBUTABLE RISKS
Figure 1 shows estimates of
the PAR of CHF due to various risk factors based on experience in the present
study. Coronary heart disease was the major cause of CHF in the general population,
accounting for approximately 61.6% of all the cases, followed by cigarette
smoking (PAR, 17.1%) and hypertension (PAR, 10.1%). The contribution of lower
physical activity (PAR, 9.2%), male sex (PAR, 8.9%), less than a high school
education (PAR, 8.9%), and overweight (PAR, 8.0%) was similar. Diabetes and
valvular heart disease accounted for only 3.1% and 2.2% of CHF cases, respectively,
because of their low prevalence at the baseline examination. In the sex-stratified
analysis, PARs of CHF in men for CHD, current cigarette smoking, hypertension,
less than a high school education, overweight, valvular heart disease, and
diabetes were 67.9%, 15.5%, 9.0%, 8.7%, 5.6%, 3.2%, and 3.0%, respectively.
The corresponding estimates for women were 55.9%, 21.5%, 12.1%, 9.5%, 9.6%,
1.8%, and 3.1%. In addition, physical inactivity was associated with a PAR
of 13.2% in women.
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Population attributable risk of congestive heart failure due to various
risk factors in 5545 men and 8098 women participating in the First National
Health and Nutrition Examination Survey Epidemiologic Follow-up Study.
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COMMENT
Congestive heart failure is not only a personal tragedy for patients
and their families but a serious public health burden for society. Patients
with CHF have a poorer quality of life and shorter life expectancy compared
with those of the same age in the general population.21
With an increasingly older population and progressive improvements in survival
after acute myocardial infarction, it is almost inevitable that CHF will continue
to be an important public health challenge in the foreseeable future. Because
of the high mortality rate associated with CHF, it is important to identify
modifiable risk factors and develop effective strategies for the prevention
of CHF in the general population. Results of prospective cohort studies3-6 have
indicated that old age, male sex, hypertension, diabetes, obesity, valvular
heart disease, and CHD are important risk factors for CHF. The present study
extends our understanding of risk factors for CHF in several important ways.
First, our analysis demonstrates that cigarette smoking is a strong
and independent risk factor for CHF. Few prospective cohort studies have examined
the relation between cigarette smoking and risk of CHF. Eriksson and colleagues22 followed 973 men born in 1913 in Gothenburg, Sweden,
for 17 years to examine risk factors for CHF. Smoking at age 50 years was
associated with a 60% higher risk of CHF (RR, 1.6; 95% CI, 1.2-3.2) in their
study. This relation was independent of hypertension, body weight, and other
important risk factors for CHF. Other prospective cohort studies3-6
have not examined the association between cigarette smoking and risk of CHF.
In our study, cigarette smoking was associated with a 45% higher risk of CHF
in men and an 88% higher risk of CHF in women after adjustment for CHD and
other known risk factors for CHF. This finding implies that cigarette smoking
might directly increase the risk of CHF in addition to its effect on increasing
the risk of CHD, a major cause of CHF. Results of our study also suggest that
cigarette smoking might cause about 17% of the incident CHF cases in the US
general population. As such, smoking cessation should be an important component
of any strategy to prevent CHF in the general population.
The results of our study also indicate that physical inactivity is an
important risk factor for development of CHF. The relation between physical
activity and risk of developing CHF has not been studied in previous prospective
cohort studies.3-6,22
Many studies23-26
have indicated that a higher level of physical activity is associated with
a lower risk of CHD, hypertension, obesity, and diabetes. The increased risk
of CHF associated with physical inactivity in our study was partially explained
by these risk factors. However, after adjustment for these risk factors, physical
inactivity was still associated with a significantly higher risk of CHF. Our
PAR estimates suggest that physical inactivity might account for approximately
9.2% of CHF cases in the US general population. Increasing physical activity
could substantially reduce the risk of CHF in the US general population.
In addition, our findings suggest that less than a high school education
(an index of lower socioeconomic status) is associated with an increased risk
of CHF. Many studies27-28 have
indicated that lower educational levels are related to limited access to higher-quality
health care and poor adherence to treatment of hypertension, diabetes, and
other risk factors for CHF. Hypertension and diabetes were important risk
factors for CHF in the NHANES I Epidemiologic Follow-up Study cohort and in
other study populations.3-6,22
These findings indicate that improving health care, including better control
of hypertension and diabetes in the general population, especially in socioeconomically
disadvantaged groups, should be an important part of attempts to reduce the
incidence of and mortality from CHF in the general population.
Finally, our study was conducted in a representative sample of the US
general population, which we took advantage of to estimate the PAR of CHF
due to various risk factors. Coronary heart disease was associated with the
largest PAR for CHF, accounting for 61.6% of CHF incident cases (67.9% in
men and 55.9% in women), followed by cigarette smoking (17.1%), hypertension
(10.1%), physical inactivity (9.2%), lower educational levels (8.9%), and
overweight (8.0%). Diabetes and valvular heart disease accounted for only
3.1% and 2.2% of CHF cases, respectively, because of their low prevalence
in the sample studied. The fact that only self-reported information was available
for diagnosis of diabetes almost certainly resulted in an underestimation
of the burden of diabetes-related CHF.29
An additional limitation of the present investigation was that study
participants were followed up in a passive rather than an active fashion.
Congestive heart failure was identified by means of information obtained from
hospital discharge diagnoses or death certificates. Therefore, the cumulative
incidence of CHF might be underestimated. However, there is no reason to believe
that these outcome measurements would differ by risk factor status. Because
of the nature of passive follow-up, echocardiographic or electrocardiographic
data were not available and left ventricular dysfunction could not be studied.
Coronary heart disease has become the single most important cause of
CHF in Western populations.30-31
Among 20 190 participants in 13 major multicenter heart failure clinical
trials, CHD was the underlying cause of CHF in 68% of patients.31
The cumulative proportion of CHD during follow-up in our study was 29.7% in
men and 17.7% in women. More than 60% of the CHF cases in our study population
were attributed to CHD. Based on these results and those from other studies,
primary prevention of CHD should play a central role in any attempts to achieve
a meaningful reduction in the burden of illness from CHF in the US general
population.
Our findings are consistent with previous studies3-6
that have reported overweight as a risk factor for CHF. In addition, our study
findings indicate that the increased risk associated with overweight is independent
of the presence or absence of CHD, diabetes, and hypertension. Thus, weight
loss should reduce the risk of CHF over and above any indirect effects that
result from lowering of the risk of CHD, diabetes, and hypertension. During
the past several decades, the prevalence of overweight has increased steadily
in the US general population for every age, sex, and race group.32
Our findings support recommendations for weight loss as a means to reduce
overall cardiovascular risk and total mortality.
In conclusion, our study results suggest that male sex, lower educational
levels, physical inactivity, cigarette smoking, overweight, diabetes, hypertension,
valvular heart disease, and CHD are all independent risk factors for CHF.
These findings indicate that attention to improvement of the overall cardiovascular
risk profile, including physical activity, weight loss, smoking cessation,
and control of hypertension and diabetes, should play an important role in
the prevention of CHF in the US general population.
AUTHOR INFORMATION
Accepted for publication September 14, 2000.
This study was supported by grant R03 HL61954 and in part by grant R01HL60300
from the National Heart, Lung, and Blood Institute, Bethesda, Md. The NHANES
I Epidemiologic Follow-up Study was developed and funded by the National Center
for Health Statistics; the National Institute on Aging; the National Cancer
Institute; the National Institute of Child Health and Human Development; the
National Heart, Lung, and Blood Institute; the National Institute of Mental
Health; the National Institute of Diabetes and Digestive and Kidney Diseases;
the National Institute of Arthritis and Musculoskeletal and Skin Diseases;
the National Institute of Allergy and Infectious Diseases; the National Institute
of Neurological and Communicative Disorders and Stroke; the Centers for Disease
Control and Prevention; and the US Department of Agriculture.
Corresponding author and reprints: Jiang He, MD, PhD, Department
of Epidemiology, Tulane University School of Public Health and Tropical Medicine,
1430 Tulane Ave, SL18, New Orleans, LA 70112 (e-mail: jhe{at}tulane.edu).
From the Departments of Epidemiology (Drs He, Bazzano, and Whelton
and Ms Vupputuri) and Biostatistics (Ms Ogden), Tulane University School of
Public Health and Tropical Medicine, New Orleans, La; and the National Heart,
Lung, and Blood Institute, Bethesda, Md (Dr Loria).
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