Preventive Cardiology

Healthy Lifestyle Factors in the Primary Prevention of

Coronary Heart Disease Among Men
Benefits Among Users and Nonusers of Lipid-Lowering and
Antihypertensive Medications
Stephanie E. Chiuve, ScD; Marjorie L. McCullough, RD, ScD;
Frank M. Sacks, MD; Eric B. Rimm, ScD

Background—Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking
may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors.
The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed
among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia.
Methods and Results—We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75
years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk
was defined as (1) absence of smoking, (2) body mass index ⬍25 kg/m2, (3) moderate-to-vigorous activity ⱖ30 min/d,
(4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over
16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In
multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk
of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no
lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with
better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercho-
lesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle.
Compared with men who did not make lifestyle changes during follow-up, those who adopted ⱖ2 additional low-risk
lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD.
Downloaded from http://ahajournals.org by on March 15, 2024

Conclusions—A majority of CHD events among US men may be preventable through adherence to healthy lifestyle
practices, even among those taking medications for hypertension or hypercholesterolemia. (Circulation. 2006;114:160-
167.)
Key Words: diet 䡲 lifestyle 䡲 risk factors 䡲 coronary disease 䡲 epidemiology

M ajor risk factors for coronary heart disease (CHD), such

as hypercholesterolemia, hypertension, and smoking,
are modifiable.1 Pharmacological therapies, including lipid-
lowering and antihypertensive medications, are efficacious in
lowering some of these risk factors,2,3 typically reducing
cardiovascular disease risk by 20% to 30%.2,4 Although
pharmacological agents successfully reduce coronary events,
the overall reduction in risk is relatively modest and could be
greatly improved by the addition of lifestyle modifications.
Clinical Perspective p 167
Healthy diet and other lifestyle practices, including not
smoking, maintaining a healthy weight, and exercising daily,
also improve these clinical risk factors as well as reduce
inflammation, homocysteine, glucose intolerance, and ar-
rhythmias.5–11 Individually, these modifiable lifestyle factors
are associated with lower risk of CHD,12 but a combination of
healthy lifestyle choices has a greater impact than any single
lifestyle factor. A healthy lifestyle has been associated with
lower risk of incident coronary events among middle-aged
women13 and lower risk of CHD mortality in a population of
elderly men and women.14 Little is known about the relation
between combined healthy lifestyle choices and incident
CHD among middle-aged and older men, especially those
who are reducing their risk by using drugs for hypertension or
hypercholesterolemia.

Received February 28, 2006; revision received April 11, 2006; accepted May 8, 2006.
From the Departments of Nutrition (S.E.C., F.M.S., E.B.R.) and Epidemiology (E.B.R.), Harvard School of Public Health, Boston, Mass; the
Cardiovascular Division (F.M.S.) and Channing Laboratory (F.M.S., E.B.R.), the Department of Medicine, Brigham and Women’s Hospital and Harvard
Medical School, Boston, Mass; and the Epidemiology and Surveillance Research Department, American Cancer Society, Atlanta, Ga (M.L.M.).
Guest Editor for this article was Donna K. Arnett, PhD.
Correspondence to Stephanie Chiuve, ScD, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail
schiuve@hsph.harvard.edu
© 2006 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.106.621417

160
 Chiuve et al Lifestyle Factors and Primary Prevention of CHD 161

TABLE 1. Multivariate Relative Risk of CHD Associated With Modifiable Lifestyle Factors
RR (95% CI)

Lifestyle Factors No. of Cases Frequency,* % Model 1† Model 2‡

Smoking (cigarettes/d)
ⱖ25 92 2 3.21 (2.57–4.01) 3.10 (2.46–3.89)
15–24 80 2 2.17 (1.72–2.75) 2.16 (1.70–2.74)
1–14 82 2 2.03 (1.61–2.57) 2.14 (1.69–2.71)
Past 1070 47 1.06 (0.97–1.17) 1.09 (0.99–1.20)
Never 791 44 1.00 (ref) 1.00 (ref)
Low risk (not current vs current) 1861 91 0.45 (0.40–0.51) 0.47 (0.42–0.54)
BMI (kg/m2)
ⱖ29.0 429 15 1.68 (1.45–1.96) 1.57 (1.34–1.83)
25.0–28.9 998 42 1.36 (1.19–1.55) 1.33 (1.17–1.52)
23.0–24.9 434 26 0.96 (0.85–1.12) 0.98 (0.84–1.14)
⬍23.0 306 17 1.00 (ref) 1.00 (ref)
Low risk (⬍25 vs ⱖ25 kg/m2) 740 43 0.68 (0.62–0.75) 0.70 (0.64–0.77)
Exercise (h/wk)§
0 1038 38 1.52 (1.32–1.73) 1.22 (1.06–1.40)
0.1–1.5 349 17 1.22 (1.04–1.43) 1.05 (0.90–1.24)
1.5–3.5 334 17 1.18 (1.00–1.38) 1.08 (0.92–1.27)
3.5–6.0 183 12 0.96 (0.79–1.16) 0.92 (0.76–1.11)
ⱖ6.0 279 17 1.00 (ref) 1.00 (ref)
Low risk (ⱖ3.5 vs ⬍3.5 h/wk) 462 29 0.72 (0.65–0.80) 0.83 (0.74–0.92)
Diet score¶
ⱕ31.6 491 20 1.58 (1.38–1.81) 1.28 (1.11–1.47)
Downloaded from http://ahajournals.org by on March 15, 2024

31.6–37.2 435 20 1.30 (1.13–1.50) 1.14 (0.99–1.32)

37.2–42.4 462 20 1.30 (1.13–1.49) 1.18 (1.03–1.36)
42.4–48.9 403 20 1.09 (0.94–1.25) 1.02 (0.89–1.18)
ⱖ48.9 392 20 1.00 (ref) 1.00 (ref)
Low risk (score ⱖ42.4 vs ⬍42.4) 795 40 0.75 (0.69–0.82) 0.84 (0.77–0.92)
Alcohol (g/d)
0 639 24 1.40 (1.25–1.55) 1.37 (1.23–1.53)
0.1–4.9 579 24 1.34 (1.20–1.50) 1.34 (1.20–1.49)
5-29.9 738 40 1.00 (ref) 1.00 (ref)
ⱖ30 226 11 1.03 (0.88–1.19) 0.88 (0.75–1.02)
Low risk (5-30 g/d vs others) 738 40 0.77 (0.70–0.84) 0.79 (0.73–0.87)
*Numbers may not add up to 100% because of missing values and rounding.
†RRs were estimated from a multivariate Cox proportional hazards model, adjusted for age, family history of MI
before age of 60, aspirin use, use of antihypertensive medication, baseline hypercholesterolemia, and baseline
hypertension. CI signifies confidence intervals.
‡Controlling for covariates in model 1⫹other lifestyle factors simultaneously.
§Exercise at moderate to vigorous intensity (ⱖ4 METs).
¶The AHEI-based diet score is based on intake of trans fat, ratio of polyunsaturated:saturated fat, ratio of chicken
and fish:red meat (in grams), fruits, vegetables, vegetable protein, cereal fiber, and multivitamin use.

We estimated the burden of CHD that could potentially be Methods

avoided through a healthy lifestyle among highly educated
middle-aged and older US men. We hypothesized that among
men taking medication for hypertension or hypercholesterol-
emia, these healthy lifestyle characteristics would still remain
associated with lower CHD risk. Finally, we examined the
association between changes in lifestyle during middle and
older ages and risk of CHD among these men.
Study Population
The Health Professionals Follow-up Study (HPFS) is a cohort of
51 529 US male health professionals, ages 40 to 75 years (mean age,
53) at baseline in 1986.15 Participants have provided information on
current medical conditions and lifestyle factors biennially starting in
1986 through the use of self-administered questionnaires. We ex-
cluded men with missing or implausible nutrient intakes at baseline
(ⱖ70 items left blank or estimated total energy intake ⱕ800 or
 162 Circulation July 11, 2006
ⱖ4200 kcal) and those with a history of chronic disease. The final
population for this analysis was 42 847. The Institutional Review
Board of the Harvard School of Public Health approved the study
protocol.
Exposure and Covariate Ascertainment
Self-reported height and family history of myocardial infarction (MI)
before 60 years of age were ascertained on the baseline question-
naire. Data on weight, medication use, current smoking status, and
physician diagnosis of hypertension and hypercholesterolemia were
assessed every 2 years. We calculated body mass index (BMI
[kg/m2]) by using self-reported measures of height and weight, which
have been validated in a subset of this cohort.16
Participants reported the average time engaged in specific activi-
ties biennially, using an activity questionnaire previously validated
within a subset of this cohort.17 We calculated hours per week of
moderate-to-vigorous activity requiring at least 4 metabolic equiva-
lents. We included walking at a brisk pace (ⱖ3 mph), jogging,
running, bicycling, swimming, tennis, squash, racquetball, rowing,
and calisthenics.
We assessed dietary information by using a 131-item, semiquan-
titative food frequency questionnaire (FFQ), administered every 4
years. The reproducibility and validity of these FFQs are high when
compared with multiple 1-week diet records and biochemical
markers.18 –20
We calculated a summary dietary score based on the Alternate
Healthy Eating Index (AHEI).21 The AHEI is a modification of the
Healthy Eating Index (HEI), created by the US Department of
Agriculture to assess how well the US population met dietary
recommendations based on the Food Guide Pyramid and the Dietary
Guidelines for Americans.22 The AHEI, which targets foods and
nutrients associated with lower risk of chronic disease, better
predicts chronic disease risk than do other measures of diet quality,
including the HEI.21,23 Although alcohol was part of the original
AHEI, for the present study we considered it a separate lifestyle
Downloaded from http://ahajournals.org by on March 15, 2024
factor. With the exception of multivitamin use, the AHEI compo-
nents were given a score ranging from 0 to 10, where 10 signified
optimal dietary behavior. The 7 specific components (criteria for
minimum, maximum scores) were percent energy from trans fat
(ⱖ4%, ⱕ0.5%), ratio of polyunsaturated:saturated fat (ⱕ0.1, ⱖ1),
and chicken plus fish:red meat (0, ⱖ4; a small percentage of
vegetarians were given a score of 10), daily servings of fruit (0, ⱖ4),
vegetables (0, ⱖ5), vegetable proteins (legumes, tofu, and soy
products) (0, ⱖ1), and grams of cereal fiber (0, ⱖ15). The eighth
component, multivitamin use for ⱖ5 years, was dichotomous, to
avoid overweighting this component (yes⫽7.5, no⫽2.5 points). Our
diet score ranged from 2.5 (worst) to 77.5 (best).
For each lifestyle factor (smoking, BMI, exercise, diet score, and
alcohol), we created a binary low-risk variable, where the men
received a 1 if they met the criteria for low risk and a 0 if otherwise.
The a priori definition of low risk was based on the current literature
and recommended guidelines but also on levels realistically obtain-
able within the general population. For smoking, we defined low risk
as not currently smoking. Because we wanted to consider only
modifiable factors, we included former smokers in our low-risk
category, as current smokers cannot attain the status of “never
smoker.” The risk of CHD among former smokers declines after
smoking cessation, approximating the risk of those who have never
smoked after 10 to 14 years.24 For exercise, at least 30 min/d of
moderate-to-vigorous intensity was considered low risk, on the basis
of current guidelines.25 Optimal body weight was defined as a BMI
of ⬍25 kg/m2, the standard World Health Organization cutoff for
healthy weight. We considered average daily alcohol intake of 5 to
30 g as low risk. This is consistent with guidelines for moderate
alcohol consumption,26 although higher amounts of alcohol intake
are associated with lower risk of CHD.27 For diet, low risk was
defined as a diet score in the top 40% of the cohort distribution, as
there are no recommendations established for the AHEI. The average
diet score among the men with low-risk diets was 50.3. An average
low-risk diet of a long-term multivitamin user would consist of
approximately 3 servings of vegetables, 2.5 servings of fruit, 0.5
servings of nuts, 9 g of cereal fiber, 1.8% of calories from trans fat,
2.5 servings of chicken and fish for 1 serving of red meat, and a
polyunsaturated:saturated fat ratio of 0.6.
We calculated a healthy lifestyle score by summing the total
number of lifestyle factors for which the men were at low risk. The
men could obtain a healthy lifestyle score from 0 (least healthy) to 5
(most healthy).
Outcome Ascertainment
The outcome for this analysis was incident CHD, defined as nonfatal
MI or fatal CHD, occurring between the return of the baseline
questionnaire in 1986 and January 31, 2002. Confirmed MIs were
defined according to World Health Organization criteria,28 and,
when available, cardiac-specific troponin levels were used. If an
individual was admitted to the hospital for an MI but medical records
were unavailable, the infarction was considered probable. Confirmed
deaths were those caused by MI, according to autopsy or hospital
records, or if CHD was listed as the cause of death and previous
evidence of CHD was obtained. Deaths were considered probable if
the cause of death was CHD without confirmation of previous CHD
or those listed as sudden deaths with no other potential cause. We
used both confirmed and probable cases, as results were similar
when we excluded probable cases (17% of cases).
Statistical Analysis
We used the cumulative average of the AHEI-based diet score from
repeated dietary assessments to represent long-term dietary informa-
tion and minimize within-person variation.29 For example, the diet
score from the 1986 FFQ was used to estimate CHD risk between
1986 and 1990, whereas an average of the 1986 and 1990 diet score
was used to predict CHD risk occurring between 1990 and 1994. The
average of the 1986, 1990, and 1994 diet scores was used to estimate
disease risk between 1994 and 1998, and so on. Because diagnosis of
diabetes, angina, hypertension, hypercholesterolemia, or revascular-
ization surgery may lead to changes in diet, we stopped updating
dietary information after new diagnoses of these outcomes during
follow-up. Nondietary factors were updated every 2 years.
For individuals missing information on any lifestyle factor, we
carried forward information from the previous questionnaire, when
available. Men with residual missing values were placed in the
high-risk category, to give the most conservative estimate. Less than
1% of values were missing for each lifestyle factor; among the
current smokers, ⬍2% of men were missing information on number
of cigarettes.
Each individual contributed person-time from the return of the
1986 questionnaire until the date of first coronary event, date of
diagnosis of cancer or stroke, death, or January 31, 2002, whichever
came first. Relative risks (RRs) and 95% confidence intervals (CIs)
were estimated by using Cox proportional hazards models adjusted
for age, calendar year, parental history of MI, history of hyperten-
sion, history of hypercholesterolemia, aspirin use, and antihyperten-
sive medication use. Further adjustment for lipid-lowering medica-
tions did not appreciably alter the results.
We calculated the population-attributable risk30 and 95% CI31 to
estimate the proportion of cases within the population that could
have been avoided had all the men adhered to the low-risk lifestyle
practices, assuming a causal relation between the low-risk lifestyle
practices and risk of CHD. To calculate the population-attributable
risk, we used Cox proportional hazards models to calculate relative
risks of CHD, comparing men at low risk in a specific combination
of lifestyle factors with the rest of the men in the population.32
To assess whether modifiable lifestyle factors were associated
with lower risk among men already undergoing drug therapy, we
examined the relation between healthy lifestyle score and risk of
CHD separately among subgroups of users and nonusers of lipid-
lowering or antihypertensive medications. We defined medication
use as current use, which was updated every 2 years.
We estimated changes in lifestyle and risk of CHD by modeling
the difference between the attained healthy lifestyle score at
follow-up and the healthy lifestyle score at baseline, controlling for
baseline score. For this analysis, we included only men who
 Chiuve et al Lifestyle Factors and Primary Prevention of CHD 163

Figure 1. Relative risk of coronary heart disease by healthy life-

style score. Low risk for each lifestyle factor was defined as not
currently smoking, BMI ⬍25 kg/m2, exercise of moderate/vigor-
ous intensity for at least 30 min/d, diet in the top 40% of AHEI-
based diet score distribution, and 5 to 30 g/d alcohol consump-
tion. Relative risks were adjusted for age, family history of MI
before age of 60, aspirin use, use of antihypertensive medica-
tion, baseline hypercholesterolemia, and baseline hypertension.
P for trend, ⬍0.0001.

completed the baseline questionnaire and at least one questionnaire

during the follow-up period (n⫽33 759).
The authors had full access to the data and take responsibility for
its integrity. All authors have read and agreed to the manuscript as
written.
Downloaded from http://ahajournals.org by on March 15, 2024

Results
After 16 years of follow-up, we documented 2183 incident
coronary events. The frequencies of each lifestyle factor
within this population are shown in Table 1. For each lifestyle
factor, we observed an inverse association with risk of CHD,
which remained significant when all 5 lifestyle factors were
included in the same model (Table 1). When categorized as a
dichotomous variable, being at low risk for each lifestyle
factor was still significantly and independently associated
with lower risk.
Overall, the healthy lifestyle score was significantly in-
versely associated with risk of CHD (P for trend, ⬍0.0001)
(Figure 1). Men at low risk for ⱖ1 lifestyle factor had a
significantly lower risk of CHD, compared with men at low
risk for none of the 5 factors. Men at low risk for all 5 factors
had the lowest risk.
Men in this population reported use of lipid-lowering or
antihypertensive medication use for 21% of the person-time
during follow-up. Among these medication users (and also
among nonusers), the healthy lifestyle score was significantly
inversely associated with risk of CHD (Figure 2). Results
were not appreciably different when we excluded men who
were diagnosed with hypertension or hypercholesterolemia
during follow-up but reported no medication use (data not
shown).
We calculated the population-attributable risk for men who
adhered to a combination of low-risk lifestyle practices
(Table 2). Men in the low-risk group for all 5 lifestyle
practices, only 4% of the population, had an RR of 0.37 (95%
Figure 2. Relative risk of CHD among reported antihypertensive
and lipid-lowering medication users (A) and nonusers (B) by
healthy lifestyle score. P for trend, ⬍0.0001 for both users and
nonusers of medication. Low risk for each lifestyle factor was
defined as not currently smoking, BMI ⬍25 kg/m2, exercise of
moderate/vigorous intensity for at least 30 min/d, diet in the top
40% of AHEI-based diet score distribution, and 5 to 30 g/d
alcohol consumption. Relative risks were adjusted for age, fam-
ily history of MI before age of 60, aspirin use, baseline hyper-
cholesterolemia, and baseline hypertension.
CI: 0.26, 0.53), compared with the remaining men in the
population. This translates to a population-attributable risk of
62% (95% CI: 49%, 74%), suggesting that a majority of
coronary disease in this population may be attributed to poor
adherence to a healthy lifestyle.
Among medication users, the population-attributable risk
for adhering to all 5 low-risk lifestyle practices was 57%
(95% CI: 32%, 79%) (Table 3). We found similar associa-
tions among antihypertensive and lipid-lowering medications
users separately albeit with wider confidence intervals. The
population-attributable risk for adhering to all 5 low-risk
lifestyle practices was much higher among middle-aged men
(⬍65 years old) (population-attributable risk: 79%; 95% CI:
61%, 90%) than among men 65 years or older (population-
attributable risk: 47%; 95% CI: 27%, 68%) (Table 3).
Because of the long follow-up period and the repeated
assessment of lifestyle characteristics over time, we were able
 164 Circulation July 11, 2006

TABLE 2. Risk of CHD According to Different Combinations of

Low-Risk Lifestyle Factors
No. of RR % Population-Attributable
Low-Risk Combination Frequency Cases (95% CI)* Risk (95% CI)†
Combination 1 14% 205 0.65 (0.57–0.76) 31 (23–41)
Not currently smoking
Diet score top 40%‡
Exercise ⱖ30 min/d
Combination 2 8% 84 0.46 (0.37–0.57) 52 (42–62)
Not currently smoking
Diet score top 40%
Exercise ⱖ30 min/d
BMI ⬍25 kg/m2
Combination 3 4% 31 0.37 (0.26–0.53) 62 (49–74)
Not currently smoking
Diet score top 40%
Exercise ⱖ30 min/d
BMI ⬍25 kg/m2
Moderate alcohol (5–30 g/d)
*RRs for men at low-risk for all listed lifestyle factors compared with the rest of the population,
adjusted for age, family history of myocardial infarction before age of 60, aspirin use, use of
antihypertensive medication, baseline hypercholesterolemia, baseline hypertension, and other
lifestyle factors. CI signifies confidence intervals.
†Population-attributable risk is the proportion of cases within the population that may have been
avoided had all men been at low risk for the lifestyle factors, adjusted for age, family history of
myocardial infarction before age of 60, aspirin use, use of antihypertensive medication, baseline
hypercholesterolemia, baseline hypertension, and other lifestyle factors. Men with missing values
were considered to be at high risk.
Downloaded from http://ahajournals.org by on March 15, 2024

‡A diet score of ⱖ42.4 represents the top 40%. The AHEI-based diet score is based on intake of
trans fat, ratio of polyunsaturated:saturated fat, ratio of chicken and fish:red meat (in grams), fruits,
vegetables, vegetable protein, cereal fiber, and multivitamin use.

to examine the CHD risk associated with changes in the
healthy lifestyle score. Among the men included in the
change in lifestyle analysis, there were 1583 incident coro-
nary events. Men who adopted at least 2 new healthy
characteristics during follow-up had a relative risk of 0.73
(95% CI: 0.57, 0.93) compared with men who did not change,
controlling for the number at baseline (Table 4). On the other
hand, men who reduced their healthy lifestyle score by 2 or
more factors had a relative risk of 1.48 (95% CI: 1.15, 1.88),
compared with men who did not change.
Discussion
In this population of male health professionals, 62% of all
coronary events may have been avoided had all men adhered
to a low-risk lifestyle of not smoking, exercising regularly,
eating prudently, consuming alcohol in moderation, and
maintaining a healthy weight. Equally important, we found
that this combination of healthy lifestyle characteristics was
strongly inversely associated with risk even among men
taking medication for coronary risk factors. Further, we found
that middle-aged and older men who adopted additional
healthy lifestyle practices over time further lowered their risk
of coronary disease.
The therapeutic benefits of antihypertensive and lipid-
lowering drugs are well documented,2,4 but coronary disease
remains elevated in this population. The addition of healthy
behaviors, such as a prudent diet and regular exercise, to
either antihypertensive or lipid-lowering drug therapy in
other populations reduced risk factors, such as systolic and
diastolic blood pressure33,34 and low-density lipoprotein cho-
lesterol,35 as well as the inflammatory biomarker C-reactive
protein,36 compared with drug therapy alone.
In our cohort, the population-attributable risk for men at
low risk for all 5 lifestyle factors was 57% among the users
of cardiovascular medications. This implies that more than
half of the cases of CHD among the medication users in
this population may have been avoided by adherence to
low-risk lifestyle practices, in addition to the benefits seen
from medication use. Cardiovascular medications should
be used as an adjunct to, not just a replacement for, healthy
lifestyle practices, especially in the setting of primary
prevention.
This study shows the extent to which healthy lifestyle
changes may lower the risk of CHD, even during middle age
or later in life. We probably underestimated the true benefit of
healthy changes, as the men who were the healthiest (those
with 4 or 5 low-risk lifestyle factors) could not increase their
score by 2 factors. Furthermore, we could not capture the
benefit among men who met the threshold for low risk but
continued to improve their lifestyle. This was an observa-
tional study, not a clinical trial; thus, these men made changes
of their own free will. Only 4% of the men adopted all healthy
 Chiuve et al Lifestyle Factors and Primary Prevention of CHD 165

TABLE 3. Relative Risks and Population-Attributable Risks of CHD Among Men With 5 Low-Risk Lifestyle
Factors* According to Medication Use and Age
No. of No. of Cases % All 5 RR % Population-Attributable
Subgroups (% Frequency) Cases All 5 Factors Factors (95% CI)† Risk (95% CI)‡
Medication use§
No (79%) 1404 20 4 0.34 (0.22–0.53) 66 (49–79)
Yes (21%) 779 11 4 0.42 (0.23–0.77) 57 (32–79)
Lipid-lowering medications (27%)¶ 165 3 5 0.31 (0.07–1.30) 68 (21–94)
Antihypertensive medications (84%)¶ 699 10 3 0.45 (0.24–0.85) 54 (27–79)
Age**
⬍65 years old (71%) 1023 8 4 0.20 (0.10–0.40) 79 (61–90)
⬎65 years old (29%) 1160 23 4 0.52 (0.34–0.79) 47 (27–68)
*Low risk for each lifestyle factor was defined as not currently smoking, BMI ⬍25 kg/m2, exercise moderate/vigorous intensity for
30 min/d, diet in the top 40% of AHEI-based diet score distribution, and 5–30 g/d alcohol consumption.
†RRs adjusted for age, family history of myocardial infarction before age of 60, aspirin use, baseline hypercholesterolemia, and
baseline hypertension. CI signifies confidence intervals.
‡Population-attributable risk is the proportion of cases within the population that may have been avoided had all men adhered to
a low-risk lifestyle, adjusted for age, family history of myocardial infarction before age of 60, aspirin use, baseline hypercholester-
olemia, and baseline hypertension. Men with missing values for lifestyle factors were considered to be at high risk.
§Reported use of lipid-lowering or antihypertensive medication.
¶Percentage of the men reporting use of specific medications among those who reported lipid-lowering or antihypertensive
medication use.
**Also adjusted for antihypertensive medication use.

practices on their own; however, whether a greater number of
these men would follow a low-risk regimen if given as a
direct intervention cannot be determined from our data.
The population-attributable risk resulting from low-risk
lifestyle practices within this population of men was lower
Downloaded from http://ahajournals.org by on March 15, 2024
Overall, these health professionals were at lower risk of
developing CHD than men in the general population. The rate
of incident CHD in this population (2.86 events/1000 person-
years) was almost half of the age-standardized rate seen in the
Atherosclerosis Risk in Communities (ARIC) study popula-

than expected. However, when we excluded men ⬎65 years tion (5.53 events/1000 person-years39), the participants of
of age, the results were similar to those seen among middle- which were selected to be representative of adults in 4
aged women from the Nurses’ Health Study13 as well as from communities across the United States.40 Summary results
studies of CHD mortality conducted among younger and from the National Health Interview Survey41– 44 indicate that
middle-aged men and women, using clinical definitions of fewer men in the United States ⱖ45 years of age met our
low risk.37,38 Even among older men (ⱖ65 years), healthy low-risk criteria for exercise (16% versus 29% in our cohort),
lifestyle factors were associated with significantly lower risk. optimal BMI (37% versus 43%), absence of current smoking
In an older Mediterranean population (70 to 90 years), risk of (84% versus 91%), and moderate alcohol consumption (19%
CHD mortality was 65% lower among participants who versus 40%). Nationally representative data needed to calcu-
committed to 4 healthy lifestyle choices.14 late the AHEI-based diet score are not available. The average
HEI score of 68.3, within this cohort,45 is slightly higher than
TABLE 4. Multivariate Relative Risk of CHD According to the mean HEI score of 65.2 among US men 51 years or
Changes in Healthy Lifestyle Score* older.46 Even though the men in our cohort were healthier
Change in Lifestyle Frequency, No. of RR than men in the United States, only 4% of men met the
Score† % Cases (95%CI) low-risk criteria for all 5 characteristics. We still conclude
Decrease by ⱖ2 5 81 1.48 (1.15–1.88) that a majority of cases of CHD among this low-risk
population of men may have been prevented through a
Decrease by 1 21 327 1.01 (0.97–1.28)
healthy lifestyle.
No change 52 797 1.00 (ref)
Although the accuracy of self-reported data within this
Increase by 1 17 302 0.91 (0.79–1.05)
population of motivated and educated health professionals
Increase by ⱖ2 4 76 0.73 (0.57–0.93) has been well documented,16 –19 measurement error in self-
P value for trend ⬍0.0001 reported variables is inevitable. Because of the prospective
*Among men who completed the baseline questionnaire (1986) and at least design of the study, this misclassification should be nondif-
one follow-up questionnaire (1988 –1998); all models are adjusted for total No. ferential with respect to disease status and would attenuate
of healthy lifestyle factors in 1986, age, family history of MI before age of 60, the true relative risk. A randomized clinical trial is ideal to
aspirin use, use of antihypertensive medication, baseline hypercholesterolemia,
establish causality of these lifestyle factors on risk of CHD.
and baseline hypertension. CI denotes confidence interval.
†Low risk for each lifestyle factor was defined as not currently smoking, BMI For some of these lifestyle factors, such as smoking and
⬍25 kg/m2, exercise moderate/vigorous intensity for 30 min/d, diet in the top alcohol consumption, a clinical trial may not be ethical.
40% of AHEI-based diet score distribution, and 5–30 g/d alcohol consumption. Short-term trials on diet, physical activity, and weight loss
 166 Circulation July 11, 2006
have shown substantial reduction in coronary risk factors as
well as coronary events.47,48 In our analysis, we estimated the
impact of multiple lifestyle factors simultaneously, which
would be difficult if not impossible to study in a trial with 16
years of follow-up. The observational design and repeated
measures of diet and lifestyle allowed us to assess the
consequences of changes in multiple lifestyle factors, which
generally occur in free-living populations.
In conclusion, a healthy lifestyle plays an important role in
the primary prevention of CHD in middle-aged and older
men, even among men on antihypertensive or lipid-lowering
medication. A healthy lifestyle can be an effective, nonphar-
macological approach to reducing coronary heart disease
among men.
Acknowledgments
The authors thank the participants of the HPFS for their continued
cooperation and participation and Drs Walter Willett and Meir
Stampfer for their comments and suggestions in the preparation of
this manuscript. We are indebted to Ellen Hertzmark for her
statistical support and Mira Kaufman and Betsy Frost-Hawes for
their expert help.
Sources of Funding
This study was supported by grant HL35464 from the National
Institutes of Health and an Established Investigator Award from the
American Heart Association. S. Chiuve was supported in part by an
institutional training grant (HL07575) from the National Heart,
Lung, and Blood Institute and in part by a Jetson Lincoln Fellowship.
Disclosures
Downloaded from http://ahajournals.org by on March 15, 2024
E. Rimm has received honoraria for several academic talks spon-
sored by the nonprofit arm of industry-related organizations (the
Distilled Spirits Council and the National Beer Wholesalers Asso-
ciation). M. McCullough has received honoraria for articles on diet
and cancer in Oncogene and for a lecture on flavonoids and
cardiovascular disease given at a cardiovascular conference in
Switzerland. The remaining authors report no disclosures.
References
1. Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, Garside DB,
Wilson PW. Major risk factors as antecedents of fatal and nonfatal
coronary heart disease events. JAMA. 2003;290:891– 897.
2. Turnbull F. Effects of different blood-pressure-lowering regimens on
major cardiovascular events: results of prospectively-designed overviews
of randomised trials. Lancet. 2003;362:1527–1535.
3. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J,
Orazem J, Magorien RD, O’Shaughnessy C, Ganz P. Statin therapy, LDL
cholesterol, C-reactive protein, and coronary artery disease. N Engl
J Med. 2005;352:29 –38.
4. Wilt TJ, Bloomfield HE, MacDonald R, Nelson D, Rutks I, Ho M, Larsen
G, McCall A, Pineros S, Sales A. Effectiveness of statin therapy in adults
with coronary heart disease. Arch Intern Med. 2004;164:1427–1436.
5. Lamon-Fava S, Wilson PW, Schaefer EJ. Impact of body mass index on
coronary heart disease risk factors in men and women: the Framingham
Offspring Study. Arterioscler Thromb Vasc Biol. 1996;16:1509 –1515.
6. Paffenbarger RS, Lee IM. Exercise and fitness. In: Manson J, Ridker PM,
Gaziano M, Hennekens CH, eds. Prevention of Myocardial Infarction.
New York, NY: Oxford University Press; 1996:172–202.
7. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D,
Obarzanek E, Conlin PR, Miller ER, Simons-Morton D, Karanja N, Lin
PH. Effects on blood pressure of reduced dietary sodium and the dietary
approaches to stop hypertension (DASH) diet. N Engl J Med. 2001;
344:3–10.
8. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate
alcohol intake and lower risk of coronary heart disease: meta-analysis of
effects on lipids and haemostatic factors. BMJ. 1999;319:1523–1528.
9. Frohlich M, Sund M, Lowel H, Imhof A, Hoffmeister A, Koenig W.
Independent association of various smoking characteristics with markers
of systemic inflammation in men: results from a representative sample of
the general population (MONICA Augsburg Survey 1994/95). Eur
Heart J. 2003;24:1365–1372.
10. Suzuki K, Ito Y, Ochiai J, Kusuhara Y, Hashimoto S, Tokudome S,
Kojima M, Wakai K, Toyoshima H, Tamakoshi K, Watanabe Y,
Hayakawa N, Maruta M, Watanabe M, Kato K, Ohta Y, Tamakoshi A;
Journal of the American College of Cardiology Study Group. Rela-
tionship between obesity and serum markers of oxidative stress and
inflammation in Japanese. Asian Pac J Cancer Prev. 2003;4:259 –266.
11. Hu FB, Willett WC. Optimal diets for prevention of coronary heart
disease. JAMA. 2002;288:2569 –2578.
12. Eyre H, Kahn R, Robertson RM, Clark NG, Doyle C, Hong Y, Gansler T,
Glynn T, Smith RA, Taubert K, Thun MJ. Preventing cancer, cardiovas-
cular disease, and diabetes: a common agenda for the American Cancer
Society, the American Diabetes Association, and the American Heart
Association. Circulation. 2004;109:3244 –3255.
13. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary
prevention of coronary heart disease in women through diet and lifestyle.
N Engl J Med. 2000;343:16 –22.
14. Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O,
Menotti A, van Staveren WA. Mediterranean diet, lifestyle factors, and
10-year mortality in elderly European men and women: the HALE proj-
ect. JAMA. 2004;292:1433–1439.
15. Al-Delaimy WK, Rimm E, Willett WC, Stampfer MJ, Hu FB. A pro-
spective study of calcium intake from diet and supplements and risk of
ischemic heart disease among men. Am J Clin Nutr. 2003;77:814 – 818.
16. Rimm EB, Stampfer MJ, Colditz GA, Chute CG, Litin LB, Willett WC.
Validity of self-reported waist and hip circumferences in men and
women. Epidemiology. 1990;1:466 – 473.
17. Chasan-Taber S, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA,
Giovannucci E, Ascherio A, Willett WC. Reproducibility and validity of
a self-administered physical activity questionnaire for male health pro-
fessionals. Epidemiology. 1996;7:81– 86.
18. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett
WC. Reproducibility and validity of an expanded self-administered semi-
quantitative food frequency questionnaire among male health profes-
sionals. Am J Epidemiol. 1992;135:1114 –1126.
19. Feskanich D, Rimm EB, Giovannucci EL, Colditz GA, Stampfer MJ,
Litin LB, Willett WC. Reproducibility and validity of food intake mea-
surements from a semiquantitative food frequency questionnaire. J Am
Diet Assoc. 1993;93:790 –796.
20. Giovannucci E, Colditz G, Stampfer MJ, Rimm EB, Litin L, Sampson L,
Willett WC. The assessment of alcohol consumption by a simple self-
administered questionnaire. Am J Epidemiol. 1991;133:810 – 817.
21. McCullough M, Feskanich D, Stampfer MJ, Giovannucci EL, Rimm EB,
Hu FB, Spiegelman D, Hunter DJ, Colditz GA, Willett WC. Diet quality
and major chronic disease risk in men and women: moving toward
improved dietary guidance. Am J Clin Nutr. 2002;76:1261–1271.
22. Kennedy ET, Ohls J, Carlson S, Fleming K. The Healthy Eating Index:
design and applications. J Am Diet Assoc. 1995;95:1103–1108.
23. Fung TT, Hu FB, McCullough ML, Newby PK, Willett WC, Holmes
MD. Diet quality is associated with the risk of estrogen receptor-negative
breast cancer in postmenopausal women. J Nutr. 2006;136:466 – 472.
24. Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Manson JE, Rosner B,
Speizer FE, Hennekens CH. Smoking cessation and time course of
decreased risks of coronary heart disease in middle-aged women. Arch
Intern Med. 1994;154:169 –175.
25. Thompson P, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH,
Berra K, Blair SN, Costa F, Franklin B, Fletcher GF, Gordon NF, Pate
RR, Rodriguez BL, Yancey AK, Wenger NK. Exercise and physical
activity in the prevention and treatment of atherosclerotic cardiovascular
disease: a statement from the council on clinical cardiology (subcom-
mittee on exercise, rehabilitation, and prevention) and the council on
nutrition, physical activity, and metabolism (subcommittee on physical
activity). Arterioscler Thromb. 2003;23:E42–E49.
26. US Department of Agriculture, US Department of Health and Human
Services. Nutrition and Your Health: Dietary Guidelines for Americans,
Fifth Edition. Washington, DC: US Government Printing Office; 2000.
27. Rimm EB, Giovannucci EL, Willett WC, Colditz GA, Ascherio A,
Rosner B, Stampfer MJ. Prospective study of alcohol consumption and
risk of coronary disease in men. Lancet. 1991;338:464 – 468.
28. Rose GA, Blackburn H. Cardiovascular Survey Methods. WHO
Monograph Series No. 58. Geneva: World Health Organization; 1982.
 Chiuve et al Lifestyle Factors and Primary Prevention of CHD 167

29. Hu FB, Stampfer MJ, Rimm E, Ascherio A, Rosner BA, Spiegelman D,
Willett WC. Dietary fat and coronary heart disease: a comparison of
approaches for adjusting total energy intake and modeling repeated
dietary measurements. Am J Epidemiol. 1999;149:531–540.
30. Bruzzi P, Green SB, Byar DP, Brinton LA, Schairer C. Estimating the
population attributable risk for multiple risk factors using case-control
data. Am J Epidemiol. 1985;122:904 –914.
31. Platz EA, Willett WC, Colditz GA, Rimm EB, Spiegelman D, Giovannucci
E. Proportion of colon cancer risk that might be preventable in a cohort of
middle-aged US men. Cancer Causes Control. 2000;11:579–588.
32. Wacholder S, Benichou J, Heineman EF, Hartge P, Hoover RN. Attrib-
utable risk: advantages of a broad definition of exposure. Am J Epidemiol.
1994;140:303–309.
33. Conlin PR, Erlinger TP, Bohannon A, Miller ER III, Appel LJ, Svetkey
LP, Moore TJ. The DASH diet enhances the blood pressure response to
losartan in hypertensive patients. Am J Hypertens. 2003;16:337–342.
34. Miller ER III, Erlinger TP, Young DR, Jehn M, Charleston J, Rhodes D,
Wasan SK, Appel LJ. Results of the Diet, Exercise, and Weight Loss
Intervention Trial (DEW-IT). Hypertension. 2002;40:612– 618.
35. Hunninghake DB, Stein EA, Dujovne CA, Harris WS, Feldman EB,
Miller VT, Tobert JA, Laskarzewski PM, Quiter E, Held J, Taylor AM,
Hopper S, Leonard SB, Brewer BK. The efficacy of intensive dietary
therapy alone or combined with lovastatin in outpatients with hypercho-
lesterolemia. N Engl J Med. 1993;328:1231–1239.
36. Milani RV, Lavie CJ, Mehra MR. Reduction in C-reactive protein
through cardiac rehabilitation and exercise training. J Am Coll Cardiol.
2004;43:1056 –1061.
37. Stamler J, Stamler R, Neaton JD, Wentworth D, Daviglus ML, Garside D,
Dyer AR, Liu K, Greenland P. Low risk-factor profile and long-term
cardiovascular and noncardiovascular mortality and life expectancy:
findings for 5 large cohorts of young adult and middle-aged men and
women. JAMA. 1999;282:2012–2018.
38. Daviglus ML, Stamler J, Pirzada A, Yan LL, Garside DB, Liu K, Wang
R, Dyer AR, Lloyd-Jones DM, Greenland P. Favorable cardiovascular
risk profile in young women and long-term risk of cardiovascular and
all-cause mortality. JAMA. 2004;292:1588 –1592.
Downloaded from http://ahajournals.org by on March 15, 2024
39. Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-
containing compounds and betaine in common foods. J Nutr. 2003;133:
1302–1307.
40. Houston DK, Stevens J, Cai J, Haines PS. Dairy, fruit, and vegetable
intakes and functional limitations and disability in a biracial cohort: the
Atherosclerosis Risk in Communities Study. Am J Clin Nutr. 2005;81:
515–522.
41. Schoenborn C, Adams P. Alcohol Use Among Adults: United States,
1997–1998. Advance Data From Vital and Health Statistics; No. 324.
Hyattsville, Md: National Center for Health Statistics; 2002.
42. Schoenborn C, Adams P, Barnes P. Body Weight of Adults: United States,
1997–1998. Advance Data From Vital and Health Statistics; No 330.
Hyattsville, Md: National Center for Health Statistics; 2002.
43. Schoenborn C, Barnes P. Leisure-time Physical Activity Among Adults:
United States, 1997–1998. Advance Data From Vital and Health Sta-
tistics; No. 325. Hyattsville, Md: National Center for Health Statistics;
2002.
44. Schoenborn C, Vickerie J, Barnes P. Cigarette Smoking Behavior of
Adults: United States, 1997–1998. Advance Data From Vital and Health
Statistics; No. 331. Hyattsville, Md: National Center for Health Statistics;
2003.
45. McCullough ML, Feskanich D, Rimm EB, Giovannucci E, Ascherio A,
Variyam JN, Spiegelmen D, Stampfer MJ, Willett WC. Adherence to the
Dietary Guidelines for Americans and risk of major chronic disease in
men. Am J Clin Nutr. 2000;72:1223–1231.
46. Basiotis P, Carlson A, Gerrior S, Juan W, Lino M. The Healthy Eating
Index: 1999 –2000. Washington, DC: US Department of Agriculture,
Center for Nutrition Policy and Promotion, CNPP-12; 2002.
47. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N.
Mediterranean diet, traditional risk factors, and the rate of cardiovascular
complications after myocardial infarction: final report of the Lyon Diet
Heart Study. Circulation. 1999;99:779 –785.
48. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer
PJ, Stevens VJ, Vollmer WM, Lin PH, Svetkey LP, Stedman SW, Young
DR. Effects of comprehensive lifestyle modification on blood pressure
control: main results of the PREMIER clinical trial. JAMA. 2003;289:
2083–2093.

CLINICAL PERSPECTIVE
Many healthy lifestyle choices, including eating well, exercising regularly, managing weight, and not smoking, may
individually lower the risk of coronary heart disease, but the impact of a combination of healthy choices may provide even
greater benefit. We monitored a population of middle-aged and older male health professionals for 16 years to assess the
effect of following a low-risk lifestyle (defined as not smoking, exercising daily, eating prudently, consuming alcohol in
moderation, and maintaining a healthy weight) on the risk of coronary heart disease. A majority of coronary events in this
population of men may have been prevented through better adherence to a low-risk lifestyle. This low-risk lifestyle was
also associated with lower risk of coronary heart disease among men taking antihypertensive and lipid-lowering
medications. Finally, we found that adopting additional low-risk lifestyle practices over time was associated with lower risk
of coronary heart disease. Our results suggest that a low-risk lifestyle may be an effective strategy to lower the risk of
coronary heart disease among middle-aged and older men, and even among men already reducing cardiovascular risk by
taking antihypertensive and lipid-lowering medications. Furthermore, beneficial changes in lifestyle habits even during
middle age or later in life may also lower the risk of coronary disease.