Exercise Type and Intensity in Relation to Coronary Heart Disease in Men FREE

Multiple epidemiologic studies have shown an inverse relationship between physical activity and risk of coronary heart disease (CHD). Sedentary individuals have almost twice the risk of CHD as those performing high-intensity exercise.^1- 2 However, the optimal level of exercise for preventing CHD is unclear. In some studies, the reduction in risk from increased levels of activity appeared to be linear up to a certain level above which there was no further benefit; in others, the effect was restricted to the highest categories of total energy expenditure.³ In addition, the effect of walking is still under debate and the effect of weight training is unknown. In this study, we assessed the association between the amount, types, and intensity of exercise in relation to risk of CHD in a large cohort of men.

The Health Professionals' Follow-up Study (HPFS) began in 1986 when 51 529 US health professionals (dentists, optometrists, pharmacists, podiatrists, osteopaths, and veterinarians), aged 40 through 75 years, answered a detailed questionnaire that included a comprehensive diet survey, lifestyle assessment (including questions on leisure-time physical activity), and medical history. Follow-up questionnaires were sent in 1988, 1990, 1992, 1994, 1996, and 1998 to update information on potential risk factors and to identify newly diagnosed cases of CHD and other illnesses. We excluded from the current analysis men with a diagnosis of cardiovascular disease (myocardial infarction [MI], angina, and/or coronary revascularization and stroke) and cancer other than nonmelanoma skin cancer prior to 1986. Men with a CHD event during the follow-up were excluded from analyses in the subsequent intervals. Men who reported difficulty in climbing stairs or walking were excluded from analysis at each time point starting from 1988. Thus, 44 452 men remained for our analyses.

Leisure-time physical activity was assessed every 2 years between 1986 and 1996, using the question: "During the past year what was your average time per week spent at each activity?" The average weekly time spent on walking or hiking outdoors, jogging (<6 mph), running (≥6 mph), bicycling, lap swimming, tennis, squash or racquetball, calisthenics, or rowing was recorded beginning in 1986. Heavy outdoor work was added in 1988 and weight training in 1990. Walking pace, categorized as casual (≤2 mph), normal (2-2.9 mph), brisk (3-3.9 mph), or striding (≥4 mph), was also recorded. The time spent at each activity in hours per week was multiplied by its typical energy expenditure, expressed in metabolic equivalent tasks (METs),⁴ then summed over all activities, to yield a MET-hour score. One MET, the energy expended by sitting quietly, is equivalent to 3.5 mL of oxygen uptake per kilogram of body weight per minute, or to 1 kcal/kg of body weight per hour. Vigorous activities were defined as those requiring 6 METs or more: jogging, running, bicycling, lap swimming, tennis, squash or racquetball, and rowing. Nonvigorous activities (<6 METs) include walking, heavy outdoor work, and weight training.

We created a measure of average exercise intensity for each individual by dividing the total weekly volume of exercise in MET-hours by the total weekly hours spent in physical activity.

The validity and reproducibility of the physical activity questionnaire were assessed in 1991 when 238 participants in the HPFS completed a 1-week activity diary at 4 periods corresponding to different seasons throughout a year.⁵ The questionnaire showed good time integration when levels of activity were compared with the average of the 4 single-week physical activity diaries administered during the 4 seasons. The correlation between scores of physical activity from the diaries and from the questionnaire was 0.65 for total physical activity and 0.58 for vigorous activity. The correlation between questionnaire-derived vigorous activity and resting pulse rate was –0.45; the correlation between vigorous activity and pulse rate after a self-administered step test was −0.41.⁵ In a subsample of participants in the HPFS (n = 466), high-density lipoprotein cholesterol levels increased by 2.4 mg/dL (0.06 mmol/L) for each increment of 20 MET-h/wk (P<.001).⁶

Combined end points for the analysis were fatal CHD and nonfatal MI occurring between the return of the 1986 questionnaire and January 31, 1998. Self-reported MIs were confirmed by a review of medical records based on World Health Organization criteria that included characteristic symptoms with either typical electrocardiographic changes or elevations of cardiac enzymes. Probable cases of MI (no available records but confirmed by hospitalization and information from telephone interview/letter) were also included in the analysis after ensuring that results were not appreciably different from those including definite cases alone.

Deaths were reported by next of kin, work associates, and postal authorities. In case of persistent nonresponse, the National Death Index was used to identify deceased cohort members. Fatal CHD was confirmed by reviewing medical records or autopsy reports with the permission of the next of kin. The cause listed on the death certificate was not sufficient alone to confirm a coronary death. Sudden deaths (ie, deaths within 1 hour of symptom onset in men without known disease that could explain death) were included in the fatal CHD category. For subjects with multiple end points, follow-up ended with onset of the first event.

Person-months of follow-up accumulated starting with the date of return of the 1986 questionnaire until occurrence of a CHD end point, death, or the end of the study period (January 31, 1998), whichever came first.

In our main analyses, we used the cumulative average of physical activity levels from all available questionnaires up to the start of each 2-year follow-up interval.⁷ For example, the level of physical activity reported on the 1986 questionnaire was related to the incidence of CHD from 1986 through 1988, and the level of average activity reported on the 1986 and 1988 questionnaires was related to the incidence from 1988 through 1990. Additional analyses were performed using baseline levels of activity and simple updated levels of physical activity in which CHD was predicted only from the most recent questionnaire.

Participants were divided into quintiles of total volume of physical activity (total MET-hours), walking, and vigorous activity. We used informative increments for exercise intensity, walking pace, and specific sport activities. Tests for trend were calculated by assigning the median values to increasing categories of activity. Relative risks (RRs) were initially calculated adjusting for age. Cox proportional hazard models were then used to estimate RRs of CHD over each 2-year follow-up interval using the cumulative average of the reported levels of activity on prior questionnaires, adjusting for other potential confounders.⁸ We also analyzed cumulative, simple-updated, and baseline (1986) activity as categorical and continuous variables. We corrected RRs corresponding to increments of simple-updated and baseline physical activity using the method of Rosner et al.⁹

All multivariate models included the following covariates unless otherwise specified: alcohol intake (nondrinker, or consuming 0.1-4.9, 5-30, or >30 g/day), smoking (never, past, or currently smoking 1-14, 15-24, or ≥25 cigarettes/day), family history of MI, use of vitamin E supplements, history of diabetes, hypertension, and hypercholesterolemia at baseline, and quintiles of dietary intake of trans fatty acids, polyunsaturated fat, fiber, and folate. In secondary analyses we additionally controlled for body mass index (BMI; calculated as participant's weight in kilograms divided by the square of participant's height in meters and stratified into 3 categories: ≤25, 25-29.9, ≥30) to estimate how this potential intermediate factor would affect the RRs. The interaction between physical activity and obesity was assessed by the difference in –2 log likelihood between the model containing the interaction with obesity in 2 categories (BMI<30, BMI≥30) and the main effects model.

In a secondary analysis, we performed a propensity analysis¹⁰ in which we used logistic regression modeling to predict the highest as opposed to the lowest quintile of physical activity. Demographic, clinical, and dietary variables were included in the propensity model. We used the resulting propensity scores to match men from the 2 groups.

We examined physical activity in relation to other potential risk factors for CHD at baseline (Table 1). Physically more active men tended to have lower BMIs, lower intakes of total fat and saturated fat, higher intakes of fiber and alcohol, a higher prevalence of vitamin E supplement use, and a lower prevalence of smoking and hypertension.

During 475 755 person-years of follow-up, we documented 1700 new cases of CHD. The age-adjusted RRs across quintiles of total physical activity decreased monotonically and were modestly attenuated after adjustment for alcohol consumption, smoking, family history of MI before age 50 years, and nutrient intake (polyunsaturated fat, trans fatty acids, folic acid, fiber, and vitamin E supplements (Table 2). The association was further attenuated by additionally adjusting for baseline presence of hypertension, diabetes, and high cholesterol levels. The RR comparing extreme quintiles was 0.70 (95% confidence interval [CI], 0.59-0.82) (P<.001 for trend). When the same analysis was performed using simple updated and baseline physical activity, the corresponding RRs were 0.70 (95% CI, 0.59-0.82; P<.001 for trend) and 0.77 (95% CI, 0.66-0.91; P<.001 for trend). Adjustment for current BMI did not appreciably alter these results.

In the secondary analysis of propensity-matched men, those who were at the highest quintile of activity still had a reduced CHD risk compared with those in the lowest quintile (adjusted RR, 0.73; 95% CI, 0.60-0.88).

When physical activity was modeled as a continuous variable, every 50 MET-h/wk increase of cumulatively updated physical activity was associated with a 26% reduction in risk of CHD (RR, 0.74; 95% CI, 0.65-0.85). The corresponding RRs were 0.79 (95% CI, 0.71-0.88) for simple-updated activity and 0.77 (95% CI, 0.67-0.89) for baseline physical activity. The association was strengthened considerably after correction for measurement error (for simple update: RR, 0.45 [95% CI, 0.28-0.72]; for baseline physical activity: RR, 0.49 [95% CI, 0.30-0.81]).

When analyzed separately, exercise intensity (low = 1-4 METs; moderate = 4-6 METs; high = 6-12 METs) was related to reduced risk of CHD (Table 2). To assess if exercise intensity is related to CHD risk independent of exercise volume, we added the average intensity to the model containing the total volume of exercise. The multivariate RRs corresponding to moderate and high exercise intensity were 0.94 (95% CI, 0.83-1.04) and 0.83 (95% CI, 0.72-0.97), respectively, compared with that for low exercise intensity (P = .02 for trend). When assessed as a continuous variable, exercise intensity was related to a reduction in risk of 4% for each 1-MET increase independent of the total exercise volume.

In supplementary analyses, we assessed the association between changes in exercise intensity and risk of CHD. Compared with men who maintained a low intensity of exercise (<4 METs over 2-year intervals), men who maintained a high level of intensity (≥6 METs) had an RR of 0.72 (95% CI, 0.55-0.93), and those who increased intensity from low to high over time had an RR of 0.88 (95% CI, 0.70-1.12).

To address the possibility that men with subclinical disease reduced their amount of physical activity thereby biasing our results, we excluded men who drastically reduced their levels of activity (>20 MET-h/wk) from one questionnaire to the next. The RRs across quintiles of physical activity, adjusted for alcohol consumption, smoking, family history of MI before age 50 years, nutrient intake (polyunsaturated fat, trans fatty acids, folic acid, fiber, vitamin E supplements), and baseline presence of hypertension, high cholesterol levels, and diabetes, were 1.0, 0.91 (95% CI, 0.79-1.05), 0.87 (95% CI, 0.74-1.04), 0.81 (95% CI, 0.68-0.97), and 0.66 (95% CI, 0.56-0.80) (P<.001 for trend).

We evaluated the effect of physical activity across different subgroups defined by established risk factors for CHD (smoking status, alcohol consumption, obesity, presence of hypertension, family history of MI, age, and presence of hypercholesterolemia). Inverse associations were observed in all subgroups (smokers and nonsmokers, drinkers and nondrinkers, hypertensives and nonhypertensives, men with or without family history of MI before age 50 years, men younger than 65 or 65 years and older, men with or without high cholesterol levels, and men with BMIs lower than 25 or between 25 and 30, with the exception of obese men [BMI>30]). However, the interaction between obesity status and physical activity was not statistically significant (P = .09).

We further assessed the effect of activity type on CHD risk (Table 3). Running, jogging, rowing, and racquet sports (tennis and racquetball) were associated with reduced risk in age-adjusted analyses. In multivariate analyses including previously mentioned covariates plus all activities, running and rowing remained significant predictors of CHD. Running for one or more hours per week was associated with a 42% risk reduction (RR, 0.58; 95% CI, 0.44-0.77) and rowing for one or more hours per week was associated with an 18% risk reduction (RR, 0.82; 95% CI, 0.68-0.99) compared with men who did not engage in these activities. Cycling and swimming were not associated with risk.

We performed separate analyses on the effect of resistance training (weight training and strength machines) on risk of CHD starting from 1990 when these activities were first assessed. Compared with men who did not perform resistance training, the RRs for men who performed resistance training for less than 30 minutes or for 30 or more minutes per week were 0.83 (95% CI, 0.67-1.02) and 0.65 (95% CI, 0.51-0.81), respectively (P<.001 for trend). In multivariate analyses that also controlled for other types of physical activity, weight training for 30 minutes or more per week was associated with a significant 23% risk reduction (RR, 0.77; 95% CI, 0.61-0.98; P = .03 for trend) (Table 4).

Walking was the most frequent form of exercise in this cohort, with 58% of men reporting at least 1 hour of walking per week, while 48% reported at least 1 hour of weekly vigorous activity. When analyzing the effect of walking and walking parameters on CHD events, we restricted the study population to men who reported less than 1 hour of weekly vigorous exercise (<6 MET-h/wk) to minimize the confounding effect of high-intensity activity. Total walking volume was associated with reduced risk of CHD in age-adjusted analysis. In multivariate analysis, risk of CHD was reduced only for men in the highest quintile, corresponding to 14.75 MET-h/wk (approximately 3.5 h/wk or a half hour per week of brisk walking) or more, with an 18% reduction in risk of CHD (RR, 0.82; 95% CI, 0.67-1.00; P = .04 for trend) (Table 5). Walking pace was significantly associated with reduced risk in age-adjusted and multivariate models. When analyzed in the same multivariate model with walking MET-hours and compared with walking at an easy pace, the RRs corresponding to normal pace (2-3 mph), brisk pace (3-4 mph), and very brisk pace (≥4 mph) were 0.72 (95% CI, 0.54-0.94), 0.61 (95% CI, 0.45-0.81), and 0.51 (95% CI, 0.31-0.84), respectively (P<.001 for trend). Thus, walking pace is related to reduced CHD risk over and above the effect of walking volume. Time spent walking and walking MET-hours were not materially related to risk in analyses that controlled for walking pace.

In this prospective study, increased total physical activity was associated with reduced risk of CHD in a dose-dependent manner. This inverse association was not explained by other known coronary risk factors, including BMI. Exercise intensity was associated with an additional risk reduction. Running, weight training, and rowing were each associated with reduced risk. Walking pace was strongly related to reduced risk independent of walking MET-hours.

The strengths of the current study include the prospective design, the large size of the cohort, detailed information on exposure and covariates, the extensive follow-up time, the strict and uniform criteria for coronary events, and the relative homogeneity of socioeconomic status among subjects. Men with cancer and previous CHD at baseline, as well as men with physical impairment, were excluded from the main analyses. These exclusions are likely to have minimized potential bias related to preexisting disease. Furthermore, when we excluded men who greatly reduced their levels of physical activity in the last 2 years, we obtained similar results.

One limitation of our study was self-report of physical activity. Although our questionnaire was validated against diary and biomarkers, some misclassification is inevitable and random misclassification usually results in bias toward the null. Our results corrected for measurement error illustrated this point. Because of the observational nature of this study, we cannot completely rule out the possibility of residual and unmeasured confounding and cannot draw a causal relationship simply based on these data. However, the magnitude and consistency of the observed association, together with evidence from randomized trials on cardiovascular risk factors, strongly suggest protective effects of increasing physical activity against CHD.

When we analyzed specific activities such as swimming and cycling, our findings were limited by their low range of exposure. For example, only 2% of the cohort spent more than 1 h/wk swimming and only 7% spent more than 1 h/wk cycling. We also suspect that some participants performed these sports at lower than typical intensity (eg, 7 METs) or spent less than reported time in actual exercise.

Walking is the most common leisure activity among US men and women,¹¹ and it offers an alternative to high-intensity exercise in older populations. Current guidelines recommend 30 minutes of moderate-intensity activity on most, and preferably all, days of the week to prevent CHD and other chronic diseases.^12- 13 However, few studies have assessed the effect of moderate-intensity activity on risk of CHD. Some studies suggest that exercise must be vigorous to reduce CHD risk,^14- 16 while others show benefit from moderate ranges of total physical activity without further risk reduction from high levels of exercise.^17- 18 More recently, several studies have shown that increasing walking is associated with reduced incidence of coronary events. In a study among 1645 men and women aged 65 years or older, LaCroix et al¹⁹ observed that walking more than 4 h/wk was associated with lower risk of hospitalization for cardiovascular disease. In the Honolulu Heart Program,²⁰ walking less than 0.25 miles/d and 0.25 to 1.5 miles/d was associated with RRs of 2.3 (95% CI, 1.3-4.1) and 2.1 (95% CI, 1.2-3.6), respectively, compared with walking more than 1.5 miles/d. Manson et al²¹ also showed an inverse relationship between walking and the risk of CHD in the Nurses' Health Study. The multivariate RRs for walking, across quintiles of walking (≤0.5, 0.6-2.0, 2.1-3.8, 3.9-9.9 and ≥10 MET-hours/week), were 1.0, 0.78 (95% CI, 0.57-1.06), 0.88 (95% CI, 0.65-1.21), 0.70 (95% CI, 0.51-0.95), and 0.65 (95% CI, 0.47-0.91), respectively.

Other data show null or marginal results for the effect of walking on risk of CHD. In the Harvard Alumni Health Study,²² the trend of reduced CHD risk with increasing levels of walking was not significant. The authors attributed this result to a threshold effect, to the imprecise measurement of moderate activities, or to the difficulty in achieving high enough energy expenditure from moderate exercise. Also, in the Atherosclerosis Risk in Communities (ARIC) study,²³ frequent walking and the composite score of light activities were not associated with significant reductions in CHD risk.

We found an inverse relationship between walking and risk of CHD, but the association was significant only for the highest quintile in multivariate analysis. Also, walking pace was strongly associated with risk, suggesting that intensity of walking was more important than time spent. Only 2 previous studies, both in women, have investigated the independent association of walking pace with risk of CHD. In the Nurses' Health Study, walking pace was associated with CHD risk independent of the number of MET-hours spent walking,²¹ while in the Women's Health Study, time spent walking, but not walking pace, was related to risk.²⁴ It has also been reported that time spent walking may be less validly reported than usual walking pace.²⁴ Brisk and very brisk walking correspond to moderate exercise while walking at an easy or moderate pace represents low-intensity activity. Therefore, our findings lend some support to current recommendations for regular moderate exercise. Nonetheless, as shown in our analyses on total physical activity, performing the same number of MET-hours at a higher intensity is associated with further risk reduction. Hence, while moderate exercise like brisk walking is associated with reduced risk, greater risk reduction can be obtained with more intense exercise.

Mechanisms that are likely to explain the effect of physical activity on risk of CHD are multiple: direct action on the heart (increased myocardial oxygen supply, improved myocardial contraction, and electrical stability), increased high-density lipoprotein cholesterol levels, decreased low-density lipoprotein cholesterol levels, lowered blood pressure, decreased blood coagulability, and increased insulin sensitivity.²⁵ Moderate-intensity activities are associated with improvements in lipoprotein profile²⁶ and glucose control,²⁷ but frequent sessions to achieve a total high-energy expenditure may be required.²⁸ The additional risk reduction observed with higher intensity may be due to its effect on aerobic fitness, which is a strong predictor of CHD risk,^29- 30 and to energy balance.

A novel finding of our study was the significant reduction in CHD risk from resistive-type activities (ie, weight training and use of strength machines). Previous prospective studies have not directly assessed this relationship, but there is increasing evidence for the beneficial effects of strength training on CHD risk factors. Weight training increases fat-free mass and possibly resting metabolic rate,³¹ improves glycemic control,³² and may improve lipoprotein profile³³ and reduce hypertension.³⁴ Currently, strength training is recommended primarily for elderly persons and individuals with cardiovascular disease¹² as a means of improving overall musculoskeletal function. More research is needed to address whether inclusion of strength training recommendations for CHD prevention is warranted.

In conclusion, our study confirms a significant inverse dose-response relationship between total physical activity and risk of CHD. Additionally, we found that running, rowing, and weight training were related to reduced CHD risk. Intensity of physical activity was related to reduced risk, as reflected by the inverse association of walking pace and overall exercise intensity with CHD incidence. Thus, increasing total volume of activity, increasing intensity of aerobic exercise from low to moderate and from moderate to high, and adding weight training to the exercise program are among the most effective strategies to reduce the risk of CHD in men.