Frequency, Type, and Volume of Leisure-Time Physical Activity and Risk of Coronary Heart Disease in Young WomenClinical Perspective
Background: The inverse association between physical activity and coronary heart disease (CHD) risk has primarily been shown in studies of middle-aged and older adults. Evidence for the benefits of frequency, type, and volume of leisure-time physical activity in young women is limited.
Methods: We conducted a prospective analysis among 97 230 women aged 27 to 44 years at baseline in 1991. Leisure-time physical activity was assessed biennially by questionnaire. Cox proportional hazards models were used to examine the associations between physical activity frequency, type, and volume, and CHD risk.
Results: During 20 years of follow-up, we documented 544 incident CHD cases. In multivariable-adjusted models, the hazard ratio (95% confidence interval) of CHD comparing ≥30 with <1 metabolic equivalent of task-hours/wk of physical activity was 0.75 (0.57–0.99) (P, trend=0.01). Brisk walking alone was also associated with significantly lower CHD risk. Physical activity frequency was not associated with CHD risk when models also included overall activity volume. Finally, the association was not modified by body mass index (kg/m2) (P, interaction=0.70). Active women (≥30 metabolic equivalent of task-hours/wk) with body mass index<25 kg/m2 had 0.52 (95% confidence interval, 0.35–0.78) times the rate of CHD in comparison with women who were obese (body mass index≥30 kg/m2) and inactive (physical activity <1 metabolic equivalent of task-hours/wk).
Conclusions: These prospective data suggest that total volume of leisure-time physical activity is associated with lower risk of incident CHD among young women. In addition, this association was not modified by weight, emphasizing that it is important for normal weight, overweight, and obese women to be physically active.
Editorial, see p 300
Leisure-time physical activity is associated with an ≈30% lower risk of coronary heart disease (CHD) in women.1,2 The majority of studies, however, have been conducted in middle-aged and older populations because cardiovascular disease morbidity and mortality rates are low in women <55 years.3 Manson et al4 reported an inverse association between physical activity and cardiovascular disease in 3 separate age groups of women in the Women’s Health Initiative Observational Study, with the youngest group including women 50 to 59 years of age at baseline. However, evidence for the benefits of exercise for CHD in younger women is very limited.
Although CHD morbidity and mortality rates are low in younger women, the CHD mortality rate among US women aged 25 to 54 years has shown minimal improvement in the past 2 decades, in contrast to rates in older adults that have consistently declined.5 A potential explanation may be the increases in the prevalence of diabetes mellitus and obesity.6,7 In addition, younger women differ from older women with regard to their lipid profiles, and psychosocial risk factors, as well, which may potentially impact the association between physical activity and CHD.8,9 We have recently shown that a healthy lifestyle that includes a healthy diet, not smoking, normal weight, and at least 2.5 hours per week of moderate- to vigorous-intensity exercise is associated with substantially lower CHD risk in younger women.10 Nonetheless, physical activity is a complex exposure because of its many dimensions, intensity, type, and frequency, all of which may be important for the prevention of CHD in younger women.
The purpose of this study was to assess the relationship between the volume of total leisure-time physical activity (in metabolic equivalent of task [MET]-hours/wk) and CHD in young women, while also examining moderate- and vigorous-intensity activity separately. In addition, we examined whether frequency and type of exercise were important attributes to general measures of overall activity in relation to CHD risk. Because rises in obesity may be a reason for the lack of decline in CHD mortality rates in young women, we investigated whether high levels of physical activity could eliminate the adverse association between excess weight and CHD risk. Finally, given the high prevalence of inactivity among adolescent girls,11 we also investigated the associations between activity during adolescence and young adulthood and CHD during adulthood.
The NHSII (Nurses’ Health Study II) is an ongoing cohort study that was established in 1989 and included 116 430 predominantly white registered nurses aged 25 to 42 years. Participants completed a baseline self-administered questionnaire used to collect information on lifestyle factors, including physical activity, health behaviors, and medical history. Follow-up biennial questionnaires were sent to participants to collect updated information on potential risk factors and newly diagnosed diseases. Biennial response rates are >90%. This study was approved by the Institutional Review Board at the Harvard T.H. Chan School of Public Health. Informed consent was implied by completion of the questionnaire.
Participants first reported on the frequency of physical activity and completed a semiquantitative food frequency questionnaire 12 in 1991, which served as the baseline for this analysis. Women were excluded if they did not complete the baseline physical activity questionnaire (n=15 418) or reported an inability to walk at baseline (n=69). After exclusion of women with cardiovascular disease, cancer, or diabetes mellitus before 1991 (n=3713), 97 230 women were included in the analysis.
Assessment of Physical Activity
Leisure-time physical activity was assessed in 1991, 1997, 2001, 2005, and 2009 through questions on average total time per week spent on various activities over the previous year. The questions included on the 2009 NHS2 questionnaire can be accessed at the Nurses’ Health Study website.13 Walking pace, categorized as casual (<2 mph), normal (2–2.9 mph), brisk (3–3.9 mph), or striding (≥4 mph), was also assessed. A MET score was assigned to each activity based on its energy cost.14 To calculate the amount of energy expended, the time spent at each activity in hours per week was multiplied by its MET score, then summed over all activities to yield total MET-hours/wk. Moderate activities (3 ≤ METs < 6) included brisk walking, outdoor work, yoga (beginning in 2001), and weight training (beginning in 2001). Vigorous activities, defined as requiring MET values ≥6, were jogging (>10 minutes/mile), running (≤10 minutes/mile), bicycling, lap swimming, tennis/squash/racquetball, and other aerobic exercise.
The validity and reproducibility of the physical activity questionnaire have been reported in detail elsewhere.15 In brief, the Pearson correlation between 4 one-week diaries and the questionnaire was 0.62 for moderate and vigorous recreational activity.
In addition to time per week spent on physical activity, frequency of exercise was assessed in 1991, 1993, 1995, 2005, and 2009. This was assessed by using a single question that read, “How many times per week do you engage in physical activity long enough to perspire heavily (including swimming)?” The responses provided were less than once/wk, once/wk, 2 to 3 times/wk, 4 to 6 times/wk, and ≥7 times/wk.
In 1997, participants were asked about their walking and leisure-time activity during 5 age periods: grades 7 to 8, grades 9 to 12, ages 18 to 22, ages 23 to 29, and ages 30 to 34. For each period, participants reported the average hours per week they engaged in each of 3 activity categories, with examples given for each: strenuous recreational activity (eg, running, aerobics, swimming laps), moderate recreational activity (eg, hiking, walking for exercise, casual cycling, and yard work), and walking to and from school or work. Seven categories were provided for responses ranging from 0 to 11+ hours per week.
The primary end point was incident CHD, which included nonfatal myocardial infarction and fatal CHD. Self-reported MIs were confirmed by medical records according to World Health Organization criteria that included symptoms plus either diagnostic ECG changes or elevated cardiac-specific enzymes.16 Fatal CHD was confirmed by hospital or autopsy records or if CHD was listed as the cause of death on the death certificate and evidence of previous CHD was available.
All analyses were performed using SAS statistical software, version 9.3 (SAS Institute Inc, Cary, NC). Each eligible participant contributed person-time from the return of the 1991 questionnaire (or 1997 questionnaire for analysis of adolescent physical activity) until the date of diagnosis of the first CHD event, death, or June 2011.
Analysis of Total, Moderate-Intensity, and Vigorous-Intensity Physical Activity
Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD outcomes. Physical activity was modeled as a time-varying exposure where simple updated levels of physical activity, using the most recent value of activity reported, were used. For example, events and person-time accrued between 1991 and 1997 were categorized according to exposures reported on the 1991 questionnaire; events and person-time accrued between 1997 and 2001 were categorized according to exposures reported on the 1997 questionnaire; and so forth. Participants were divided into quintiles (<1, 1–5.9, 6–14.9, 15–29.9, and ≥30 MET-hours/wk) for total leisure-time physical activity. For moderate- and vigorous-intensity activity, categories were based on the distribution of these variables as well as informative cut points. For example, 3 MET-hours/wk corresponds to 1 hour of moderate or 0.5 hours of vigorous activity and 7.5 MET-hours/wk corresponds to 2.5 hours of moderate or 1.25 hours of vigorous activity (the current recommendations based on the Physical Activity Guidelines for Americans).3 Tests for linear trend were computed by using the medians for categories modeled as a continuous variable.
Analysis of Individual Types of Physical Activity
In addition, we examined each individual activity separately while adjusting for all other activity using categories of 0, 0.1 to 0.9, and 1+ hours per week (except for walking, where categories were 0, 0.1–0.9, 1–2.4, and 2.5+ hours per week due to a larger number of women reporting walking compared to other types of activities). For this analysis we used hours rather than MET-hours to be able to use the same categories for all activities, both those requiring more METs (eg, running) and fewer METs (eg, yard work). Yoga and weight training were not assessed until 2001; as such, we did not have enough power to look at these individually.
The multivariable models were stratified by age (in months) and calendar year and included parental history of myocardial infarction before 60 years of age (yes/no), smoking (never, former, current: 1–15 cigarettes/d, current: ≥15 cigarettes/d), hours per week of television watching (quartiles), Alternative Healthy Eating Index-2010 diet score (quintiles), aspirin use (yes/no), menopausal status (pre/postmenopausal), postmenopausal hormone use (never, past, current), parity (none, 1–2 children, 3–4 children, 5+ children), oral contraceptive use (never, past, current), and history of hypertension (yes/no) or hypercholesterolemia (yes/no) at baseline. All covariables were updated over time, except for hypertension and hypercholesterolemia because the incidence of these conditions may be in the causal pathway relating physical activity to CHD. Information from previous questionnaires was used when covariable data in a given cycle were missing.
To minimize bias attributable to reverse causation in situations where preclinical cardiovascular disease may limit the ability to exercise, in the main analysis, we stopped updating physical activity when an individual reported difficulty climbing a flight of stairs or walking. In addition, we performed sensitivity analyses with a 2- and 4-year lag to exclude preclinical cases at baseline. For example, in a 2-year lag analysis, physical activity reported in 1991 would be used for the 1993 to 1995 follow-up period.
In addition to using simple updated levels of physical activity, we also conducted a secondary analysis where we calculated the cumulative average of physical activity levels from all available questionnaires up to the start of each 2-year follow-up interval to represent long-term levels of exercise.17
Analysis of Joint Association and Effect Modification
Finally, we assessed the joint association of leisure-time physical activity and body mass index (BMI) with risk of CHD. Participants were cross-classified into 15 groups according to the levels of physical activity (<1, 1–5.9, 6–14.9, 15–29.9, and ≥30 MET-hours/wk) and BMI (<25, 25–29.9, and ≥30 kg/m2). The interaction was assessed using the likelihood ratio test between the models with and without the cross-classified physical activity–BMI variables. Potential effect modification between physical activity and other cardiovascular risk factors (smoking, age, alcohol, and diet) was similarly assessed.
The mean (SD) age of the study population at baseline was 36.6 (4.6) years. During 20 years of follow-up, 544 women developed documented incident CHD of which 254 cases occurred in women <50 years of age. We examined total leisure-time physical activity in relation to other potential risk factors for CHD at baseline (Table 1). Women who reported more physical activity were younger, had lower BMI, were less likely to smoke, watched less television, and had a higher Alternative Healthy Eating Index-2010 - diet score.
In multivariable-adjusted models, women reporting the highest amount of leisure-time physical activity (≥30 MET-hours/wk) were at significantly lower risk of CHD in comparison with women who were the least active (<1 MET-hour/wk; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57–0.99, P for trend=0.01) (Table 2). When examined separately, moderate- and vigorous-intensity physical activity were both inversely associated with CHD risk. In comparison with women reporting 0 MET-hours/wk of moderate-intensity physical activity, women reporting ≥15 MET-hours/wk of moderate activity had a 33% lower risk of CHD (HR, 0.67; 95% CI, 0.51–0.87; P for trend=0.01). Similarly, women reporting ≥15 MET-hours/wk of vigorous activity had a 23% lower risk of CHD (HR, 0.77; 95% CI, 0.57– 1.03) in comparison with women reporting no vigorous activity (P for trend=0.04). When the analysis was repeated with a 2- and 4-year lag, results for total leisure-time activity and moderate activity were attenuated and no longer statistically significant, whereas results for vigorous activity were similar and remained significant. In secondary analysis, when we used cumulative average physical activity instead of simple updated activity, similar results were obtained although the hazard ratios in the highest 2 categories were slightly attenuated (online-only Data Supplement Table I).
We also examined the association between frequency of exercise and risk of CHD (Table 3). In comparison with women reporting exercise less than once per week, the age-adjusted HR for women reporting exercise 4+ times per week was 0.60 (95% CI, 0.46–0.78; P for trend=0.0001). However, the correlation between frequency and volume of exercise ranged from 0.41 to 0.44 in the questionnaire cycles where both were asked (1991, 2005, 2009). In the multivariable model that included volume of physical activity, the association between exercise frequency and CHD risk was attenuated and no longer significant (HR comparing extreme categories, 0.94; 95% CI, 0.70–1.26, P for trend=0.84), whereas the association for volume of physical activity was nearly identical to that above (HR, 0.76; 95% CI, 0.56–1.02 comparing ≥30 with <1 MET-hours/wk).
Table 4 shows the association between individual activities and CHD risk. In multivariable-adjusted analyses where each activity was modeled separately, but adjusted for total volume of all other activity, aerobics, outdoor work, and brisk walking were each significantly inversely associated with CHD (P for trend=0.04, 0.04, and 0.001, respectively) (Table 4). Engaging in aerobics ≥1 hour/wk was associated with a 26% CHD risk reduction (HR, 0.74; 95% CI, 0.55-0.99) and outdoor work with a 16% CHD risk reduction (HR, 0.84; 95% CI, 0.68–1.04) in comparison with women not participating in these activities (Table 4). Brisk walking for ≥2.5 hours/wk was associated with a 35% risk reduction (HR, 0.65; 95% CI, 0.48–0.87) in comparison with women who reported no brisk walking. In addition, increasing speed of usual walking pace was associated with lower CHD risk. After adjusting for hours per week of walking, other physical activity, and covariables, the HRs for easy/casual pace (<2 mph), normal/average pace (2–2.9 mph), brisk pace (3–3.9 mph), and very brisk/striding pace (≥4 mph) were: 1.00, 0.81 (95% CI, 0.66–0.98), 0.57 (95% CI, 0.44–0.73), and 0.33 (95% CI, 0.17–0.65). Finally, results for running and tennis also suggested an inverse association with incidence of CHD but, most likely because of the small number of cases in the upper categories, reductions in risk were not statistically significant.
The joint association of physical activity and BMI on risk of CHD is shown in the Figure. As the interaction between physical activity and BMI was not statistically significant (P for interaction=0.70), the inverse association between physical activity and CHD was not modified by BMI category. In comparison with obese women reporting <1 MET-hour/wk of physical activity, the HR of CHD for normal weight women reporting ≥30 MET-hours/wk was 0.52 (95% CI, 0.35–0.78). Furthermore, among women in the highest category of exercise, those with normal BMI had lower CHD risk than women who were overweight or obese.
We additionally examined the association between physical activity recalled from earlier in life and CHD risk in adulthood (online-only Data Supplement Table II). There was no association between physical activity during ages 12 to 22 years and risk of CHD; the multivariable-adjusted HR comparing the highest with the lowest category was 1.12 (95% CI, 0.83–1.52). We also assessed physical activity measured at baseline only (1991) in relation to events occurring throughout the 20 years of follow-up, which differs from the primary analysis where physical activity levels were updated every 4 to 6 years during follow-up. Similar to early-life activity, the association between baseline physical activity and risk of CHD was null; the multivariable-adjusted HR comparing the highest with lowest quintile was 0.98 (95% CI, 0.74–1.29) (online-only Data Supplement Table III). These results suggest that the favorable association between physical activity and CHD may be best documented with levels proximal to the date of CHD incidence for young and middle-aged women.
Finally, we evaluated whether the inverse association between physical activity and CHD was modified by other cardiovascular risk factors (online-only Data Supplement Table IV). Physical activity was associated with lower CHD risk for women <50 years of age and for women ≥50 years of age, as well. In addition, there was no evidence of effect modification by smoking, Alternative Healthy Eating Index-2010 diet score, or alcohol intake.
In this large, prospective study of young US women, individuals in the highest category (≥30 MET-hours/wk) of leisure-time physical activity were at a 25% lower risk of incident CHD. In addition, both moderate-intensity physical activity (eg, brisk walking) and vigorous-intensity activity were associated with reduced CHD risk. Importantly, physical activity was associated with lower CHD risk regardless of BMI group.
The mean age at baseline of participants in this study was 36.6 years, providing a unique opportunity to examine physical activity and CHD in younger women. According to a recent review, the median or mean ages of subjects in studies included in the 2008 Physical Activity Guidelines primarily ranged from 45 to 60 years.18 Thus, this article is a valuable contribution to the existing literature on modifiable lifestyle factors that could prevent CHD in younger women. Primordial prevention of CHD in this group is critical because recent data suggest that the CHD mortality rate in women aged 25 to 54 years may not be declining as it is in other groups, possibly because of the increases in the prevalence of obesity and type 2 diabetes mellitus.5–7
We found no association between recalled physical activity during adolescence or early adulthood and risk of CHD in adulthood. This finding is similar to that of Conroy et al19who found that, although physical activity during high school and ages 18 to 22 was associated with meeting physical activity recommendations in middle adulthood, it was not associated with the risk of CHD during middle age and older. Furthermore, when we performed the analysis lagged 2 and 4 years, the association between total physical activity and CHD risk was attenuated. Taken together, these findings suggest that associations between physical activity and CHD prevention may be driven by most recent levels. This is consistent with evidence suggesting that exercise has acute effects on cardiovascular disease risk factors such as blood lipids, blood pressure, and glucose control.20 Specifically, physical activity is correlated with lower triglycerides, lower apolipoprotein B, higher high-density lipoprotein, change in low-density lipoprotein particle size, and lower coronary artery calcium.21 Therefore, an important message to communicate to the public is that, regardless of how inactive you may be, it is possible to experience cardiovascular benefits soon after becoming physically active. Nonetheless, physical activity early in life should be encouraged because it has important health benefits for children and adolescents, including improved cardiovascular and metabolic health.3,22,23 Furthermore, in this same cohort of women, there was a suggestive inverse association between physical activity during ages 14 to 22 years and risk of premenopausal breast cancer.24 Previous studies have also indicated that past physical activity is associated with physical activity later in life.19,25 Thus, engaging in regular exercise is important for young and old as physical activity has important health benefits throughout life.
In the current study, there was no association between weekly frequency of physical activity and CHD risk once adjusted for volume of physical activity. This is in contrast to a recent finding from the Million Women Study, which showed that, in comparison with women reporting strenuous activity 2 to 3 times per week, those reporting strenuous physical activity daily were at higher risk of CHD.26 This inconsistency could be explained, in part, by differences in analysis methods. In the Million Women Study, the analysis for frequency of physical activity did not adjust for total volume of activity because the duration of activity was not assessed until 3 years after baseline. With the exception of activity frequency, however, findings from the current study are similar to those of the Million Women Study among women 50 to 64 years of age, in particular, with regard to the benefits of moderate physical activity for CHD.
Our results suggest that both moderate- and vigorous-intensity physical activity are associated with CHD risk reduction, similar to other studies.27–30 Nonetheless, these previous studies in older men and women indicate a greater magnitude of association for vigorous activity compared with moderate,27–30 whereas we saw a modestly stronger association for moderate over vigorous activity. The result in the present study may be a consequence of the physical activity questionnaire used. We were unable to include an assessment of the intensity at which a participant performed many of the activities. So, although we categorized activities like bicycling and swimming as vigorous, some participants may actually perform these activities at a much lower intensity. Thus, the inability to distinguish between the same activity performed at a truly vigorous intensity versus a lower intensity could have contributed random error and attenuated our assessment. This is further supported by the activity-specific hazard ratios where the traditional vigorous activities such as running, tennis, and aerobics were more strongly inversely associated with CHD than activities like swimming, biking, and jogging that likely have a much broader range of intensity. Furthermore, walking pace was assessed in the current study and found to be strongly inversely associated with risk of CHD.
Importantly, our study suggests that leisure-time physical activity is associated with a reduction in CHD risk in younger women who are normal weight, overweight, or obese. Although this finding has been reported in previous studies among middle-aged and older men and women, it is worth emphasizing, given the high prevalence of overweight and obesity in young and middle-aged US women (58.5% for women 20–39 years of age, 71.7% for women 40–59 years of age).31–33 An elevated BMI is still a significant risk factor for development of CHD, but the increased risk associated with being overweight or obese is attenuated, although not completely, by engaging in physical activity.
Strengths of this study include its prospective design, the detailed information on physical activity collected multiple times during follow-up, the large number of confirmed CHD cases despite the relatively young age of study participants, and minimal loss to follow-up.
Our study also has several limitations that should be considered. Our study population, consisting of predominantly white nurses, is not representative of the general population. Thus, we cannot necessarily generalize our results to men or other populations with different educational levels, incomes, or distributions of race and ethnicity. Physical activity was self-reported, but this questionnaire has been previously validated in this population.15 Moreover, measurement error is unlikely to bias our results because physical activity was assessed prospectively so any reporting errors would be nondifferential with respect to subsequent disease status. Nonetheless, the lack of association between physical activity during adolescence and CHD during adulthood may be a consequence of measurement error as participants had to recall physical activity levels from 20 to 35 years earlier. As in any observational study, the possibility of residual confounding by other lifestyle characteristics must be considered; however, we were able to adjust for many known CHD risk factors.
In conclusion, this study indicates that physical activity is associated with a lower risk of CHD in young women. Furthermore, exercise did not have to be strenuous to have such associations; moderate-intensity physical activity, including brisk walking, was associated with lower risk of CHD. There was no association between physical activity earlier in life and CHD risk in adulthood, suggesting that previously inactive women who become physically active can still decrease their risk of CHD. Finally, the favorable associations between physical activity and lower CHD risk were evident regardless of BMI, emphasizing that it is important for normal weight, overweight, and obese women to be physically active.
Sources of Funding
This study was supported by National Institute of Health grants UM1 CA176726 and R01 CA050385. Dr Chomistek was supported by an institutional training grant (DK007703) from the National Institute of Diabetes and Digestive and Kidney Diseases.
Sources of Funding, see p 298
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.116.021516/-/DC1.
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- Received January 14, 2016.
- Accepted June 16, 2016.
- © 2016 American Heart Association, Inc.
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What Is New?
Findings from this study indicate that physical activity is associated with lower risk of coronary heart disease (CHD) in young women.
Exercise did not have to be strenuous to have such associations; moderate-intensity physical activity, including brisk walking, was associated with lower risk of CHD.
In addition, we found that frequency of physical activity was not associated with CHD risk after adjusting for total volume of physical activity.
We found no association between physical activity earlier in life and CHD risk in adulthood.
Finally, the associations between physical activity and lower CHD risk were evident regardless of body mass index.
What Are the Clinical Implications?
For patients who are currently inactive and find joining a gym intimidating, emphasizing the benefits of walking may help them get active.
Findings from this study indicate that the frequency of physical activity is not as important as the total volume; thus, patients can achieve the recommended 150 minutes of moderate- to vigorous-intensity physical activity per week in as many or as few sessions as they wish.
Our results suggest that previously inactive women who become physically active can still decrease their risk of CHD.
It is important for normal weight, overweight, and obese women to be physically active.