Andrea K. Chomistek

Vigorous physical activity, mediating biomarkers, and risk of myocardial infarction

PURPOSE The effects of physical activity on risk of myocardial infarction (MI) are well documented and may include beneficial changes in blood lipids, inflammatory markers, and insulin sensitivity. The degree to which these and other traditional and nontraditional cardiovascular biomarkers mediate the inverse association between physical activity and risk of MI in men remains unclear. METHODS We conducted a nested case-control study among 18,225 men in the Health Professionals Follow-up Study followed from 1994 to 2004. A total of 412 men with incident MI were matched 1:2 with control participants on age and smoking status using risk-set sampling. From detailed responses to a modified Paffenbarger physical activity questionnaire, we determined the association between average hours of vigorous-intensity activity (activities requiring METs ≥ 6) and MI risk. RESULTS For a 3-h·wk(-1) increase in vigorous-intensity activity, the multivariate relative risk (RR) of MI was 0.78 (95% confidence interval (CI) = 0.61-0.98). In models including preexisting CVD-related conditions, further adjustment for HDL-C, vitamin D, apolipoprotein B, and hemoglobin A1c attenuated the RR by 70% (95% CI = 12%-127%) to an RR of 0.93 (95% CI = 0.72-1.19). CONCLUSIONS Participating in 3 h·wk(-1) of vigorous-intensity activity is associated with a 22% lower risk of MI among men. This inverse association can be partially explained by the beneficial effects of physical activity on HDL-C, vitamin D, apolipoprotein B, and hemoglobin A1c. Although the inverse association attributable to these biomarkers is substantial, future research should explore benefits of exercise beyond these biomarkers of risk.

Vigorous-intensity leisure-time physical activity and risk of major chronic disease in men

PURPOSE Although studies have shown health benefits for moderate-intensity physical activity, there is limited evidence to support beneficial effects for high amounts of vigorous activity among middle-age and older men. The objective of this study was to examine the relationship between vigorous-intensity physical activity, compared with moderate-intensity activity, and risk of major chronic disease in men. METHODS We prospectively examined the associations between vigorous- and moderate-intensity physical activity and risk of major chronic disease among 44,551 men age 40-75 yr in 1986. Leisure-time physical activity was assessed biennially by questionnaire. During 22 yr of follow-up, we documented 14,162 incident cases of major chronic disease, including 4769 cardiovascular events, 6449 cancer events, and 2944 deaths from other causes. RESULTS The HR of major chronic disease comparing ≥ 21 to 0 MET.h.wk(-1) of exercise was 0.86 (95% confidence interval (CI), 0.81-0.91) for vigorous-intensity activity and 0.85 (95% CI, 0.80-0.90) for moderate activity. For cardiovascular disease (CVD), the corresponding HRs were 0.78 (95% CI, 0.70-0.86) and 0.80 (95% CI, 0.72-0.88), respectively. When examined separately, running, tennis, and brisk walking were inversely associated with CVD risk. Furthermore, more vigorous activity was associated with lower disease risk; the HR comparing >70 to 0 MET.h.wk(-1) of vigorous-intensity exercise was 0.79 (95% CI, 0.68-0.92; P < 0.0001 for trend) for major chronic disease and 0.73 (95% CI, 0.56-0.96; P < 0.0001 for trend) for CVD. CONCLUSIONS Vigorous- and moderate-intensity physical activities were associated with lower risk of major chronic disease and CVD. Increasing amounts of vigorous activity remained inversely associated with disease risk, even among men in the highest categories of exercise.

Physical Activity, Genes for Physical Fitness, and Risk of Coronary Heart Disease

PURPOSE Both physical activity and physical fitness are associated with decreased coronary heart disease (CHD) risk. Our objective was to determine whether genes associated with physical fitness modify the association between physical activity and CHD. METHODS We conducted a prospective cohort study among 23,016 initially healthy women in the Womens Genome Health Study. Leisure time physical activity was reported at entry and during follow-up. A total of 58 single nucleotide polymorphisms associated with physical fitness were identified from published literature and summed to create four separate genetic scores related to phenotypes of endurance, muscle strength, V˙O2max, and overall fitness. RESULTS During a median of 14.4 yr, 320 incident CHD events occurred. Increased physical activity was associated with lower CHD risk in multivariable-adjusted models (P = 0.0008). Independent of physical activity, only muscle strength genetic score was inversely associated with CHD risk (P = 0.05). There was no evidence that the inverse relation between physical activity and CHD was modified by any of the genetic scores for physical fitness. For overall fitness genetic score, the hazard ratio (HR) per 500 kcal·wk of physical activity was 0.85 (95% confidence interval [CI] = 0.72-1.00) in the highest quartile of genetic score and 0.79 (95% CI = 0.67-0.92) in the lowest quartile (P, interaction = 0.50). For V˙O2max genetic score, the HR was 0.86 (95% CI = 0.72-1.02) and 0.84 (95% CI = 0.72-0.98), respectively (P, interaction = 0.59). CONCLUSIONS In this large prospective cohort of women, genes associated with physical fitness did not modify the inverse association between physical activity and CHD risk.

Physical activity and chronic prostatitis/chronic pelvic pain syndrome.

PURPOSE Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relation between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. METHODS We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated on the basis of the responses on the 2008 questionnaire. Participants with pain scores ≥8 were considered CP/CPPS cases (n = 689). RESULTS Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio comparing >35.0 to ≤3.5 MET·h·wk of physical activity was 0.72 (95% confidence interval, 0.56-0.92; P for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (P for trend = 0.64). CONCLUSIONS Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-age and older men.

Frequency, Type, and Volume of Leisure-Time Physical Activity and Risk of Coronary Heart Disease in Young Women

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.

Association Between a Healthy Heart Score and the Development of Clinical Cardiovascular Risk Factors Among Women Potential Role for Primordial Prevention

Background—The prevailing efforts for cardiovascular disease (CVD) prevention focused on treatment of common CVD risk factors rather than primordial prevention of risk factors through health behaviors. The previously validated Healthy Heart Score effectively predicted the 20-year risk of CVD in midadulthood; however, it is unknown whether this risk score is associated with clinically relevant CVD risk factors. Methods and Results—We analyzed the association between the Healthy Heart Score and the incidence of clinical CVD risk factors, including diabetes mellitus, hypertension, and hypercholesterolemia among 69 505 US women in the Nurses’ Health Study II (NHSII; 1991–2011). The Healthy Heart Score estimates the 20-year CVD risk based on 9 lifestyle factors; thus, a higher score reflected a higher predictive CVD risk. During 20 years, we documented 3275 incident cases of diabetes mellitus, 17 420 of hypertension, and 24 385 of hypercholesterolemia. Women with higher predicted CVD risk based on the Healthy Heart Score (highest quintile versus lowest quintile) had significantly greater risk of each clinical risk factor individually (hazard ratios: 18.1 [95% confidence interval, 14.4–22.7] for diabetes mellitus, 5.10 [4.66–5.57] for hypertension, and 2.57 [2.40–2.75] for hypercholesterolemia). The hazard ratio for developing the high-CVD profile was 52.5 (33.6–82.1). These associations were most pronounced among women who were younger, were nonsmokers, or had optimal weight. Conclusions—An absolute 20-year risk of CVD, estimated by the Healthy Heart Score, was strongly associated with the development of CVD clinically relevant risk factors. This risk score may serve as the first step for CVD risk assessment in primordial prevention.

Objective Measures of Physical Activity and Cardiometabolic and Endocrine Biomarkers

Purpose Although physical activity is an established risk factor for chronic disease prevention, the specific mechanisms underlying these relationships are poorly understood. We examined the associations between total activity counts and moderate-vigorous physical activity (MVPA) measured by accelerometer, and physical activity energy expenditure measured by doubly labeled water, with plasma levels of proinsulin, insulin, c-peptide, insulin growth factor binding protein-3, insulin growth factor-1, adiponectin, leptin, and leptin-sR. Methods We conducted a cross-sectional analysis of 526 healthy US women in the Women’s Lifestyle Validation Study, 2010 to 2012. We performed multiple linear regression models adjusting for potential lifestyle and health-related confounders to assess the associations between physical activity, measured in quartiles (Q) and biomarkers. Results Participants in Q4 versus Q1 of total activity counts had lower proinsulin (−20%), c-peptide (−7%), insulin (−31%), and leptin (−46%) levels, and higher adiponectin (55%), leptin-sR (25%), and insulin growth factor-1 (9.6%) levels (all P trend ⩽ 0.05). Participants in Q4 versus Q1 of MVPA had lower proinsulin (−26%), c-peptide (−7%), insulin (−32%), and leptin (−40%) levels, and higher adiponectin (31%) and leptin-sR (22%) levels (all P trend ⩽ 0.05). Further adjustment for body mass index (BMI) attenuated these associations, but the associations with adipokines remained significant. Those in Q4 versus Q1 of physical activity energy expenditure had lower leptin (−21%) and higher leptin-sR (10%) levels (all P trend ⩽ 0.05), after additional adjustment for BMI. In the sensitivity analysis, the associations were similar but attenuated when physical activity was measured using the subjective physical activity questionnaire. Conclusions Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity.

Adolescent Diet Quality and Cardiovascular Disease Risk Factors and Incident Cardiovascular Disease in Middle-Aged Women

Background Primary prevention of cardiovascular disease (CVD) focuses on treatment of risk factors, including hypercholesterolemia, hypertension, and type 2 diabetes mellitus. We investigated whether a healthy diet in adolescence prevents development of clinical risk factors or incidence of CVD in adulthood. Methods and Results We examined the time to the first development of ≥1 clinical risk factor (hypercholesterolemia, hypertension, or type 2 diabetes mellitus) or CVD in relation to a high school Alternative Healthy Eating Index (HS‐AHEI) within the Nurses’ Health Study II. Among those who completed a food frequency questionnaire about their high school diet and adult diet (mean age 42 years), 27 406 women free of clinical risk factors and 42 112 women free of CVD in 1998 were followed to June 2011. Hazard ratios (HRs) and 95% CIs were adjusted for potential confounders in high school and adulthood. We documented 11 542 first diagnoses of clinical risk factors and 423 CVD events. The HS‐AHEI was associated with a lower rate of risk factors (HR highest versus lowest quintiles 0.82; 95% CI, 0.77–0.87 [P trend <0.001]), was inversely associated with risk of developing ≥1 clinical risk factor in women with a low, medium, and high AHEI score during adulthood (HR high HS‐AHEI/high adult AHEI versus low/low 0.79 [95% CI, 0.74–0.85]), but was not statistically significantly associated with incident CVD. Conclusions A healthy diet during adolescence is associated with lower risk of developing CVD risk factors. As diet tracks throughout life, and adult diet prevents CVD, healthy dietary habits that begin early are important for primordial prevention of CVD.

Change in Physical Activity and Sitting Time After Myocardial Infarction and Mortality Among Postmenopausal Women in the Women's Health Initiative‐Observational Study

Background How physical activity (PA) and sitting time may change after first myocardial infarction (MI) and the association with mortality in postmenopausal women is unknown. Methods and Results Participants included postmenopausal women in the Womens Health Initiative‐Observational Study, aged 50 to 79 years who experienced a clinical MI during the study. This analysis included 856 women who had adequate data on PA exposure and 533 women for sitting time exposures. Sitting time was self‐reported at baseline, year 3, and year 6. Self‐reported PA was reported at baseline through year 8. Change in PA and sitting time were calculated as the difference between the cumulative average immediately following MI and the cumulative average immediately preceding MI. The 4 categories of change were: maintained low, decreased, increased, and maintained high. The cut points were ≥7.5 metabolic equivalent of task hours/week versus <7.5 metabolic equivalent of task hours/week for PA and ≥8 h/day versus <8 h/day for sitting time. Cox proportional hazard models estimated hazard ratios and 95% CIs for all‐cause, coronary heart disease, and cardiovascular disease mortality. Compared with women who maintained low PA (referent), the risk of all‐cause mortality was: 0.54 (0.34–0.86) for increased PA and 0.52 (0.36–0.73) for maintained high PA. Women who had pre‐MI levels of sitting time <8 h/day, every 1 h/day increase in sitting time was associated with a 9% increased risk (hazard ratio=1.09, 95% CI: 1.01, 1.19) of all‐cause mortality. Conclusions Meeting the recommended PA guidelines pre‐ and post‐MI may have a protective role against mortality in postmenopausal women.

Physical Activity and Incident Cardiovascular Disease in Women: Is the Relation Modified by Level of Global Cardiovascular Risk?

Background The inverse association between physical activity and cardiovascular disease (CVD) is well‐ established and has previously been shown in people with and without single CVD risk factors. We examined whether level of global cardiovascular risk, on the basis of the pooled cohort equation or Reynolds risk score, which include multiple risk factors, modified the physical activity–CVD association. Methods and Results Participants in the prospective WHS (Womens Health Study; n=27 536) reported their leisure‐time physical activity at study entry (1992–1995) and during follow‐up through 2013. Participants were divided into 10‐year cardiovascular risk groups on the basis of the pooled cohort equation and Reynolds risk score. The primary outcome was incident total CVD. The CVD hazard ratio for active (≥500 kcal/wk of physical activity) compared with inactive (<500 kcal/wk) individuals was 0.73 (95% confidence interval, 0.66–0.80) in multivariable models. This association was not modified by level of cardiovascular risk; physical activity was inversely associated with CVD within all pooled cohort equation and Reynolds risk score groups (P=0.17 and P=0.66 for interaction, respectively). When the joint association of physical activity and level of cardiovascular risk was examined, women with higher risk on the basis of either the pooled cohort equation or Reynolds risk score had higher CVD rates compared with those at low risk, regardless of physical activity. However, among women at both high and low risk, being physically active was associated with lower risk of CVD events. Conclusions In this large prospective cohort of women, level of global cardiovascular risk did not modify the inverse association between leisure‐time physical activity and incident CVD. Thus, promoting physical activity is important in women at both low and high cardiovascular risk.