shows the baseline characteristics of participants according to their activity levels. Active women had a healthier lifestyle, weighed less, and had better risk factor profiles than inactive women. There were modest, but statistically significant, differences in all biomarkers except for lipoprotein (a), with higher activity associated with better profiles (P for linear trend, <0.001).
Baseline Characteristics of Participants According to Physical Activity
During a mean follow-up of 10.9±1.6 years, a total of 979 first CVD events occurred, including 640 CHD events (253 MI, 398 PCI, and 219 CABG) and 266 ischemic strokes. The risk of incident CVD decreased linearly with higher levels of activity (P for linear trend, <0.001; ). Using the reference group of <200 kcal/week of activity and after adjusting for age and randomized-treatment assignment, the relative risk reductions associated with 200–599, 600–1499, and ≥1500 kcal/week were 27%, 32%, and 41%, respectively. In separate Cox regression models which considered each risk factor variable, one at a time, and adjusted for age and treatment assignment (), there was some attenuation noted in the HRs comparing the most active women with the least active, before and after adjustment for all variables, except for creatinine, lipoprotein (a), and postmenopausal status/hormone use. However, when all risk factors were combined together in one model, the HR comparing the most active women with the least active was substantially attenuated (0.90, 95% CI 0.73–1.11, after adjusting for all risk factors, compared with 0.59, 95% CI 0.49–0.71, after only adjusting for age and treatment assignment), and the linear trend across activity levels was no longer significant (P for linear trend, 0.37).
Association of Physical Activity with Cardiovascular Disease Events after Adjusting for CVD Risk Factors
Next, to determine the extent to which the reduced risk of CVD associated with activity was influenced by potential mediators representing various physiological pathways, each set of mediators was added, one set at a time, to the basic model (, top panel). For CVD, the addition of blood pressure/hypertension resulted in an attenuation of the inverse relation, which became non-significant (P, trend=0.09), with similar results for the inflammatory/hemostatic biomarkers (P, trend=0.10). The addition of body mass index, hemoglobin A1c/diabetes, traditional lipids, and novel lipids, one set at a time, resulted in smaller attenuations in the inverse relation between activity and CVD (all P, trend ≤0.05). When all sets of risk factors were added simultaneously to the basic model, this resulted in further attenuation of the HRs, and no significant associations were observed (P, trend=0.36).
Association of Physical Activity with Cardiovascular and Coronary Heart Disease Events after Adjusting for Sets of Potential Mediators
For CHD, a broadly similar pattern was observed (, bottom panel). Unlike CVD, there remained a borderline significant inverse association with CHD, after adjustment for all sets of risk factors (P, trend=0.05).
The associations of activity with nonfatal MI, PCI, and CABG, when examined as separate endpoints, are shown in . When the sets of potential mediators were added to the basic model, the effect of physical activity was attenuated in a manner similar to that seen with CHD. The association of activity with ischemic stroke was non-linear (corresponding age and treatment-adjusted HRs and 95% CIs: 1.00, 0.68 [0.49–0.95], 0.69 [0.50–0.95], and 0.72 [0.51–1.01], respectively; P, trend=0.16).
Association of Physical Activity with Myocardial Infarction and Coronary Revascularization Procedures after Adjusting for Sets of Potential Mediators
Finally, we computed the proportion of the physical activity-related reduction in CVD or CHD events explained by each set of potential mediators (). A large proportion (59.0%) of the inverse relation between physical activity and CVD risk was explained by the potential mediators that we investigated. When examined as sets of risk factors, inflammatory/hemostatic biomarkers were the largest contributors to lower risk (32.6%), followed by blood pressure (27.1%). Novel lipids (lipoprotein [a], apolipoprotein A1 and B100) contributed less to CVD risk reduction compared with traditional lipids (total, LDL, and HDL cholesterol); 15.5% and 19.1%, respectively. Smaller contributions were attributed to body mass index (10.1%) and hemoglobin A1c/diabetes (8.9%), while homocysteine had negligible effects (<1%). A similar pattern, but smaller was observed for CHD (35.5% of the CHD event risk reduction explained by risk factors, compared with 59.0% for CVD).
Figure Percentage reduction in CVD events associated with physical activity that is explained by risk factors. The proportion of the risk reduction for ≥1500 kcal/wk of physical activity (compared with the reference group of <200 kcal/wk, Panel (more ...)
We repeated our analyses (, Panel B), calculating activity expenditure in MET-hours/week instead of kcal/week. Almost identical results were obtained, except for body mass index, whose contribution increased from 10.1% to 21.9%, and hemoglobin A1c/diabetes, which increased from 8.9% to 12.2%.