Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms

Abstract

Background: Higher levels of physical activity are associated with fewer cardiovascular disease (CVD) events. Although the precise mechanisms underlying this inverse association are unclear, differences in several cardiovascular risk factors may mediate this effect.

Methods and results: In a prospective study of 27,055 apparently healthy women, we measured baseline levels of hemoglobin A1c, traditional lipids (total, low-density lipoprotein, and high-density lipoprotein cholesterol), novel lipids [lipoprotein(a) and apolipoprotein A1 and B-100], creatinine, homocysteine, and inflammatory/hemostatic biomarkers (high-sensitivity C-reactive protein, fibrinogen, soluble intracellular adhesion molecule-1) and used women's self-reported physical activity, weight, height, hypertension, and diabetes. Mean follow-up was 10.9+/-1.6 years, and 979 incident CVD events occurred. The risk of CVD decreased linearly with higher levels of activity (P for linear trend < 0.001). Using the reference group of < 200 kcal/wk of activity yielded age- and treatment-adjusted relative risk reductions associated with 200 to 599, 600 to 1499, and > or = 1500 kcal/wk of 27%, 32%, and 41%, respectively. Differences in known risk factors explained a large proportion (59.0%) of the observed inverse association. When sets of risk factors were examined, inflammatory/hemostatic biomarkers made the largest contribution to lower risk (32.6%), followed by blood pressure (27.1%). Novel lipids contributed less to CVD risk reduction compared with traditional lipids (15.5% and 19.1%, respectively). Smaller contributions were attributed to body mass index (10.1%) and hemoglobin A1c/diabetes (8.9%), whereas homocysteine and creatinine had negligible effects (< 1%).

Conclusions: The inverse association between physical activity and CVD risk is mediated in substantial part by known risk factors, particularly inflammatory/hemostatic factors and blood pressure.

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 A), and for >20.5 MET hrs/wk (compared with the reference group of <2.8 MET hrs/wk, Panel B), that is explained by each set of potential risk factors, calculated as (HR_{basic model} – HR_{adjusted model})/(HR_{basic model} -1) X 100%. These proportions were calculated from HRs expressed up to 5 decimal points for greater accuracy, and thus may differ slightly from the data shown in Table 3.

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 A), and for >20.5 MET hrs/wk (compared with the reference group of <2.8 MET hrs/wk, Panel B), that is explained by each set of potential risk factors, calculated as (HR_{basic model} – HR_{adjusted model})/(HR_{basic model} -1) X 100%. These proportions were calculated from HRs expressed up to 5 decimal points for greater accuracy, and thus may differ slightly from the data shown in Table 3.