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(Circulation. 2007;116:2110-2118.)
© 2007 American Heart Association, Inc.

Epidemiology

Physical Activity and Reduced Risk of Cardiovascular Events

Potential Mediating Mechanisms

Samia Mora, MD, MHS; Nancy Cook, ScD; Julie E. Buring, ScD; Paul M Ridker, MD, MPH; I-Min Lee, MBBS, ScD

From the Donald W. Reynolds Center for Cardiovascular Research and the Center for Cardiovascular Disease Prevention (S.M., N.C., J.E.B., P.M.R.), Leducq Center for Molecular and Genetic Epidemiology (S.M., P.M.R.), and Divisions of Preventive Medicine (S.M., N.C., J.E.B., P.M.R., I.-M.L.) and Cardiovascular Medicine (S.M., P.M.R.), Brigham and Women’s Hospital, Harvard Medical School, and the Department of Epidemiology, Harvard School of Public Health (N.C., J.E.B., P.M.R., I.-M.L.), Boston, Mass.

Correspondence to Samia Mora, MD, MHS, Brigham and Women’s Hospital, 900 Commonwealth Ave E, Third Floor, Boston, MA 02215. E-mail smora2{at}partners.org

Received July 24, 2007; accepted September 14, 2007.

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 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.

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