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How much of the excess risk for coronary artery disease (CAD) and stroke associated with high body-mass index (BMI) is mediated through metabolic risk factors (i.e., blood pressure, cholesterol, and glucose), and how much is inherent in high BMI itself? In the largest meta-analysis to address this question, researchers combined data from 97 international prospective cohort studies involving adults without histories of CAD or stroke. Participants were followed for a median 13 years.
After adjustment for age, sex, and smoking status, every 5 kg/m2 higher BMI was associated with a hazard ratio of 1.27 for CAD and 1.18 for stroke. After further adjustment for blood pressure — the most important metabolic mediator for both endpoints — HRs fell to…