At Least Half of Cardiovascular Risk Associated with Adiposity Is Mediated by Metabolic Risk Factors

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…