Mediators of the Effect of Obesity on Stroke and Heart Disease Risk: Decomposing Direct and Indirect Effects

Background: The prevalence of overweight and obesity are well known risk factors of atherosclerotic cardiovascular disease (ASCVD). We aimed to examine the association between body mass index (BMI) and ASCVD over a 23-year follow-up in young adults. We also qualified how much of the effects of obesity on ASCVD were mediated through blood pressure, cholesterol, and glucose. Methods: Data are from the Korean Life Course Health Study, a cohort study of 226,955 Korean young adults aged 20–39. At baseline, the participants undertook routine health assessments where their BMI was measured in 1992–1994; and the metabolic mediators including systolic blood pressure (SBP), fasting serum glucose (FSG), and total cholesterol (TC) were re-measured in 2002–2004. The main outcomes of the study include incident events of ischemic heart disease (IHD), stroke, and ASCVD between 2005 and 2015. Cox proportional model was used to calculate adjusted hazard ratios (HRs) for ASCVD. Results: In both men and women, the direct effect of BMI on ASCVD was greater than the indirect effect. The percentage of excess HR of BMI mediated by all of the metabolic mediators, including SBP, FSG, and TC, was 45.7% for stroke and 18.7% for IHD in men and 27.5% for stroke and 17.6% for IHD in women. Conclusion: High BMI in young adults increases the risk of metabolic mediators in their middle age, and metabolic mediators explain the adverse effects of high BMI on stroke risk than IHD risk