Contribution of obesity and cardiometabolic risk factors in patients with cardiovascular disease: A population based cohort study

Background: The mechanisms linking adiposity to associated clinical conditions such as type 2 diabetes, cardiovascular disease, and related metabolic and inflammatory disturbances. are poorly understood.This study aimed to identify sex-specific direct and indirect effects of central and general adiposity on cardiovascular disease, mediated by cardiometabolic risk factors and how much is independent of these factors. Methods We analyzed data from the TLGS cohort study with 6280 participants aged ≥ 30 years, free of cardiovascular disease at baseline with a median follow-up of 13.9 years. The total effects were broken down into natural direct and indirect effects using a 2-stage regression model in the context of the survival model. We also calculated the proportion mediated by systolic blood pressure, total serum cholesterol, and fasting plasma glucose as mediators. Results There was no interaction between BMI and its mediators in the multiplicative scale (P > 0.05 for all). Blood pressure was the most important mediator for general (HR NIE 1.11, 95% CI:1.17–1.24) and central obesity (HR NIE 1.11, 95% CI:1.07–1.15) with proportion mediated of 60% and 36% respectively in the total population. The percentage mediated through all three metabolic risk factors together was 46% (95% confidence interval = 31%-75%) for overweight, 66% (45%-100%) for general obesity and 52% (39%-87%) for central obesity. Blood pressure was the most important mediator for overweight and central adiposity in male population with 29% and 36% proportion mediated respectively while in female population percentage mediated through all three metabolic risk factors together was 23% (95% confidence interval = 13%-50%) for overweight, 36% (21%-64%) for general obesity and 52% (39%-87%) for central obesity. Conclusions Metabolic mediators explain more than 60% of the adverse effects of high BMI on CVD in the male population. Also, managing these metabolic mediators in women does not effectively contribute to reducing CVD risks without decreasing weight.