Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk

Background Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal follow-up, with inconsistent results. Objectives We hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of metabolic syndrome explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality. Methods Among 6,809 participants of the Multi-Ethnic Study of Atherosclerosis we used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30kg/m2) and MetS (IDF consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions. Results Compared to metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (OR=1.60 (1.14-2.25)), compared to those with stable MHO and healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR=1.62 (1.27-2.07); 2 visits OR=1.92 (1.48-2.49); 3+ visits OR=2.33 (1.89-2.87); p-value for trend <0.001) and MetS mediated approximately 62% (44-100%) of the relationship between obesity at any point during follow-up and CVD. Conclusions Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.