Abstract

Background: Debate over the cardiometabolic risk associated with metabolically healthy obesity continues.Many studies have investigated this relationship by examining metabolically healthy obesity at baseline with longitudinal follow-up, with inconsistent results.We hypothesized that metabolic health in obesity at baseline is transient and that transition to metabolic syndrome (MetS) and duration of metabolic syndrome would explain heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality.Methods: Among 6809 participants of the Multi-Ethnic Study of Atherosclerosis with nonmissing MetS components and incident event follow-up, we used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30kg/m 2 ) and MetS (IDF consensus definition) with CVD and mortality in a variety of ways.We formally tested for interaction and conducted sensitivity analyses for a number of conditions.Results: Compared to metabolically healthy normal weight, baseline metabolically healthy obesity was not significantly associated with CVD; however, almost half of those participants developed MetS and were at increased risk for CVD (OR=1.60 (1.14-2.25)).Dose response for duration of MetS was significantly and linearly associated with higher CVD (1 visit 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 the relationship between obesity at any point during follow-up and CVD was 62% (44-100%) mediated by MetS. Conclusion:Metabolically healthy obesity is not a stable or accurate indicator of future risk for CVD.Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.