High Burden of Subclinical and Cardiovascular Disease Risk in Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk in Communities (ARIC) Study

It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF). We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese. At baseline (1990-1992), mean age was 56 years, 56% were female, 23% were Black, and 25% had detectable hs-cTnT (≥6 ng/L). Over a median of 17 years of follow-up, there were 2,603 clinical CVD events. Those with the metabolically healthy obese (hazard ratio [HR] 1.38, 95% CI 1.15-1.67), metabolically unhealthy normal weight (HR 1.51, 95% CI 1.30-1.76), metabolically unhealthy overweight (HR 1.60, 95% CI 1.41-1.82), and metabolically unhealthy obese (HR 2.14, 95% CI 1.88-2.44) phenotypes had higher CVD risks in comparison with metabolically healthy normal weight. Detectable hs-cTnT (≥6 ng/L) was associated with higher CVD risk, even among metabolically healthy normal-weight adults. Metabolically healthy obese adults had higher HF risk (HR 1.65, 95% CI 1.30-2.09) in comparison with metabolically healthy normal weight. The metabolically healthy obese phenotype was associated with excess burden of clinical CVD, primarily driven by an excess risk of HF. hs-cTnT was useful in stratifying CVD risk across all obesity phenotypes, even among obese individuals who appear otherwise metabolically healthy.