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

OBJECTIVE: It is controversial whether adults who are obese, but "metabolically healthy" have cardiovascular disease (CVD) risk comparable to 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).

RESEARCH DESIGN AND METHODS: 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 body mass index (BMI) to define obesity phenotypes as metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOv), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOv), and metabolically unhealthy obese (MUO).

RESULTS: At baseline (1990-1992), mean age was 56 years, 56% were female, 23% Black, 25% detectable hs-cTnT(≥ 6 ng/L). Over a median 17 years of follow-up, there were 2,603 clinical CVD events. The MHO (HR 1.38, 95%CI:1.15-1.67), MUNW (HR 1.51, 95%CI:1.30-1.76), MUOv (HR 1.60, 95%CI:1.41-1.82) and MUO (HR 2.14, 95%CI: 1.88-2.44) phenotypes had higher CVD risks than the MHNW. Detectable hs-cTnT(≥ 6 ng/L) was associated with higher CVD risk, even among MHNW adults. MHO adults had higher HF risk (HR 1.65, 95%CI:1.30-2.09) than the MHNW.

CONCLUSIONS: The MHO 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 persons who appear otherwise metabolically healthy.