Individuals with metabolically healthy obesity have been found to have an excess burden of clinical cardiovascular disease (CVD), according to research published in Diabetes Care. High-sensitivity cardiac troponin T (hs-cTnT) can be useful for stratifying CVD risk across obesity phenotypes, even in those who appear to be metabolically healthy.
Whether metabolically healthy obesity is a benign condition is frequently debated in the medical literature, and the full spectrum of CV risk among those with the metabolically healthy obese phenotype is “unclear.” To address this, researchers conducted cross-sectional and prospective analyses of adult participants in the Atherosclerosis Risk in Communities (ARIC) study to categorize obesity phenotypes and study their associations with both subclinical and clinical CVD subtypes.
ARIC is a prospective cohort that includes 15,792 adults between 45 and 64 years of age from North Carolina, Mississippi, Minnesota, and Maryland. Visit 2, conducted between 1990 and 1992, was used as the baseline for the current study.
The primary outcome of this study was composite CVD incidence, which included adjudicated fatal or nonfatal coronary heart disease (CHD), coronary revascularization, silent and unrecognized myocardial infarction, fatal or nonfatal ischemic or hemorrhagic stroke confirmed via imaging, or hospitalization or death from heart failure. Secondary outcomes included separate examinations of CHD and heart failure.
The total study cohort included 9477 participants (mean age, 56 years; 56% women; 23% Black) followed for a median of 27 years. Metabolically healthy obesity was the least common obesity phenotype (7%); metabolically unhealthy overweight and obesity were most common at 23% and 19%, respectively.
Women and Black participants were more likely to be categorized as metabolically healthy obese compared with men and White participants. Participants in this group were more likely to have higher systolic and diastolic blood pressure values, higher body mass index, and were more likely to be diagnosed with hypertension compared with those who were metabolically healthy normal weight or overweight.
Detectible hs-cTnT (≥6 ng/L) was common in those who were overweight or obese (21% and 22%, respectively) but who were metabolically healthy according to other traditional risk factors. Larger waist and hip circumferences were also associated with higher levels of hs-cTnT in both men and women.
Patients with phenotypes that included metabolically healthy obese (prevalence ratio [PR], 1.31), metabolically unhealthy normal weight (PR, 1.23), metabolically unhealthy overweight (PR, 1.28), and metabolically unhealthy obese (PR, 1.78) were more likely to have hs-cTnT levels in the range of 6 to <14 ng/L vs those with a metabolically healthy normal weight phenotype, following adjustment for other risk factors. These groups also had higher odds of elevated hs-cTnT levels (≥14 ng/L) compared with those who were metabolically healthy normal weight.
The median time to event for those who developed CVD (n=2603) was 17 years. Incidence rates of CVD for people who were metabolically healthy obese were intermediate between the metabolically healthy normal weight and metabolically unhealthy obese phenotypes.
Following adjustment for factors such as age, sex, race, smoking status, physical activity level, high sensitivity C-reactive protein, estimated glomerular filtration rate, and N-terminal pro-B-type natriuretic peptide (NT-proBNP), those with a metabolically healthy obese phenotype were more likely to develop CVD compared with those with metabolically healthy normal weight (hazard ratio [HR], 1.38; 95% CI, 1.15-1.67). Those in the metabolically unhealthy obese group had a nearly 2-fold higher CVD risk (HR, 2.14; 95% CI, 1.88-2.44) and a higher risk of heart failure (HR, 1.65; 95% CI, 1.30-2.09) compared with the metabolically healthy normal weight group. The association for CHD was not significant.
Adults who had detectible hs-cTnT had a significantly higher CVD risk compared with those with undetectable levels across all obesity phenotypes. Detectible hs-cTnT was “more strongly associated” with heart failure compared with CHD. Those who were obese with detectable hs-cTnT but who were classified as metabolically healthy had a significantly elevated risk of both CHD and HF (HR, 1.75 and 2.48) vs normal weight individuals with no detectable hs-cTnT levels.
Study limitations include the exclusion of data on impaired glucose tolerance, no assessment of diet information at visit 2 of the study, the hs-cTnT cutoff point limiting generalizability to other assays, exclusion of participants missing hs-cTnT at visit 2, and an inability to eliminate the possibility of residual confounding.
“Routine screening of CVD risk with hs-cTnT among the obese, regardless of current metabolic health, may provide an opportunity to institute intensive lifestyle changes targeting weight loss and pharmacological therapy to prevent subsequent CVD,” the researchers concluded.
Disclosure: Reagents for an assay were donated by Roche Diagnostics. One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Commodore-Mensah Y, Lazo M, Tang O, et al. High burden of subclinical and cardiovascular disease risk in adults with metabolically healthy obesity: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. Published online May 5, 2021. doi:10.2337/dc20-2227