Myocardial Injury, Obesity, and the Obesity Paradox: The ARIC Study

Abstract

Objectives: This study sought to determine whether pre-heart failure (HF) myocardial injury explains the differential mortality after HF across weight categories.

Background: Obesity is a risk factor for HF, but pre-HF obesity is associated with lower mortality after incident HF. High-sensitivity cardiac troponin T (hs-cTnT) is a sensitive marker of myocardial injury, and predicts incident HF and mortality.

Methods: Stratifying 1,279 individuals with incident HF hospitalizations by their pre-HF hs-cTnT levels (< and ≥ 14 ng/l), we examined the association of pre-HF body mass index (BMI) with mortality after incident HF hospitalization in the ARIC (Atherosclerosis Risk In Communities) study.

Results: Mean age at HF was 74 years (53% women, 27% black). Individuals with pre-HF hs-cTnT ≥14 ng/l had higher mortality after incident HF (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.18 to 1.80) compared to individuals with hs-cTnT <14 ng/l in an adjusted model including BMI. Compared with normal weight subjects, the mortality was lower in overweight (HR: 0.69, 95% CI 0.48-0.98) and obese individuals (HR: 0.50; 95% CI: 0.35 to 0.72) with hs-cTnT <14 ng/l; and in those with hs-cTnT ≥14 ng/l (overweight HR: 0.50; 95% CI: 0.30 to 0.83; obese HR: 0.56; 95% CI: 0.34 to 0.91; interaction: p = 0.154 between BMI and hs-cTnT). The lower mortality risk in obese and overweight subjects remained similar when log hs-cTnT was added as a continuous variable to a multivariable model, and in sensitivity analyses after further adjusting for left ventricular hypertrophy or high-sensitivity C-reactive protein.

Conclusion: Although greater pre-existing subclinical myocardial injury was associated with higher mortality after incident HF hospitalization, it did not explain the obesity paradox in HF, which was observed irrespective of subclinical myocardial injury. (Atherosclerosis Risk In Communities [ARIC]; NCT00005131).

Keywords: heart failure; myocardial injury; obesity paradox; outcomes.

Figure 1. Development of the Study Cohort

BMI = body mass index, HF = heart failure, hs-cTnT = cardiac troponin T measured using high-sensitivity assay

Figure 2

A. Kaplan-Meier Survival Curves by BMI groups in individuals with pre-HF hs-cTnT <14ng/L B. Kaplan-Meier Survival Curves by BMI groups in individuals with pre-HF hs-cTnT ≥14ng/L HF = heart failure, hs-cTnT = cardiac troponin T measured using high-sensitivity assay

Figure 3. Hazard ratios for all-cause mortality by pre-HF BMI and hs-cTnT

Hazard ratios for each group based on reference group of normal weight with pre-HF hs-cTnT levels <14 ng/ml. The model was adjusted for age, gender, race, education level, health insurance, systolic blood pressure, physical activity, total cholesterol, current smoking, current alcohol use, eGFR, diabetes mellitus, hypertension, history of coronary heart disease, TIA/stroke and cancer.