Abstract

BACKGROUND: Obesity is a major risk factor for heart failure (HF). Natriuretic peptides (NPs) are cardioprotective hormones released in response to left ventricular (LV) wall stress (WS). Paradoxically, body mass index (BMI) and NP levels are inversely related, suggesting that the associations between BMI, WS, and NPs are not fully understood, particularly among individuals without HF. OBJECTIVES: The purpose of this study was to test the hypothesis that WS mediates, in part, the relationship between BMI and NP levels. METHODS: In 4,444 Atherosclerosis Risk in Communities study participants without HF who underwent transthoracic echocardiography (median 75 years, BMI 27.7 kg/m², 58% women, 18% Black), LV end-diastolic and end-systolic WS (DWS, SWS) were calculated from chamber dimensions, E/e', and blood pressure. Mediation analysis was performed using the product of coefficients method adjusted for demographics, cardiovascular risk factors, cardiovascular disease, medications, creatinine, glucose, LV ejection fraction, and LV mass index. RESULTS: BMI inversely associated with log-transformed N-terminal pro B-type natriuretic peptide (NT-proBNP) (β = -0.069 per 5 kg/m²; 95% CI: -0.096 to -0.042). BMI positively associated with DWS (β = 0.264 per 5 kg/m²; 95% CI: 0.073-0.453) but not SWS (β = -0.168 per 5 kg/m²; 95% CI: -0.708 to 0.403). DWS and SWS positively associated with log-transformed NT-proBNP (DWS: β = 0.011; 95% CI: 0.005-0.015; SWS: β = 0.004; 95% CI: 0.002-0.006). The association of BMI and NT-proBNP was partially mediated by DWS (mediation effect: 0.0028; 95% CI: 0.0006-0.0055) but not SWS (mediation effect: -0.0006; 95% CI: -0.0032 to 0.0015). CONCLUSIONS: Among older adults without HF, BMI positively associates with DWS, and DWS positively relates with NT-proBNP, which does not account for the net inverse relationship between BMI and NT-proBNP.