Abstract
BACKGROUND: Adiponectin, an atheroprotective adipokine, is associated with adverse outcomes in older age. It is unclear whether this is due to overlapping pathophysiological pathways with N-terminal pro-B-type natriuretic peptide (NT-proBNP). OBJECTIVES: The authors investigated adiponectin's associations with cardiovascular disease (CVD) risk in older adults. METHODS: Among Atherosclerosis Risk in Communities prospective cohort study participants without baseline CVD at visit 5 (n = 4,729, mean age 75), adiponectin and adiponectin/NT-proBNP category associations with incident CVD events (heart failure [HF], atherosclerotic cardiovascular disease, and death during median follow-up of 5.5 years) and echocardiographic parameters were assessed. Metabolomic signatures of adiponectin/NT-proBNP categories were explored. RESULTS: Higher adiponectin was associated with older age, female sex, and less obesity, diabetes, and hypertension but increased risk for incident HF (HR: 1.91 [95% CI: 1.49-2.44], per natural-log unit increase) and CVD death (HR: 1.67 [95% CI: 1.19-2.32]). Interaction of NT-proBNP with adiponectin was significant for HF (P-interaction = 0.03). There was no significant association between adiponectin and heart failure with preserved ejection fraction after adjusting for NT-proBNP. Elevations of both biomarkers (A+ [upper tertile]/N+ [≥125 pg/mL]) had higher risk (vs A+/N-; HF: HR 5.41 [95% CI: 2.72-10.78]; CVD death: HR 3.50 [95% CI: 1.48-8.24]). Compared with A+/N-, A-/N+ had increased risk for HF (HR 2.84 [95% CI: 1.41-5.72]) while A-/N- had no increased event risk. A+/N+'s metabolomic signature (88% similar to NT-proBNP's) showed acylcarnitine species consistent with incomplete beta-oxidation; top-associated metabolites were significantly associated with HF and CVD death. CONCLUSIONS: Elevated adiponectin and NT-proBNP in older adults are associated with increased risk for HF and CVD death beyond traditional risk factors.