Does Adiponectin Inform Cardiovascular Risk in Older Adults?: The ARIC Study.

Abushamat LA, Jia X, Xu L, Cheng C, Ndumele CE, Sun C, Windham BG, Matsushita K, Yu B, Nambi V, Bozkurt B, Reusch JEB, Rebholz CM, Selvin E, Ballantyne CM, Hoogeveen RC. Does Adiponectin Inform Cardiovascular Risk in Older Adults?: The ARIC Study. JACC. Advances. 2025 Mar 1; 4(3):101625, DOI: 10.1016/j.jacadv.2025.101625.

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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.