JACC: Advances (Mar 2025)

Does Adiponectin Inform Cardiovascular Risk in Older Adults?

  • Layla A. Abushamat, MD, MPH,
  • Xiaoming Jia, MD,
  • Lu Xu, MD,
  • Chao Cheng, PhD,
  • Chiadi E. Ndumele, MD, MHS, PhD,
  • Caroline Sun, MPH,
  • B. Gwen Windham, MD, MHS,
  • Kunihiro Matsushita, MD, PhD,
  • Bing Yu, PhD,
  • Vijay Nambi, MD, PhD,
  • Biykem Bozkurt, MD, PhD,
  • Jane E.B. Reusch, MD,
  • Casey M. Rebholz, PhD, MS, MNSP, MPH,
  • Elizabeth Selvin, PhD, MPH,
  • Christie M. Ballantyne, MD,
  • Ron C. Hoogeveen, PhD

Journal volume & issue
Vol. 4, no. 3
p. 101625

Abstract

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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.

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