Intrinsic capacity and the trajectory of ischemic heart disease and its complications: the mediating role of insulin resistance indices.

Authors

Nana Wang, Yongli Yang, Xiaocan Jia, Chaojun Yang, Yuping Wang, Jingwen Fan, Chenyu Zhao, Yali Niu, Zhixing Fan, Xuezhong Shi

Published in

Maturitas. Volume 211. Pages 109049. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

This study investigated the associations of intrinsic capacity, a multidomain measure of functional health, with the incidence and progression of ischemic heart disease, and the mediation of such associations by indices related to insulin resistance (IR).
We included 386,462 adults from the UK Biobank who were free of ischemic heart disease and its associated complications, including heart failure and arrhythmia, at baseline. Associations were estimated using Cox models, and multistate models for transitions. Mediation by IR-related indices was quantified in a counterfactual framework.
Over a median 13.68 years of follow-up, 29,994 ischemic heart disease events occurred. Hazard ratios (95% confidence intervals) for ischemic heart disease were 1.15 (1.11-1.18), 1.38 (1.33-1.43), 1.68 (1.61-1.75), and 2.24 (2.12-2.37) for intrinsic capacity scores of 1, 2, 3, and ≥4 versus 0. Estimates from the multistate model for the transition from baseline to ischemic heart disease were consistent with the Cox results. Hazard ratios (95% confidence intervals) for transition from ischemic heart disease to death were 1.32 (1.14-1.53) for intrinsic capacity score 3 and 1.46 (1.21-1.74) for intrinsic capacity score ≥ 4, and 1.30 (1.09-1.56) from complications to death for intrinsic capacity score ≥ 4. IR-related indices accounted for 6.77-22.40% of the association between intrinsic capacity and ischemic heart disease, 5.38-24.24% for complications, and 2.22-10.04% for death.
Lower intrinsic capacity was associated with higher risks of ischemic heart disease and its progression, partly through IR-related pathways, supporting metabolic dysfunction as a modifiable target for early risk stratification.

PMID:
42401064
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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