ArticleJournal of global health2026
Associations of cumulative exposure and dynamic trajectories of the combined atherogenic-frailty index with incident cardiometabolic multimorbidity: a prospective cohort study.
Article in Journal of global health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Cardiometabolic multimorbidity (CMM) poses a growing global health burden, yet effective tools for early risk stratification remain limited. The combined impact of atherogenic dyslipidaemia and physiological frailty, captured by the atherogenic index of plasma-frailty index (AIP-FI), on CMM development is poorly understood. This study aimed to investigate the associations of cumulative exposure and longitudinal trajectories of AIP-FI with incident CMM. Methods: This prospective cohort study included 4,157 participants aged ≥45 years without baseline CMM from CHARLS. The AIP-FI was constructed as the product of AIP and a 37-deficit frailty index. Cumulative AIP-FI was calculated from repeated measurements. Longitudinal trajectories were identified using K-means clustering. Associations with incident CMM were evaluated by multivariable Cox models, RCS, K-M curves, ROC/NRI/IDI, mediation, interaction, subgroup, and sensitivity analyses. Results: Over a mean 8.5-year follow-up, 612 incident CMM cases occurred. Both higher baseline and cumulative AIP-FI were significantly associated with increased CMM risk, with cumulative exposure showing a stronger effect (fully-adjusted HR per SD increment: 1.46; 95% CI = 1.38-1.54). Participants in the highest quartile of cumulative AIP-FI had a near 4-fold higher CMM risk compared to the lowest (HR = 3.95; 95% CI = 2.95-5.29). Clustering analyses revealed that groups with high-stable AIP-FI exhibited the highest CMM risks. Cumulative AIP-FI demonstrated superior predictive performance for CMM (AUC = 71.17%) and significantly improved risk reclassification over traditional markers (NRI = 0.157). Mediation analyses suggested bidirectional synergistic effects between AIP and FI. Conclusions: In this national cohort, both the cumulative burden and adverse longitudinal trajectories of AIP-FI were independently associated with an elevated risk of CMM. Dynamic monitoring of this composite biomarker could facilitate the early identification of high-risk individuals, thereby informing targeted prevention strategies for middle-aged and older adults in China.
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