Associations of cumulative exposure and dynamic trajectories of the combined atherogenic-frailty index with incident cardiometabolic multimorbidity: a prospective cohort study.
- 1Department of Cardiology, The First Hospital of Jilin University, Changchun, China.
- 2Department of Geriatrics, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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.
Related
- Associations of cumulative exposure and dynamic trajectories of the combined estimated glucose disposal rate and frailty index with incident cardiometabolic multimorbidity comprising diabetes, heart disease, and stroke: a longitudinal analysis based on the China health and retirement longitudinal study (CHARLS)
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- Ultra-processed food indices and component food groups in relation to incident type 2 diabetes and cardiometabolic multimorbidity: a prospective cohort study
- Longitudinal joint trajectories of the dietary inflammatory index and physical activity and risk of incident cardiometabolic multimorbidity among women: evidence from the China Health and Nutrition Survey
- Differential associations of baseline, dynamic change, and cumulative average TyG-BMI with incident cardiometabolic multimorbidity: a longitudinal landmark analysis of CHARLS
BibTeX
@article{wu2026associations,
title = {{Associations of cumulative exposure and dynamic trajectories of the combined atherogenic-frailty index with incident cardiometabolic multimorbidity: a prospective cohort study.}},
author = {Haidi Wu and Zikai Song and Tengfei Ye and Chunhua Yang},
journal = {Journal of global health},
year = {2026},
month = oct,
doi = {10.7189/jogh.16.04319},
url = {https://europepmc.org/article/MED/42895260},
note = {CC BY},
}
RIS
TY - JOUR
TI - Associations of cumulative exposure and dynamic trajectories of the combined atherogenic-frailty index with incident cardiometabolic multimorbidity: a prospective cohort study.
AU - Haidi Wu
AU - Zikai Song
AU - Tengfei Ye
AU - Chunhua Yang
PY - 2026
DA - 2026/10/19
JO - Journal of global health
DO - 10.7189/jogh.16.04319
UR - https://europepmc.org/article/MED/42895260
AB - 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.
SN - 2047-2978
SN - 2047-2986
ER -