Associations of cumulative exposure and dynamic trajectories of the combined atherogenic-frailty index with incident cardiometabolic multimorbidity: a prospective cohort study.
Wu H, Song Z, Ye T, Yang C • Journal of global health • 2026
In this national cohort, both the cumulative burden and adverse longitudinal trajectories of AIP-FI were independently associated with an elevated risk of CMM.
Key Findings
Results
Higher baseline and higher cumulative AIP-FI were both significantly associated with increased risk of incident cardiometabolic multimorbidity (CMM), with cumulative exposure showing the stronger effect.
The cohort comprised 4,157 CHARLS participants aged ≥45 years without baseline CMM, followed for a mean of 8.5 years, with 612 incident CMM cases.
Fully-adjusted HR per SD increment of cumulative AIP-FI was 1.46 (95% CI = 1.38-1.54).
AIP-FI was constructed as the product of the atherogenic index of plasma (AIP) and a 37-deficit frailty index; cumulative AIP-FI was calculated from repeated measurements.
Associations were evaluated with multivariable Cox models and restricted cubic splines.
Results
Participants in the highest quartile of cumulative AIP-FI had nearly a 4-fold higher CMM risk than those in the lowest quartile.
HR = 3.95 (95% CI = 2.95-5.29) for the highest versus lowest quartile.
This indicates a graded association between cumulative AIP-FI burden and incident CMM.
Results
Longitudinal trajectory analysis showed that the high-stable AIP-FI group had the highest CMM risk.
Trajectories were identified using K-means clustering of repeated AIP-FI measurements.
Groups with high-stable AIP-FI exhibited the highest CMM risks compared with other trajectory groups.
Kaplan-Meier curves were used to compare risk across groups.
Results
Cumulative AIP-FI showed superior predictive performance for CMM and improved risk reclassification over traditional markers.
AUC = 71.17% for cumulative AIP-FI.
NRI = 0.157, indicating significantly improved risk reclassification versus traditional markers.
Evaluation used ROC, NRI, and IDI analyses.
Results
Mediation analyses suggested bidirectional synergistic effects between AIP and the frailty index in relation to CMM.
Mediation analyses were conducted between AIP and FI components of the composite index.
The authors interpret the findings as bidirectional synergistic effects.
Interaction, subgroup, and sensitivity analyses were also performed.
Conclusions
The authors conclude that dynamic monitoring of AIP-FI could facilitate early identification of high-risk middle-aged and older adults in China.
Both cumulative burden and adverse longitudinal trajectories were independently associated with elevated CMM risk.
The data come from a national cohort (CHARLS).
What This Means
This study followed 4,157 middle-aged and older adults in China who did not initially have cardiometabolic multimorbidity (having two or more conditions such as heart disease, stroke, and diabetes). Researchers combined two measures: a blood-based marker of unhealthy blood fats (the atherogenic index of plasma) and a frailty index based on 37 health deficits. They multiplied these to form a single score and tracked it over about 8.5 years, during which 612 people developed multimorbidity.
People whose scores were higher, especially when accumulated over time, had a greater risk of developing multiple cardiometabolic diseases. Those in the highest quartile of cumulative score had nearly four times the risk of those in the lowest. People whose scores stayed high over time had the highest risk. The cumulative score also predicted risk better than traditional markers, though its predictive accuracy was moderate (AUC about 71%).
This research suggests that tracking blood-fat abnormalities and frailty together over time may help identify people at higher risk of developing multiple cardiometabolic conditions. Because this is an observational study, it shows associations rather than proving cause, and the findings apply to a Chinese population aged 45 and older.
Wu H, Song Z, Ye T, Yang C. (2026). Associations of cumulative exposure and dynamic trajectories of the combined atherogenic-frailty index with incident cardiometabolic multimorbidity: a prospective cohort study.. Journal of global health. https://doi.org/10.7189/jogh.16.04319