Acta Neurol Belg. 2026 Jul 10. doi: 10.1007/s13760-026-03134-5. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: The predictive value of the atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hsCRP) for stroke is established; however, evidence is largely derived from diabetic cohorts, limiting the generalizability of findings to non-diabetic populations. We therefore conducted this study to specifically assess their combined and interactive associations with stroke in individuals without diabetes.
METHODS: This study included 8,721 participants from the CHARLS baseline (wave1) with no history of stroke or diabetes at baseline. The AIP was calculated as lg[Triglycerides (mmol/L)/HDL-C(mmol/L)]. In a subset of 5,763 participants with repeated measurements, we further analyzed the associations of CumAIP and CumhsCRP with incident stroke.
RESULTS: The results showed that compared to individuals with both low AIP and low hsCRP, those with elevated levels of both had the highest overall risk of stroke (adjusted Hazard Ratio [aHR]: 1.715; 95% Confidence Interval (CI): 1.380-2.130). Compared with the traditional risk factor model, the model adding AIP and hsCRP improved the AUC from 0.664 to 0.673 (P < 0.05), with a continuous Net Reclassification Improvement (NRI) of 0.182 (95% CI: 0.075-0.289) and Integrated Discrimination Improvement (IDI) of 0.009 (95% CI: 0.003-0.015).A total of 435 stroke events were observed during the 5-year follow-up subanalysis, individuals with high levels of both cumulative exposures also had a significantly increased risk (aHR: 1.421; 95% CI: 1.133-1.783).Furthermore, using repeated measurements, mediation analyses demonstrated no statistically significant mediating effect of hsCRP in the association between AIP and stroke. In contrast, AIP exerted a significant mediating effect, accounting for 11.6% of the total effect of hsCRP on stroke.
CONCLUSIONS: The study findings confirm that AIP and hsCRP exert combined effects on stroke risk among non-diabetic middle-aged and older adults. Notably, AIP plays a significant mediating role in the association between elevated hsCRP and stroke. Therefore, integrating both markers into risk assessment is recommended to refine primary stroke prevention and address residual risk among non-diabetic populations, particularly middle-aged adults.
PMID:42426492 | DOI:10.1007/s13760-026-03134-5
