Nonlinear Association Between the C-Reactive Protein-To-Albumin Ratio and Post-Stroke Epilepsy Risk

The C-reactive protein-to-albumin ratio (CAR) is an integrated biomarker of inflammation and nutritional status. Its potential association with the risk of post-stroke epilepsy (PSE) after ischemic stroke (IS) requires comprehensive evaluation.

We analyzed data from 21,459 IS patients admitted to hospitals in Chongqing, China, between June 2017 and July 2023. CAR was calculated from admission laboratory values. The primary outcome was the development of PSE within 1 year. Multivariable logistic regression with three progressively adjusted models was used to control for demographic factors, stroke severity (NIHSS), comorbidities, neuroimaging findings, and extensive laboratory parameters. A restricted cubic spline (RCS) analysis explored the relationship's nonlinearity. Subgroup and sensitivity analyses tested robustness.

Elevated admission CAR was independently associated with increased PSE risk. After full adjustment, each unit increase in CAR yielded an odds ratio (OR) of 1.88 (95% CI: 1.64-2.16, p < 0.001). The ROC analysis showed that the AUC for CAR in predicting PSE was 0.84 (95% CI: 0.83-0.85). RCS analysis revealed a significant nonlinear relationship (p-nonlinearity < 0.001) with an inflection point at CAR = 1.15. A pronounced dose-response relationship was observed across CAR quartiles, with the highest quartile (Q4) showing a substantially elevated risk (adjusted OR = 34.42, 95% CI: 18.58-69.70) compared to the lowest (Q1). Subgroup analyses indicated particularly strong associations in patients with diabetes, coronary artery disease, and middle cerebral artery involvement, confirmed by sensitivity analyses.

CAR is a potent, independent predictor of PSE in IS patients, demonstrating a nonlinear, threshold-based relationship. As an integrative marker, it may enhance early risk stratification and guide personalized interventions, warranting further prospective validation.