Development and internal validation of an inflammation-platelet synergy score for anterior circulation cerebral...

Inflammatory and thrombotic pathways interact in atherothrombotic stroke pathogenesis, yet combined assessment of these markers for distinguishing patients with anterior circulation cerebral infarction from high-risk controls remains underexplored. We aimed to develop and internally validate an inflammation-platelet synergy score in an exploratory case-control framework.

This retrospective case-control study enrolled 203 patients with anterior circulation cerebral infarction and 98 high-risk controls with carotid atherosclerosis from January 2018 to June 2024. The synergy score incorporated six parameters: C-reactive protein (CRP), mean platelet volume (MPV), platelet distribution width (PDW), platelet count, intima-media thickness (IMT), and unstable plaque status. Discriminative performance was assessed using receiver operating characteristic analysis with bootstrap internal validation. Decision curve analysis was performed to evaluate potential clinical utility. Risk stratification was evaluated across low-risk (0-2 points), intermediate-risk (3-4 points), and high-risk (5-7 points) categories.

Cases exhibited significantly elevated CRP (median 6.2 vs. 3.5 mg/L, p < 0.001), MPV (10.64 vs. 9.64 fL, p < 0.001), and IMT (1.16 vs. 0.90 mm, p < 0.001) compared with controls. The synergy score demonstrated good discriminative ability (AUC = 0.824; 95% CI: 0.781-0.867; optimism-corrected AUC = 0.812), outperforming all individual markers (AUC range: 0.582-0.762). Decision curve analysis demonstrated positive net benefit across a range of clinically relevant threshold probabilities (20-60%). Cerebral infarction prevalence increased progressively from 36.0% in low-risk to 87.2% in high-risk groups (OR = 12.10; 95% CI: 5.40-27.15; p < 0.001). In exploratory secondary analyses among cases, higher scores were associated with greater stroke severity (Spearman rho = 0.312, p < 0.001) and unfavorable functional outcome at discharge (51.6% vs. 85.3% for low-risk vs. high-risk; P for trend <0.001).

In this exploratory case-control study, the inflammation-platelet synergy score demonstrated good discriminative ability for anterior circulation cerebral infarction using routinely available parameters. These preliminary findings require prospective validation with pre-event biomarker measurement before any clinical application can be considered.