Prognostic Value of High-Sensitivity C-reactive Protein, Interleukin-6, and Lipoprotein(a) in Acute Ischemic Stroke and Recurrent Cerebrovascular Events: A Systematic Review and Meta-Analysis

High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and lipoprotein(a) (Lp(a)) are circulating biomarkers that reflect distinct components of the inflammatory and atherothrombotic cascade implicated in acute ischemic stroke (AIS).Elevated hs-CRP, a sensitive acute-phase reactant, has been associated with worse functional outcomes after AIS, while IL-6, a pleiotropic pro-inflammatory cytokine, has been linked to infarct severity and neurological deficit.Lp(a), a pro-atherogenic and pro-thrombotic lipoprotein particle, has been implicated in both incident and recurrent cerebrovascular events.However, individual studies have reported heterogeneous associations, and the comparative prognostic value of these biomarkers for poor functional outcomes and recurrent cerebrovascular events remains uncertain.This systematic review and meta-analysis aimed to determine the prognostic value of hs-CRP, IL-6, and Lp(a) for predicting poor functional outcomes and recurrent cerebrovascular events among patients with AIS.A systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted for studies published from January 2000 to December 2025.Studies reporting associations between baseline biomarker levels and AIS outcomes were included.Random-effects models were used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs).Subgroup analyses were performed according to biomarker type, timing of biomarker measurement, geographic region, and timing of outcome assessment.Twelve studies involving 13,523 patients were included.Elevated biomarker levels were significantly associated with poor functional outcomes (pooled OR: 2.28, 95% CI: 1.77-2.80,p = 0.001), with substantial heterogeneity (I² = 90.38%).hs-CRP demonstrated the most consistent association with poor outcomes (OR: 2.29, 95% CI: 1.96-2.61,I² = 26.84%),followed by IL-6 (OR: 2.30, 95% CI: 0.21-4.40,I² = 95.33%),which did not reach statistical significance.Similar prognostic associations were observed according to biomarker measurement timing (<24 hours: OR 2.30; 24-72 hours: OR 2.18) and geographic region (Asia: OR 2.30; Europe: OR 2.37).Timing of outcome assessment accounted for approximately 40% of the observed heterogeneity, with stronger associations observed at assessments conducted at ≤three months and >six months.Egger's test did not indicate significant publication bias (p = 0.073).Elevated levels of hs-CRP and IL-6, together with Lp(a), were associated with unfavorable clinical outcomes and recurrent cerebrovascular events in patients with AIS.These findings suggest that inflammatory biomarkers may have potential utility in prognostic risk stratification among patients with AIS, although further research is required to establish their clinical applicability.