Associations of hematological and biochemical markers with intracranial atherosclerotic stenosis in stroke-free populations: A systematic review and meta-analysis of observational studies

Background and aims: Intracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack. We aimed to synthesize relevant evidence on the associations of hematological and biochemical markers with ICAS in stroke-free populations.

Methods and results: We searched MEDLINE and EMBASE for articles reporting associations of hematological and biochemical markers with ICAS presence in stroke-free populations. Weighted mean difference (WMD) and 95% confidence interval (CI) for each biomarker were pooled using fixed- or random-effects models. Among 32 studies included in the systematic review, 23 studies (48,326 subjects) with 22 biomarkers were meta-analyzed. Compared with subjects without ICAS, those with ICAS had significantly higher white blood cell (4118 subjects, WMD 0.28 per 10⁹/L, 95% CI 0.01-0.56), neutrophil (4326 subjects, WMD 0.24 per 10⁹/L, 0.10-0.38), neutrophil/lymphocyte ratio (4326 subjects, WMD 0.16, 0.07-0.26), low-density lipoprotein (28,606 subjects, WMD 0.12 mmol/L, 0.05-0.19), non-high-density lipoprotein (3671 subjects, WMD 0.17 mmol/L, 0.08-0.25), C-reactive protein (CRP; 5355 subjects, WMD 0.06 mg/dL, 0.04-0.07), high-sensitivity CRP (9383 subjects, WMD 0.07 mg/dL, 0.01-0.13), uric acid (5966 subjects, WMD 17.91 μmol/L, 11.16-24.66), creatinine (5731 subjects, WMD 4.03 μmol/L, 0.77-7.29), and homocysteine (7053 subjects, WMD 2.25 μmol/L, 1.02-3.48), but lower lymphocyte (4326 subjects, WMD -0.12 per 10⁹/L, -0.19--0.04). Sensitivity analyses showed similar results.

Conclusions: Several hematological and biochemical markers easily accessible were associated with ICAS presence in stroke-free populations. This can facilitate early identification of subjects at a high risk of ICAS, who may benefit from ICAS screening and prevention.

Prospero registration number: CRD42021247990.