Systemic immune-inflammation index predicts first stroke and affects the efficacy of folic acid in stroke prevention

Systemic immune-inflammation index (SII) is a novel biomarker of growing interest in predicting stroke. The aim of this study was to investigate its predictive value and explore its effect modification on folic acid supplement for stroke primary prevention in a Chinese population with hypertension. A total of 10,013 participants from the China Stroke Primary Prevention Trial with available neutrophil, platelet and lymphocyte count were included, including 5,019 subjects in the enalapril group and 4,994 in the enalapril-folic acid group. SII was calculated as (platelet × neutrophil)/lymphocyte. The primary endpoint was first stroke. Cox proportional hazards models were used to evaluate the association between SII and first stroke. A U-shape association between SII and first stroke risk was observed in enalapril group. Compared with the reference group (Quartile 2: 335.1 to <443.9 × 10 9  cell/L), the adjusted HRs were 1.68 (95 % CI: 1.06–2.66, P  = 0.027) in Quartile 1 (<335.1 × 10 9  cell/L), 1.43 (95 % CI: 0.90–2.27, P  = 0.126) in Quartile 3 (443.9 to <602.6 × 10 9  cell/L), and 1.61 (95 % CI: 1.03–2.51, P  = 0.035) in Quartile 4 (≥602.6 × 10 9  cell/L). There was no significant association between SII and first stroke in the enalapril-folic acid group, with adjusted HR of 0.92 (95%CI: 0.54–1.56, P  = 0.749) in Quartile 1(<334.7 × 10 9  cell/L), 1.36 (95%CI: 0.84–2.21, P  = 0.208) in Quartile 3 (446.2 to <595.2 × 10 9  cell/L), and 1.41 (95%CI: 0.87–2.27, P  = 0.163) in Quartile 4 (≥595.2 × 10 9  cell/L). A remarkable interaction between baseline SII and folic acid supplement for stroke prevention was observed, with particularly reduced risk by 44 % (HR: 0.56; 95 % CI: 0.34–0.90; P  = 0.018) in the lowest SII group ( P for interaction = 0.041). Among Chinese adults with hypertension, both low and high SII at baseline predicted increased first stroke risk. And compensatory folic acid particularly reduced first stroke risk in the lowest SII subgroup.