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Systemic immune-inflammation index predicts first stroke and affects the efficacy of folic acid in stroke prevention
Xiying Chi1,2, Nan Zhang1,2, Fangfang Fan1,2
1Department of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
Insights
Systemic immune-inflammation index (SII) predicts stroke risk in hypertensive adults. Folic acid supplementation significantly reduced stroke risk, especially in individuals with the lowest SII levels.
Area of Science:
- Cardiovascular Medicine
- Inflammation Research
- Biomarker Discovery
Background:
- Systemic immune-inflammation index (SII) is an emerging biomarker for stroke prediction.
- Hypertension is a major risk factor for stroke.
- Investigating novel biomarkers and preventive strategies is crucial for cardiovascular health.
Purpose of the Study:
- To evaluate the predictive value of SII for first stroke in a Chinese hypertensive population.
- To explore the modifying effect of folic acid supplementation on the association between SII and stroke risk.
- To determine the optimal intervention strategy for stroke prevention based on SII levels.
Main Methods:
- Analysis of 10,013 participants from the China Stroke Primary Prevention Trial.
- Calculation of SII using neutrophil, platelet, and lymphocyte counts: (platelet × neutrophil)/lymphocyte.
- Application of Cox proportional hazards models to assess the association between SII and first stroke.
Main Results:
- A U-shaped association was observed between SII and first stroke risk in the enalapril group, with both low and high SII predicting increased risk.
- No significant association between SII and first stroke was found in the enalapril-folic acid group.
- A significant interaction revealed that folic acid supplementation reduced stroke risk by 44% in the lowest SII subgroup (P for interaction = 0.041).
Conclusions:
- Both low and high baseline SII levels are associated with increased first stroke risk in Chinese hypertensive adults.
- Folic acid supplementation demonstrates a compensatory effect, particularly reducing stroke risk in individuals with the lowest SII.
- SII may serve as a valuable biomarker for stratifying stroke risk and guiding preventive interventions.
Background:
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.
Methods:
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.
Results:
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 × 109 cell/L), the adjusted HRs were 1.68 (95 % CI: 1.06-2.66, P = 0.027) in Quartile 1 (<335.1 × 109 cell/L), 1.43 (95 % CI: 0.90-2.27, P = 0.126) in Quartile 3 (443.9 to <602.6 × 109 cell/L), and 1.61 (95 % CI: 1.03-2.51, P = 0.035) in Quartile 4 (≥602.6 × 109 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 × 109 cell/L), 1.36 (95%CI: 0.84-2.21, P = 0.208) in Quartile 3 (446.2 to <595.2 × 109 cell/L), and 1.41 (95%CI: 0.87-2.27, P = 0.163) in Quartile 4 (≥595.2 × 109 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).
Conclusions:
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.
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