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

Xiying Chi; Nan Zhang; Fangfang Fan; Jia Jia; Jianhang Zheng; Lishun Liu; Yun Song; Binyan Wang; Genfu Tang; Xianhui Qin; Yong Huo; Jianping Li

doi:10.1016/j.heliyon.2024.e24837

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

Heliyon. 2024 Jan 19;10(3):e24837. doi: 10.1016/j.heliyon.2024.e24837. eCollection 2024 Feb 15.

Authors

Xiying Chi^{1

2}, Nan Zhang^{1

2}, Fangfang Fan^{1

2}, Jia Jia^{1

2}, Jianhang Zheng³, Lishun Liu^{4

5}, Yun Song^{5

6

7}, Binyan Wang⁶, Genfu Tang⁸, Xianhui Qin⁹, Yong Huo^{1

2}, Jianping Li^{1

2}

Affiliations

¹ Department of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
² Institute of Cardiovascular Disease, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
³ Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
⁴ Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
⁵ Shenzhen Evergreen Medical Institute, Shenzhen, China.
⁶ Institute for Biomedicine, Anhui Medical University, Hefei, China.
⁷ AUSA Research Institute, Shenzhen AUSA Pharmed Co Ltd, Shenzhen, China.
⁸ School of Health Administration, Anhui Medical University, Hefei, 230000, China.
⁹ National Clinical Research Study Center for Kidney Disease, The State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Abstract

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.

Keywords: CSPPT; First stroke; Hypertension; Systemic immune-inflammation index.