Author:
Jiang Lingling,Cai Xueli,Yao Dongxiao,Jing Jing,Mei Lerong,Yang Yingying,Li Shan,Jin Aoming,Meng Xia,Li Hao,Wei Tiemin,Wang Yongjun,Pan Yuesong,Wang Yilong
Abstract
Abstract
Background
This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD).
Methods
A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed.
Results
At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05–1.70; cOR 1.28, 95% CI 1.02–1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00–1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25–3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14–2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16–2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08–1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20–2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04–1.39) and small vessel stroke (OR 1.21, 95% CI 1.06–1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p < 0.05).
Conclusions
This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC.
Funder
The National Natural Science Foundation of China
Zhejiang provincial program for the Cultivation of High-level Innovative Health talents
Key Science & Technologies R&D Program of Lishui City
grants from AstraZeneca Investment (China) Co., Ltd
Beijing Outstanding Young Scientist Program
Youth Beijing Scholar Program
Beijing Talent Project-Class A: Innovation and Development
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Reference47 articles.
1. Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019;18(7):684–96.
2. Evans LE, Taylor JL, Smith CJ, Pritchard HAT, Greenstein AS, Allan SM. Cardiovascular comorbidities, inflammation, and cerebral small vessel disease. Cardiovasc Res. 2021;117(13):2575–88.
3. Low A, Mak E, Rowe JB, Markus HS, O’Brien JT. Inflammation and cerebral small vessel disease: a systematic review. Ageing Res Rev. 2019;53: 100916.
4. Fu Y, Yan Y. Emerging role of immunity in cerebral small vessel disease. Front Immunol. 2018;9:67.
5. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159–75.