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Association of inflammatory markers with cerebral small vessel disease in community-based population
Lingling Jiang1,2, Xueli Cai3, Dongxiao Yao1,2
1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing, 100070, China.
Insights
Higher neutrophil count (NC) is suggestively linked to cerebral small vessel disease (CSVD) and its markers like lacunes and enlarged perivascular spaces. Neutrophil count also shows prognostic significance for CSVD presence.
Area of Science:
- Neurology
- Immunology
- Vascular Medicine
Background:
- Cerebral small vessel disease (CSVD) is a significant cause of stroke and cognitive decline.
- Inflammatory markers, including neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), are increasingly recognized for their role in vascular pathologies.
Purpose of the Study:
- To investigate the associations between NC, NLR, and SII and the presence and burden of CSVD.
- To explore the prognostic value of these inflammatory markers in predicting CSVD.
Main Methods:
- Cross-sectional analysis of 3052 community-dwelling residents from the PRECISE study.
- Assessment of CSVD burden and imaging markers (WMH, lacunes, CMBs, BG-EPVS) using a total CSVD burden score.
- Logistic regression models and two-sample Mendelian randomization (MR) analysis to evaluate associations and genetic predictions.
- Evaluation of prognostic performance using net reclassification and integrated discrimination indices.
Main Results:
- Higher NC was suggestively associated with increased total CSVD burden, lacunes, and moderate-to-severe BG-EPVS.
- Elevated NLR was linked to moderate-to-severe BG-EPVS.
- Higher SII was associated with increased modified WMH burden and moderate-to-severe BG-EPVS.
- MR analysis indicated genetically predicted higher NC is associated with increased risk of lacunar and small vessel stroke.
- NC improved the predictive ability for CSVD presence when added to traditional risk factors.
Conclusions:
- Suggestive association found between neutrophil count and cerebral small vessel disease, particularly BG-EPVS and lacunes.
- Neutrophil count demonstrates prognostic significance for the presence of CSVD.
- Inflammatory markers, especially NC, may serve as valuable indicators in CSVD assessment and prediction.
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.
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