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Association between neutrophil-to-lymphocyte ratio and cerebral small vessel disease: a systematic review and
1Department of Neurology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Insights
The neutrophil-to-lymphocyte ratio (NLR) is linked to cerebral small vessel disease (CSVD) markers, especially white matter hyperintensities and lacunes. This suggests NLR may indicate inflammatory pathways in ischemic small vessel injury.
Area of Science:
- Neurology
- Inflammation Research
- Vascular Biology
Background:
- Cerebral small vessel disease (CSVD) is a significant cause of stroke and dementia.
- The neutrophil-to-lymphocyte ratio (NLR) is a readily available inflammatory marker.
- Previous studies on NLR and CSVD have yielded inconsistent results.
Purpose of the Study:
- To conduct a meta-analysis to quantify the association between NLR and CSVD imaging markers.
- To investigate NLR's relationship with overall CSVD burden and specific imaging subtypes.
Main Methods:
- A systematic search of PubMed, Embase, and Cochrane Library was conducted up to August 10, 2025.
- Fifteen studies with 62,961 participants were included in the meta-analysis.
- Outcomes assessed included CSVD presence, total burden, white matter hyperintensities (WMH), lacunes, microbleeds (CMBs), and enlarged perivascular spaces (EPVS).
Main Results:
- Elevated NLR was associated with the presence of CSVD (OR 1.43) and higher total CSVD burden (OR 1.55).
- NLR showed associations with WMH (severe WMH: OR 1.36; WMH volume: β=0.08) and lacunes (OR 1.26).
- No significant association was found between NLR and CMBs (OR 0.94), with limited data for EPVS.
Conclusions:
- Higher NLR is consistently associated with ischemic CSVD markers, particularly WMH and lacunes.
- NLR may reflect inflammatory processes involved in ischemic small vessel injury.
- Further longitudinal studies are required to confirm the causal and clinical significance of NLR in CSVD.
Background And Objectives:
Cerebral small vessel disease (CSVD) causes about 25% of ischemic strokes, most intracerebral hemorrhages, and is a major cause of vascular dementia. The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, has shown inconsistent associations with CSVD. We performed a meta-analysis to quantify the association between NLR and CSVD imaging markers.
Methods:
Pubmed, Embase, and Cochrane Library were searched through August 10, 2025 for studies of NLR and CSVD. Fifteen studies (n = 62,961) were included. Outcomes included CSVD presence, total CSVD burden, and imaging subtypes (white matter hyperintensities [WMH], lacunes, microbleeds [CMBs], enlarged perivascular spaces [EPVS]).
Results:
Elevated NLR was associated with presence of CSVD (OR 1.43, 95% CI 1.07-1.93) and greater total CSVD burden (OR 1.55, 95% CI 1.11-2.18). NLR also had associations with WMH (severe WMH: OR 1.36, 95% CI 1.04-1.76; WMH volume: β=0.08, 95% CI 0.02-0.15) and lacunes (OR 1.26, 95% CI 1.16-1.36); it was not associated with CMBs (OR 0.94, 95% CI 0.82-1.09), and EPVS data were limited. Substantial heterogeneity was noted for CSVD and WMH but not for lacunes or CMBs. Removing one study resolved heterogeneity for total CSVD burden, and excluding a high-bias study eliminated the WMH severity association.
Conclusion:
Higher NLR showed a limited but consistent association with ischemic CSVD markers, particularly WMH and lacunes, whereas no association was observed with hemorrhagic markers such as CMBs. NLR may therefore reflect inflammatory pathways more closely related to ischemic small vessel injury, but larger longitudinal studies are needed to confirm its causal and clinical relevance.
Systematic Review Registration:
https://www.crd.york.ac.uk/PROSPERO/view/CRD420251125195, identifier: CRD420251125195.
