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Sex differences in Cerebral Small Vessel Disease: a systematic review and meta-analysis.

By Lorena Jimenez Sanchez, Olivia KL Hamilton, Una Clancy, Ellen V Backhouse, Catriona R Stewart, Michael S Stringer, Fergus N Doubal, Joanna Wardlaw

Posted 08 Mar 2021
medRxiv DOI: 10.1101/2021.03.04.21252853

Background: Cerebral small vessel disease (SVD) is an important cause of acute ischemic stroke and vascular dementia. Several studies recruiting more males than females have reported sex differences regarding SVD incidence and severity, but it is unclear whether this reflects underlying sex-specific mechanisms or recruitment bias. This work aimed to systematically review and meta-analyze potential sex differences in SVD by assessing the male-to-female ratio (M:F) of recruited participants and incidence of SVD, risk factor presence, distribution and severity of SVD features. Methods: Full text of 228 studies from four databases of recent systematic reviews on SVD and an independent search of MEDLINE were evaluated against inclusion and exclusion criteria (registered protocol: CRD42020193995). Data from participants with clinical or non-clinical presentations of SVD with radiological evidence of SVD were extracted. Sex ratios of total participants or SVD groups were calculated and differences in sex ratios across time, countries, SVD severity and risk factors for SVD were explored. Results: Amongst 123 relevant studies (n = 36,910 participants) including 53 community-based, 67 hospital-based and 3 mixed studies, more males were recruited in hospital-based than in community-based studies (M:F = 1.16 (0.70) vs M:F = 0.79 (0.35), respectively; p <0.001). More males had moderate to severe SVD (M:F = 1.08 (0.81) vs M:F = 0.82 (0.47) in healthy to mild SVD; p <0.001), especially in stroke presentations where M:F was 1.67 (0.53). M:F of recent research (2015-2020) did not differ from that published pre-2015 and no geographical trends were apparent. There were insufficient sex-stratified data to explore M:F and risk factors for SVD. Conclusions: Our results highlight differences in male-to-female ratios in SVD that may reflect sex-specific variability in risk factor exposures, study participation, clinical recognition, genuine SVD severity, or clinical presentation and have important clinical and translational implications.

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