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Published on: April 23, 2021
Sex Differences in Frequency, Severity, and Distribution of Cerebral Microbleeds
Simon Fandler-Höfler1,2, Sebastian Eppinger1,3, Gareth Ambler4
1Department of Neurology, Medical University of Graz, Graz, Austria.
Importance:
Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce.
Objective:
To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex.
Design, Setting, And Participants:
This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023.
Main Outcomes And Measures:
Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death.
Results:
A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences.
Conclusions And Relevance:
This cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.
Insights
Sex differences exist in cerebral small vessel disease (SVD) markers like cerebral microbleeds (CMB) and lacunes. These variations suggest potential underlying pathophysiological differences between males and females in SVD manifestation and outcomes.
Area of Science:
- Neurology
- Radiology
- Epidemiology
Background:
- Cerebral small vessel disease (SVD) is a significant contributor to cerebrovascular outcomes.
- Limited data exists regarding sex-based differences in the prevalence, severity, and impact of SVD.
Purpose of the Study:
- To investigate sex-specific differences in the frequency, severity, and distribution of cerebral microbleeds (CMB) and other SVD markers.
- To explore sex differences in outcomes such as mortality and recurrent cerebrovascular events following SVD.
Main Methods:
- Pooled individual patient data from 38 prospective cohort studies (Microbleeds International Collaborative Network) were analyzed.
- Magnetic resonance imaging (MRI) was used to identify SVD markers including CMB, lacunes, and white matter hyperintensities.
- Multivariable regression models were employed to assess sex differences in SVD markers and clinical outcomes.
Main Results:
- Cerebral microbleeds (CMB) were more frequent in male patients (adjusted odds ratio [aOR], 0.86; P < .001).
- Female patients exhibited fewer lacunes (aOR, 0.82; P < .001) but more severe white matter hyperintensities (aOR, 1.10; P = .04) compared to males.
- CMB presence was linked to increased mortality risk in females (hazard ratio, 1.15; P = .01), but not in males.
Conclusions:
- Significant sex differences were observed in the prevalence of SVD markers, suggesting distinct pathophysiological pathways.
- Further research is warranted to elucidate the specific pathomechanisms and clinical implications of SVD in relation to sex.
