Objective: To determine any sex differences in age-specific prevalence or severity of leukoaraiosis, a marker of white matter ischemia, in population-based and clinic cohorts of TIA/stroke and in a systematic review of the literature.
Methods: Age-specific sex differences were calculated for both CT and MRI in the Oxford Vascular Study (OXVASC) and in an MRI-based clinic cohort. We pooled odds ratios (ORs) for leukoaraiosis in women vs men from published studies by fixed-effect meta-analysis, stratified by patient characteristics (stroke vs nonstroke) and CT vs MRI.
Results: Among 10 stroke studies (all CT-based), leukoaraiosis was most frequent in women (OR = 1.42, 95% confidence interval [CI] 1.27-1.57, p < 0.0001), with little heterogeneity between studies (p = 0.28). However, no such excess was seen in 10 reports of nonstroke cohorts (0.91, 0.67-1.24, p = 0.56). Moreover, excess leukoaraiosis in women on CT-imaging in OXVASC (1.38, 1.15-1.67, p = 0.001) was explained by their older age (age-adjusted OR = 1.01, 0.82-1.25, p = 0.90). Leukoaraiosis was more severe in older (≥ 75) women (CT-1.50, 1.14-1.97, p = 0.004 in OXVASC; MRI-1.70, 1.17-2.48, p = 0.006 in OXVASC and clinic cohort). However, leukoaraiosis was independently associated with early mortality (hazard ratio = 1.46, 1.23-1.73, p < 0.0001), suggesting that comparisons in older age groups will be biased by prior premature death of men with leukoaraiosis. Sex differences in severity of leukoaraiosis were not addressed in previous studies.
Conclusions: Previously reported excess leukoaraiosis in women with TIA/stroke is likely to be confounded by age and apparently greater severity in older women is likely to be biased by premature death in men with leukoaraiosis.