Background: A recent study found that US women aged 45–54 years in 1999–2004 were twice as likely as men to report previous stroke. The aim of this study was to evaluate the validity of this finding by assessing the sex-specific midlife stroke prevalence in the most recent nationally representative, cross-sectional sample of US individuals. Methods: Sex-specific stroke prevalence, sex-specific vascular risk factor prevalence and sex-specific independent predictors of stroke were assessed among 35- to 64-year olds who participated in the National Health and Nutrition Examination Surveys in 2005–2006 (n = 2,274). Results: Women aged 35–64 years were almost 3 times more likely than men to report prior stroke (2.90 vs. 1.07%; p < 0.001). This disparity was driven by the 45- to 54-year age group, where women had thrice the odds of prior stroke compared with men (OR 3.12, 95% CI 1.30–7.50). Among 45- to 54-year olds, men were more likely than women to have a history of smoking, elevated homocysteine and elevated triglyceride levels, but less likely to be abdominally obese (p < 0.001). Independent stroke risk factors among women aged 35–64 years were a homocysteine level >8.5 µmol/l (OR 6.19, 95% CI 2.57–14.93), a history of myocardial infarction (OR 5.35, 95% CI 1.09–26.27) and diabetes mellitus (OR 6.63, 95% CI 2.47–17.81). Conclusion: The midlife sex disparity in US stroke prevalence persists. Greater emphasis on prompt recognition and treatment of cardiovascular risk factors among young and middle-aged women may ameliorate this worrisome trend.

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