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Background: Unfavorable sleep habits have been linked with ischemic stroke in observational studies, but the causality remains unclear. The aim of this study is to investigate the potential causal role of three sleep traits, including sleep duration, insomnia, and chronotype, in ischemic stroke and its subtypes. Methods: We conducted two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms associated with sleep duration, insomnia, and chronotype as instruments to estimate causal associations with ischemic stroke and its subtypes, among 34,217 ischemic stroke cases and 406,111 controls from the MEGASTROKE consortium. Inverse-variance weighted method was used as the main analyses. Alternative MR methods and sensitivity analyses were further performed. Results: We found suggestive evidence that per doubling of genetic liability for short sleep duration (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01-1.58) and frequent insomnia symptoms (OR, 1.19; 95% CI, 1.00-1.41) were associated with a modest increase in risk of large artery stroke (LAS) but not with small vessel stroke, cardioembolic stroke, or any ischemic stroke. The association of frequent insomnia symptoms with LAS was stronger after the exclusion of the outlier (OR, 1.25; 95% CI, 1.04-1.50). No significant association was observed for chronotype with any ischemic stroke subtype. Results were overall robust to sensitivity analyses, and there was little evidence of horizontal pleiotropy. Conclusion: We provided suggestive evidence for a potential causal role of short sleep duration and insomnia symptoms in LAS. Future researches are required to investigate whether improved sleep habits could help to mitigate LAS risk.

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Compared with patients who received usual care for osteoporotic fracture, patients participating in a postfracture disease management program had substantially higher rates of medical attention given for osteoporosis; however, the overall yield of the program was low. This low uptake rate was related to factors not previously appreciated: many patients refused participation in the program; a high proportion of younger women-and men of all ages-did not qualify for treatment; and treatment was refused by one in three study-qualified women and by one in seven study-qualified men. Additional efforts are needed to overcome patient barriers to improved osteoporosis evaluation, treatment and participation in postfracture programs.