Sleep Patterns and the Risk of Acute Stroke: Results From the INTERSTROKE International Case-Control Study

Background and Objectives: Symptoms of sleep disturbance are common and may represent important modifiable risk factors of stroke. We evaluated the association between a spectrum of sleep disturbance symptoms and the risk of acute stroke in an international setting. Methods: The INTERSTROKE study is an international case-control study of patients presenting with first acute stroke and controls matched by age (±5 years) and sex. Sleep symptoms in the previous month were assessed through a questionnaire. Conditional logistic regression estimated the association between sleep disturbance symptoms and acute stroke, expressed as odds ratios (ORs) and 95% CIs. The primary model adjusted for age, occupation, marital status, and modified Rankin scale at baseline, with subsequent models adjusting for potential mediators (behavioral/disease risk factors). Results: Overall, 4,496 matched participants were included, with 1,799 of them having experienced an ischemic stroke and 439 an intracerebral hemorrhage. Short sleep (<5 hours: OR 3.15, 95% CI 2.09-4.76), long sleep (>9 hours: OR 2.67, 95% CI 1.89-3.78), impaired quality (OR 1.52, 95% CI 1.32-1.75), difficulty getting to sleep (OR 1.32, 95% CI 1.13-1.55) or maintaining sleep (OR 1.33, 95% CI 1.15-1.53), unplanned napping (OR 1.48, 95% CI 1.20-1.84), prolonged napping (>1 hour: OR 1.88, 95% CI 1.49-2.38), snoring (OR 1.91, 95% CI 1.62-2.24), snorting (OR 2.64, 95% CI 2.17-3.20), and breathing cessation (OR 2.87, 95% CI 2.28-3.60) were all significantly associated with an increased odds of acute stroke in the primary model. A derived obstructive sleep apnea score of 2-3 (2.67, 2.25-3.15) and cumulative sleep symptoms (>5: 5.38, 4.03-7.18) were also associated with a significantly increased odds of acute stroke, with the latter showing a graded association. After an extensive adjustment, significance was maintained for most of the symptoms (not difficulty getting to/maintaining sleep and unplanned napping), with similar findings for stroke subtypes. Discussion: We found that sleep disturbance symptoms were common and associated with a graded increased risk of stroke. These symptoms may be a marker of increased individual risk or represent independent risk factors. Future clinical trials are warranted to determine the efficacy of sleep interventions in stroke prevention.