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

Abstract

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.

Figure 1. Odds of All Stroke, ICH, and Ischemic Stroke*

*Conditional logistic regression adjusted for age, occupation, marital status, and mRS at baseline (primary model). OR presented on a log scale. ICH = intracranial hemorrhage; mRS = modified Rankin scale; OR = odds ratio.

Figure 2. Odds of All Stroke for Poor or Fair Sleep Quality, Sleep-onset Latency, Waking More Than Once, and Napping Status

Adjustment models are as follows: model 1: univariate (conditional); model 2: adjusted for occupation, age, marital status, and mRS at baseline (conditional); model 3: adjusted for occupation, age, marital status, mRS at baseline, alcohol consumption, smoking history, leisure physical activity, total AHEI score, waist-to-hip ratio, body mass index (kg/m²), depressive symptoms, and global stress (conditional); model 4: adjusted for occupation, age, marital status, mRS at baseline, alcohol consumption, smoking history, leisure physical activity, total AHEI score, waist-to-hip ratio, body mass index (kg/m²), depressive symptoms, global stress, a history of hypertension or adjusted BP >140/90 mm Hg at admission, a history of diabetes or hemoglobin A1c ≥6.5%, a history of atrial fibrillation/flutter, and a diagnosis of OSA (conditional). *For all panels (A–D), the reference level for each individual sleep parameter is displayed in brackets. AHEI = Alternative Healthy Eating Index; BP = blood pressure; mRS = modified Rankin scale; OR = odds ratio; OSA = obstructive sleep apnea.

Figure 3. Odds of All Stroke for Snoring, Snorting, Breathing Cessation, and OSA Score

Panels A–C demonstrate odds of all stroke for symptoms of, or uncertainty surrounding, snoring, snorting, or gasping and breathing cessation, respectively. Panel D demonstrates the odds of all stroke, ischemic stroke, and ICH with a potential OSA score of 2–3. Adjustment models are as follows: model 1: univariate (conditional); model 2: adjusted for occupation, age, marital status, and mRS at baseline (conditional); model 3: adjusted for occupation, age, marital status, mRS at baseline, alcohol consumption, smoking history, leisure physical activity, total AHEI score, waist-to-hip ratio, body mass index (kg/m²), depressive symptoms, and global stress (conditional); model 4: adjusted for occupation, age, marital status, mRS at baseline, alcohol consumption, smoking history, leisure physical activity, total AHEI score, waist-to-hip ratio, body mass index (kg/m²), depressive symptoms, global stress, a history of hypertension or adjusted BP >140/90 mm Hg at admission, a history of diabetes or hemoglobin A1c ≥6.5%, a history of atrial fibrillation/flutter, and a diagnosis of OSA (conditional). *For all panels (a-d), the reference level for each individual sleep parameter is displayed in brackets. AHEI = Alternative Healthy Eating Index; BP = blood pressure; ICH = intracerebral hemorrhage; mRS = modified Rankin scale; OR = odds ratio; OSA = obstructive sleep apnea.

Figure 4. Sleep Disturbance Symptom Burden

(A) Cumulative number of sleep disturbance symptoms in cases and controls, where sleep disturbance symptoms include the following: sleeping for <6 or >7 hours at night, SOL, waking more than once, napping for >1 hour, unplanned napping, and presence or uncertainty surrounding snorting, snorting or gasping, and breathing cessation or choking. (B) Odds of all stroke in sleep disturbance symptom number categories. OR presented on a log scale. Model 1 is univariate (conditional); model 2 adjusts for occupation, age, marital status, and mRS at baseline (conditional); model 3 adjusts for occupation, age, marital status, mRS at baseline, alcohol consumption, smoking history, leisure physical activity, total AHEI score, waist-to-hip ratio, body mass index (kg/m²), depressive symptoms, and global stress (conditional); model 4 adjusts for occupation, age, marital status, mRS at baseline, alcohol consumption, smoking history, leisure physical activity, total AHEI score, waist-to-hip ratio, body mass index (kg/m²), depressive symptoms, global stress, a history of hypertension or adjusted BP >140/90 mm Hg at admission, a history of diabetes or hemoglobin A1c ≥6.5%, a history of atrial fibrillation/flutter, and a diagnosis of OSA (conditional). AHEI = Alternative Healthy Eating Index; BP = blood pressure; mRS = modified Rankin scale; OR = odds ratio; OSA = obstructive sleep apnea; SOL = sleep-onset latency.