Isabella Canavero, MD

Titova OE, Michaëlsson K, Larsson SC. Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis. Stroke. 2020;51:3279–3285.

The relationship between sleep and stroke has always represented an intriguing topic. Indeed, it is known that sleep relates to stroke by means of shared medical conditions and risk factors, such as sleep apnea syndrome and nocturnal hypertension. Sleep disturbances are associated to common vascular risk factors, including hypertension, obesity, diabetes, and dyslipidemia. The occurrence of wake-up strokes, in addition, points to further, deeper pathogenic connections.

Beyond the impact of sleep disorders on global vascular risk, a new perspective has been offered by studies investigating the effects that sleep features have on patients’ stroke risk. Previous studies centered on sleep duration and stroke found variable associations. Here, Titova et al. explored the relationship between sleep duration and risk of stroke by evaluating data from a large Swedish cohort made of nearly 80,000 subjects. Data were obtained from cross-matching large national prospective databases. Patients selected were those included in the national Patient Register who were administered a questionnaire about sleep features in the late ‘90s. The latter was done with the objective of covering an extended follow up timeframe to detect the occurrence of cerebrovascular events over time. Of interest, both hemorrhagic and ischemic stroke, including ischemic subtypes, were considered, and follow up covered up to 17 years (mean 14.6 years). To further examine causality, their analysis was empowered by mendelian randomization (MR) design. To this effect, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were extracted from publicly available international registries. Unfortunately, sleep features were assessed only once during observation.

Sleep duration was categorized in short (<7 hours per day), normal (7-<9 hours), and long (≥ 9 hours). Compared with normal sleep duration, both sides of abnormality resulted in increased stroke risk, being long sleep associated with increased risk of total and ischemic stroke, and short sleep to higher risk of intracerebral hemorrhage. In this dataset, by evaluating demographics and vascular risk factors of the so-grouped sleepers, subjects having abnormal sleep duration were featured by older age and higher incidence of vascular risk factors (hypertension, diabetes, dyslipidemia, alcohol abuse), suggesting the presence of confounders that were actually ruled out by multivariate analysis and the MR analysis. The only MR- confirmed association was that of short sleep duration and higher odds of large atherosclerotic stroke. Although the impact of genetic-biological factors cannot be excluded, this association is likely multifactorial, being sleep deprivation notoriously linked to cardiovascular conditions such as insulin-resistance and hypertension.

The study highlights the role of sleep duration in determining stroke risk with important data from a large sample and a noteworthy follow up period. As a modifiable risk factor, sleep deserves further investigations concerning its relationship with stroke in order to target therapeutic and preventive interventions in patients at risk. Furthermore, sleep features often reveal underlying medical conditions, mainly vascular risk factors. Besides recommending lifestyle adjustments, a better characterization of sleep could help in finding awareness about comorbidities and set their prompt correction.

As acknowledged, establishing sleep duration on a single self-report represents a major limitation of the study. Further investigations could target sleep features more specifically, ideally with repeated measurements over time, since sleep features possibly change over time due to social and ageing factors.