Insomnia and stroke risk: A systematic review with meta-analysis of analytical observational studies and mendelian randomization studies

Stroke is one of the leading causes of death worldwide, with ischemic stroke being the most frequent subtype. Factors such as sleep disorders may increase the risk of stroke; however, solid evidence is lacking. Therefore, the objective was to synthesize current evidence on the relationship between insomnia and its role as a risk factor for stroke. A systematic review and meta-analysis were conducted, with searches performed in PubMed, Embase, Scopus, Google Scholar, and Web of Science up to March 2024. The included studies were observational or Mendelian randomized studies that evaluated the diagnosis or symptoms of insomnia and any type of stroke as an outcome. The study selection process, data extraction, and risk of bias assessment were conducted in pairs. A random-effects meta-analysis was performed to estimate the effect of the outcome. Trial Registration: PROSPERO CRD42024519745. A total of 17 studies (12 observational studies and 5 Mendelian randomization studies) were analyzed, representing a total population of 7,696,920 patients. In the pooled analysis, no significant association was observed between the risk of developing any type of stroke and the presence of any insomnia symptom (HR: 1.16; 95% CI: 0.88–1.52; I 2 = 60%), but a higher risk of developing ischemic stroke was found (HR: 1.07; 95% CI: 1.04–1.10; I 2 = 60%) with a high level of evidence certainty. Conversely, an increased risk of any type of stroke was observed when insomnia was diagnosed (HR: 1.45; 95% CI: 1.32–1.61). • First systematic review integrating observational and Mendelian randomization studies. • Distinguishes insomnia symptoms from clinically diagnosed insomnia in stroke risk. • Insomnia symptoms are associated with increased risk of ischemic stroke. • Diagnosed insomnia shows stronger associations with all stroke subtypes. • Findings support biological plausibility and guide future objective sleep research.