Mostafa A Khalifa, Diaaeldin Hassanein, Abd Alrahman I Alsabbagh, Ahmed Samir Gamil, Darin Emad Abdelhaleem, Ayham R A Zidat, Eman Atef Megahed, Malak A Ghazi, Mahmoud Hamza Abdelfattah, Moustafa Mahmoud Aboutabl, Osama A Ibrahim, Abrar M Adil, Amal F Ahmed, Hassan Ahmed AbdelKareem, Mohamed Mounir Gharib, Mustafa H Khazali
Psychosocial stress is associated with an increased risk of first-ever stroke, particularly psychological and vocational stressors, supporting psychosocial factors as potentially modifiable components of stroke prevention.
BACKGROUND: Psychosocial stress has been recognized as a potential risk factor for stroke; however, the strength and consistency of its association with first-ever stroke remain uncertain. This systematic review and meta-analysis aimed to determine the overall association between psychosocial stress and the risk of first stroke in a stroke-free population.
METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA and MOOSE guidelines. PubMed, Scopus, Web of Science, and Ovid were searched from inception to 1 January 2026 for cohort or case-control studies. Eligible studies enrolled participants without a prior history of stroke and reported adjusted risk estimates with 95% confidence intervals. Psychosocial stressors were categorized into psychological, vocational, interpersonal, and behavioral domains. Stroke outcomes included ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, transient ischemic attack, and unspecified stroke.
RESULTS: Eighty-four studies were included (72 prospective cohort and 12 case-control), comprising 4,128,167 participants. In cohort studies, psychological stress was associated with a higher risk of first-ever stroke (hazard ratio [HR] 1.27, 95% confidence interval 1.19-1.36). Vocational stressors were also associated with increased stroke risk (HR 1.32, 95% CI 1.23-1.43). Interpersonal stressors showed a smaller but statistically significant association (HR 1.11, 95% CI 1.03-1.20). Behavioral stress-related traits showed the largest effect estimate (HR 1.51, 95% CI 1.05-2.15), although this finding should be interpreted cautiously because it was based on only three cohort studies. In sex-stratified analyses, the association was significant among men (HR 1.19, 95% CI 1.07-1.32) but not among women (HR 0.86, 95% CI 0.58-1.28); however, the subgroup interaction was not statistically significant and should be interpreted as inconclusive rather than evidence of a definite sex-specific difference.
CONCLUSION: Psychosocial stress is associated with an increased risk of first-ever stroke, particularly psychological and vocational stressors, supporting psychosocial factors as potentially modifiable components of stroke prevention.