Psychosocial Stress and Stroke Risk: Meta-Analysis of Observational Studies

Mostafa A. Khalifa^1,2*Albandari Alardhi³Ghadah Faleh⁴Abdulmajeed Mousa⁵Batoul Ali Taqi⁶Falwah Sami Alsalman⁷Mohand Basher⁸Saleh Alzahrani⁹Hessah Abul¹⁰Hayat Safwat Hassan¹¹Ashwaq Dhafer Alqarni¹²Shaima ShamsEldeen KhalfAllah Ahmed¹³Sarah M. Hegazy¹⁴Omer Hussein Alwi Bin-Sahel¹⁵Dalia Abdalla Mohamed¹⁶

• ¹Faculty of Medicine, Cairo University, Cairo, Egypt
• ²Cairo University Kasr Alainy Faculty of Medicine, Cairo, Egypt
• ³Al Jahra Hospital, Jahra, Kuwait
• ⁴Qassim University, Buraydah, Saudi Arabia
• ⁵King Abdulaziz Medical City - Jeddah, Jeddah, Saudi Arabia
• ⁶Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
• ⁷Alfaisal University, Riyadh, Saudi Arabia
• ⁸Riyadh Second Health Cluster, Riyadh, Saudi Arabia
• ⁹King Salman Hospital, Riyadh, Saudi Arabia
• ¹⁰Sheikh Jaber Al-Ahmad Al-Sabah Hospital, Kuwait City, Kuwait
• ¹¹University of Jeddah, Jeddah, Saudi Arabia
• ¹²University of Tabuk, Tabuk, Saudi Arabia
• ¹³University of Khartoum, Khartoum, Sudan
• ¹⁴Umm Al-Qura University College of Medicine, Mecca, Saudi Arabia
• ¹⁵Seiyun University, Seiyun, Yemen
• ¹⁶Almana Group of Hospitals, Al Khobar, Saudi Arabia

Background: Psychological stress has been increasingly recognised as a potential risk factor for stroke, but the strength and consistency of this association remained uncertain. This systematic review and meta-analysis aims to determine the overall association between broad psychological stress and broad stroke risk. Methodology: Systematic searches of PubMed, Scopus, Web of Science, and OVID databases from 1990 to March of 2025. These searches utilized a strategy combining subject headings and keywords related to psychosocial risk factors and stroke. Twenty-eight studies met inclusion criteria (23 prospective cohort and 5 case-control), comprising over 950,000 participants. We excluded studies involving participants with a history of depression. Stroke was broadly defined to include ischemic, hemorrhagic, subarachnoid, TIA, and unspecified subtypes. Results Our meta-analysis of 23 prospective cohort studies found that individuals exposed to psychological stress had a 46% higher risk of experiencing stroke (HR = 1.46; 95% CI: 1.29–1.66; P < 0.01). Initial analysis revealed substantial heterogeneity (I² = 82%), which was significantly reduced to 39% (HR = 1.45; 95% CI: 1.32–1.59; P = 0.02) after a sensitivity analysis. Analysis of five case-control studies yielded a pooled odds ratio (OR) of 1.10 (95% CI: 1.01–1.20; P < 0.01), also indicating a modest but significant elevation in stroke risk; however, heterogeneity remained high (I² = 92%). Sex-stratified analysis showed comparable increases in stroke risk for males (HR = 1.33; 95% CI: 1.19–1.49) and females (HR = 1.44; 95% CI: 1.07–1.95), with no statistically significant subgroup difference (P = 0.61). Conclusion: Psychological stress is significantly associated with an increased risk of fatal stroke, though publication bias and study heterogeneity highlight the need for cautious interpretation. Further research should aim to address methodological variability and selective reporting to refine our understanding of this relationship.