Depressive symptoms, chronic stress and hostility associated with increased stroke risk

Chronic Stress, Depressive Symptoms, Anger, Hostility, and Risk of Stroke and Transient Ischemic Attack in the Multi-Ethnic Study of Atherosclerosis

Literature - Everson-Rose SA et al., Stroke. 2014 - Stroke. 2014 Jul 10

Everson-Rose SA, Roetker NS, Lutsey PL et al.
Stroke. 2014 Jul 10. pii: STROKEAHA.114.004815


Stress and negative emotions adversely affect cardiovascular disease morbidity and mortality, but little is known about their impact on stroke risk. Most existing evidence is from homogenous white populations [1,2]. The international Study of the Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World (INTERSTROKE) demonstrated that single-item measures of psychosocial stress and depression were significant stroke risk factors [3].
Much of the available evidence is limited by the absence of adjudicated stroke events, and/or limited risk factor data or limited assessment of psychosocial factors. This study therefore used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to investigate the association of chronic stress and negative emotions with a combined endpoint of incident stroke and transient ischaemic attacks (TIAs). Mean follow-up in this longitudinal observational study was 8.5 years (range: 0.02-10.9 years).

Main results

  • A 1 point higher score on the Center for Epidemiologic Studies Depression Scale (CES-D) gave a higher risk of stroke/TIA (HR: 1.03, 95%CI: 1.01-1.04), as did chronic stress (HR: 1.19, 95%CI: 1.05-1.34) and hostility (HR: 1.10, 95%CI: 1.01-1.19), after controlling for race, sex, age, education and research site. Anger was not significantly related to stroke/TIA risk.
  • When psychosocial measures were modelled categorically, persons in the top groups for CES-D, chronic stress and hostility were at 1.5 to > 2-fold increased risk of stroke/TIA during follow-up, as compared with the lowest scoring groups.
  • No interactions were observed between psychosocial measures and age, sex or race/ethnicity (small numbers limited power to detect in race/ethnicity analyses).
  • Models that also adjusted for intima media thickness, C-reactive protein or interleukin-6 were unchanged.
  • When total incident strokes or incident ischaemic strokes were analysed  separately, associations were similar to the combined endpoint.
  • Both models adjusting for known stroke risk factors at baseline and time-dependent models with time-varying covariates yielded similar associations.


This study shows that more depressive symptoms, greater chronic stress and higher levels of hostility were associated with an increased risk of stroke and TIA, which could not be explained by traditional stroke risk factors, inflammatory markers or subclinical atherosclerosis. The association between anger and stroke/TIA did not reach statistical significance.
These results underscore the importance of considering non-traditional factors when assessing stroke/TIA risk. MESA is a population-based study, including participants from 4 racial/ethnic groups, which enhances the generalisability of the findings.

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1. Pan A, Sun Q, Okereke OI et al. Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review. JAMA. 2011;306:1241–1249.
2. Dong JY, Zhang YH, Tong J, et al. Depression and risk of stroke: A meta-analysis of prospective studies. Stroke. 2011;4:188–196.
3. O’Donnell MJ, Xavier D, Liu L, et al; INTERSTROKE investigators. Risk factors for ischaemic and
intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112–123.

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