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Author Notes:

Address for Correspondence: Dr. Viola Vaccarino, MD, PhD, Emory University, Department of Epidemiology, Rollins School of Public Health, 1518 Clifton Rd NE, Room 3011, Atlanta, GA 30322. Phone: 404-727-8710; Fax: 404-727-8737; viola.vaccarino@emory.edu; Twitter handle: @violavaccarino.

Ernest V. Garcia receives royalties from the sale of the Emory Cardiac Toolbox, used for some analyses in this study.

None of the other authors report conflict of interest relevant to this article.


Research Funding:

This work was supported by the NIH, through the following grants: R01 HL109413, R01HL109413-02S1, R01 HL125246, R01 HL136205, P01 HL101398, KL2TR000455, K24HL077506, K24 MH076955, K23HL127251, and THL130025A.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cardiac & Cardiovascular Systems
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • ischemia
  • microcirculation
  • sex
  • stress
  • vascular function
  • RISK

Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction Sex Differences and Mechanisms

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Journal Title:



Volume 137, Number 8


, Pages 794-805

Type of Work:

Article | Post-print: After Peer Review


BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown. METHODS: We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received 99mTc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress. RESULTS: The mean age of the sample was 50 years (range, 22-61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%, P=0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%, P=0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in MSIMI, they were predictive of MSIMI in women only. CONCLUSIONS: Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women's proclivity toward ischemia because of microcirculatory abnormalities.

Copyright information:

© 2018 American Heart Association, Inc.

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