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Association of Mental Stress–Induced Myocardial Ischemia With Cardiovascular Events in Patients With Coronary Heart Disease

Educational Objective
To learn the association between myocardial ischemia induced by mental stress and adverse cardiovascular events in patients with coronary heart disease.
1 Credit CME
Key Points

Question  Is myocardial ischemia provoked by mental stress associated with adverse cardiovascular events in patients with coronary heart disease?

Findings  In this pooled analysis of 2 prospective cohort studies that included 918 participants, the presence of ischemia with mental stress, compared with no ischemia with mental stress, was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction (hazard ratio, 2.5).

Meaning  Mental stress–induced myocardial ischemia was significantly associated with an increased risk of cardiovascular events in patients with coronary heart disease, but further research is needed to assess whether testing for mental-stress ischemia has utility in clinical practice.

Abstract

Importance  Mental stress–induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated.

Objective  To compare the association of mental stress–induced or conventional stress–induced ischemia with adverse cardiovascular events in patients with CHD.

Design, Setting, and Participants  Pooled analysis of 2 prospective cohort studies of patients with stable CHD from a university-based hospital network in Atlanta, Georgia: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 (last follow-up, February 2020).

Exposures  Provocation of myocardial ischemia with a standardized mental stress test (public speaking task) and with a conventional (exercise or pharmacological) stress test, using single-photon emission computed tomography.

Main Outcomes and Measures  The primary outcome was a composite of cardiovascular death or first or recurrent nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure.

Results  Of the 918 patients in the total sample pool (mean age, 60 years; 34% women), 618 participated in MIPS and 300 in MIMS2. Of those, 147 patients (16%) had mental stress–induced ischemia, 281 (31%) conventional stress ischemia, and 96 (10%) had both. Over a 5-year median follow-up, the primary end point occurred in 156 participants. The pooled event rate was 6.9 per 100 patient-years among patients with and 2.6 per 100 patient-years among patients without mental stress–induced ischemia. The multivariable adjusted hazard ratio (HR) for patients with vs those without mental stress–induced ischemia was 2.5 (95% CI, 1.8-3.5). Compared with patients with no ischemia (event rate, 2.3 per 100 patient-years), patients with mental stress–induced ischemia alone had a significantly increased risk (event rate, 4.8 per 100 patient-years; HR, 2.0; 95% CI, 1.1-3.7) as did patients with both mental stress ischemia and conventional stress ischemia (event rate, 8.1 per 100 patient-years; HR, 3.8; 95% CI, 2.6-5.6). Patients with conventional stress ischemia alone did not have a significantly increased risk (event rate, 3.1 per 100 patient-years; HR, 1.4; 95% CI, 0.9-2.1). Patients with both mental stress ischemia and conventional stress ischemia had an elevated risk compared with patients with conventional stress ischemia alone (HR, 2.7; 95% CI, 1.7-4.3). The secondary end point occurred in 319 participants. The event rate was 12.6 per 100 patient-years for patients with and 5.6 per 100 patient-years for patients without mental stress–induced ischemia (adjusted HR, 2.0; 95% CI, 1.5-2.5).

Conclusions and Relevance  Among patients with stable coronary heart disease, the presence of mental stress–induced ischemia, compared with no mental stress–induced ischemia, was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction. Although these findings may provide insights into mechanisms of myocardial ischemia, further research is needed to assess whether testing for mental stress–induced ischemia has clinical value.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Authors: Viola Vaccarino, MD, PhD, Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd NE, Atlanta, GA 20322 (viola.vaccarino@emory.edu) and Arshed A. Quyyumi, MD, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 1462 Clifton Rd NE, Ste 507, Atlanta, GA 30322 (aquyyum@emory.edu).

Accepted for Publication: September 17, 2021.

Author Contributions: Dr Vaccarino had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Vaccarino, A. J. Shah, Lima, Kutner, Garcia, Bremner, Quyyumi.

Acquisition, analysis, or interpretation of data: Vaccarino, Almuwaqqat, Kim, Hammadah, Ko, Elon, Sullivan, A. Shah, Alkhoder, Lima, Pearce, Ward, Hu, Lewis, Garcia, Nye, Sheps, Raggi, Bremner, Quyyumi.

Drafting of the manuscript: Vaccarino, Almuwaqqat, A. J. Shah, Alkhoder, Kutner, Nye, Raggi, Quyyumi.

Critical revision of the manuscript for important intellectual content: Vaccarino, Almuwaqqat, Kim, Hammadah, A. J. Shah, Ko, Elon, Sullivan, A. Shah, Lima, Pearce, Ward, Hu, Lewis, Garcia, Nye, Sheps, Raggi, Bremner.

Statistical analysis: Almuwaqqat, Kim, Hammadah, Ko, A. Shah, Lima, Kutner, Hu, Sheps.

Obtained funding: Vaccarino, Sullivan, Sheps, Bremner, Quyyumi.

Administrative, technical, or material support: Vaccarino, Almuwaqqat, Kim, Hammadah, A. J. Shah, Sullivan, Garcia, Raggi, Bremner, Quyyumi.

Supervision: Vaccarino, Raggi, Bremner, Quyyumi.

Other - helped on overall concept: Pearce.

Other - data management and quality control, statistical programming: Elon.

Conflict of Interest Disclosures: Dr Garcia reported receiving royalties for the sale of the Emory Cardiac Toolbox, an imaging software used for some analyses in this study. No other disclosures were reported.

Funding/Support: This work was supported by grants P01 HL101398, R01 HL109413, R01HL109413-S1, P20HL113451, P01HL086773, R56HL126558, R01 HL125246, R01HL136205, T32 HL130025, K23HL127251, and K24HL077506 from the National Heart, Lung, and Blood Institute: K24 MH076955 from the National Institute of Mental Health; TL1TR002382 from the National Center for Advancing Translational Sciences; and K12HD085850 from the National Institute of Child Health and Human Development.

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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