Viola Vaccarino1,2, Zakaria Almuwaqqat2, Jeong Hwan Kim2, Muhammad Hammadah2, Amit J Shah1,2,3, Yi-An Ko4, Lisa Elon4, Samaah Sullivan1, Anish Shah1,2, Ayman Alkhoder2, Bruno B Lima2, Brad Pearce1, Laura Ward4, Michael Kutner4, Yingtian Hu4, Tené T Lewis1, Ernest V Garcia5, Jonathon Nye5, David S Sheps6, Paolo Raggi1,7, J Douglas Bremner3,8, Arshed A Quyyumi2. 1. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia. 2. Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. 3. Atlanta VA Medical Center, Decatur, Georgia. 4. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia. 5. Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia. 6. Division of Cardiovascular Medicine, Department of Medicine, University of Florida College of Medicine, Gainesville. 7. Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada. 8. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
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.
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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Authors: W Jiang; M Babyak; D S Krantz; R A Waugh; R E Coleman; M M Hanson; D J Frid; S McNulty; J J Morris; C M O'Connor; J A Blumenthal Journal: JAMA Date: 1996-06-05 Impact factor: 56.272
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