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Wei Jiang, MD; Michael Babyak, PhD; David S. Krantz, PhD; Robert A. Waugh, MD; R. Edward Coleman, MD; Michael M. Hanson, MD; David J. Frid, MD; Steve McNulty, MS; James J. Morris, MD; Christopher M. O'Connor, MD; James A. Blumenthal, PhD

JAMA. 1996;275(21):1651-1656.

Abstract
Objective.
—To assess the clinical significance of mental stress—induced myocardial ischemia in patients with coronary artery disease (CAD).

Design and Setting.
—Cohort study in outpatients in a tertiary care teaching hospital assessed at baseline and followed up for up to 5 years.

Subjects.
—A total of 126 volunteer patients (112 men, 14 women; mean age, 59 years) with documented CAD and exercise-induced myocardial ischemia.

Outcome Measures.
—Patients underwent baseline mental stress and exercise testing using radionuclide ventriculography and 48-hour Holter monitoring. Patients were subsequently contacted by mailed questionnaires or telephone to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. Logistic regression and Cox proportional hazards models were used to examine the prognostic value of the ischemic measures after adjusting for such potential confounding factors as age, baseline left ventricular ejection fraction (LVEF), and history of myocardial infarction.

Results.
—Twenty-eight patients (22%) experienced at least 1 cardiac event. Baseline mental stress—induced ischemia was associated with significantly higher rates of subsequent cardiac events (odds ratio, 2.8; 95% confidence interval [CI], 1.0-7.7; P<.05). The LVEF change during mental stress was significantly related to event-free survival (risk ratio [RR], 2.4; 95% CI, 1. 12-5. 14; P=.02), controlling for age, history of prior myocardial infarction, and baseline LVEF. This relationship remained significant after controlling for electrocardiogram (ECG)—defined ischemia during exercise (RR, 2.2; 95% CI, 1.01-4.81; P<.05). The RR for ECG-defined ischemia during exercise testing was 1.9 (95% CI, 0.95-3.96; P=.07) and the RR for ambulatory ECG ischemia was 0.75 (95% CI, 0.35-1.64; P=.47).

Conclusions.
—The presence of mental stress—induced ischemia is associated with significantly higher rates of subsequent fatal and nonfatal cardiac events, independent of age, baseline LVEF, and previous myocardial infarction, and predicted events over and above exercise-induced ischemia. These data suggest that the relationship between psychological stress and adverse cardiac events may be mediated by the occurrence of myocardial ischemia.

(JAMA. 1996;275:1651-1656)

Author Affiliations
From the Departments of Medicine (Drs Jiang, Waugh, Frid, Morris, O'Connor, and Blumenthal and Mr McNulty), Psychiatry and Behavioral Sciences (Dr Babyak and Blumenthal), and Radiology (Drs Coleman and Hanson), Duke University Medical Center, and the Duke University Center for Living (Dr Blumenthal), Durham, NC; and the Department of Medical Clinical Psychology, Uniformed Services University of the Health Sciences, Bethesda, Md (Dr Krantz). Dr Frid is now with the Department of Medicine, The Ohio State University, Columbus.

Footnotes
Reprints: James A. Blumenthal, PhD, Box 3119, Duke University Center for Living, Durham, NC 27710.

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