Methods

We performed an analysis of the Coronary Psychosocial Evaluation Studies (COPES), a multisite, observational cohort study designed to investigate the cause and naturalistic course of depressive symptoms after an ACS event. Participants were recruited from patients admitted to 3 university hospitals (Mount Sinai Hospital, New York, New York, and Yale–New Haven Hospital and Hospital of St. Raphael, New Haven, Connecticut) for an ACS event from May 2003 to June 2005. The institutional review board of each hospital approved the study. ACS events were defined according to American Heart Association/American College of Cardiology criteria as acute MI (with or without ST-segment elevation) or UA. Patients with UA had symptoms consistent with acute myocardial ischemia and ≥1 of the following: ischemic electrocardiographic changes (i.e., ST-segment depression and/or T-wave abnormalities), angiogram indicative of coronary artery disease on current admission, and/or documented history of coronary artery disease. Patients with an acute increase in serum cardiac enzyme levels were excluded. A study cardiologist confirmed ACS eligibility for all patients.

The Beck Depression Inventory (BDI), a self-report measurement of depressive symptom severity, was administered within 1 week after the index ACS event, and patients who scored 0 to 4 (indicative of no depressive symptoms) or ≥10 (at least mild depressive symptoms) were included. Patients with BDI scores from 5 to 9 were excluded to delineate more clearly depressed and nondepressed groups at baseline. For this analysis, depressive symptoms were categorized into 2 groups according to BDI score ≥10 versus 0 to 4.

In addition to assessment of depressive symptom severity with the BDI, a diagnosis of major depression was also determined using the Diagnostic Interview with Structured Hamilton (DISH), an interview format developed for the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) clinical trial. Interviews were conducted by trained research staff, and 1 clinical psychologist and 1 psychiatrist independently reviewed audiotapes and written notes for each interview to verify all diagnoses.

Medical risk factors for long-term mortality were measured with the Global Registry of Acute Coronary Events risk score and the Charlson co-morbidity index. The Global Registry of Acute Coronary Events model includes advanced age, history of MI and heart failure, increased pulse rate and systolic blood pressure at presentation to the hospital, increased initial serum creatinine level, increased initial cardiac enzyme level, ST-segment depression on electrocardiogram at presentation, and percutaneous coronary intervention performed in the hospital. The Global Registry of Acute Coronary Events risk score ranges from 1 to 263 points, with higher scores indicating higher mortality risk. A score from 1 to 80 predicts a 1% mortality rate at 6 months; 100, a 2% mortality rate; and >210, a mortality rate >50%. The Charlson index includes 12 long-term conditions with weights according to their association with 1-year mortality and has been associated with long-term survival in patients with coronary artery disease.

Left ventricular ejection fraction was measured quantitatively by left ventriculogram during cardiac catheterization (48% of patients), echocardiogram (38%), or radionuclide study (12%). If multiple measurements were available, the value from the ventriculogram was used first, followed by the value from the echocardiogram. Left ventricular ejection fraction was then classified as normal to mild dysfunction (left ventricular ejection fraction ≥0.40) and moderate to severe dysfunction (left ventricular ejection fraction <0.40). Data on left ventricular ejection fraction were missing for 19 patients.

The primary end point was ACM. At 1 month and 3, 6, 18, 30, and 42 months after enrollment, patients were contacted and follow-up assessments were completed by telephone or in person. For patients who could not be contacted or who were reported by a relative to be deceased, the Social Security Death Index was searched to verify vital status.

Fisher’s exact chi-square tests and 2-sample t tests were used to compare categorical and continuous measurements between the depressed (BDI ≥10) and nondepressed (BDI 0 to 4) groups. Actuarial survival curves were plotted according to BDI score category. Cox proportional hazards models were used to estimate the hazard ratio for ACM associated with BDI score ≥10, stratified by hospital. Based on published findings of factors that might confound the depression–ACM association, age, gender, left ventricular ejection fraction, medical co-morbidities (Charlson index), and clinical prognostic index (Global Registry of Acute Coronary Events) were included in multivariable analyses. All analyses were performed using SPSS 16 (SPSS, Inc., Chicago, Illinois).