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Andrew Sherwood, PhD; James A. Blumenthal, PhD; Ranak Trivedi, PhD; Kristy S. Johnson, MPH; Christopher M. O’Connor, MD; Kirkwood F. Adams Jr, MD; Carla Sueta Dupree, MD; Robert A. Waugh, MD; Daniel R. Bensimhon, MD; Laura Gaulden, MS; Robert H. Christenson, PhD; Gary G. Koch, PhD; Alan L. Hinderliter, MD

Arch Intern Med. 2007;167(4):367-373.

Background  Depression is widely recognized as a risk factor in patients with coronary heart disease. However, patients with heart failure (HF) have been less frequently studied, and the effect of depression on prognosis, independent of disease severity, is uncertain.

Methods  Two hundred four outpatients having a diagnosis of HF, with a ventricular ejection fraction of 40% or less, underwent baseline assessments including evaluation of depressive symptoms using the Beck Depression Inventory and of HF severity determined by plasma N-terminal pro–B-type natriuretic peptide. Cox proportional hazards regression analyses were used to examine the effects of depressive symptoms on a combined primary end point of death and hospitalizations because of cardiovascular disease (hereafter referred to as cardiovascular hospitalization) during a median follow-up of 3 years.

Results  Symptoms of depression (Beck Depression Inventory score) were associated with risk of death or cardiovascular hospitalization (P<.001) after controlling for established risk factors including HF disease severity, ejection fraction, HF etiology, age, and medications. Clinically significant symptoms of depression (Beck Depression Inventory score 10) were associated with a hazard ratio of 1.56 (95% confidence interval, 1.07-2.29) for the combined end point of death or cardiovascular hospitalization. Contrary to our expectation, antidepressant medication use was associated with increased likelihood of death or cardiovascular hospitalization (hazard ratio, 1.75; 95% confidence interval,1.14-2.68, P  =.01) after controlling for severity of depressive symptoms and for established risk factors.

Conclusions  Symptoms of depression were associated with an adverse prognosis in patients with HF after controlling for HF severity. The unexpected association of antidepressant medications with worse clinical outcome suggests that patients with HF requiring an antidepressant medication may need to be monitored more closely.

Author Affiliations: Departments of Psychiatry (Drs Sherwood, Blumenthal, Trivedi, and Ms Johnson) and Medicine (Drs O’Connor, Waugh, Bensimhon, and Ms Gaulden), Duke University Medical Center, Durham, NC; Department of Medicine, School of Medicine (Drs Adams, Dupree, and Hinderliter), and Department of Biostatistics, School of Public Health (Dr Koch), University of North Carolina, Chapel Hill; and Department of Pathology, University of Maryland School of Medicine, Baltimore (Dr Christenson).

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