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Robert M. Carney, PhD; James A. Blumenthal, PhD; Kenneth E. Freedland, PhD; Phyllis K. Stein, PhD; William B. Howells, MS; Lisa F. Berkman, PhD; Lana L. Watkins, PhD; Susan M. Czajkowski, PhD; Junichiro Hayano, MD; Peter P. Domitrovich, PhD; Allan S. Jaffe, MD

Arch Intern Med. 2005;165:1486-1491.

Background  Depression is associated with an increased risk for mortality after acute myocardial infarction (MI). The purpose of this study was to determine whether low heart rate variability (HRV) mediates the effect of depression on mortality.

Methods  Twenty-four–hour ambulatory electrocardiograms were obtained from 311 depressed patients with a recent acute MI who were enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial and from 367 nondepressed patients who met the ENRICHD medical inclusion criteria. Standard HRV indexes were extracted from the recordings.

Results  The log of very low-frequency (LnVLF) power, an index of HRV derived from power spectral analysis of the electrocardiogram signal (0.0033-0.04 Hz [in milliseconds squared]), was lower in the depressed than in the nondepressed patients (P<.001). There were 47 deaths (6.1%) during a 30-month follow-up. After adjusting for potential confounders, the depressed patients remained at higher risk for all-cause mortality compared with the nondepressed patients (hazard ratio, 2.8; 95% confidence interval [CI], 1.4-5.4; P<.003). When LnVLF power was entered into the model, the hazard ratio for depression dropped to 2.1 (95% CI, 1.1-4.2; P = .03). The proportion of the risk for depression attributable to LnVLF power was 0.27 (95% CI, 0.23-0.31; P<.001).

Conclusions  Low HRV partially mediates the effect of depression on survival after acute MI. This finding helps to clarify the physiological mechanisms underlying depression’s role as a risk factor for mortality in patients with coronary heart disease. It also raises the possibility that treatments that improve both depression and HRV might also improve survival in these patients.

Author Affiliations: Departments of Psychiatry (Drs Carney and Freedland and Mr Howells) and Medicine (Drs Stein and Domitrovich), Washington University School of Medicine, St Louis, Mo; Department of Psychiatry, Duke University Medical Center, Durham, NC (Drs Blumenthal and Watkins); Department of Epidemiology, Harvard University, Boston, Mass (Dr Berkman); National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Czajkowski); Department of Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan (Dr Hayano); and Department of Medicine, Mayo Clinic, Rochester, Minn (Dr Jaffe).

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