Clinical depression is a powerful risk factor for mortality after an acute myocardial infarction (MI), yet little is known about the underlying mechanisms that account for this effect. The primary purpose of this study is to examine one of the most plausible candidate mechanisms, altered autonomic tone. Four hundred eighty post-MI patients with DSM-IV major or minor depression who are enrolled in the Usual Care arm of the NHLBI-sponsored ENRICHD (Enhancing Recovery in Coronary Heart Disease) clinical trial, and 480 non-depressed post-MI patients excluded from ENRICHD, will be recruited for this study during a two year period from four ENRICHD clinical centers. A 24 hour ambulatory ECG will be recorded after hospital discharge to obtain data on heart rate variability, myocardial ischemia, and ventricular arrhythmias. Patients will be followed up at 18 months, and psychosocial and medical endpoints, including mortality, will be ascertained. The primary analysis will determine whether heart rate variability accounts for the significantly higher mortality expected in the depressed compared to the non-depressed group, and whether this effect is largely concentrated in patients with ventricular arrhythmias and left ventricular dysfunction. The second purpose of the study is to identify clinical features or subtypes of depression that may be associated with a particularly high mortality risk and with altered autonomic tone, such as symptom severity, comorbid anxiety, or hostility. This mechanistic study will complement the clinical data to be obtained from the ENRICHD trial, and it would be considerably more costly and difficult to conduct a comparable study independently. Clarification of the underlying mechanism will greatly enhance the credibility of the epidemiological evidence that depression increases mortality in post-MI patients, and permit further refinements in risk stratification so that the patients at highest risk can be identified and treated the most aggressively.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Behavioral Medicine Study Section (BEM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Freedland, Kenneth E; Carney, Robert M; Hayano, Junichiro et al. (2012) Effect of obstructive sleep apnea on response to cognitive behavior therapy for depression after an acute myocardial infarction. J Psychosom Res 72:276-81
Carney, Robert M; Freedland, Kenneth E; Veith, Richard C (2005) Depression, the autonomic nervous system, and coronary heart disease. Psychosom Med 67 Suppl 1:S29-33
Carney, Robert M; Blumenthal, James A; Catellier, Diane et al. (2003) Depression as a risk factor for mortality after acute myocardial infarction. Am J Cardiol 92:1277-81
Carney, Robert M; Freedland, Kenneth E; Stein, Phyllis K et al. (2003) Effects of depression on QT interval variability after myocardial infarction. Psychosom Med 65:177-80
Clouse, Ray E; Lustman, Patrick J; Freedland, Kenneth E et al. (2003) Depression and coronary heart disease in women with diabetes. Psychosom Med 65:376-83
Carney, Robert M; Freedland, Kenneth E; Miller, Gregory E et al. (2002) Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J Psychosom Res 53:897-902
Turner, Ryan B; Liu, Lin; Sazonova, Irina Y et al. (2002) Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin. J Biol Chem 277:33068-74
Watkins, Lana L; Blumenthal, James A; Carney, Robert M (2002) Association of anxiety with reduced baroreflex cardiac control in patients after acute myocardial infarction. Am Heart J 143:460-6
Carney, R M; Blumenthal, J A; Stein, P K et al. (2001) Depression, heart rate variability, and acute myocardial infarction. Circulation 104:2024-8
Carney, R M; Freedland, K E; Stein, P K et al. (2000) Change in heart rate and heart rate variability during treatment for depression in patients with coronary heart disease. Psychosom Med 62:639-47

Showing the most recent 10 out of 12 publications