Depression and coronary heart disease: Association and implications for treatment

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Growing evidence indicates that depression is an important primary and secondary risk factor for coronary heart disease (CHD). Depression is quite common among patients with CHD: prevalence estimates are 14% or higher, and an additional 20% of patients have subclinical or minor depression. This review summarizes evidence that depression is a risk factor for cardiac events in patients with established CHD, suggests potential mechanisms underlying the relationship between depression and adverse cardiac outcomes, and provides evidence for the efficacy of exercise in improving both depression and clinical outcomes in depressed patients with CHD.



Depression refers to an emotional condition ranging from a transient negative mood state of sadness or mild dysphoria to a chronic and severe psychiatric illness. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) identifies two depressive disorders: major depressive disorder (MDD) and dysthymic disorder.1 The essential feature of MDD is a clinical course characterized by one or more major depressive episode (whose diagnostic criteria are presented in Table 1) without a history of manic, mixed, or hypomanic episodes. The diagnosis requires the presence of a total of at least five symptoms over a period of at least 2 weeks, which must include either depressed mood or loss of interest or pleasure. Dysthymic disorder is marked by mild depressive symptoms that are more chronic in nature, lasting at least 2 years.1

Minor depressive disorder (mDD) is not an official DSM-IV diagnosis but is used for research purposes; it is similar to MDD in duration but requires that only two to four symptoms be present.


Depression is a widespread and often chronic condition. Lifetime prevalence estimates for MDD are approximately 15% to 20%;2,3 1-year prevalence estimates are 5% to 10%;2,4 and point prevalence estimates range from 4% to 7%.3,5 Moreover, MDD is characterized by high rates of relapse: 22% to 50% of patients suffer recurrent episodes within 6 months after recovery.6

Women are twice as likely as men to be diagnosed with MDD, with lifetime prevalence rates of 10% to 25% in women versus 5% to 12% in men.1

Although rates of depression do not appear to increase with age, MDD often goes undertreated in older adults3 and in cardiac patients.7


The gold standard for diagnosing MDD is a clinical interview. Commonly used instruments include the Diagnostic Interview Schedule8 and the Composite International Diagnostic Interview.9 The Structured Clinical Interview for DSM-IV Axis I Disorders10 and the Schedule for Affective Disorders and Schizophrenia11 are frequently used semistructured interviews.

The most common clinical instruments for assessing the severity of depressive symptoms are the Hamilton Rating Scale for Depression (HAM-D),12 which is a clinician-rated scale, and various psychometric questionnaires, including the Beck Depression Inventory (BDI)13,14 and the Center for Epidemiological Studies Depression Scale (CES-D).15


Depression as a primary risk factor

Reprinted from Rozanski A, et al. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005; 45:637–651, © 2005, with permission from the ACC.
Figure 1. Risk ratios of traditional risk factors for coronary heart disease (CHD) observed in the Framingham study as compared with risk ratios of depressive symptoms and depressed mood as derived from the recent meta-analysis by Rugulies.17 The risk of CHD conferred by depressive symptoms is comparable to that conferred by traditional risk factors, and the presence of clinical depression appears to raise this risk. For traditional risk factors, risk ratios were calculated for cardiac death, myocardial infarction, coronary artery insufficiency, and angina. For depressed mood and clinical depression, risk ratios were calculated for cardiac disease and myocardial infarction.18
Evidence that depression is a primary risk factor for coronary heart disease (CHD) in healthy individuals has been reviewed previously.16 A recent meta-analysis of 11 prospective cohort studies of initially healthy individuals indicated that depression (either depressive mood or clinical MDD) conferred a relative risk of 1.64 for adverse cardiac events, including myocardial infarction (MI) and cardiac death; the presence of MDD was associated with the greatest risk (relative risk of 2.69).17Figure 1 shows that clinical depression is comparable to traditional risk factors for CHD, such as smoking and elevated blood lipid levels, as observed in the Framingham study.18

Depression as a secondary risk factor

Depression is an even stronger risk factor for cardiac events in patients with established CHD. Point estimates range from 14% to as high as 47%, with higher rates in patients with unstable angina and in patients awaiting coronary artery bypass graft (CABG) surgery; an additional 20% of patients exhibit elevated depressive symptoms or minor depression (mDD).19–25

Prospective studies have shown that depression increases the risk for death or nonfatal cardiac events approximately 2.5-fold in patients with CHD. For instance, Frasure-Smith et al followed 896 patients with a recent acute MI and found that the presence of depressive symptoms as indicated by an elevated BDI score was a significant predictor of cardiac mortality after controlling for multivariate predictors of mortality (odds ratio [OR] = 3.29 for women and 3.05 for men).26

Two recent meta-analyses confirmed the association between depression and adverse clinical outcomes in patients with CHD.27,28 For example, van Melle et al reported that post-MI depression was associated with a 2- to 2.5-fold increase in the risk of adverse health outcomes.28 In this analysis, depression’s effect on cardiac mortality and all-cause mortality was especially pronounced in older studies (before 1992) (OR = 3.2) compared with more recent studies (after 1992) (OR = 2.01).28

Duke University researchers have conducted several prospective studies in various cardiac populations.29–31 Barefoot et al assessed 1,250 patients with documented CHD using the Zung Self-Rating Depression Scale at the time of diagnostic coronary angiography and followed them for up to 19.4 years.29 Results showed that patients with moderate to severe depression were at 69% greater risk for cardiac death and 78% greater risk for all-cause death than were their nondepressed counterparts.

Reprinted from The Lancet (Blumenthal JA, et al. Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet 2003; 362:604–609.), copyright 2003, with permission from Elsevier.
Figure 2. Kaplan-Meier survival curves for all-cause mortality among coronary surgery patients according to their presurgery (baseline) depressive symptoms as measured by the Center for Epidemiological Studies Depression Scale (CES-D). Compared with the absence of depressive symptoms, the presence of moderate to severe symptoms was associated with a hazard ratio of 2.4 (95% CI = 1.40 to 4.00; P = .001) for all-cause mortality. Mild symptoms were associated with no difference in risk relative to the absence of symptoms (hazard ratio = 1.08, 95% CI = 0.70 to 1.67; P = .723).30
In a prospective study of patients undergoing CABG surgery, we assessed the effect of depression on mortality in 817 patients followed for up to 12 years (mean, 5.2 years).30 Using the CES-D instrument, patients were categorized on the day before surgery as having either no depression (CES-D score < 16), mild depression (score of 16 to 26), or moderate to severe depression (score ≥ 27). We found that moderate to severe depression was independently associated with a twofold to threefold increase in the risk of death, even after controlling for age, gender, number of grafts, diabetes, smoking, left ventricular ejection fraction, and history of acute MI (Figure 2). Moreover, patients who exhibited persistent depression, with CES-D scores of 16 or greater at baseline and after 6 months, had more than a doubling in risk relative to patients who were never depressed.

We also recently reported results from a prospective study that followed 204 patients with heart failure over a median interval of 3 years.31 Clinically significant symptoms of depression (BDI score ≥ 10) were associated with a hazard ratio of 1.56 (95% CI, 1.07 to 2.29) for the combined end point of death or cardiovascular hospitalization. These observations included adjustment for plasma NT-proBNP level, ejection fraction, and other established risk factors, suggesting that heightened risk of adverse clinical outcomes associated with depressive symptoms is not simply a reflection of the severity of heart failure.

In summary, a number of observational studies have demonstrated that depression is associated with increased risk of morbidity and mortality both in healthy populations and in a variety of populations with established cardiac disease.


A number of biobehavioral mechanisms have been hypothesized to underlie the relationship between depression and CHD. Most evidence is derived from cross-sectional studies and suggests that depression is associated with traditional risk factors for CHD, such as hypertension, diabetes, and insulin resistance,32,33 as well as changes in platelet reactivity,34 dysregulation of the autonomic nervous system35 and hypothalamic-pituitary-adrenal axis,36 and alterations in the immune response/inflammation.37 Depression is also associated with behavioral factors that are in turn associated with CHD risk, such as reduced treatment adherence,38 smoking,39 and physical inactivity.40

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