Over the past several decades, a large body of evidence has emerged demonstrating the adverse impact of depressive disorder on heart disease. This evidence confirms the early suspicion of observant clinicians that psychological factors play a significant role in the genesis and course of heart disease, as well as confirming the ancient belief in a mind-body connection in general and a connection between human moods and the heart in particular. Given the high prevalence of these two disorders, we need a better understanding of the impact of depressive disorder on heart disease, the proposed underlying pathophysiologic mechanisms, and the effects of treating depression in relation to risk reduction in patients with heart disease.
In this article, I will focus on (1) reviewing the results of meta-analyses examining the association of depression with cardiac diseases, (2) discussing the relationship between depression and mental stress–induced myocardial ischemia, (3) reviewing the available studies of the treatment of depression in patients with cardiac disease, and (4) discussing future directions for research in this area.
ASSOCIATION OF DEPRESSION WITH PROGRESSION OF CARDIAC DISEASES
As a disease of the brain, depression is common. The lifetime prevalence of major depressive disorder, a significant form of depression, is 16.2%.1 The point prevalence of depression in medically ill patients is much higher, ranging from 20% to 50%, and the prevalence of milder depression is even more common. Despite this substantial prevalence, depression (especially in its milder forms) is rarely recognized. It often occurs insidiously, confusing its sufferer into believing that it is part of his or her character rather than an illness.
An invisible killer
The adverse effects of depression manifest in many aspects of life—from relationships to job performance to compliance with medical treatments—and can be so severe as to render the condition an “invisible killer.” The first evidence of this emerged in the medical literature in 1937 when Malzberg2 reported that patients with melancholia had a significantly higher death rate than the general population and that cardiac death occurred in more than 40% of those patients. Although it took another several decades for the field to accelerate, ample data have now been gathered to prove an unshakable association between depression and progression of cardiac diseases. Instead of reviewing results of each study, I will present the results of several meta-analyses.
Prognosis of post–myocardial infarction patients with depression
In a meta-analysis published in 2004, van Melle et al3 examined data derived from the MEDLINE, EMBASE, and PsycINFO databases between 1975 and 2003 on the prognostic association of post–myocardial infarction (MI) depression with mortality and cardiovascular events. Twenty-two studies met the selection criteria (post-MI status with measurement of depression and up to 2 years of follow-up); these studies included a total 6,367 post-MI patients and had an average follow-up of 13.7 months. The analysis revealed that post-MI depression was associated with each of the following:
- All-cause mortality (fixed-effects odds ratio [OR] = 2.38; 95% confidence interval [CI], 1.76 to 3.22; P < .00001)
- Cardiac mortality (fixed-effects OR = 2.59; 95% CI, 1.77 to 3.77; P < .00001)
- Occurrence of cardiovascular events (random-effects OR = 1.95; 95% CI, 1.33 to 2.85; P = .0006).
Prognosis of depressed patients with ischemic heart disease
In another 2004 meta-analysis, Barth et al4 examined the association of depression with mortality among patients with other forms of ischemic heart disease (IHD) (ie, beyond just MI) using data derived from English- and German-language databases (MEDLINE, PsycINFO, and PSYNDEX) from 1980 to 2003. A total of 11,905 patients from 20 cohorts were included. Although depression assessment was heterogeneous among the studies included, the unfavorable impact of depression on mortality among IHD patients was consistently observed regardless of whether the depression was self-reported or detected by psychiatric professionals. The risk of dying in the first 2 years after initial assessment was more than two times higher in patients with high depressive symptoms than in those with low depressive symptoms (OR = 2.24; 95% CI, 1.37 to 3.60). This negative prognostic impact remained over the long term and after adjustment for other risk factors (hazard ratio [HR] = 1.76; 95% CI, 1.27 to 2.43). Although clinical depression had no significant effect on mortality within the first 6 months after initial assessment (OR = 2.07; 95% CI, 0.82 to 5.26), after 2 years it was associated with a greater than twofold higher risk of death (OR = 2.61; 95% CI, 1.53 to 4.47).4
Prognosis of depressed patients with heart failure
Several studies over the past decade, including one from my research group,5 have prospectively examined the impact of depression on outcomes in patients with heart failure (HF). Rutledge et al6 used meta-analysis to summarize the findings of eight independent cohort studies that tracked the association between depression and mortality or cardiac events in a total of 1,845 patients with HF; follow-up ranged from 6 months to more than 4 years. They found that those patients who were depressed had higher rates of death and secondary events (relative risk [RR] = 2.1; 95% CI, 1.7 to 2.6) compared with their nondepressed counterparts, as well as trends toward increased health care use and higher rates of hospitalization and emergency room visitation.
Development of ischemic heart disease in depressed patients
To assess depression’s role as a potential predictor of IHD development, Rugulies7 reviewed data from MEDLINE (1966 to 2000) and PsycINFO (1887 to 2000), selecting 11 cohort studies based on assessment of patients by standardized psychometric scale (clinical depression or depressed symptoms) and “hard” events (fatal/nonfatal MI, coronary death, or cardiac death). Among the 36,549 individuals in these studies, the overall RR for development of IHD in depressed subjects (as compared with nondepressed subjects) was 1.64 (95% CI, 1.29 to 2.08; P < .001). Sensitivity analysis revealed that clinical depression was a stronger predictor of IHD (RR = 2.69; 95% CI, 1.63 to 4.43; P < .001) than depressive symptoms were (RR = 1.49; 95% CI = 1.16 to 1.92; P = .02).
In summary, individuals with depressive disorder, even mild forms, are more likely to develop IHD than are individuals without depression. The increased likelihood of developing IHD is independent of conventional risk factors. Therefore, depression is a primary risk factor for IHD. Depression is also a secondary risk factor, independent of conventional risk factors, for significantly worse prognosis in patients with MI, other forms of IHD, and HF. Depression’s adverse effect on HF prognosis is independent of the baseline impairment in cardiac function and of the ischemic etiology of HF.