Depression and Cardiovascular Disease: Just an Urban Legend?

| November 4, 2008 | 0 Comments

by Randy A. Sansone, MD, and Lori A. Sansone, MD

Dr. R. Sansone is a professor in the Departments of Psychiatry and Internal Medicine at Wright State University School of Medicine in Dayton, Ohio, and Director of Psychiatry Education at Kettering Medical Center in Kettering, Ohio; Dr. L. Sansone is a family medicine physician (government service) and Medical Director of the Primary Care Clinic at Wright-Patterson Air Force Base. The views and opinions expressed in this column are those of the authors and do not reflect the official policy or the position of the United States Air Force, Department of Defense, or US government.

Psychiatry (Edgemont) 2008;5(11):45–48

ABSTRACT

For years, there has been speculation among clinicians about possible relationships between (a) depression and the development of cardiovascular disease (CVD) and (b) comorbid depression and adverse CVD outcomes. In a review of the recent literature, we noted that there are data to support both of these clinical urban legends. In addition, while data are preliminary, several studies indicate modest medical benefits with antidepressant treatment among individuals with comorbid depression and CVD. Clearly, additional studies are warranted in this intriguing area of the mind/body interface.

INTRODUCTION

Like a clinical urban legend, there have been proposed relationships between mood disorders and cardiovascular disease (CVD) for years—primarily that depression is a risk factor for the development of CVD and may result in poorer treatment outcomes in those with existing CVD. However, these relationships have not been explicitly and empirically explored until the last decade or so.[1] We hope to succinctly summarize the more recent empirical data in this article.

PRE-EXISTING DEPRESSION AS A RISK FACTOR FOR SUBSEQUENT CVD

A number of researchers hav examined whether pre-existing mood disorders increase the risk for subsequent cardiac disease. Recent studies support this impression. For example, among African-American women, Collins-McNeil et al[2] confirmed statistical associations between depression scores and cardiovascular risk scores. In a group of caregivers of dementia patients, Mausbach et al[3] determined that higher levels of depressive symptoms correlated with shorter time periods to CVD diagnosis. In an Australian study of 755 women, participants with angina were about four times more likely than controls to report past histories of depression.[4] In a controlled study, Janszky et al[5] found that participants with a first myocardial infarction had a greater likelihood of being previously hospitalized for depression. In a 12- year, prospective, follow-up study of nearly 1200 elderly Finnish individuals, depression scores at the outset correlated with highe subsequent risks of mortality from CVD or myocardial infarction.[6] Similar data have emerged from Hungary. In a community sample of over 12,000 individuals, Kopp et al[7] found that depression was a meaningful contributory factor to subsequent premature cardiovascular mortality. Compared with nondepressed controls, Gromova et al[8] found that depressed Russian men had a two-times-higher risk of subsequent myocardial infarction. Finally, Boulware et al[9] found, among dialysis patients, a relationship between depression and subsequent cardiovascular events and deaths.

The preceding studies proffer several tentative conclusions. First, depressive symptoms (not necessarily formal Diagnostic and Statistical Manual of Mental Disorders [DSM] diagnoses, such as major depression or dysthymia) are associated with a higher risk of CVD as well as more forthcoming cardiac events and mortality. Second, these data come from a number of different patient, community, and national samples, and probably reflect a universal phenomenon.

THE EFFECTS OF CURRENT DEPRESSION ON EXISTING CVD

The preceding data indicate that, among other contributory variables (e.g., lifestyle, obesity), depression appears to modestly predict for higher rates of CVD and mortality. What about the effects of current depression in the presence of existing CVD? Several investigators have explored this relationship. For example, in a study of 468 patients with myocardial infarction, de Jonge et al[10] found that those with new onset depression (as opposed to ongoing or recurrent depressions, or no depression at all) were at an increased risk of post-infarction cardiovascular events. Among over 500 women with cardiac ischemia, Rutledge et al[11] found an association between depressive symptoms and a subsequent increased incidence of cardiac events and death. In a similar vein, among post-myocardial-infarction patients with current depression, Jaffe et al[12] found an increased risk of nonfatal reinfarction or death. Sherwood et al[13] examined outpatients with ventricular ejection fractions of 40 percent or less (i.e., those with heart failure) and determined that current depression increased the risk for cardiovascular hospitalization as well as death.

The preceding data suggest that current depression in those with existing CVD has a negative impact on medical outcome. Specifically, higher levels of depression are associated with greater risks of subsequent cardiovascular events as well as mortality.

ETIOLOGICAL POSSIBILITIES

What might explain the relationship between depression and CVD? A number of authors have offered hypotheses, both pathophysiological and psychosocial.

Pathophysiological hypotheses. Garcia-Gomez et al[14] suggest that the relationship between depression and CVD might be explained by dysfunction in the central autonomic network, specifically in the areas of the hippocampus, prefrontal cortex, and brain stem nuclei. They propose that dysfunction in these areas results in lowered levels of serotonin, sympathetic excess, and a loss of cardiac vagal tone. Bounhoure et al[15] suggest that the relationship may be mediated by sympathetic stimulation, endothelial dysfunction, low heart rate variability, and abnormal platelet function. Fenton and Stover[16] implicate dysregulation in the hypothalamic-pituitary-adrenal axis. Finally, Parissis et al[17] propose immune activation, inflammation, hypercoagulation, cardiac rhythm disturbances, and metabolic disorders as possible explanations. It is worth noting that several investigators have identified mechanisms that do not seem to mediate the relationship between depression and CVD. These empirical dead ends include cardiovascular reactivity[18,19] and inflammatory markers.[20]

Psychosocial hypotheses. Various psychosocial factors have also been recently explored. For example, Kamphuis et al[21] found that in men depression was associated with physical inactivity, and that during a 10-year follow-up period, physical inactivity was subsequently associated with greater cardiovascular mortality. Spernak and colleagues found an association between depression and less adherence to a postoperative cardiac rehabilitation program.[22] Fenton and Stover[16] discuss the negative impact of poor diet on CVD in depressed individuals. Finally, among the depressed, Parissis et al[17] implicate poor self care, continued smoking, low motivation, nonadherence with treatment, and low participation in cardiac rehabilitation programs.

Summary. While empirically elusive, it is likely that there are multiple factors, both pathophysiological and psychosocial, that mediate the complex relationshi between depression and cardiovascular phenomena—yet another complex interaction in the mind/body interface.

THE ROLE OF ANTIDEPRESSANTS

If depression contributes to CVD, both prospectively and concurrently, does depression treatment exert an impact on medical outcome? There is very little available research in this area. In examining the use of nontricyclic antidepressants in patients with cardiac disease, sertraline is the most studied, but there are also studies with citalopram and mirtazapine. All three antidepressants have been well tolerated and safe in patients with cardiac disease. The two selective serotonin reuptake inhibitors (SSRIs) (i.e., sertraline and citalopram) have clearly demonstrated efficacy in treating depression in this population[23] and appear to improve quality of life.[24] However, the predictive effect of antidepressant treatment with regard to cardiovascular outcome remains unclear.[24]

Scant available data suggest that several antidepressants may modestly improve CVD outcome. For example, Glassman et al[25] examined the efficacy of sertraline in preventing subsequent cardiac events in a group of depressed, hospitalized patients with myocardial infarctions.[25] In this controlled study, the subgroup of patients on sertraline experienced fewer subsequent cardiac events (14.5%) compared with nontreated individuals (22.4%), but there was not a statistically significant difference. In a study by de Jonge et al[26] compared with antidepressant-nonresponders and untreated controls, antidepressant-responders to citalopram and mirtazapine were the least likely subgroup to develop new cardiac events following myocardial infarction. Finally, in a small study by Mohapatra et al[27] of depressed post-myocardial-infarction patients, cardiac events were around three times more frequent in the nonantidepressant subgroup compared to participants on antidepressant treatment with sertraline. So, preliminary findings clearly but modestly lean in the direction of a positive effect of nontricyclic antidepressants on cardiovascular outcome.

If nontricyclic antidepressants, particularly SSRIs, are ultimately confirmed to be effective, their effects may not be limited to the alleviation of depression. Parissis et al[17] have suggested that there are relevant SSRI effects on platelets (e.g., an inhibition of platelet activity). In addition, Paraskevaidis et al28 indicate that SSRIs may deter immune activation (i.e., prevent an inflammatory response) as well as normalize neurohormonal dysfunction (e.g., autonomic dysregulation) in patients.

CONCLUSION

According to available data, there is convincing evidence that depression is one of several contributory variables in the evolution of subsequent CVD. In addition, acute depression appears to influence the outcome of those with existing CVD. While the reasons remain unclear, antidepressant therapy with nontricyclics (particularly SSRIs) may modestly reduce the risk of subsequent cardiac events in individuals with current disease. Like many other areas in medicine, this mind/body interface will clearly benefit from additional research—particularly the degree to which nontricyclic antidepressant therapy (principally treatment with SSRIs) will consistently prevent CVD in the depressed as well as stave off cardiac complications in those with comorbid depression and CVD.

References
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Category: Medical Issues, Mood Disorders, Past Articles, Primary Care, Psychiatry, The Interface

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