Clinical Briefs: Heartache and Heart Failure

With Comments from Russell H. Greenfield, MD

Dr. Greenfield is Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, and Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC.

Source: Ferketich AK, et al. Depressive symptoms and inflammation among heart failure patients. Am Heart J 2005;150: 132-136.

Goal: To assess levels of pro-inflammatory cytokines in people with heart failure both with and without increased symptoms of depression.

Study Design: Prospective, cross-sectional study.

Subjects: Fifty adults with heart failure, ischemic or non-ischemic, recruited from an outpatient heart failure clinic (data available for analysis from 32 subjects).

Methods: Depressive symptoms were measured using the Beck Depression Inventory (BDI), with subjects classified as having increased symptoms of depression with scores ³ 10. A subscale of the BDI (cognitive-affective subscale score) was also employed that permits classification of depressive symptoms attributable to the process of heart failure as opposed to those caused by an intrinsic affective disorder (symptoms shared by both groups may include fatigue, weight loss, and sleep disorders). Blood samples were obtained to determine levels of IL-6, IL-1b, and TNF-a.

Results: No relationship between BDI or BDI subscale scores and IL-6 or IL-1b was found. A significant relationship between BDI and BDI subscale scores and TNF-a, however, was identified. Pro-inflammatory cytokine levels were not significantly correlated.

Conclusion: Depression-specific activation of a pro-inflammatory cytokine, TNF-a, occurs apart from the process of heart failure itself, and may contribute to morbidity and mortality in people with heart failure.

Study strengths: Use of BDI subscale to tease out influence of depressed mood on cardiac function.

Study weaknesses: Not all participants had cytokine measures performed for reasons not adequately explained; technical difficulties experienced with certain cytokine measurements; small sample size.

Of note: Multiple linear regression models were employed that controlled for age, gender, smoking, and antidepressant use; total BDI score may be influenced by both the physical symptoms of heart failure and the presence of an intrinsic cognitive-affective disorder; only one of the three pro-inflammatory cytokines measured (TNF-a) increased in response to elevated symptoms of depression.

We knew that: Depression has been associated with increased risk of heart failure as well as poor prognosis in patients with established heart failure; evidence suggests that pro-inflammatory cytokines are elevated in people with heart failure; pro-inflammatory cyto-kines exert negative effects on cardiac function including promotion of left ventricular remodeling, induction of contractile dysfunction, and uncoupling of myocardial beta-adrenergic receptors; elevated levels of IL-6, IL-1b, and TNF-a have been associated with major depressive disorder (MDD) as well as depression in the absence of MDD.

Comments: This interesting, yet underpowered, trial suggests an association between depressed mood state and increased levels of pro-inflammatory cytokines in people with heart failure. The notion that anxiety, depression, or inadequately managed stress may contribute to systemic activation of the inflammatory cascade has long been considered and has not been lost on researchers, yet to this day continues to escape many clinicians. Inflammation represents the pathophysiologic process central to some of the most troubling chronic maladies experienced by patients. Few people with chronic illness are counseled that with proper treatment of depression, or through the use of proven techniques for amelioration of stress, they may be able to control some aspects of their disease and lessen physical symptoms. This trial is flawed in important ways, but it does support an association between mental processes and physiology, between mind and body, that mandates continued study.

What to do with this article: Remember that you read the abstract.