Chicago, IL - Clinical depression significantly raises the risk of death or CV hospitalization in patients with heart failure independently of the syndrome's severity, suggests a prospective study appearing in the February 26, 2007 Archives of Internal Medicine [1].

The finding is consistent with prior research but makes a stronger case because natriuretic-peptide levels were used as a gauge of HF severity, observed coauthor Dr James Blumenthal (Duke University, Durham, NC). The earlier studies tended to rely on less-objective functional measures that were more susceptible to the influence of depressive symptoms, he told heartwire.

Depression is common in this patient population, and it carries its own independent risk, even in these patients with significantly compromised hearts.

"Being depressed isn't simply a marker for more severe disease," Blumenthal said. "Depression is common in this patient population, and it carries its own independent risk, even in these patients with significantly compromised hearts."

In the study from Dr Andrew Sherwood (Duke University) and colleagues, clinically significant depression—defined as a score of >10 on the Beck Depression Inventory (BDI) self assessment—was identified in 94 of 204 patients with predominantly NYHA class 2-3 heart failure and LV systolic dysfunction. About one quarter of the total died and about half were hospitalized due to cardiovascular disease over an average of three years.

The hazard ratio for death or CV hospitalization went up significantly with increasing baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and with higher BDI scores. Remarkably, the use of antidepressant medications—selective serotonin reuptake inhibitors in 80% of cases—elevated risk. Age, LVEF, and HF etiology showed no independent effects on the composite end point.

If depression has an independent effect on HF severity, the pathophysiologic mechanisms could be behavioral, physiologic, or a combination of the two. Blumenthal observes that people who are depressed may be less active than others, more likely to smoke, and less likely to comply with prescribed therapies. And, he noted, depression has been associated with increased sympathetic activity and platelet activation, reduced heart-rate variability, and endothelial dysfunction.

It would be a misinterpretation of the data to suggest that somehow antidepressants caused an increase in events.

"Our study provides no clear explanation for the observation that antidepressant use was associated with poorer HF prognosis, and limitations of the study design underscore the importance of interpreting this observation with caution," according to the authors. The study was small and didn't control for all potential confounders, for example, and the BDI scores may not have captured the cohort's true degree of depression and its effect on CV outcomes, they write. "We did not have information about duration of antidepressant use, and we did not know whether depressive symptoms were stable, remitting, or worsening. Taking an antidepressant may be a marker for chronic, recurrent, or treatment-resistant depression."

According to Blumenthal, "It would be a misinterpretation of the data to suggest that somehow antidepressants caused an increase in events."

Depression now deserves to be thought of as a potential therapeutic target in heart failure, Blumenthal said. "The time is now right for examining the impact of treating depression in this high-risk population, not only in terms of improving quality of life—because I think depression should be treated in its own right—but also for its potential to improve clinical outcomes."