Higher Levels of Inflammatory Marker Associated with Depression in HF

Susan Jeffrey

April 11, 2007

April 11, 2007 (New Orleans) — A new study shows that heart failure patients with higher levels of tumor necrosis factor receptor 1 (TNFr1), a marker of inflammation, had an increased risk for depression, up to almost 5-fold for those with levels in the highest quartile.

"The question this doesn't answer is whether depression is a brain response to cytokines or whether it is actually the depression that's causing the cytokines to be elevated," coauthor Wayne D. Levy, MD, from the University of Washington, in Seattle, a heart failure cardiologist, told Medscape.

Mark Sullivan, MD, PhD, associate professor of psychiatry, also at the University of Washington, was principal investigator of the overall study, of which this was a subanalysis. He told Medscape that depression has been shown to worsen patient outcomes in heart failure. "This study begins to demonstrate some of the pathophysiological mechanisms by which this may occur," he said. "It suggests that proinflammatory cytokines may be important."

Their report was presented here at the American College of Cardiology 56th Annual Scientific Sessions.

Heart Failure Plus Depression Equals Events

Proinflammatory cytokines have been implicated in the development and progression of both depression and heart failure, the authors point out in their abstract.

A previous study by this group showed that in patients with advanced heart failure, those with a diagnosis of depression at baseline had a significantly increased risk of experiencing 1 of a composite end point of death or transplantation over follow-up, with a hazard ratio of 2.54 (95% CI, 1.16 – 5.55) (Sullivan M et al. Am J Cardiol
. 2004;94:1577 – 1580). Depressed patients also had more heart failure–related hospitalizations and clinic visits. "The question is whether cytokines mediate that," Dr. Levy said.

In this analysis, a subanalysis of their previous paper, the researchers examined the relationship between circulating inflammatory cytokines and depression in this group of 141 ambulatory patients with heart failure. Of these, 29% were depressed at baseline, defined as antidepressant use or according to a validated interview.

They report that in bivariate unadjusted comparisons, mean values of TNFr1 were significantly higher in heart failure patients meeting the definition for depression. After adjustment for age, sex, ejection fraction, systolic blood pressure, New York Heart Association functional class, and creatinine, those in the highest quartile for TNFr1 levels had a nearly 5-fold increased risk for depression compared with those in the lowest quartile.

Risk for Depression in Highest vs Lowest Quartile for TNFr1 in Patients with Heart Failure
End Point
Hazard Ratio
95% CI
P for Trend
1.4 – 17.5

There was also a significant positive relationship between TNFr1 levels and scores on the Hamilton Depression Rating score.

Interestingly, though, the use of antidepressants in the depressed heart failure patients reduced depression scores but not the level of TNFr1, which remained significantly elevated in treated patients,at almost 60% higher than the reference group. "Antidepressants may improve how you feel but may not lower the mediators, that is, TNFr1 and other factors, so it may require other interventions to reduce the risk associated with depression in these patients," Dr. Levy said.

Dr. Sullivan is now participating in a 4-site Veterans Affairs study of depression-focused disease management for heart failure patients with poor health status, due to start late this year. John Rumsfeld, MD, PhD, a cardiologist at the Denver VA Medical Center and Colorado Health Sciences Center, is principal investigator on that study.

American College of Cardiology 56th Annual Scientific Sessions: Abstract 1004-61. March 24 – 27, 2007.


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