Cytokines and Cytokine Receptors in Advanced Heart Failure. An Analysis of the Cytokine Database from the Vesnarinone Trial (VEST) - Cytokines and Cytokine Receptors in Advanced Heart Failure (VEST)

Mar 07, 2002
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Date Presented:
01/01/2001
Date Published:
01/01/2001
Date Updated:
03/07/2002
Original Posted Date:
03/07/2002
References

Description:

Cytokines and Cytokine Receptors in Advanced Heart Failure. An Analysis of the Cytokine Database from the Vesnarinone Trial (VEST)

Hypothesis:

Previous reports have shown that elevated circulating levels of cytokines and/or cytokine receptors predict adverse outcomes in patients with heart failure. However, these studies were limited by small numbers of patients and/or they were performed in a single center. In addition, these studies did not have sufficient size to address the influence of age, race, sex and cause of heart failure on the circulating levels of these inflammatory mediators in patients with heart failure.

Study Design

Study Design:

Patients Enrolled: 1200

Drug/Procedures Used:

The authors analyzed circulating levels of cytokines (tumor necrosis factor [TNF] and interleukin-6) and their cognate receptors in 1,200 consecutive patients who were enrolled in a multicenter clinical trial of patients with advanced heart failure.

Principal Findings:

Analysis of the relationship of cytokines to survival (placebo treated group of this randomized trial of vesnarinone) indicated that increased circulating levels of cytokines or their soluble receptors were associated with increased mortality. In men, there was a linear increase in circulating levels of TNF with advancing age. Women ≤50 years of age had relatively low levels of TNF, but TNF levels were disproportionately higher in women >50 years of age. No differences existed in cytokines and/or cytokine receptors in whites vs. nonwhites, and circulating levels of cytokines and cytokine receptors were significantly greater in patients with ischemic heart disease. Conclusions: Cytokines and cytokine receptors are independent predictors of mortality in patients with advanced heart failure. Moreover, circulating levels of cytokines are modified by age, sex, and cause of heart failure. There was an age-related increase of cytokines, similar to that which has been demonstrated in normal aging subjects without cardiovascular disease.

Interpretation:

This study provides important new insights regarding cytokines, which are strengthened by the large number of consecutive patients that comprised the database. First, increased circulating cytokine levels are an independent predictor of mortality. Second, there is an age and gender interaction, with a suggestion that females suppress cytokine abnormalities until some point after the range of menopause. These findings support a pathophysiologic contribution of cytokine abnormalities in heart failure, particularly in the elderly.

References:

Deswal A, Petersen NJ, Feldman AJ, Young JB, White BG, Mann DL. Circulation.2001;102:2055-9.

Keywords: Phosphodiesterase Inhibitors, Myocardial Ischemia, Receptors, Cytokine, Cytokines, Interleukin-6, Quinolines, Tumor Necrosis Factor-alpha, Menopause, Heart Failure, Cardiotonic Agents


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