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(Circulation. 2005;111:863-870.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Tumor Necrosis Factor- Receptor 1 Is a Major Predictor of Mortality and New-Onset Heart Failure in Patients With Acute Myocardial Infarction

The Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) Study

Marco Valgimigli, MD; Claudio Ceconi, MD; Patrizia Malagutti, MD; Elisa Merli, MD; Olga Soukhomovskaia, MD; Gloria Francolini, BsC; Giordano Cicchitelli, MD; Adriana Olivares, BsC; Giovanni Parrinello, PhD; Gianfranco Percoco, MD; Gabriele Guardigli, MD; Donato Mele, MD; Roberto Pirani, MD; Roberto Ferrari, MD, PhD

From the Chair of Cardiology, University of Ferrara, Ferrara (M.V., C.C., P.M., E.M., O.S., G. Percoco, G.G., D.M., R.P., R.F.); Cardiovascular Research Center, Salvatore Maugeri Foundation, IRCCS, Gussago, Brescia (M.V., C.C., G.F., A.O., R.F.); and Medical Statistics Unit, University of Brescia, Brescia (G. Parrinello), Italy.

Correspondence to Marco Valgimigli, MD, Chair of Cardiology, University of Ferrara Cardiovascular Institute, Arcispedale S. Anna, C.rso Giovecca 203, 44100 Ferrara, Italy. E-mail vlgmrc{at}unife.it

Received June 16, 2004; revision received October 18, 2004; accepted November 1, 2004.

Background— Tumor necrosis factor alpha- (TNF-) activation is an independent prognostic indicator of mortality in patients with heart failure (HF). Despite the recognition that several TNF family cytokines are elevated during myocardial infarction, their role in predicting subsequent prognosis in these setting remains poorly understood.

Methods and Results— We performed a systematic evaluation of TNF- and its type 1 and 2 soluble receptors, together with interleukin (IL)-6, IL-1 receptor antagonist, and IL-10, in 184 patients (132 men; mean age, 64±12) consecutively admitted for myocardial infarction. We correlated their values to short- and long-term incidence of death and HF (primary outcome). In 10 patients, we also studied the presence of transcardiac gradients for TNF- and its soluble receptors. The control group comprised 45 healthy subjects who were sex and age matched (33 men; mean age, 65±6 years) to the patients. All tested cytokines were increased in patients, and no transcardiac or systemic AV difference was found. After a median follow-up of 406 days (range, 346 to 696 days), 24 patients died and 32 developed HF. Univariate analysis showed that all cytokines were related to outcome, whereas after adjustment for baseline and clinical characteristics, sTNFR-1 remained the only independent predictor of death and HF (hazard ratio, 2.9; 95% CI, 1.9 to 3.8, tertile 1 versus 3), together with left ventricular ejection fraction, Killip class, and creatine kinase-MB at peak.

Conclusions— sTNFR-1 is a major short- and long-term predictor of mortality and HF in patients with acute myocardial infarction.

Key Words: heart failure • interleukins • mortality • myocardial infarction • tumor necrosis factor-

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