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(Circulation. 2008;118:625-631.)
© 2008 American Heart Association, Inc.

Epidemiology

Tumor Necrosis Factor- and Mortality in Heart Failure

A Community Study

Shannon M. Dunlay, MD; Susan A. Weston, MS; Margaret M. Redfield, MD; Jill M. Killian, BS; Véronique L. Roger, MD, MPH

From the Division of Cardiovascular Diseases (S.M.D., M.M.R., V.L.R.) and Department of Health Services Research (S.A.W., J.M.K., V.L.R.), Mayo Clinic and Foundation, Rochester, Minn.

Correspondence to Véronique L. Roger, Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail roger.veronique{at}mayo.edu

Received December 11, 2007; accepted May 29, 2008.

Background— Tumor necrosis factor- (TNF), an inflammatory cytokine, was reported to be elevated in trials of heart failure (HF) with reduced ejection fraction (EF) and associated with mortality. Whether this is true for HF with preserved EF is unknown, and community data are lacking. We evaluated the distribution of TNF, its association with baseline characteristics and mortality, and its benefit in assessing risk in community HF patients.

Methods and Results— Olmsted County residents with active HF from July 2004 to March 2007 (n=486; mean age, 76.7 years; EF 50%, 55%) were prospectively recruited. Clinical characteristics and TNF were measured. Elevated TNF (more than the assay limit of normal of 2.8 pg/mL) was present in 143 (29%). Higher TNF was associated with decreased creatinine clearance, nonsmoking status, anemia, and greater comorbidity (P_trend<0.05 for all). Mortality increased with increasing TNF (P=0.016), with 1-year mortality estimates of 16%, 18%, 23%, and 32% from the lowest to highest quartile, respectively. After adjustment for age, sex, and EF, the hazard ratios for death were 1.24, 1.37, and 1.90 from the second to the highest TNF quartile, respectively (P_trend=0.007). TNF contributed to risk assessment as indicated by increases in the area under the receiver operating characteristic curves in all models examined (P<0.05 for all). Results did not differ by EF (P=0.60 interaction term of TNF and EF).

Conclusions— TNF was elevated in a large portion of community HF patients, was associated with a large decrease in survival, and provided a significant incremental increase in risk assessment above established indicators. TNF is useful for risk assessment in HF patients with preserved and reduced EF.

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CLINICAL PERSPECTIVE

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