Tumor Necrosis Factor-α and Mortality in Heart Failure

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Abstract
Background— Tumor necrosis factor-α (TNFα), 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 TNFα, 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 TNFα were measured. Elevated TNFα (more than the assay limit of normal of 2.8 pg/mL) was present in 143 (29%). Higher TNFα was associated with decreased creatinine clearance, nonsmoking status, anemia, and greater comorbidity (PtrendP=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 TNFα quartile, respectively (Ptrend=0.007). TNFα contributed to risk assessment as indicated by increases in the area under the receiver operating characteristic curves in all models examined (PP=0.60 interaction term of TNFα and EF). Conclusions— TNFα 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. TNFα is useful for risk assessment in HF patients with preserved and reduced EF.