Tumor necrosis factor-α and mortality in heart failure -: A community study

Background - Tumor necrosis factor-alpha (TNF alpha), 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 alpha, 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 alpha were measured. Elevated TNF alpha ( more than the assay limit of normal of 2.8 pg/ mL) was present in 143 ( 29%). Higher TNF alpha was associated with decreased creatinine clearance, nonsmoking status, anemia, and greater comorbidity ( P-trend < 0.05 for all). Mortality increased with increasing TNF alpha ( 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 alpha quartile, respectively (P-trend < 0.007). TNF 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 alpha and EF). Conclusions - TNF alpha 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 alpha is useful for risk assessment in HF patients with preserved and reduced EF.