Tumor necrosis factor-alpha and mortality in heart failure: a community study

Abstract

Background: Tumor necrosis factor-alpha (TNFalpha), 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 TNFalpha, 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 > or =50%, 55%) were prospectively recruited. Clinical characteristics and TNFalpha were measured. Elevated TNFalpha (more than the assay limit of normal of 2.8 pg/mL) was present in 143 (29%). Higher TNFalpha was associated with decreased creatinine clearance, nonsmoking status, anemia, and greater comorbidity (P(trend)<0.05 for all). Mortality increased with increasing TNFalpha (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 TNFalpha quartile, respectively (P(trend)=0.007). TNFalpha 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 TNFalpha and EF).

Conclusions: TNFalpha 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. TNFalpha is useful for risk assessment in HF patients with preserved and reduced EF.

Figure 1

Tumor Necrosis Factor α (TNFα) levels by Creatinine Clearance and Hemoglobin. Caption: TNFα levels by creatinine clearance (A) and hemoglobin (B) are shown. Each box displays the median, 25^th percentile, and 75^th percentile values; horizontal bars represent 1.5 times the interquartile range. No.= number

Figure 1

Tumor Necrosis Factor α (TNFα) levels by Creatinine Clearance and Hemoglobin. Caption: TNFα levels by creatinine clearance (A) and hemoglobin (B) are shown. Each box displays the median, 25^th percentile, and 75^th percentile values; horizontal bars represent 1.5 times the interquartile range. No.= number

Figure 2

Kaplan-Meier Mortality Curves by TNFα Quartile. Caption: Mortality during follow-up was analyzed by TNFα quartile. HF= heart failure