Soluble Tumor Necrosis Factor Receptors and Heart Failure Risk in Older Adults: Health, Aging, and Body Composition (Health ABC) Study

Background Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear. Methods and Results Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age, 74.02.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels was 3.14 (2.42-4.06), 1.46 (1.25-1.76), and 3.43 (2.95-4.02) ng/mL, respectively. During a median follow-up of 11.4 (6.9-11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log(2) increase) and sTNF-R1 (HR, 1.68; 95% CI, 1.15-2.46 per log(2) increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80-1.63 per log(2) increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2; interaction P=0.531, 0.091, and 0.795, respectively) and in both sexes (TNF, sTNF-R1, sTNF-R2; interaction P=0.491, 0.672, and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95% CI, 1.03-3.18; P=0.038 for preserved versus HR, 0.90; 95% CI, 0.56-1.44; P=0.667 for reduced ejection fraction; interaction P=0.05). Conclusions In older adults, elevated levels of sTNF-R1 are associated with increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification.