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

Study Questions:

Are soluble tumor necrosis factor type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors associated with risk for incident heart failure (HF)?

Methods:

The study cohort was comprised of 1,285 participants of the Health, Aging, and Body Composition Study (age, 74.0 ± 2.9 years; 51.4% women; 41.1% black). The authors utilized Cox proportional hazard models to examine the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk.

Results:

The median follow-up period was 11.4 (6.9-11.7) years. The authors found that 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 the median follow-up period, 18.1% (n = 233) of the participants developed HF. They found that TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log2 increase) and sTNF-R1 (HR, 1.68; 95% CI, 1.15-2.46 per log2 increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80-1.63 per log2 increase), were associated with a higher risk for HF. Consistent associations were observed across whites and blacks (TNF, sTNF-R1, sTNF-R2; interaction p = 0.531, 0.091, and 0.795, respectively) and in both genders (TNF, sTNF-R1, sTNF-R2; interaction p = 0.491, 0.672, and 0.999, respectively). A higher risk for HF was associated with TNF-R1 for preserved versus reduced ejection fraction (HR, 1.81; 95% CI, 1.03-3.18; p = 0.038 for preserved vs. HR, 0.90; 95% CI, 0.56-1.44; p = 0.667 for reduced ejection fraction; interaction p = 0.05).

Conclusions:

The authors concluded that elevated levels of sTNF-R1 are associated with increased risk for incident HF in older patients. There was no incremental value of adding TNF-R1 to the previously validated Health ABC HF risk model.

Perspective:

This is an important study because the findings suggest that diastolic HF in the elderly is possibly related to inflammation. The hypothesis-generating findings should prompt further investigation into the potential role of inflammation in the pathogenesis and natural history of diastolic HF of the elderly.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Inflammation, Follow-Up Studies, Tumor Necrosis Factor-alpha, Systole, Proportional Hazards Models, Biological Markers, Troponin I, Heart Failure, Receptors, Tumor Necrosis Factor, Confidence Intervals, Diastole, African Continental Ancestry Group


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