Interleukin‐6, C‐Reactive Protein, and Tumor Necrosis Factor‐Alpha as Predictors of Mortality in Frail, Community‐Living Elderly Individuals

Abstract

To investigate whether interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) protein levels predict all-cause mortality in older persons living in the community. Prospective cohort study. Data were from the Aging and Longevity Study in the Sirente Geographic Area, a prospective cohort study. Individuals aged 80 and older living in an Italian mountain community (N = 362). Participants were classified according to the median value of the three inflammation markers (IL-6, 2.08 pg/mL; TNF-α, 1.43 pg/mL; CRP, 3.08 mg/L). A composite summary score of inflammation was also created. The main outcome was risk of death after 4 years of follow-up. One hundred fifty deaths occurred during 4 years of follow-up. In the unadjusted model, high levels of each of the three markers were associated with greater mortality. After adjusting for potential confounders, high levels of IL-6 (hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.29-3.69) and CRP (HR = 2.58, 95% CI = 1.52-4.40) were associated with a significantly greater risk of death, whereas the association between TNF-α protein levels and mortality was no longer significant (HR = 1.26, 95% CI = 0.74-2.15). The composite summary score of inflammation was strongly associated with mortality, with the highest risk estimated for individuals with all three inflammatory markers above the median. Low levels of inflammatory markers are associated with better survival in older adults, independent of age and other clinical and functional variables.