Association between Serum Interleukin-6 Concentrations and Mortality in Older Adults: The Rancho Bernardo Study

Abstract

BackgroundInterleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.AimsTo determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality.MethodsA prospective cohort study included 1843 participants who attended a research visit in 1984–87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.ResultsThe mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (±10.6) years and 25 (±3.7) Kg/m2, respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (±IQR) length of follow-up was 15.3±10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33–1.64), 1.38 (95% CI, 1.16–1.65), 1.35 (95% CI, 1.02–1.79), and 1.88 (95% CI, 0.97–3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.ConclusionsIn community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.

Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes

“…IL-6 has been characterised as a risk factor for CVD in several cohorts [30] and we confirm its importance here. In a subanalysis of the MONICA/KORA samples that also included C-reactive protein (CRP) measurement, the association between IL-6 and CVD was attenuated but the association of IL-15 with CVD remained (data not shown).…”

Interleukin-6 as a first-rated serum inflammatory marker to predict mortality and hospitalization in the oldest old: A regression and CART approach in the BELFRAIL study

“…1) is complementary to the findings of previous research in community-dwelling older adults (Baune et al, 2011;Harris et al, 1999;Lee et al, 2012;Newman et al, 2009;Roubenoff et al, 2003;Walston et al, 2009), even though our population was considerably older than the populations in the previous studies. Similarly, Giovanni and coworkers reported a very significant association between high serum IL-6 levels and mortality in persons 80 years of age or older (Giovannini et al, 2011).…”

Associations Between Fibrin D‐Dimer, Markers of Inflammation, Incident Self‐Reported Mobility Limitation, and All‐Cause Mortality in Older Men

“…High circulating levels of markers of inflammation and coagulation, most notably CRP, IL-6, and D-dimer increase with advancing age1,6 and have been associated with functional decline, cardiovascular disease (CVD), and total mortality 7–22. Whether the association between CRP and mobility limitation and mortality reflects upregulation by IL-6 is not well established.…”