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Interleukin-1 Receptor Antagonist, Interleukin-6, and C-Reactive Protein as Predictors of Mortality in Nonagenarians: The Vitality 90+ Study

¹ Tampere School of Public Health, University of Tampere, Finland.
Departments of ² Clinical Chemistry, ³ Forensic Medicine, ⁴ Microbiology and Immunology, University of Tampere Medical School, Finland.
⁵ Research Unit of the Laboratory Center, Tampere University Hospital, Finland.
⁶ Department of Social Welfare and Health Services, State Provincial Office of Western Finland.

Address correspondence to Marja Jylhä, MD, PhD, Tampere School of Public Health, FIN-33014 University of Tampere, Finland. E-mail: marja.jylha{at}uta.fi

Background. Inflammation plays a major role in both aging and chronic disease. Longitudinal studies in very old people can improve our understanding of these processes. We investigated blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and their combinations as predictors of mortality in nonagenarians.

Methods. This is a prospective population-based study including both community-dwelling and institutionalized nonagenarians enrolled in the Vitality 90+ Study. Altogether 285 persons participated in the baseline interview and gave blood. Information on chronic disease was drawn from health center registers. Data on mortality over 4 years were obtained from the Population Register Center. In Cox proportional hazards models, chronic disease and major risk factors were adjusted for.

Results. Plasma levels of IL-1ra, IL-6, and CRP were higher in persons who died during the follow-up than in those who survived. When sex, education, cardiovascular disease, diabetes, cancer, history of infections, high density lipoprotein cholesterol, Mini-Mental State Examination, body mass index, smoking status, and exercise were adjusted for, only IL-1ra was a significant predictor of mortality (hazard ratio [HR] 2.12; 95% confidence interval [CI], 1.24–3.62). Persons in the upper tertiles of both CRP and IL-1ra (HR 2.72; 95% CI, 1.25–6.00), or in the upper tertile of all three markers (HR 2.34; 95% CI, 1.23–4.61), had higher mortality than those who were not in the upper tertile in any of the markers.

Conclusions. IL-1ra is a powerful prognostic marker in very old people. Our results implicate its role in the complex interaction between inflammatory markers in aging and disease.