Interleukin-1 receptor antagonist, interleukin-6, and C-reactive protein as predictors of mortality in nonagenarians: the vitality 90+ study.
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.
Jylhä
Marja
M
Tampere School of Public Health, FIN-33014 University of Tampere, Finland. marja.jylha@uta.fi
Paavilainen
Paula
P
Lehtimäki
Terho
T
Goebeler
Sirkka
S
Karhunen
Pekka J
PJ
Hervonen
Antti
A
Hurme
Mikko
M
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D009026:Mortality; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D002097:C-Reactive Protein