Three-year change in inflammatory markers in elderly people and mortality: The Invecchiare in Chianti study

OBJECTIVES: To describe changes in interleukin-6 (IL-6) and C-reactive protein (CRP) and to determine how changes are related to mortality in elderly people. DESIGN: Prospective cohort study. SETTING: Two communities in the Tuscany region of Italy. PARTICIPANTS: Randomly selected residents aged 65 and older who participated in the first two waves of data collection (N=736). MEASUREMENTS: Two serum measurements of IL-6 and CRP taken 3 years apart. Mortality was observed for the 3 years after the second measurement; 79 deaths were observed in 2,079 person-years. RESULTS: Correlations indicated marginal to moderate stability in IL-6 and CRP, with clinical categories remaining relatively stable over time. Baseline levels were not related to mortality between follow-up Years 3 and 6, but increases in IL-6 and CRP predicted 3- to 6-year mortality. Controlling for follow-up IL-6 and CRP attenuated the relationship between inflammatory changes and mortality, but increases in CRP continued to increase odds of mortality. After controlling for sociodemographic characteristics, biological risk factors, health behaviors, and disease at both times, increases in CRP, but not IL-6, were related to mortality. Odds of death were more than three times as great in subjects in whom any CRP increase was observed (odds ratio=3.10, 95% confidence interval=1.25-7.68) as in subjects with stable or declining CRP. CONCLUSION: CRP and IL-6 levels within individuals vary over time, and increases in CRP are associated with greater mortality risk. Three-year changes in inflammatory markers are better predictors of mortality than baseline measures.