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

OBJECTIVES To examine the independent relationships between fibrin D-dimer, interleukin 6 (IL-6), C-reactive protein (CRP), and fibrinogen and incident mobility limitation and mortality. DESIGN Prospective. SETTING General practice in 24 British towns. PARTICIPANTS Men aged 60 to 79 without prevalent heart failure followed up for an average of 11.5 years (N = 3,925). MEASUREMENTS All-cause mortality (n = 1,286) and self-reported mobility disability obtained at examination in 1998 to 2000 and in a postal questionnaire 3 to 5 years later in 2003. RESULTS High D-dimer (top vs lowest tertile: adjusted odds ratio (aOR) = 1.46, 95% confidence interval = 1.02-2.05) and IL-6 (aOR = 1.43, 95% CI = 1.01-2.02) levels (but not CRP or fibrinogen) were associated with greater incident mobility limitation after adjustment for confounders and prevalent disease status. IL-6, CRP, fibrinogen, and D-dimer were significantly associated with total mortality after adjustment for confounders. Only D-dimer and IL-6 predicted total mortality independent of each other and the other biomarkers. The adjusted hazard ratio (aHR) was 1.16 (95% CI = 1.10-1.22) for a standard deviation increase in log D-dimer and 1.10 (95% CI = 1.04-1.18) for a standard deviation increase in log IL-6. D-dimer was independently related to vascular and nonvascular mortality, and IL-6 was independently related to vascular mortality. Risks of mobility limitation and mortality were greatest in those with a combination of high D-dimer and IL-6 levels. CONCLUSION D-dimer and IL-6 are associated with risk of mobility limitation and mortality in older men without heart failure. The findings suggest that coagulation leads to functional decline and mortality s that inflammation does not explain.