Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: A cohort study

Background: Traditional atherosclerotic risk factors predict long-term cardiovascular disease events but are poor predictors of near-term events. Objective: To determine whether elevated levels of D-dimer and biomarkers of inflammation were more closely associated with near-term than long-term mortality in patients with lower-extremity peripheral arterial disease (PAD) and whether greater increases in biomarker levels were associated with higher mortality rates during the first year after the increase than during later years. Design: Prospective cohort study with a mean follow-up of 3.4 years. Setting: Academic medical center. Patients: 377 men and women with PAD. Measurements: Mortality within 1 year after biomarker measurement, 1 to 2 years after biomarker measurement, and 2 to 3 years after biomarker measurement. Cox regression analyses were used to evaluate associations of biomarkers levels and changes in biomarkers with cardiovascular and all-cause mortality. Hazard ratios were calculated for each 1-unit increase in log_1.5(biomarker level). Analyses were adjusted for age, sex, race, comorbid conditions, ankle-brachial index, and other confounders. Results: Seventy-six patients (20%) died during follow-up. Higher levels of D-dimer, C-reactive protein, and serum amyloid A were associated with higher all-cause mortality among patients who died within 1 year after biomarker measurement (hazard ratio, 1.20 [95% CI, 1.08 to 1.33], 1.13 [CI, 1.05 to 1.21], and 1.12 [CI, 1.04 to 1.20], respectively; P < 0.001, P < 0.001, and P = 0.003) and among patients who died 1 to 2 years after biomarker measurement (hazard ratio, 1.14 [CI, 1.02 to 1.27], 1.15 [CI, 1.06 to 1.24], and 1.13 [CI, 1.04 to 1.24]; P = 0.022, P = 0.001, and P = 0.005]). However, higher levels of each biomarker were not associated with all-cause mortality for deaths occurring 2 to 3 years after biomarker measurement. Similar results were observed for cardiovascular mortality. Greater increases in each biomarker were associated with higher all-cause and cardiovascular mortality during the following year. Limitation: The small number of deaths limited the statistical power of the analyses. Conclusion: Among persons with PAD, circulating levels of D-dimer and inflammatory markers are higher in the 1 to 2 years before death than in periods more remote from death. Increasing levels of D-dimer and inflammatory biomarkers are independently associated with higher mortality in persons with PAD.