Inflammatory biomarkers predict short-term mortality in patients with peripheral arterial disease

January 26, 2008 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

A new study has examined the value of various inflammatory biomarkers for predicting short- and long-term mortality in patients with peripheral arterial disease (PAD). Their findings, published in the Annals of Internal Medicine, demonstrate that elevations in D-dimer, c-reactive protein (CRP) and amyloid A are associated with elevations in short-term but not long-term mortality in patients with PAD. Three hundred seventy-seven patients with PAD (defined as ankle-brachial index < 0.9) were included in the study. Exclusion criteria included patients with dementia, amputations, non-English speakers, residents of nursing homes, patient who were wheelchair bound, and any patient who had recent major surgery. Blood samples were drawn at baseline and then at follow up appointments for the following 4 years. During this time period 76 patients died (20%), 31 of which were from cardiovascular causes. Among survivors, serum samples were unavailable for 112 patients at the third follow-up visit.

The authors carefully compared levels of various biomarkers with timings of observed deaths. Data were adjusted for age, sex, race, history of diabetes or cancer, co-morbid cardiovascular diseases, smoking status, and baseline ankle-brachial index. After adjustment for covariates, elevations in D-dimer, CRP, and amyloid A remained statistically associated with higher all-cause and cardiovascular mortality within 1 or 2 years. Hazard ratios for all-cause mortality at 1 year were 1.20 [CI, 1.08 to 1.33] for elevated D-dimer, 1.13 [CI, 1.05 to 1.21] for elevated CRP, and 1.12 [CI, 1.04 to 1.20] for elevated amyloid A. Interestingly, these biomarkers better predicted 1-year than 2-year mortality, and did not predict risk of death at 3 or 4 years follow-up.

This was a small cohort study with few cardiovascular events and a high rate of missing data, which could limit the power to clearly define temporal associations between biomarkers elevations and outcomes. The discrepancy between short-term and longer-term risk prediction is a novel aspect of this work. Tracking inflammatory markers over time to screen for short-term mortality risk could be a powerful clinical tool. Larger studies are required to validate this association and further define the clinical use of these biomarkers in PAD patients.