Biomarkers in peripheral arterial disease patients and near- and longer-term mortality

Abstract

Background: Whether novel biomarkers improve risk prediction of mortality beyond standard cardiovascular disease (CVD) risk markers in peripheral arterial disease (PAD) patients, and whether any such prediction differs with length of follow-up, remains controversial. Our objective was to determine in patients with PAD whether novel biomarkers improve prediction of CVD mortality and total mortality.

Methods: A cohort of 397 patients who were referred to a vascular lab had PAD diagnosed by noninvasive testing. Fifty-eight percent also had coronary or cerebrovascular disease at baseline. Predictors of total, CVD, and non-CVD mortality were assessed with Cox proportional hazards models, and the incremental value of predictors was evaluated with both the C-statistic and the integrated discrimination improvement (IDI) index.

Results: Total mortality was 11% at 2-year follow-up and 65% at an average of 6.6-year of follow-up (maximum, 11.4 years). At 2 years, hs-CRP was a strong and significant predictor of mortality, with a hazard ratio (HR) of 1.56 per standard deviation (P = .006). However, at full follow up, standard CVD risk markers were significant (age, gender, ankle-brachial index, other CVD, and hypertension), but hs-CRP no longer showed a significant relationship (HR 1.12; P = .11). None of the other biomarkers studied showed a significant independent association with mortality. Hs-CRP improved the C-statistic and the IDI beyond standard risk markers at 2 years, but not at full follow-up.

Conclusions: hs-CRP was a strong predictor of short-term mortality in this cohort of PAD patients, while standard risk markers were better at predicting longer-term mortality.