Soluble P-selectin predicts lower extremity peripheral artery disease incidence and change in the ankle brachial index: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

ObjectiveTo determine the association of circulating P-selectin with prevalent and incident peripheral artery disease (PAD), the ankle brachial index (ABI), and change in the ABI. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort study including 6814 European descent, African American, Hispanic and Chinese men and women aged 45–84 at baseline. Four clinical exams took place after the baseline exam. After excluding those with ABI>1.4, prevalent and incident PAD were defined as an ABI≤0.90. ABI progression was defined as progression from a normal ABI (0.91–1.4) to abnormal (≤0.90 or >1.4) at a later exam. ResultsIn adjusted models, each SD (13 ng/mL) higher P-selectin was significantly associated with 0.007 lower ABI (95% CI ((−0.011, −0.004)), p < 0.001), and an average change in the ABI of −0.006 ((−0.010, −0.003, p < 0.001). P-selectin was significantly associated with a 1.17-fold greater odds of prevalent PAD ((1.02, 1.33), p = 0.03), and a 30% greater risk of incident PAD ((1.11, 1.53), p = 0.001), as well as progression from a normal ABI to an ABI≤ 0.90 (p = 0.003), but not to an ABI>1.4 (p = 0.96). Addition of P-selectin to models containing traditional PAD risk factors and markers of inflammation/coagulation significantly improved the net reclassification for ABI progression (p = 0.03), but was only marginally significant for incident PAD (p = 0.06). ConclusionsP-selectin is significantly associated with the development of PAD. However, further research is needed in population-based studies to confirm prospective associations of P-selectin with incident PAD and change in the ABI, as well as its potential predictive ability.