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

Objective: To 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. Methods: The 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. Results: In adjusted models, each SD (13ng/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). Conclusions: P-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.