Abstract 3450: Plasma Levels of Soluble Selectins and Risk for Peripheral Arterial Disease in Middle-Aged Men and Women: The Atherosclerosis Risk in Communities (ARIC) Study
Selectins belong to a family of cellular adhesion molecules, which mediate the recruitment of leukocytes to the vascular endothelium and have been implicated in the progression of atherosclerosis. Although smaller clinical studies have found elevated levels of soluble P-selectin (sP-selectin) and, with less consistency, lower levels of soluble L-selectin (sL-selectin) in various vascular disorders, including unstable angina, coronary heart disease, and peripheral arterial disease (PAD), only very limited data are available from large epidemiologic studies. To examine the relationship between circulating levels of selectins and PAD, we measured sP-selectin and sL-selectin in plasma of 209 cases with lower extremity PAD and 733 subjects without PAD in the Atherosclerosis Risk in Communities (ARIC) cohort, a biracial cohort of 15,792 adults from 4 U.S. communities. Mean plasma sP-selectin levels were significantly higher and sL-selectin levels tended to be lower in PAD cases compared to noncases (51.4 vs. 45.0 ng/mL; p=0.031 and 1057.1 vs. 1117.2; p=0.073, respectively). Plasma levels of sP-selectin and sL-selectin in noncases were significantly correlated with a number of inflammatory markers, including CRP, white blood cell count, ICAM-1, and VCAM-1. Logistic regression analyses showed a significant association of sP-selectin with PAD, in a basic model (Table⇓, Model 1) adjusted for age, gender, and race, with an odds ratio of 1.39 (95% CI, 1.09 –1.77) per 1-standard deviation difference in plasma sP-selectin. The ratio of plasma sP-selectin to sL-selectin was associated with a significant increased risk for PAD, independent of other cardiovascular risk factors, including inflammatory markers (Table⇓, Model 2). These data show that the ratio of circulating levels of sP-selectin to sL-selectin was associated with increased risk for PAD in middle-aged men and women.