Circulating Leukocyte-Derived Microparticles Predict Subclinical Atherosclerosis Burden in Asymptomatic Subjects

Abstract

Objective— To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. Methods and Results— In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk ( P <0.05), metabolic syndrome ( P <0.01), high C-reactive protein (CRP) ( P <0.05), or 2- to 3-sites disease ( P <0.01), and correlated positively with number of metabolic syndrome components ( P <0.001), tertiles of fibrinogen ( P <0.001), and number of diseased sites ( P <0.01). In multivariate analysis, 2- to 3-sites disease was independently associated with leukocyte-derived MP level ( P <0.05), Framingham risk ( P <0.001), and metabolic syndrome ( P <0.01). None of the other MP types correlated with risk markers or atherosclerosis. Conclusions— Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research.