Evidence that high-density lipoprotein cholesterol is an independent predictor of acute platelet-dependent thrombus formation

Plasma total and low-density lipoprotein (LDL) cholesterol are established risk factors for atherosclerotic vascular disease and may also contribute t o a prothrombotic risk via enhanced platelet reactivity, This study examine s whether high-density lipoprotein (HDL) cholesterol, which is inversely co rrelated with coronary artery disease, is associated with a reduced thrombo genic potential. Platelet thrombus formation was evaluated by exposing porc ine aortic media placed in Badimon perfusion chambers to flowing nonanticoa gulated venous blood for 5 minutes at a shear rate of 1,000 s(-1). Forty-fi ve subjects, 23 normal (LDL 104 +/- 31, HDL 50 + /- 15 mg/dl) and 22 hyperc holesterolemic (LDL 181 +/- 45, HDL 41 + 10 mg/dl) patients without coronar y artery disease were studied. Platelet aggregation and CD62 antigen expres sion, and assay for circulating prothrom botic factors were also performed. In univariate analysis platelet thrombus formation correlated with weight (r = 0.33, p = 0.03), diastolic blood pressure (r = 0.39, p = 0.01), HDL ch olesterol (r -0.45, p = 0.003), total/HDL cholesterol (r = 0.43, p = 0.004) and LDL/HDL (r = 0.38, p = 0.01) ratios, and platelet CD62 expression (r = 0.41, p = 0.02), In multiple regression analysis only HDL cholesterol show ed significant correlation with platelet thrombus formation (p = 0.03), Pla telet aggregation and circulating prothrombotic factors did not correlate w ith platelet thrombus formation. A comparison between normal and hyperchole sterolemic subjects revealed enhanced thrombus area (0.026 +/- 0.20 vs 0.04 5 +/- 0.039 mm(2)/mm; p = 0.04), resting CD62 expression (6 + 7% vs 15 +/- 10% positive platelets, p = 0.02), and platelet aggregation (16.7 + 5.2 vs 21.7 +/- 6.7 ohms, p = 0.04) in hypercholesterolemic subjects. Our results demonstrate that HDL cholesterol is ct significant independent predictor of ex vivo platelet thrombus formation. (C) 1999 by Excerpta Medica, Inc.