Lipid-lowering therapy corrects endothelial cell dysfunction in a short time but does not affect hypercoagulable state even after long-term use in hyperlipidemic patients

Lipid-lowering therapy reduces cardiac events to an extent that is dispropo rtionate to the small degree of regression of coronary atherosclerosis obse rved among hyperlipidemic patients. We prospectively investigated the effec ts of lipid reduction using simvastatin on the endothelial dysfunction and hypercoagulability found in hyperlipidemic patients. We measured levels of coagulation factors [factor VII (FVII) coagulant activity (FVIIc), MI antig en (FVIIAg), activated FVII (FVIIa), and fibrinogen], and markers of coagul ation activation [prothrombin fragment 1 + 2 (F1 + 2)] and endothelial cell dysfunction [von Willebrand factor (vWF)] in 20 hyperlipidemic patients, 2 0 hypertensive patients, and 20 normotensive normolipidemic controls. The l evels of FVIIa, FVIIc, FVIIAg, F1 + 2, and vWF were all higher in hyperlipi demic patients, but only FVIIa, F1 + 2, and VWF levels were higher in hyper tensive patients than in controls. We measured the above parameters in 13 h yperlipidemic patients before and after 1, 3, 6, 12 and 24 months of simvas tatin therapy and compared these values with those in 15 hypertensive patie nts at baseline and after 12 and 24 months. The median (25th-75th percentil e) level of total cholesterol was decreased from 259 (255-278) to 206 (176- 220) mg/dl after 1 month of simvastatin therapy and this reduction persiste d for 2 years. The plasma level of vWF [136% (113-158%)] was not changed af ter 1 month of administration of simvastatin [132% (115-153%)], but was dec reased after 3 months of treatment [114% (96-128%), P < 0.01]. This decreas e also persisted for 2 years during simvastatin therapy and both of these r eductions were significant, compared with levels in hypertensive patients. In contrast, levels of fibrinogen, FVIIc, FVIIAg, FVIIa, and Fl + 2 did not change throughout the 2 years of simvastatin therapy. We conclude that lip id reduction using simvastatin corrects endothelial cell dysfunction but no t hypercoagulability in hyperlipidemic patients. The improvement in endothe lial cell function brought about by lipid-lowering therapy might contribute to the reduction in cardiac events within a relatively short time period i n hyperlipidemic patients. Blood Coag Fibrinol 10:269-276 (C) 1999 Lippinco tt Williams & Wilkins.