Effects of Benzafibrate and Simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments☆

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Conclusion: Circulating levels of endothelial adhesion molecules in hypercholesterolemic patients are decreased with Simvastatin but not Benzafibrate.

Summary: Endothelial adhesion moleculeNmediated leukocyte adhesion and transendothelial migration are fundamental steps in atherogenesis. The authors studied the effects in hypercholesterolemic patients of two lipid-lowering agents on circulating levels of endothelial adhesion molecules. Never-treated hypercholesterolemic outpatients (n = 67) and 32 controls matched for sex, age, blood pressure, inflammatory indexes, and acute phase reactive proteins were studied. Hypercholesterolemic patients were divided into four groups. Group 1 was treated with simvastatin (40mg/d), group 2 received benzafibrate (80mg/d), group 3 was treated with simvastatin plus vitamin E, and group 4 was treated with benzafibrate plus vitamin E. Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were evaluated at baseline in all four patient groups and controls, and in the four patient groups following 1, 3, 4, and 6 months of treatment.

Circulating ICAM-1, VCAM-1, and E-selectin levels were higher in the hypercholesterolemic patient groups (groups 1-4) than in control subjects. Both simvastatin (group 1) and benzafibrate (group 2), significantly reduced total and low-density lipoprotein (LDL) cholesterol concentrations (P < .0001). Simvastatin treatment was more effective than benzafibrate. Vitamin E supplementation did not further reduce total or LDL cholesterol levels in either simvastatin- or benzafibrate-treated patients.

Plasma ICAM-1, VCAM-1, and E-selectin significantly decreased during the 6 months of the simvastatin treatment (P < .0001). There was no decrease in endothelial adhesion molecule levels in patients treated with benzafibrate alone. The addition of vitamin E resulted in further decreases in endothelial adhesion molecules in patients treated with simvastatin and in a decrease in endothelial adhesion molecules in the patients treated with benzafibrate (P < .0003 to P < .0001).

Comment: The data demonstrate drug-induced cholesterol lowering is not necessarily associated with a reduction of endothelial activation in hypercholesterolemic patients. The beneficial effects of statin therapy in treatment of patients with hypercholesterolemia may be independent of, or additive to, cholesterol-lowering effects.