The mechanism of high-density lipoprotein cholesterol elevation in patients treated with simvastatin

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Abstract

Fourteen patients with untreated hypercholesterolemia were given simvastatin 5 mg/d for 12 weeks. Cholesteryl ester transfer protein (CETP) activity and lecithin-cholesterol acyltransferase (LCAT) activity were determined every 4 weeks during treatment. Total cholesterol (TC) decreased from 279.1 ± 55.1 mg/dL before treatment to 224.6 ± 30.7 mg/dL after 12 weeks, and high-density lipoprotein cholesterol (HDL-C) rose from 56.2 ± 13 mg/dL to 61.2 ± 15.2 mg/dL. These changes were statistically significant. CETP activity decreased significantly from 26.8 ± 6.4% before treatment to 23.6 ± 6.3% after 12 weeks, and LCAT activity at 37 °C increased significantly from 43.3 ± 33.5 nmol/mL per hour to 68.4 ± 32.6 nmol/mL per hour. The changes in TC correlated with those in CETP activity at each time point (r = .674), but not with those in LCAT activity. The HDL-C level was negatively correlated with CETP activity at each time point (r = .655) but not with LCAT activity. These findings show that CETP activity may play a more important role than LCAT activity in simvastatin-induced HDL-C elevation and suggest that simvastatin increases HDL-C by reducing CETP activity secondary to low-density lipoprotein cholesterol reduction.

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