Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Simultaneous determination of four non-cholesterol sterols in like desmosterol human plasma using gas chromatography-mass spectrometry with selective ion monitoring / 中国药学杂志

OBJECTIVE: To establish a method for simultaneous determination of phytosterols and cholesterol precursors in human plasma by GC-MS to understand the metabolism of cholesterol in patients. METHODS: Sterols as TMS derivatives were separated and identified on HP-5MS column (30 m × 0.25 μm × 0.25 mm). The initial column temperature of 200°C. was held for 2 min, then increased at a rate of 15°C · min-1 to 280°C and maintained at this temperature for further 30 min. The internal standard was 5α-cholestane. The method was based on the alkaline hydrolysis of sterol esters, extraction of free sterols and derivatization. RESULTS: The calibration curves of the sterols were linear. Inter-day and intra-day RSDs were lower than 7.9% and 9.8%. The recoveries based on replicate analyses of plasma samples spiked with known amounts of sterol standards were between 89.5% - 106.3%. Plasma samples of 20 patients with hyperlipemia were determined by the method. The mean values of non-cholesterol sterols were: desmosterol (0.39 ± 0.08) mg · L-1, lathosterol (3.41 ± 0.83) mg · L-1, campesterol (3.12 ± 0.53) mg · L-1, and sitosterol (4.22 ± 0.67) mg · L-1. CONCLUSION: An optimized analytical method for simultaneous analysis of cholesterol, desmosterol, lathosterol, campesterol and sitosterol in plasma has been developed using capillary gas chromatography coupled to mass spectrometry (GC-MS) with multiple selected ion monitoring (SIM). With good accuracy and precision, it is suitable for the analysis of the individual difference of cholesterol metabolism. Copyright 2012 by the Chinese Pharmaceutical Association.