Abstract 19947: Comparison Of Directly Measured Cholesterol Synthesis To Plasma Lathosterol Levels In Hyperlipidemic Humans
Plasma concentrations of the cholesterol precursors lathosterol and desmosterol are used as surrogate markers of de novo cholesterol synthesis (DNCS). These markers are easily accessible, less cumbersome and have been used in numerous cholesterol-lowering studies to describe changes in cholesterol metabolism, as well as to predict the response to cholesterol-lowering treatment. Although associations exist, few studies have investigated whether changes in these plasma markers indeed reflect directly measured baseline or treatment-induced changes in cholesterol synthesis in large numbers of subjects. We measured DNCS by means of the deuterium incorporation method in 26 subjects before and after treatment with ezetimibe and 24 subjects before and after fenofibrate treatment. At the same time-intervals, plasma lathosterol and desmosterol concentrations were determined by GC-FID. As has been previously reported lathosterol/cholesterol ratio correlated best with DNCS. Desmosterol concentrations did not correlate with DNCS (r2 = 0.03). Preliminary data in 12 subjects before and after ezetimibe treatment showed a, statistically significant correlation between DNCS and plasma lathosterol concentrations for all subjects (r2=0.48), p<.05 Correlations within each treatment period were weaker, 0.32 and 0.40 for placebo and ezetimibe phases respectively. Ezetimibe treatment increased DNCS by 57%, p<0.01 where as lathosterol concentrations increased by only 20% p<0.05. Our data suggest that baseline plasma lathosterol levels may serve as a crude indicator of cholesterol synthesis, but should be used with caution when assessing treatment-induced changes in cholesterol synthesis or between subject DNCS. The complete data set from all subjects will be presented.
- © 2010 by American Heart Association, Inc.