In order to study the effects of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, on VLDL apolipoprotein (apo) E production rate, pool size, and fractional catabolic rate, Millar et al. designed a single-blind, placebo-controlled, fixed sequence study of 19 subjects (9 of whom were pre-treated with atorvastatin). In subjects treated with torcetrapib alone, VLDL apo E pool size decreased by 28%, a finding due mainly to the increased VLDL apo E fractional catabolic rate. In subjects pre-treated with atorvastatin, VLDL apo E pool size remained unchanged after treatment with torcetrapib despite a 25% increase in VLDL apo E fractional catabolic rate. In that group, VLDL apo E production rate increased by 21%. These findings provide new insights into the mechanisms responsible for the changes in lipoprotein-lipid metabolism associated with CETP inhibition by showing that the combination of torcetrapib and atorvastatin might increase VLDL apo E content and thereby decrease the conversion of VLDL particles into LDL particles, reducing LDL production and circulating levels in the process.
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