| Effects of apolipoprotein and low density lipoprotein receptor gene polymorphisms on lipid metabolism, and the lipid risk factors of coronary artery disease | ||
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The effect of RS-86505-007 on plasma lipids is favourable: it lowers LDL cholesterol without any effect on HDL cholesterol, and thus improves the LDL-to-HDL ratio. No firm conclusions on the effect of RS-86505-007 on elevated plasma triglycerides can be drawn from our results, since the patients had normal or only slightly elevated plasma triglyceride concentrations. Gastrointestinal side-effects, however, are frequent and would limit the use of the drug in long-term treatment of hypercholesterolemia.
The changes in plasma lipids were more favourable after lovastatin treatment than after colestipol treatment. Lovastatin lowered LDL cholesterol more effectively than colestipol, and it also lowered the triglycerides, which were elevated after colestipol treatment. The variation in the responses to colestipol and lovastatin treatments was different in the patients with different apo E phenotypes. This could be due to the different mechanisms of action of the drugs, lovastatin being able to modify the structure of the lipoprotein particles (Homma et al. 1995) and colestipol acting mainly by enhancing the loss of cholesterol in bile (Gaw et al. 1996). Statins reduce the CETP-mediated transfer of cholesterol esters from HDL to VLDL and LDL by lowering the plasma CETP activity (Kleinveld et al. 1993) without modifying the plasma CETP mass, suggesting that the reduction in cholesterol transfer results from a reduction in the LDL acceptor particles (Guerin et al. 1995). The apo E phenotype seems to modify the interaction between LDL cholesterol and CETP activity, but does not affect the LDL-lowering efficacy of the drugs.