| 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 diagnosis of familial hypercholesterolemia can be achieved by the PCR method alone for the majority of FH patients in a homogenous population, such as that of Northern Finland.
Deficient binding of the LDL particle to the apo B-E receptor is not a major cause of hypercholesterolemia in Northern Finland. The slow catabolism of LDL in hypercholesterolemia does not seem to be primarily due to modulations in the LDL particle, since the homologous LDL particles from normocholesterolemic individuals were also catabolised slowly. However, some of the apo B and the apo E polymorphisms are associated with variations in the composition of lipoprotein particles, the catabolic rate of apo B, and the plasma lipid concentrations. The apo E 4 allele seems to associate with smaller changes in plasma lipids during hypocholesterolemic drug treatment.
Male and female CAD patients seem to have different risk profiles. High LDL cholesterol and low HDL cholesterol are the most important risk factors in men. Women with two- or three-vessel disease also have low HDL cholesterol and high LDL cholesterol, but associated with high VLDL lipids and other risk factors, such as hypertension, diabetes or smoking.
The capacity of RS-86505-007 to lower LDL cholesterol is moderate. As its potential site of action is the gastrointestinal tract, it would be a good long-term treatment alternative for other hypolipidemic drugs, and also a useful drug to combine with drugs acting in the liver. Unfortunately, side-effects seem to limit its clinical use. Lovastatin is more potent than colestipol in lowering plasma total and LDL cholesterol. Colestipol treatment results in a slight elevation of plasma triglycerides, compared to a decrease during lovastatin treatment, and the drugs have similar effects on CETP and apo A I. Side-effects, on the other hand, are more frequent during colestipol than lovastatin treatment. Of the drugs used in these studies, lovastatin seems to have the best hypocholesterolemic effect and to be the most palatable. As statins have also been shown to prevent cardiovascular events, they are now the most widely used hypocholesterolemic drugs.