Statins cholesterol-lowering effects

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

The serum cholesterol-lowering effect of plant sterols and stanols has been proven in several clinical studies. The hypocholesterolemic effects have been verified in normocholesterolemic individuals, in individuals with mild to moderate hypercholesterolemia or with familial hypercholesterolemia, in women with coronary heart disease, and in men with non-insulin-dependent diabetes -in conjunction with cholesterol-lowering statin therapy and irrespective of the background diet. In addition, studies have been conducted with normocholesterolemic children and with children with slightly elevated cholesterol levels, or with familial hypercholesterolemia. 

Apolipoprotein AIV (apo AIV) is produced in the intestine and is found in chylomicrons, VLDL and HDL. It may modulate enzymes involved in lipoprotein metabolism and may serve as a saturation signal [49]. In a study with 144 participants the apo AIV His360Glu polymorphism showed no significant effect on cholesterol lowering in response to statin therapy [50]. 

Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, interrupting the conversion of HMG-CoA to mevalonate, the rate-limiting step in de novo cholesterol biosynthesis. Reduced synthesis of LDL and enhanced catabohsm of LDL mediated through LDL-Rs appear to be the principal mechanisms for lipid-lowering effects. 

Skeletal muscle myopathy often leads to release of CK of the MM type. Rhabdomyolysis Is one of the major side effects of treatment with the cholesterol-lowering drugs the statins. 

The statins are considered as a major breakthrough in the development of hypolipaemic drugs. These agents inhibit the biosynthesis of cholesterol (Fig. 8) and also increase the density of LDL-receptors. They induce a potent lowering of total cholesterol, LDL, and a weak lowering effect on the triglycerides. The plasma HDL-cholesterol level is moderately enhanced. 

The introduction of the fungal metabolite lovastatin (26-9) has led to a sizeable class of clinically effective cholesterol lowering drugs. These agents, known familiarly as the statins, block an enzyme, HMG-CoA reductase, that is involved in the synthesis of mevalonate, an early precursor of cholesterol. Extensive work has... 

A recently developed antihyperlipidemic is ezetimibe (Zetia, A.113) (Figure A.31). Ezetimibe inhibits the absorption of cholesterol across the intestinal wall. Like fibrates, ezetimibe is often prescribed with statins, although the effectiveness of ezetimibe has recently been called into question. A compound that may soon be approved for the treatment of high cholesterol is anacetrapib (A.114). Anacetrapib, a product of Merck, is currently in phase III trials. The compound inhibits cholesteryl ester transfer protein (CETP). The net effect of CETP inhibition is elevated HDL cholesterol and lower LDL cholesterol levels. 

Evidence from well-conducted prospective epidemiological studies does not suggest that consumption of saturated fat and cholesterol is associated with an increased risk of CHD. Randomized clinical trials that reduced the intake of saturated fatty acids and cholesterol and increased the intake of polyunsaturated fatty acids to lower plasma cholesterol levels did not significantly improve CHD or total mortality. The minor improvement in CHD events for trials of the potent cholesterol-lowering statin drugs may result, to an unknown extent, from their pleiotropic effects and cannot be used to justify the lipid hypothesis. 

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