Alpha-tocopherol acetate (vitamin E) has no effect on lipid levels but is a powerful antioxidant. Considerable evidence points to oxidation of LDL as an essential step in the development of atheroma, and therefore interest has centred on the role of either endogenous or therapeutic vitamin E in prevention of atheroma. Reduced concentrations of vitamin E in both blood and fat (vitamin E is a fat soluble vitamin) are found in inhabitants of countries with a high prevalence of ischaemic heart disease, and (within these countries) in patients who develop ischaemic heart disease. A high dose reduced by half the risk of myocardial infarction in 2000 patients with angina and positive coronary angiogram.9 However most other studies have failed to confirm this finding and there is no indication at present for routine prescribing of a-tocopherol in the treatment or prevention of atherosclerosis.
• Most treatment works by reducing the intracellular concentration of cholesterol in hepatocytes. leading to compensatory increase in low density lipoprotein (LDL) receptors on their surface, and increased uptake of cholesterol-rich LDL particles from the bloodstream.
• The most effective drugs are the statins, which inhibit the rate-limiting step in cholesterol synthesis.
• Additional agents may be required for mixed or severe hyperlipidaemia.
• In outcome trials with these drugs, reductions in blood cholesterol by 25-35% is associated with a 35—45% reduction in risk of coronary heart disease.
• The main indications for their use are in patients with even slight elevations of cholesterol (> 5mmol/l) after a myocardial infarction or any other microvascular event, in patients with familial hypercholesterolaemia, and in patients with a significant absolute CHD risk, especially where there is a family history of premature CHD,
Omega-3 marine triglycerides (Maxepa) contain the triglyceride precursors of two polyunsaturated fatty acids (eicosapentaenoic acid and docosa-hexaenoic acid) derived from oily fish. They have no place in treating hypercholesterolaemia. Some patients with moderate to severe hypertrigly-ceridaemia may respond to oral use, although LDL-cholesterol may rise. There is an associated 90 calorie per day energy load.
Orlistat, a weight-reducing agent, lowers the glycaemia of diabetes mellitus to a degree that accords with the weight loss, and improves hyperlipidaemia to an extent greater than would be expected (see p. 696). Since it is a lipase inhibitor there is a risk of steatorrhoea and malabsorption of fat-soluble vitamins A, D and E.
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