Effects of Diet and Drugs on Atherosclerosis

The events leading to atherosclerotic lesions and cardiovascular disease are manifold and not known with certainty. Therapy has been based on the goals of reducing the concentration of LDL-cholesterol and increasing that of HDL-choles-terol in the plasma. Reduction of LDL-cholesterol is expected to limit the uptake of cholesterol by cells in fatty streaks. An increase in HDL-cholesterol is considered to be of value because its presence indicates an increased rate of removal of cholesterol from the walls of arteries. 

A typical American diet contains about 40% of its total energy content as fat. About half this energy is in the form of saturated fatty adds, one-fourth as monounsatu-rated fatty acids, and one-fourth as pol5nmsaturated fatty acids (PUFAs) (Ginsberg et al, 1990). The quantity and nature of dietary fats can influence the level of plasma cholesterol. A reduction in total fat from the t3q ical 40% of energy intake to 30% can result in a decrease in plasma cholesterol. 

High levels of saturated fats in the diet result in an increase in plasma LDL-cholesterol. The mechanism of this effect is not dear, but it appears that these fats interfere with the ability of LDL receptors to clear LDLs from the bloodstream. Further details on the mechanism appear at a later point in this chapter. 

Maintenance of the 40% contribution of fat to energy intake with substitution of monounsaturated for saturated fats can lead to a reduction in plasma cholesterol also. The level of LDL-cholesterol is reduced, and the level of HDL-cholesterol is imchanged. Olive oil is a well-known source of monounsaturated fatty acids. This oil contains about 12% 16 0 and 2% 18 0 (saturated), 75% 18 1 (monounsaturated), 2% 16 1 (monounsaturated), and 8% 18 2 (PUFA). 

Dietary PUFAs decrease the plasma LDL-cholesterol level. Vegetable oils contain high levels of PUFAs such as linoleic acid (18 2), which constitutes about 25, 50, 63, and 75% of the fatty acids in peanut, soy, sunflower, and safflower oils, respectively. The quantity of 18 2 in beef and pork fat is only 5-10% and is under 3% in tropical oils. PUFAs produce decreases in LDL-cholesterol, possibly by the same (unknown) mechanism as monounsaturates. The question of whether dietary PUFAs have a greater or similar effect on LDL-cholesterol remains rmsettled. 

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Cardiovascular Disease Effects of Diet and Drugs on Atherosclerosis... 

Probucol is a lipid-lowering agent, but the results are not consistent with respect to LDL cholesterol. It lowers HDL cholesterol hence it is not the first drug of choice in therapy. The ability of probucol to correct atherosclerosis has been attributed to its antioxidant properties.77 The usual oral dose is 500 mg twice daily and is administered after food. Many experts use it as adjuvant therapy in familial hypercholesterolemia. The drug is well tolerated but causes GI side effects such as nausea and flatulence, headache, and dizziness. Patients taking probucol must be on a low-fat diet. Probucol should not be used in patients with recent myocardial infarction, and it should not be given to children or pregnant women. 

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