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Prevention of Atherosclerosis
The most important measures to protect against the development of atherosclerosis and its progression to serious vascular disease are (1) maintaining a healthy weight, being physically active, and eating a diet that contains mainly unsaturated fat with a low cholesterol content; (2) preventing hypertension by maintaining a healthy diet and being physically active, or effectively controlling blood pressure with antihypertensive drugs if hypertension does develop; (3) effectively controlling blood glucose with insulin treatment or other drugs if diabetes develops; and (4) avoiding cigarette smoking.
Several types of drugs that lower plasma lipids and cholesterol have proved to be valuable in preventing atherosclerosis. Most of the cholesterol formed in the liver is converted into bile acids and secreted in this form into the duodenum; then, more than 90 per cent of these same bile acids is reabsorbed in the terminal ileum and used over and over again in the bile. Therefore, any agent that combines with the bile acids in the gastroin-testinal tract and prevents their reabsorption into the circulation can decrease the total bile acid pool in the circulating blood. This causes far more of the liver cho-lesterol to be converted into new bile acids. Thus, simply eating oat bran, which binds bile acids and is a con-stituent of many breakfast cereals, increases the pro-portion of liver cholesterol that forms new bile acids rather than forming new low-density lipoproteins and atherogenic plaques. Resin agents can also be used to bind bile acids in the gut and increase their fecal excre-tion, thereby reducing cholesterol synthesis by the liver.
Another group of drugs called statins competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in the synthesisof cholesterol. This inhibition decreases cholesterol syn-thesis and increases low-density lipoprotein receptors in the liver, usually causing a 25 to 50 per cent reduction in plasma levels of low-density lipoproteins. The statins may also have other beneficial effects that help prevent atherosclerosis, such as attenuating vascular inflamma-tion. These drugs are now widely used to treat patients who have increased plasma cholesterol levels.
In general, studies show that for each 1 mg/dl decrease in low-density lipoprotein cholesterol in the plasma, there is about a 2 per cent decrease in mortal-ity from atherosclerotic heart disease. Therefore, appro-priate preventive measures are valuable in decreasing heart attacks.
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