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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