DOCTOR'S VIEW ARCHIVE

The Statins...Doing More Than Lowering Your Cholesterol?

PARIS - This is about the "statins", an important group of drugs that lower cholesterol. They may do much more, it appears, than just reduce cholesterol, as if that were not enough!

The statins are grouped together as "Antilipemic Agents" by the PDR (Physicians' Desk Reference). Lipemia is an excess of lipid (fat) in the blood, so an antilipemic agent obviously acts to reduce lipids. Among the different types of "Antilipemic Agents", the PDR has the "HMG-CoA Reductase Inhibitors", better known as the statins. The statins now on pharmacy shelves in the U.S. (putting the brand name first in capital letters followed by the generic name in parentheses) are:

More about the statins later. First for some background beginning with the prime target of the statins, cholesterol.

Cholesterol is generally thought to be the major contributor to atherosclerosis, the process by which cholesterol is deposited in artery walls . These cholesterol deposits harden arteries and narrow their interior diameter. Atherosclerosis of the coronary arteries that supply blood and oxygen to the heart muscle leads to angina and raises the risk of heart attacks. Atherosclerosis of the carotid and vertebral arteries, the vessels that supply blood and oxygen to the brain, increases the risk of strokes.

Lowering the cholesterol, especially LDL ("bad") cholesterol, is clearly good. It helps prevent and may reverse atherosclerosis and it decreases the risk of heart attacks.

In the 1970's and 1980's, studies of diet and lipid-lowering agents (such as niacin and clofibrate) were in conclusive. They failed to prove that that lowering blood cholesterol prolonged life. Even though deaths related to heart attacks were modestly reduced, this was offset by an apparent increase in deaths related to cancer and other causes.

Only in the last 10 years has conclusive evidence surfaced showing that medications can indeed lower the "bad" LDL cholesterol. More to the point, it has been proved that reducing LDL cholesterol reduces heart attacks and lengthens life. Many of these critically important studies have used the HMO-CoA reductase inhibitors, the statins.

Now in the 90s, it is common place to be not only on a diet low in cholesterol and saturated fats but also on a drug to reduce the levels of cholesterol. And that drug is likely to be a statin.

However, there is much that is not fully understood about the statins. Among the questions before biomedical scientists is, do the statins prevent heart attacks purely by lowering blood levels of cholesterol? Or might some of the beneficial effects of the statins be related to other actions of the statins on blood vessels?

The statins act by inhibiting an enzyme called 3-hydroxy-3- methylglutaryl-coenzyme A reductase (blessedly abbreviated to HMG-CoA. This enzyme's normal job is to catalyze the conversion of HMG-CoA to mevalonate, an early step in the synthesis of cholesterol. In biochemical terms, it is a rate-limiting step in the body's cholesterol production by the body. Inhibit that step and you inhibit your ability to make cholesterol.

The liver is the primary site where the body makes cholesterol and the liver is the primary site of action of the statins. The statins lower the blood levels of total and LDL cholesterol by blocking the liver's production of cholesterol.

In addition to lowering LDL cholesterol, the statins lower the triglycerides (another form of fat in the blood) and increase the HDL ("good") cholesterol. While LDL cholesterol causes atherosclerosis, HDL actually removes cholesterol from artery walls and protects them from atherosclerosis. HDL cholesterol; therefore, deservedly is called the "good" cholesterol an higher levels are desirable.