Heart attacks are the most frequent cause of death in France as in every western industrialized nation. The disease begins in the teenage years when cholesterol-carrying lipoproteins begin to penetrate into the walls of the coronary arteries that carry blood to the heart muscle. Lipoprotein penetration causes an inflammatory reaction that narrows the channel. Eventually, a blood clot forms, blocking the flow of blood and depriving the heart muscle of oxygen. The result is the crushing chest pain of a heart attack.
The cholesterol-carrying protein that deposits in arteries is called low-density lipoprotein or LDL. Incontrovertible evidence has established that LDL causes atherosclerosis. Indeed, the number of heart attacks rises in direct proportion to plasma LDL. Moreover, drugs that lower LDL prevent heart attacks.
In the 1970s, Dr. Joseph Goldstein and I discovered that the concentration of LDL in blood is determined by a receptor on the surface of cells in the liver. The receptor binds to LDL and carries it into the liver cell where it is rapidly degraded. When LDL receptor levels are high, LDL is rapidly removed from plasma and the circulating level is low. When LDL receptors are reduced, LDL remains in plasma and the level increases. LDL receptors are regulated by genetic and environmental factors. About 1 in 500 people inherits a mutant LDL receptor gene, leading to elevated LDL levels and premature heart attacks. Even in people with normal receptor genes, diets that are high in cholesterol and animal fats suppress the production of LDL receptors resulting in heart attacks.
LDL receptors can be increased by the consumption of vegetarian diets that are low in cholesterol and saturated fats. They can also be increased by drugs called statins that block cholesterol synthesis in the liver and induce the liver to produce more LDL receptors. Statin treatment has been demonstrated to reduce heart attacks and extend life in people at high risk for heart attacks. Progress in understanding the relation between plasma LDL and heart attacks has already reduced the frequency of heart attacks.
