Tuesday, June 17, 2008
What Causes Coronary Artery Disease?
In January 1961 a physiologist named Ancel Keys was featured on the cover of Time magazine. His appearance marked the victory of the idea that heart disease is caused by high blood cholesterol. Beginning in the 1940's, Dr. Keys had noted correlations between dietary fat intake and heart disease. He believed that high dietary fat produced high blood cholesterol, which in turn produced coronary artery disease. When the data Dr. Keys used is examined more carefully, the causal relationships between dietary fat, blood cholesterol and heart disease are less persuasive. In spite of that, by December 1960, the American Heart Association was willing to state that cholesterol is the leading risk factor for heart disease and that Americans should reduce their intake of fat, particularly of saturated fat.
However, there is an alternative hypothesis for the cause of coronary artery disease. As we have seen, insulin is a storage hormone. When insulin is released, it promotes the storage of fat in our adipose tissue. It also promotes the storage of cholesterol and fat in our arterial walls. Not only that, insulin promotes the synthesis of cholesterol and fat in the lining of our arteries. Although we haven't discussed this, another role of insulin is as a growth factor--it causes an increase in the number of smooth muscle cells lining our arteries, which in turn causes the artery walls to thicken.
Insulin is released in response to elevated glucose in the blood. When blood sugar is high, cells will preferentially burn glucose for fuel. In certain tissues, the burning of glucose produces reactive oxygen species, which include oxygen ions, free radicals, and peroxides. If the body does not have sufficient antioxidant protection, the reactive oxygen species will interact with cells and cause cellular breakdown. Another cause of breakdown was discussed in a previous post. Advanced Glycation Endproducts (AGEs) are produced when sugar molecules attach to proteins and crosslink them, eventually making our tissues, including our arteries, stiff and inelastic.
The two hypotheses for the cause of coronary artery disease suggest two very different lines of treatment. The cholesterol-lipid hypothesis implies that we should cut back on dietary cholesterol and fat, taking cholesterol-lowering medication if necessary, which will reduce cholesterol deposits, which will produce fewer heart attacks. The carbohydrate hypothesis implies that we should cut back on carbohydrates, which will lower blood glucose and blood insulin, which will cause less damage to arterial walls, which will produce fewer heart attacks. It appears that Tim Russert's physician believed the cholesterol-lipid hypothesis, and Tim Russert followed his advice. At age 58, Tim Russert died of sudden caradiac arrest. Tim was only one man, and his medical history might not be representative of the American population as a whole. On the other hand, Tim's unexpected death might signal that it is time for us to reconsider our approach to heart disease. It might be time for the medical community to do some long-range studies to see if the cholesterol-lipid hypothesis or the carbohydrate hypothesis produces better outcomes in the prevention and treatment of coronary artery disease.