Atherosclerosis
Atherosclerosis is a chronic, diffuse disease of large arteries of unknown cause. In "Westernized" societies the disease begins in childhood and progresses inexorably unless lifestyle is changed. One prevalent hypothesis is that it is caused by damage to the endothelium, the single-cell thick layer lining all blood vessels and the largest organ in the body. Until about 20 years ago the endothelium was thought to be a passive organ whose only job was to prevent clotting of blood on the inside of blood vessels. But since the Nobel Prize winning research of Furchgott, Ignarro and Murad we know that endothelium is a very active organ whose normal function is to keep the arterial wall healthy but which is also very sensitive to substances in the blood and the flow of blood itself. Healthy endothelium releases nitric oxide, a gas that keeps the arterial wall healthy but that is rapidly inactivated by blood. A number of factors can cause endothelial dysfunction, the most important being, diet, tobacco, and inactivity. By as yet unknown mechanisms, possibly related to the production of modified LDL (low density lipoprotein) in the arterial wall, endothelial dysfunction leads to the build up of atherosclerotic plaque. Most importantly, endothelial dysfunction and plaque are reversible if those damaging factors are removed.
Fortunately, as plaque builds up the artery tends to dilate in an attempt to keep the lumen open. This phenomenon is call compensatory dilation.
Blockage of arteries by atherosclerosis usually first causes symptoms related to heart function because the coronary arteries that deliver blood to the heart muscle are only about 2 mm in diameter. The heart muscle (myocardium) extracts more oxygen from its blood supply than any other organ in the body and cannot tolerate any reduction in blood flow.
Angiography outlines the lumen of the artery and, because the wall is not visualized, shows only a small fraction of the disease, the "tip of the iceberg".
Angioplasty (balloon dilation) or graft bypass of the constriction may relieve angina temporarily but leaves untouched the great majority of the disease. These procedures will not prolong life or prevent a heart attack.
Heart attacks are caused by rupture of atherosclerotic plaques, formation of a clot and rapid occlusion of a coronary artery. When the endotheilum, which normally provides a non-thrombogenic surface is broken, blood is exposed to tissue factors in the wall of the artery which promote clotting. The same happens with any trauma. Blot clots when exposed to tissue factors outside of the endothelium.
Sudden death is usually caused by a heart attack. Heart muscle, as well as contracting, also conducts electical impulses like a nerve. When a piece of heart muscle dies the normal smooth flow of conduction is disturbed and can result in a totally disorganized kind of electrical activity called ventricular fibrillation and an absence of coordiinated pump function.
Paradoxically, a heart attack or sudden death is much more likely to be caused by plaque rupture in regions of the diseased artery which are not very constricted and not even seen on an angiogram, early unstable plaque. Plaque rupture can be prevented and the plaque stabilized by regression of the fatty deposits in the plaque. Regression can only be accomplished by adoption of a low-fat, mostly vegetarian diet, exercise and smoking cessation. Except in high, potentially toxic doses, cholesterol lowering drugs will only slow progression of atherosclerosis not reverse it.
