1-1 CAN WE PREDICT ACUTE CORONARY EVENTS IN PATIENTS WITH STABLE CORONARY DISEASE?
In patients with stable coronary disease our ability to prognosticate based on ischemia (ambulatory monitoring) is imperfect. At least one important reason is that acute events, particularly acute myocardial infarction (AMI) are not related to the severity of the stenosis. Acute coronary events (unstable angina, MI, and sudden cardiac death) are usually related to a sudden disruption or fissuring of an atherosclerotic plaque with the formation of an intracoronary thrombus. In patients with unstable angina, the thrombus is usually only partially occlusive. In patients with AMI and sudden death, the thrombus is usually completely occlusive.
Vulnerable plaques contain a large lipid core, a thin fibrous cap with an abundance of inflammatory cells (mainly macrophages), capable of degrading the fibrous cap and expressing tissue factors which contribute to thrombus formation. The plaques responsible for unstable angina and AMI as a rule cause less than 50% narrowing prior to disruption. These lesions would be unlikely to cause ischemia detectable on ambulatory monitoring. The more occlusive plaques which cause transient ischemia (stable angina) may not be the site of thrombus formation responsible for an acute event.
Patients with multivessel disease have a higher mortality than those with single-vessel disease because they have more non-stenotic or mildly stenotic unstable plaques that are sites for future acute coronary events. Acute syndromes are the end result of thrombus formation on an atherosclerotic plaque in which atherosclerosis has impaired the ability of the artery to vasodilate because of endothelial dysfunction. Traditional antianginal therapy will not significantly alter these factors. Other strategies are needed:

1. aspirin or other antiplatelet agents to decrease likelihood of thrombus formation;
2. cholesterol lowering strategies to stabilize plaques, and
3. estrogen therapy in post menopausal women to reduce cholesterol and improve endothelial function.

Nevertheless, noninvasive testing is of value. Identification of coronary artery disease by itself is a good marker for future events and a better marker if angiography documents the presence of extensive and severe disease. JAMA January 22/29, 1997; 277: 343-44 Editorial from Mt. Sinai Medical Center, New York
See Also: "Ischemia During Ambulatory Monitoring as a Prognostic Indicator in Patients with Stable Coronary Artery Disease" JAMA January 22/29, 1997; 277: 318-24 . Acute cardiac events in predominantly low-risk stable angina patients with confirmed coronary disease are unpredictable. Those more likely to suffer such an event cannot be identified by the detection of ambulatory ischemia.

Comment:
This is the new pathophysiology. There are two different aspects: 1) The atherosclerosis which is chronic and 2) the thrombosis which is acute. Atherosclerosis comes first. It must be (variably) present for thrombosis to occur. It is potentially reversible, at least in part, by long-term lipid controlling therapy. It does not occur at all if cholesterol levels remain low enough (total-cholesterol < 160 mg/dL). The degree of atherosclerosis need not be great to predispose to thrombus formation.
Thrombosis occurs because of instability of plaques. (The more extensive the atherosclerosis, the greater the likelihood of unstable plaques.) Lowering cholesterol helps to stabilize plaques. Antiplatelet therapy helps to minimize thrombosis. Estrogen therapy and smoking cessation may lessen risk of thrombus formation. Lipid control may slightly reduce the degree of stenosis caused by atherosclerosis, but, if it occurs at all, the process is slow (years).
Lipid control also stabilizes plaques (ie, strengthens the cap and modifies the lipid core). This process occurs more rapidly. Thus, lipid control may lessen the likelihood of an acute thrombotic episode without causing any detectable angiographic change.
In patients with established coronary atherosclerosis, the goal is to stabilize plaques. Since lipid control will aid in accomplishing this over the short-term (months), control is reasonably indicated in the elderly as well as in younger patients. RTJ

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