Ruptured Plaques and Leaking Cells: Cost-Effectiveness in the Diagnosis of Acute Coronary Syndromes

• Creatine kinase isoenzymes
• Troponin I
• Myocardial ischemia
• Myocardial infarction
• Cost-benefit analysis

Acute coronary syndromes arise when an atherosclerotic plaque becomes unstable. The cap develops either superficial erosions with overlying thrombus or, more commonly, deep fissures that cause the plaque to swell with clotted blood and encroach on the arterial lumen. Plaques become unstable when the fibrous matrix surrounding the lipid core is attenuated by the action of cytokines from T lymphocytes, which inhibit the synthesis of the matrix, and by metalloproteinases from activated macrophages, which degrade the matrix. The cause of the initial surface breach of the weakened cap may be chemical, caused by reactive oxygen species, or mechanical, caused by focal stresses. The consequent growing fault may reach the plaque center; the resulting acute eruption of the lipid core amplifies local thrombosis. Abrupt occlusion of an artery unprotected by recruitable collaterals leads to acute regional ischemia. Complete and persistent occlusion produces myocardial infarction. Partial occlusion or occlusion that waxes and wanes results in unstable angina. Plaques can be multiple or single, regress, develop recurrent instability, or remain dormant for years (1-3). Study of the unstable plaque thus resembles volcanology and plate tectonics; the detection of clinical and biological markers of plaque instability, ischemia, and infarction is like seismography.

The most important early clinical markers of ischemic events are chest pain and abnormalities in electrocardiographic repolarization. Their significance has been validated repeatedly, and they parallel development of regional hypokinesis and release of lactate and nucleosides (4). Cell necrosis follows total occlusion and is marked by liberation of cytoplasmic enzymes, such as creatine kinase (CK)-MB (the predominant cardiac isoform of CK), and structural components, such as troponin I. When patients present to the emergency department with the classic clinical markers of myocardial infarction, clinicians have little difficulty making the diagnosis. However, such patients constitute fewer than 14% of those who …