Coronary Heart Disease Syndromes: Pathophysiology and Clinical Recognition

Abstract

Atherosclerotic plaque fi ssuring or ulceration generally causes the development of the acute coronary artery disease syndromes. Vulnerable, or “unstable,” atherosclerotic plaques have temperature and pH heterogeneity, thin fi brous caps, infl ammatory cells (primarily macrophages), and activated T cells on their surfaces, as well as an adjacent lipid pool. Some patients have multiple unstable atherosclerotic plaques simultaneously. Several serum markers, when elevated, help identify patients at increased risk for future vascular events. These markers include C-reactive protein, CD40SL, pregnancy-asso- ciated protein, serum amyloid protein, brain natriuretic peptide, vascular cell adhesion molecules, intracellular adhesion molecules, and interleukin-6. Unstable angina and non- ST-segment elevation myocardial infarction (NSTEMI) are associated with atherosclerotic plaque fi ssuring or ulceration; adherence of platelets at the same sites; the accumulation of thromboxane A 2 , serotonin, adenosine diphosphate, thrombin, tissue factor, and oxygen- derived free radicals; and endothelin, promoting growth of the thrombus and dynamic vasoconstriction with transient coronary artery occlusion (unstable angina or NSTEMI) or sustained coronary artery occlusion (ST-segment elevation MI [STEMI]). The functional absence or diminished effect of nitric oxide, tissue-type plasminogen activator, and pros- tacyclin at sites of vascular injury contributes to dynamic thrombosis, vasoconstriction, fi broproliferation, and infl ammation at sites of coronary artery atherosclerosis and plaque fi ssuring and ulceration. Unstable angina, NSTEMI, and STEMI represent a continuum of thrombosis and vaso- constriction, in that unstable angina is often caused by transient and recurrent coronary artery thrombosis and vasoconstriction; NSTEMI by slightly more prolonged (but still usu- ally transient) thrombosis and vasoconstriction or subtotal coronary artery occlusion; and STEMI by prolonged and often permanent coronary artery occlusion. Power-failure com- plications of MIs occur in patients with ≥40 % irreversible damage to the left ventricle and include cardiogenic shock, medically refractory congestive heart failure, and medically refractory arrhythmias. Even with relatively small MIs, mechanical problems, such as acute mitral regurgitation, ventricular septal defects, and ventricular aneurysms, may lead to shock and congestive heart failure. J.