Coronary Heart Disease Syndromes: Pathophysiology and Clinical Recognition

Abstract

Atherosclerotic plaque fissuring or ulceration generally causes thedevelopment of the acute coronary artery disease syndromes. Vulnerable,or ``unstable,{''} atherosclerotic plaques have temperature and pHheterogeneity, thin fibrous caps, inflammatory cells (primarilymacrophages), and activated T cells on their surfaces, as well as anadjacent lipid pool. Some patients have multiple unstableatherosclerotic plaques simultaneously. Several serum markers, whenelevated, help identify patients at increased risk for future vascularevents. These markers include C-reactive protein, CD40SL,pregnancy-associated protein, serum amyloid protein, brain natriureticpeptide, vascular cell adhesion molecules, intracellular adhesionmolecules, and interleukin-6. Unstable angina and non-ST-segmentelevation myocardial infarction (NSTEMI) are associated withatherosclerotic plaque fissuring or ulceration; adherence of plateletsat the same sites; the accumulation of thromboxane A 2, serotonin,adenosine diphosphate, thrombin, tissue factor, and oxygen-derived freeradicals; and endothelin, promoting growth of the thrombus and dynamicvasoconstriction with transient coronary artery occlusion (unstableangina or NSTEMI) or sustained coronary artery occlusion (ST-segmentelevation MI {[}STEMI]). The functional absence or diminished effect ofnitric oxide, tissue-type plasminogen activator, and prostacyclin atsites of vascular injury contributes to dynamic thrombosis,vasoconstriction, fibroproliferation, and inflammation at sites ofcoronary artery atherosclerosis and plaque fissuring and ulceration.Unstable angina, NSTEMI, and STEMI represent a continuum of thrombosisand vasoconstriction, in that unstable angina is often caused bytransient and recurrent coronary artery thrombosis and vasoconstriction;NSTEMI by slightly more prolonged (but still usually transient)thrombosis and vasoconstriction or subtotal coronary artery occlusion;and STEMI by prolonged and often permanent coronary artery occlusion.Power-failure complications of MIs occur in patients with >= 40 %irreversible damage to the left ventricle and include cardiogenic shock,medically refractory congestive heart failure, and medically refractoryarrhythmias.Even with relatively small MIs, mechanical problems, such as acutemitral regurgitation, ventricular septal defects, and ventricularaneurysms, may lead to shock and congestive heart failure.