CH.

24 ACUTE CORONARY SYNDROMES INTRODUCTION Cardiovascular disease is the leading cause of death Acute Coronary Syndromes (ACS) are forms of Coronary Heart Disease (CHD) Unstable angina Myocardial infarction ACS are caused by the erosion or rupture of an atherosclerotic plaque with subsequent platelet adherence, activation, aggregation, and activation of the clotting cascade which ultimate leads to the formation of clot that contains fibrin and platelets Pharmacotherapy includes: Fibrinolytics Antiplatelets Anticoagulants Nitrates Beta blockers Reperfusion therapy and revascularization with percutaneous intervention (PCI) and coronary artery bypass graft (CABG) surgery ETIOLOGY Atherosclerotic plaques are formed from cholesterol excess and inflammation Endothelial dysfunction, the induction and/or repression of genes, occurs due to sheer stress of blood flowing over the plaque on the endothelial lining of the artery Gene induction and repression can lead to: Decreased synthesis of nitric oxide in endothelial cells Increased oxidation of lipoproteins and facilitation of lipoprotein entry into arterial walls Adherence of monocytes to vessel walls and deposition of extracellular matrix Smooth muscle proliferation Release of local vasoconstrictors and prothrombotic substances into blood Inflammatory response Factors that lead to development and progression of endothelial dysfunction: Hypertension Male gender Age Tobacco use Diabetes Obesity Dyslipidemias PATHOPHYSIOLOGY Acute coronary syndromes includes all syndromes of acute myocardial ischemia which result from an imbalance in myocardial oxygen demand and supply ACS results from diminished myocardial blood flow secondary to an occlusive or partially occlusive artery thrombus ACS are classified based on ECG changes: STE MI NSTE ACS NSTE MI UA (unstable angina) NSTE MI differs from UA in that ischemia is severe enough to produce myocardial necrosis, which causes the release of biochemical markers (troponins I or T and creatine kinase myocardial band) from necrotic myocytes into the bloodstream Following an STEMI, Q waves may be seen on the ECG [this is less common in NSTEMI] The presence of Q waves usually indicates transmural MI Plaque Rupture and Clot Formation

In >90% of ACS, the cause is atheromatous plaque rupture, fissuring, or erosion of an unstable atherosclerotic plaque Plaques that encompass <50% of the coronary lumen are more likely to rupture than those than occlude 70-90% Plaques that are more susceptible to rupture are characterized by an eccentric shape, a thin fibrous cap, large fatty core, high content in inflammatory cells (such as macrophages and lymphocytes), limited amounts of smooth muscle, and significant compensatory enlargement The stable 70-90% stenoses are characteristic of stable angina They have a small lipid core, thick fibrous cap, more calcification, and less compensatory enlargement Compensatory enlargement is the growth of the lesion pushing the vessel outward rather than the growth of the plaque inward; so compensatory enlargement may result in underestimation of the atherosclerotic stenosis as measured by coronary angiography Inflammatory cells promote the thinning of the fibrous cap through release of proteolytic enzymes (mainly matrix metalloproteinases) Following plaque rupture, a clot forms on top of the ruptured plaque The clot may be a partially occlusive or completely occlusive thrombus The thrombogenic contents of the plaque are exposed to blood elements Exposure of subendothelial collagen and tissue factor via shear forces promotes platelet adhesion to the injury site via platelet glycoprotein (PG) Ib to von Willebrand factor This causes platelets to become activated they change shape and synthesize and release thromboxane a2, adenosine diphosphate, and vasoactive and other prothrombotic substances from dense a-grandules During platelet activation, ADP binds to the platelet P2Y1 and P2 and P212 receptors, and P2Y12 binding promotes a conformational change in the GP IIb/IIIa surface receptors of platelets, increasing their affinity for fibrinogen that results in cross-linking of platelets to each other through fibrinogen bridges This is considered the final common pathway of platelet aggregation