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PBL CV 2. Pathophysiology of coronary artery disease. Coronary artery disease (CAD). Leading cause of death in US Accounts for half of the nearly 1 million deaths from CVD each year Atherosclerosis of the coronary arteries is the major cause of CAD
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PBL CV 2 Pathophysiology of coronary artery disease
Coronary artery disease (CAD) • Leading cause of death in US • Accounts for half of the nearly 1 million deaths from CVD each year • Atherosclerosis of the coronary arteries is the major cause of CAD • Although atherothrombosis (intra-coronary thrombosis) also plays a role • CAD is progressive degenerative disease that begins in childhood and manifests itself in middle to late adulthood as an acute coronary syndrome (ACS) • In affluent societies, coronary artery disease causes severe disability and more death than any other disease, including cancer. • It manifests as • angina • silent ischaemia • unstable angina • myocardial infarction • arrhythmias • heart failure • sudden death.
Cardiac vessels • Heart receives blood through left and right coronary arteries • Come off as first branches of aorta • Right coronary artery (RCA) gives off acute marginal branches to the RV and in 85% of people gives off branches to inferior aspect (posterior descending artery [PDA]) and posterior aspect (posterolateral branches) of the LV • This is referred to as right-dominant circulation • Left main coronary artery is quite short and bifurcates into left anterior descending (LAD) and left circumflex (LCx) arteries • LAD gives off diagonal branches that supply to the anterior aspect of the LV, and the LCx gives off obtuse marginal branches that supply the lateral aspect of the LV • In 10% of people, the LCx gives rise to both the posterior descending and posterolateral arteries (left-dominant circulation) • In 5% of people, the RCA gives rise to the posterior descending artery and the LCx gives rise to the posterolateral arteries (codominant circulation) • Small collateral vessels interconnect the coronary arteries • THESE COLLATERALS ARE NONFUNCTIONAL IN THE NORMAL SETTING BUT PROVIDE AN ALTERNATE ROUTE OF BLOOD FLOW IF THE CORONARY ARTERY BECOMES STENOSED.
Atherosclerosis • Atheroclerosis is a chronic inflammatory and healing response of the arterial wall to endothelial injury. Lesion progression occurs through the interaction of modified lipoproteins, macrophages and T lymphocytes with the normal cellular constituents of the arterial wall
Pathophysiology of atherosclerosis Atherosclerosis occurs through the following events: • Endothelial injury • Causes increased vascular permeability, leukocyte adhesion and thrombosis • Accumulation of lipoproteins in the vessel wall • Mainly LDL and its oxidised forms • Monocyte adhesion to the endothelium • Followed by migration into the intima and transformation into macrophages and foam cells • Platelet adhesion • Factor release from activated platelets, macrophages and vascular wall cells inducing smooth muscle cell recruitment • Smooth muscle cell proliferation and ECM production • Lipid accumulation both extracellularly and within cells (macrophages and smooth muscle cells)
Histology of atherosclerotic plaque • F – fibrous cap • C – central necrotic lipid core • L – lumen • Arrow points to segment of wall that is free of plaque • Therefore this plaque is termed ‘eccentric’ • Higher magnification at junction of fibrous cap and core • Arrowheads point to areas of calcification • Arrows point to areas of new vascularisation
Progression and outcomes of atherosclerotic plaques • When a plaque produces: • > 50% diameter stenosisor • > 75% reduction in cross sectional area • reduced blood flow through the coronary artery during exertion may lead to angina.
Outcomes of plaques • Plaques with a large lipid core and a relatively thin fibrous cap are more likely to rupture than those with a thick fibrous cap • Outcomes of plaques are: • aneurysm and ruptur • occlusion of vessel by thrombus • critical stenosis • It is important to note that the composition of plaques is dynamic • It has been shown that the precipitating lesion in patients who develop MI or other ACS (acute coronary syndromes) is not necessarily a severely stenotic and haemodynamically significant lesion before its acute change • This means that an asymptomatic individual with plaques showing only mild to moderate luminal stenosis may have an unpredictable risk of a severe coronary event A shows plaque rupture without superimposed thrombus, B shows acute coronary thrombosis superimposed on an atherosclerotic plaque with disruption of the fibrous cap leading to MI Arrows point to site of plaque rupture
References • Robbins and Cottran • BMJ Review article 2003 • “ABC of interventional cardiology - Pathophysiologyand investigation of coronary artery disease” • Ever D Grech