Atherosclerosis
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Atherosclerosis
12/01/09
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Atherosclerosis is a progressive inflammatory disorder of the arterial wall that is characterized by focal lipid-rich deposits of atheroma that remains clinically silent until they become large enough to impair arterial perfusion or until ulceration or disruption of the lesion results in thrombotic occlusion or embolization of the affected vessel
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Atherosclerosis may manifest as : • Coronary heart disease( angina, MI, sudden death) • Cerebrovascular disease ( stroke, TIAs) • Peripheral vascular disease (claudication and critical limb ischemia)
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Pathophysiology • Abnormal lipid metabolism or excessive intake of cholesterol and saturated fats—especially when superimposed on a genetic predisposition—is important in early stages of the atherosclerotic process
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• The initial step is the "fatty streak," or subendothelial accumulation of lipids and lipid-laden monocytes (macrophages) • Following vascular injury, monocytes bind to the endothelium, then cross it to the subendothelial space and become activated tissue microphages • LDLs are the major atherogenic lipid • HDLs, in contrast, are protective by virtue of their role in reverse cholesterol transport, removing cholesterol from the vascular wall
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• LDLs undergo in situ oxidation, which makes them more difficult to mobilize as well as locally cytotoxic • Oxidized LDL enter the macrophages and smooth muscle cells, forming foam cells • HDL carry cholesterol from tissues to the liver for excretion in the bile, and LDL receptors in the liver take up VLDL, IDL, and LDL, lowering circulating cholesterol 12/01/09
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• As the plaque progresses, smooth muscle cells also migrate into the lesion • At this stage, the lesion may be hemodynamically insignificant, but endothelial function is abnormal and its ability to limit the entry of lipoproteins into the vessel wall is impaired • If the plaque remains stable, a fibrous cap forms, the lesion becomes calcified, remodeling of the vessel wall occurs, and ultimately the vessel lumen may become narrowed • Although extensive atherosclerosis may be present even before this occurs 12/01/09
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• Although many atherosclerotic plaques remain stable or progress only gradually, others may rupture, often related to the inflammatory process and metalloproteinase activity • The rupture causes turbulent flow, extrusion of lipids and fatty gruel, and exposure of tissue factor that result in a cascade of events culminating in intravascular thrombosis • The outcome of these events is determined in large part by whether the vessel becomes occluded, which depends on the lesion anatomy as well as the balance of pro- and antithrombotic and pro- and antifibrinolytic forces
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• The result may be partial or complete vessel occlusion (causing the symptoms of unstable angina or myocardial infarction), or the plaque may become restabilized, often with more severe stenosis • Transient occlusion and/or embolization of platelet and thrombin debris, which may result in elevation in serum troponin, predispose to clinical events and portend a worse prognosis 12/01/09
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•
Several features are associated with enhanced plaque vulnerability, including
1. a higher lipid content 2. a higher concentration of macrophages, especially in the plaque shoulder 3. a very thin fibrous cap •
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Lesions with these characteristics are often relatively early lesions that can be responsible for acute myocardial infarction or sudden death as the first manifestation of coronary disease Free Template from www.brainybetty.com
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Risk Factors for CAD • Most patients with coronary heart disease have some identifiable risk factor • These include: • Positive family history (the younger the onset in a firstdegree relative, the greater the risk) • Male gender • Blood lipid abnormalities • Diabetes mellitus • Hypertension • Physical inactivity • Obesity • Cigarette smoking 12/01/09
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• Smoking remains the number one preventable cause of cardiovascular disease worldwide • According to the World Health Organization, 1 year after quitting, the risk of coronary heart disease decreases by 50% • Various interventions, including physician counseling, formal smoking cessation programs, nicotine replacement therapy, and bupropion, have been shown to increase the likelihood of successful cessation 12/01/09
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• Hypercholesterolemia and other lipid abnormalities provide an important modifiable risk factor for coronary heart disease • Risk increases progressively with higher levels of low-density lipoprotein (LDL) cholesterol and declines with higher levels of high-density lipoprotein (HDL) cholesterol
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• The metabolic syndrome is defined as a constellation of three or more of the following: • abdominal obesity • triglycerides 150 mg/dL • HDL cholesterol < 40 mg/dL for men and < 50 mg/dL for women • fasting glucose > 110 mg/dL • Hypertension • This syndrome, recognized as a major contributor to coronary heart disease risk, is increasing in prevalence at an alarming rate 12/01/09
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• Related to the metabolic syndrome, the epidemic of obesity is likewise a major factor contributing to coronary heart disease risk • Particularly alarming is the rapidly increasing incidence of obesity in adolescents • Increasing physical activity is an important goal to help combat obesity and its consequences • Low carbohydrate may improve the cholesterol profile in overweight men, at least temporarily • Fish, rich in omega-3 fatty acids, may help protect against vascular disease and it is recommended that it be eaten three times a week by patients at risk 12/01/09
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• It is now clear that markers of inflammation are strong risk factors for CAD • High sensitivity CRP is the best-characterized inflammatory marker and is available for clinical use • Use of CRP may be helpful in determining which patients at intermediate risk or are at high risk to warrant more intensive primary prevention, including use of statins to lower LDL cholesterol • CRP levels are often elevated in patients who have other conditions associated with accelerated atherosclerosis, such as diabetes, the metabolic syndrome, and obesity
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Coronary heart disease Coronary heart disease, or atherosclerotic CAD, is the number one killer in the world
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Coronary heart disease is clinically manifested as: • • • • • • 12/01/09
Stable angina Unstable angina Myocardial Infarction Heart failure Arrhythmias Sudden death Free Template from www.brainybetty.com
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Stable Angina Angina Pectoris • It is a symptom complex caused by transient myocardial ischemia and may occur whenever there is an imbalance between myocardial oxygen supply and demand • Coronary atheroma is the most common cause of angina
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Stable Angina It is ischemia which occurs when coronary perfusion is impaired by fixed or stable atheroma of the coronary arteries
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Clinical Features Symptoms
Circumstances that precipitate and relieve angina • Angina occurs most commonly during activity and is relieved by resting • The amount of activity required to produce angina may be relatively consistent under comparable physical and emotional circumstances or may vary from day to day • Angina also occurs after meals, during excitement, or on exposure to cold
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Characteristics of the discomfort • • •
Patients often do not refer to angina as "pain" but as a sensation of tightness, squeezing, burning, pressing, choking, aching, bursting, "gas," indigestion, or an ill-characterized discomfort It is often characterized by clenching a fist over the mid chest The distress of angina is rarely sharply localized and is not spasmodic
Duration of attacks • • • •
Angina is of short duration and subsides completely without residual discomfort If the attack is precipitated by exertion and the patient promptly stops to rest, it usually lasts less than 3 minutes Attacks following a heavy meal or brought on by anger often last 15–20 minutes Attacks lasting more than 30 minutes are unusual and suggest the development of unstable angina, myocardial infarction, or an alternative diagnosis
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Location and radiation •
Discomfort is felt behind or slightly to the left of the mid sternum • Although angina may radiate to any dermatome from C8 to T4, it radiates most often to the left shoulder and upper arm, frequently moving down the inner volar aspect of the arm to the elbow, forearm, wrist, or fourth and fifth fingers • Occasionally, angina may be felt initially in the lower jaw, the back of the neck, the interscapular area, high in the left back, or in the volar aspect of the wrist
Effect of nitroglycerin •
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The diagnosis of angina pectoris is strongly supported if sublingual nitroglycerin promptly and invariably shortens an attack and if prophylactic nitrates permit greater exertion or prevent angina entirely
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Signs • Examination during an attack frequently reveals a significant elevation in systolic and diastolic BP, although hypotension may also occur • Occasionally, a gallop rhythm and an apical systolic murmur due to transient mitral regurgitation from papillary muscle dysfunction are present during pain only • Supraventricular or ventricular arrhythmias may be present • Detect signs of diseases that may contribute to or accompany atherosclerotic heart disease, eg, diabetes mellitus xanthelasma, tendinous xanthomas, hypertension, thyrotoxicosis, myxedema, or peripheral vascular disease 12/01/09
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Investigations
Laboratory Findings
• Serum lipid levels should be determined in all patients with suspected angina • Anemia and diabetes may also be investigated if clinically appropriate.
ECG Resting ECG: • The resting ECG is normal in many patients with angina • In the remainder, abnormalities include old myocardial infarction, nonspecific ST–T changes, AV or intraventricular conduction defects, and changes of LVH • During anginal episodes, the characteristic ECG change is horizontal or downsloping ST-segment depression that reverses after the ischemia disappears • T wave flattening or inversion may also occur 12/01/09
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Resting ECG showing normal baseline ST segments
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ECG showing significant STsegment depression
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Exercise ECG • Exercise testing is the most useful noninvasive procedure for evaluating the patient with angina • Exercise testing can be done on a motorized treadmill or with a bicycle ergometer • The usual ECG criterion for a positive test is 1 mm (0.1 mV) horizontal or downsloping STsegment depression measured 80 milliseconds after the J point 12/01/09
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A - planar ST depression is usually indicative of myocardial ischaemic; B - downsloping depression also usually indicates myocardial ischaemic; C - upsloping depression however may be a normal finding
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Scintigraphic Assessment of Ischemia •
Two nuclear medicine studies provide additional information about the presence, location, and extent of CAD
1. Myocardial perfusion scintigraphy 2. Radionuclide angiography
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Isotope scan suggestive of reversible myocardial There is reduced uptake of thallium shown by the arrow suggesting a perfusion defect
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Echocardiography • Echocardiography can image the LV and reveal segmental wall motion abnormalities, which may indicate ischemia or prior infarction • It is a convenient technique for assessing LV function, which is an important indicator of prognosis and determinant of therapy • Echocardiography contrast agents allow for perfusion imaging and may improve the diagnostic accuracy of this form of testing 12/01/09
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Coronary Angiography • Selective coronary arteriography is the definitive diagnostic procedure for CAD • Coronary arteriography visualizes the location and severity of stenoses • Coronary arteriography also shows whether the obstructions are amenable to bypass surgery or percutaneous transluminal coronary angioplasty 12/01/09
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Treatment Treatment of Anginal Episodes • • • • • • •
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Sublingual nitroglycerin is the drug of choice; it acts in about 1–2 minutes Nitrates decrease arteriolar and venous tone, reduce preload and afterload, and lower the oxygen demand of the heart As soon as the attack begins, one fresh tablet is placed under the tongue. This may be repeated at 3- to 5-minute intervals The dosage (0.3, 0.4, or 0.6 mg) and the number of tablets to be used before seeking further medical attention must be individualized Nitroglycerin buccal spray is also available as a metered (0.4 mg) delivery system Nitroglycerin can also be used prophylactically before activities likely to precipitate angina Pain not responding to three tablets or lasting more than 20 minutes may represent evolving infarction, and the patient should be instructed to seek immediate medical attention Free Template from www.brainybetty.com
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Prevention of Further Attacks Aggravating factors • Angina may be aggravated by hypertension, LV failure, arrhythmia (usually tachycardias), strenuous activity, cold temperatures, and emotional states. These factors should be identified and treated when possible.
Nitroglycerin • Nitroglycerin, 0.3–0.6 mg sublingually or 0.4–0.8 mg translingually by spray, should be taken 5 minutes before any activity likely to precipitate angina • Long-acting nitrates include isosorbide dinitrate, isosorbide mononitrate, nitroglycerin ointment and transdermal nitroglycerin • The main limitation to long-term nitrate therapy is tolerance • The degree of tolerance can be limited by using a regimen that includes a minimum 8- to 10-hour period per day without nitrates • Nitrate therapy is often limited by headache. Other side effects include nausea, light-headedness, and hypotension.
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β-Blockers • β-Blockers prevent angina by reducing myocardial oxygen requirements during exertion and stress. This is accomplished by reducing the heart rate, myocardial contractility, and, to a lesser extent, BP • The β-blockers are the only antianginal agents that have been demonstrated to prolong life in patients with coronary disease (post-myocardial infarction). • They should be considered for first-line therapy in most patients with chronic angina. • The major contraindications are severe bronchospastic disease, bradyarrhythmias, and decompensated heart failure . 12/01/09
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Calcium channel blocking agents • Verapamil, diltiazem, and the dihydropyridine group of calcium blockers prevent angina by reducing myocardial oxygen requirements and by inducing coronary artery vasodilation • Myocardial oxygen demand is decreased by reducing BP, LV wall stress and, in the case of verapamil and diltiazem, resting or exercise heart rate • Nifedipine, nicardipine, and amlodipine are also approved agents for angina 12/01/09
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Platelet-inhibiting agents • Coronary thrombosis is responsible for most episodes of myocardial infarction and many unstable ischemic syndromes • Unless contraindicated, small doses of aspirin (81–325 mg daily) should be prescribed for patients with angina • Clopidogrel is an antiplatelet agent that acts by blocking the ADP receptor and resulting platelet aggregation • It can reduce cardiac events in patients with acute coronary syndromes and is an appropriate alternative in aspirin-intolerant patients • It may rarely induce thrombotic thrombocytopenic purpura as a side effect
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Revascularization Procedures for Patients with Angina Pectoris Coronary Artery Bypass Grafting (CABG) •
Grafts using one or both internal mammary arteries provide the best longterm results in terms of patency and flow
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Segments of the saphenous vein or the radial artery are also used
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After successful surgery, symptoms generally abate
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Graft failure is common in patients who continue smoking and those with untreated hyperlipidemia
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Antiplatelet therapy with aspirin improves graft patency rates
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Smoking cessation and vigorous treatment of blood lipid abnormalities are necessary, with a goal for LDL cholesterol of < 100 mg/dL and of HDL cholesterol > 45 mg/dL
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Repeat revascularization is often necessitated by progressive native vessel
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Percutaneous Coronary Intervention Including Stenting Coronary artery stenoses can be effectively dilated by inflation of a balloon under high pressure This procedure is performed in the cardiac catheterization laboratory under local anesthesia The mechanism of dilation involves both rupture of the atheromatous plaque and remodeling of the vessel 12/01/09
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The major early complication is intimal dissection with vessel occlusion. This can usually be treated by deployment of an intracoronary stent The use of platelet glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) has substantially reduced the rate of acute vessel closure, and placement of intracoronary stents has markedly improved initial and long-term angiographic results Early stents were complicated by an unacceptable rate of acute thrombosis, this problem is prevented by aggressive antithrombotic therapy (long-term aspirin plus clopidogrel with acute use of platelet glycoprotein IIb/IIIa inhibitors in high-risk patients Stents are now used in the majority of patients undergoing percutaneous revascularization 12/01/09
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Coronary Vasospasm & Angina with Normal Coronary Arteriograms Most symptoms of myocardial ischemia result from fixed stenosis of the coronary arteries or intraplaque hemorrhage or thrombosis at the site of lesions, some ischemic events may be precipitated or exacerbated by coronary vasoconstriction
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• Spasm of the large coronary arteries with resulting decreased coronary blood flow may occur spontaneously or may be induced by exposure to cold, emotional stress, or vasoconstricting medications, such as ergot derivative drugs • Spasm may occur both in normal and in stenosed coronary arteries and may be silent or result in angina
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Prinzmetal's (variant) angina • It is a clinical syndrome in which chest pain occurs without the usual precipitating factors and is associated with ST-segment elevation rather than depression • It often affects women under 50 years of age • It characteristically occurs in the early morning, awakening patients from sleep, tends to involve the right coronary artery, and is apt to be associated with arrhythmias or conduction defects • There may be no fixed stenoses • Ischemia usually results from coronary 12/01/09 vasoconstriction Free Template from www.brainybetty.com
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• Patients with this pattern of pain or any chest pain syndrome associated with ST-segment elevation should undergo coronary arteriography to determine whether fixed stenotic lesions are present • If they are, aggressive medical therapy or revascularization is indicated, since this may represent an unstable phase of the disease • If significant lesions are not seen and spasm is suspected, avoidance of precipitants such as cigarette smoking and cocaine is the top priority • Episodes of coronary spasm generally respond well to nitrates, and both nitrates and calcium channel blockers (including long-acting nifedipine, diltiazem, or amlopidine) are effective prophylactically
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Syndrome X There is a growing consensus that myocardial ischemia may also occur in patients with normal coronary arteries as a result of disease of the coronary microcirculation or abnormal vascular reactivity This has been termed "syndrome X.“
Cocaine It can induce myocardial ischemia and infarction by causing coronary artery vasoconstriction or by increasing myocardial energy requirements.
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Unstable Angina Unstable angina is characterized by • New-onset angina • Rapidly worsening angina (crescendo angina) • Angina on minimal exertion • Angina at rest
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Acute coronary syndrome • Unstable angina • Myocardial infarction • These entities comprise of a spectrum of diseases that encompasses ischemia with no myocardial damage, → ischemia with minimal myocardial
→ partial thickness( non-Q wave myocardial infarction → full thickness (Q-wave) damage,
myocardial infarction
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Culprit lesion of acute coronary syndrome It is usually an ulcerated or fissured atheromatous plaque with adherent platelet-rich thrombus and local coronary artery spasm
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Diagnosis • ECG will show ST/T wave changes including ST depression, transient ST elevation and T wave inversion • T wave changes are often prolonged
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Management • Patient should be admitted immediately as there is risk of AMI or death during the unstable phase • Appropriate treatment will reduce the incidence of adverse effects
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Initial management • Bed rest • Anti-platelet therapy with aspirin 300 mg followed by 75-325 mg daily and clopidogeral 300 mg followed by 75 mg daily for 12 months • Anticoagulation therapy with Unfractionated or Low-molecular weight heparin 12/01/09
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• β- Blocker (atenolol 50-199 mg daily or metoprolol 50-100 mg 12-hourly • Calcium channel blocker may be added to βblocker or replace it if β-blocker is contraindicated If pain persists or recurs then: • Infusion of intravenos nitrates are given (GTN 0.6-1.2 mg/hr or isosorbide dinitrate 1-2 mg/hr
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• Hemodynamically unstable patients will also be given glycoprotein IIb/IIIa receptor blockers ( abciximab, tirofiban), intra-aortic baloon pump or early coronary angiography with revascularization • If lesions are unsuited to PCI then urgent CABG should be considered
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Atherosclerosis is a progressive inflammatory disorder of the arterial wall that is characterized by focal lipid-rich deposits of atheroma that remains clinically silent until they become large enough to impair arterial perfusion or until ulceration or disruption of the lesion results in thrombotic occlusion or embolization of the affected vessel
12/01/09
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Atherosclerosis may manifest as : • Coronary heart disease( angina, MI, sudden death) • Cerebrovascular disease ( stroke, TIAs) • Peripheral vascular disease (claudication and critical limb ischemia)
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Pathophysiology • Abnormal lipid metabolism or excessive intake of cholesterol and saturated fats—especially when superimposed on a genetic predisposition—is important in early stages of the atherosclerotic process
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• The initial step is the "fatty streak," or subendothelial accumulation of lipids and lipid-laden monocytes (macrophages) • Following vascular injury, monocytes bind to the endothelium, then cross it to the subendothelial space and become activated tissue microphages • LDLs are the major atherogenic lipid • HDLs, in contrast, are protective by virtue of their role in reverse cholesterol transport, removing cholesterol from the vascular wall
12/01/09
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• LDLs undergo in situ oxidation, which makes them more difficult to mobilize as well as locally cytotoxic • Oxidized LDL enter the macrophages and smooth muscle cells, forming foam cells • HDL carry cholesterol from tissues to the liver for excretion in the bile, and LDL receptors in the liver take up VLDL, IDL, and LDL, lowering circulating cholesterol 12/01/09
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• As the plaque progresses, smooth muscle cells also migrate into the lesion • At this stage, the lesion may be hemodynamically insignificant, but endothelial function is abnormal and its ability to limit the entry of lipoproteins into the vessel wall is impaired • If the plaque remains stable, a fibrous cap forms, the lesion becomes calcified, remodeling of the vessel wall occurs, and ultimately the vessel lumen may become narrowed • Although extensive atherosclerosis may be present even before this occurs 12/01/09
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• Although many atherosclerotic plaques remain stable or progress only gradually, others may rupture, often related to the inflammatory process and metalloproteinase activity • The rupture causes turbulent flow, extrusion of lipids and fatty gruel, and exposure of tissue factor that result in a cascade of events culminating in intravascular thrombosis • The outcome of these events is determined in large part by whether the vessel becomes occluded, which depends on the lesion anatomy as well as the balance of pro- and antithrombotic and pro- and antifibrinolytic forces
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• The result may be partial or complete vessel occlusion (causing the symptoms of unstable angina or myocardial infarction), or the plaque may become restabilized, often with more severe stenosis • Transient occlusion and/or embolization of platelet and thrombin debris, which may result in elevation in serum troponin, predispose to clinical events and portend a worse prognosis 12/01/09
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•
Several features are associated with enhanced plaque vulnerability, including
1. a higher lipid content 2. a higher concentration of macrophages, especially in the plaque shoulder 3. a very thin fibrous cap •
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Lesions with these characteristics are often relatively early lesions that can be responsible for acute myocardial infarction or sudden death as the first manifestation of coronary disease Free Template from www.brainybetty.com
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Risk Factors for CAD • Most patients with coronary heart disease have some identifiable risk factor • These include: • Positive family history (the younger the onset in a firstdegree relative, the greater the risk) • Male gender • Blood lipid abnormalities • Diabetes mellitus • Hypertension • Physical inactivity • Obesity • Cigarette smoking 12/01/09
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• Smoking remains the number one preventable cause of cardiovascular disease worldwide • According to the World Health Organization, 1 year after quitting, the risk of coronary heart disease decreases by 50% • Various interventions, including physician counseling, formal smoking cessation programs, nicotine replacement therapy, and bupropion, have been shown to increase the likelihood of successful cessation 12/01/09
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• Hypercholesterolemia and other lipid abnormalities provide an important modifiable risk factor for coronary heart disease • Risk increases progressively with higher levels of low-density lipoprotein (LDL) cholesterol and declines with higher levels of high-density lipoprotein (HDL) cholesterol
12/01/09
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• The metabolic syndrome is defined as a constellation of three or more of the following: • abdominal obesity • triglycerides 150 mg/dL • HDL cholesterol < 40 mg/dL for men and < 50 mg/dL for women • fasting glucose > 110 mg/dL • Hypertension • This syndrome, recognized as a major contributor to coronary heart disease risk, is increasing in prevalence at an alarming rate 12/01/09
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• Related to the metabolic syndrome, the epidemic of obesity is likewise a major factor contributing to coronary heart disease risk • Particularly alarming is the rapidly increasing incidence of obesity in adolescents • Increasing physical activity is an important goal to help combat obesity and its consequences • Low carbohydrate may improve the cholesterol profile in overweight men, at least temporarily • Fish, rich in omega-3 fatty acids, may help protect against vascular disease and it is recommended that it be eaten three times a week by patients at risk 12/01/09
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• It is now clear that markers of inflammation are strong risk factors for CAD • High sensitivity CRP is the best-characterized inflammatory marker and is available for clinical use • Use of CRP may be helpful in determining which patients at intermediate risk or are at high risk to warrant more intensive primary prevention, including use of statins to lower LDL cholesterol • CRP levels are often elevated in patients who have other conditions associated with accelerated atherosclerosis, such as diabetes, the metabolic syndrome, and obesity
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Coronary heart disease Coronary heart disease, or atherosclerotic CAD, is the number one killer in the world
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Coronary heart disease is clinically manifested as: • • • • • • 12/01/09
Stable angina Unstable angina Myocardial Infarction Heart failure Arrhythmias Sudden death Free Template from www.brainybetty.com
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Stable Angina Angina Pectoris • It is a symptom complex caused by transient myocardial ischemia and may occur whenever there is an imbalance between myocardial oxygen supply and demand • Coronary atheroma is the most common cause of angina
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Stable Angina It is ischemia which occurs when coronary perfusion is impaired by fixed or stable atheroma of the coronary arteries
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Clinical Features Symptoms
Circumstances that precipitate and relieve angina • Angina occurs most commonly during activity and is relieved by resting • The amount of activity required to produce angina may be relatively consistent under comparable physical and emotional circumstances or may vary from day to day • Angina also occurs after meals, during excitement, or on exposure to cold
12/01/09
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Characteristics of the discomfort • • •
Patients often do not refer to angina as "pain" but as a sensation of tightness, squeezing, burning, pressing, choking, aching, bursting, "gas," indigestion, or an ill-characterized discomfort It is often characterized by clenching a fist over the mid chest The distress of angina is rarely sharply localized and is not spasmodic
Duration of attacks • • • •
Angina is of short duration and subsides completely without residual discomfort If the attack is precipitated by exertion and the patient promptly stops to rest, it usually lasts less than 3 minutes Attacks following a heavy meal or brought on by anger often last 15–20 minutes Attacks lasting more than 30 minutes are unusual and suggest the development of unstable angina, myocardial infarction, or an alternative diagnosis
• . 12/01/09
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Location and radiation •
Discomfort is felt behind or slightly to the left of the mid sternum • Although angina may radiate to any dermatome from C8 to T4, it radiates most often to the left shoulder and upper arm, frequently moving down the inner volar aspect of the arm to the elbow, forearm, wrist, or fourth and fifth fingers • Occasionally, angina may be felt initially in the lower jaw, the back of the neck, the interscapular area, high in the left back, or in the volar aspect of the wrist
Effect of nitroglycerin •
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The diagnosis of angina pectoris is strongly supported if sublingual nitroglycerin promptly and invariably shortens an attack and if prophylactic nitrates permit greater exertion or prevent angina entirely
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Signs • Examination during an attack frequently reveals a significant elevation in systolic and diastolic BP, although hypotension may also occur • Occasionally, a gallop rhythm and an apical systolic murmur due to transient mitral regurgitation from papillary muscle dysfunction are present during pain only • Supraventricular or ventricular arrhythmias may be present • Detect signs of diseases that may contribute to or accompany atherosclerotic heart disease, eg, diabetes mellitus xanthelasma, tendinous xanthomas, hypertension, thyrotoxicosis, myxedema, or peripheral vascular disease 12/01/09
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Investigations
Laboratory Findings
• Serum lipid levels should be determined in all patients with suspected angina • Anemia and diabetes may also be investigated if clinically appropriate.
ECG Resting ECG: • The resting ECG is normal in many patients with angina • In the remainder, abnormalities include old myocardial infarction, nonspecific ST–T changes, AV or intraventricular conduction defects, and changes of LVH • During anginal episodes, the characteristic ECG change is horizontal or downsloping ST-segment depression that reverses after the ischemia disappears • T wave flattening or inversion may also occur 12/01/09
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Resting ECG showing normal baseline ST segments
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ECG showing significant STsegment depression
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Exercise ECG • Exercise testing is the most useful noninvasive procedure for evaluating the patient with angina • Exercise testing can be done on a motorized treadmill or with a bicycle ergometer • The usual ECG criterion for a positive test is 1 mm (0.1 mV) horizontal or downsloping STsegment depression measured 80 milliseconds after the J point 12/01/09
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A - planar ST depression is usually indicative of myocardial ischaemic; B - downsloping depression also usually indicates myocardial ischaemic; C - upsloping depression however may be a normal finding
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Scintigraphic Assessment of Ischemia •
Two nuclear medicine studies provide additional information about the presence, location, and extent of CAD
1. Myocardial perfusion scintigraphy 2. Radionuclide angiography
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Isotope scan suggestive of reversible myocardial There is reduced uptake of thallium shown by the arrow suggesting a perfusion defect
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Echocardiography • Echocardiography can image the LV and reveal segmental wall motion abnormalities, which may indicate ischemia or prior infarction • It is a convenient technique for assessing LV function, which is an important indicator of prognosis and determinant of therapy • Echocardiography contrast agents allow for perfusion imaging and may improve the diagnostic accuracy of this form of testing 12/01/09
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Coronary Angiography • Selective coronary arteriography is the definitive diagnostic procedure for CAD • Coronary arteriography visualizes the location and severity of stenoses • Coronary arteriography also shows whether the obstructions are amenable to bypass surgery or percutaneous transluminal coronary angioplasty 12/01/09
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Treatment Treatment of Anginal Episodes • • • • • • •
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Sublingual nitroglycerin is the drug of choice; it acts in about 1–2 minutes Nitrates decrease arteriolar and venous tone, reduce preload and afterload, and lower the oxygen demand of the heart As soon as the attack begins, one fresh tablet is placed under the tongue. This may be repeated at 3- to 5-minute intervals The dosage (0.3, 0.4, or 0.6 mg) and the number of tablets to be used before seeking further medical attention must be individualized Nitroglycerin buccal spray is also available as a metered (0.4 mg) delivery system Nitroglycerin can also be used prophylactically before activities likely to precipitate angina Pain not responding to three tablets or lasting more than 20 minutes may represent evolving infarction, and the patient should be instructed to seek immediate medical attention Free Template from www.brainybetty.com
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Prevention of Further Attacks Aggravating factors • Angina may be aggravated by hypertension, LV failure, arrhythmia (usually tachycardias), strenuous activity, cold temperatures, and emotional states. These factors should be identified and treated when possible.
Nitroglycerin • Nitroglycerin, 0.3–0.6 mg sublingually or 0.4–0.8 mg translingually by spray, should be taken 5 minutes before any activity likely to precipitate angina • Long-acting nitrates include isosorbide dinitrate, isosorbide mononitrate, nitroglycerin ointment and transdermal nitroglycerin • The main limitation to long-term nitrate therapy is tolerance • The degree of tolerance can be limited by using a regimen that includes a minimum 8- to 10-hour period per day without nitrates • Nitrate therapy is often limited by headache. Other side effects include nausea, light-headedness, and hypotension.
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β-Blockers • β-Blockers prevent angina by reducing myocardial oxygen requirements during exertion and stress. This is accomplished by reducing the heart rate, myocardial contractility, and, to a lesser extent, BP • The β-blockers are the only antianginal agents that have been demonstrated to prolong life in patients with coronary disease (post-myocardial infarction). • They should be considered for first-line therapy in most patients with chronic angina. • The major contraindications are severe bronchospastic disease, bradyarrhythmias, and decompensated heart failure . 12/01/09
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Calcium channel blocking agents • Verapamil, diltiazem, and the dihydropyridine group of calcium blockers prevent angina by reducing myocardial oxygen requirements and by inducing coronary artery vasodilation • Myocardial oxygen demand is decreased by reducing BP, LV wall stress and, in the case of verapamil and diltiazem, resting or exercise heart rate • Nifedipine, nicardipine, and amlodipine are also approved agents for angina 12/01/09
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Platelet-inhibiting agents • Coronary thrombosis is responsible for most episodes of myocardial infarction and many unstable ischemic syndromes • Unless contraindicated, small doses of aspirin (81–325 mg daily) should be prescribed for patients with angina • Clopidogrel is an antiplatelet agent that acts by blocking the ADP receptor and resulting platelet aggregation • It can reduce cardiac events in patients with acute coronary syndromes and is an appropriate alternative in aspirin-intolerant patients • It may rarely induce thrombotic thrombocytopenic purpura as a side effect
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Revascularization Procedures for Patients with Angina Pectoris Coronary Artery Bypass Grafting (CABG) •
Grafts using one or both internal mammary arteries provide the best longterm results in terms of patency and flow
•
Segments of the saphenous vein or the radial artery are also used
•
After successful surgery, symptoms generally abate
•
Graft failure is common in patients who continue smoking and those with untreated hyperlipidemia
•
Antiplatelet therapy with aspirin improves graft patency rates
•
Smoking cessation and vigorous treatment of blood lipid abnormalities are necessary, with a goal for LDL cholesterol of < 100 mg/dL and of HDL cholesterol > 45 mg/dL
•
Repeat revascularization is often necessitated by progressive native vessel
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Percutaneous Coronary Intervention Including Stenting Coronary artery stenoses can be effectively dilated by inflation of a balloon under high pressure This procedure is performed in the cardiac catheterization laboratory under local anesthesia The mechanism of dilation involves both rupture of the atheromatous plaque and remodeling of the vessel 12/01/09
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The major early complication is intimal dissection with vessel occlusion. This can usually be treated by deployment of an intracoronary stent The use of platelet glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) has substantially reduced the rate of acute vessel closure, and placement of intracoronary stents has markedly improved initial and long-term angiographic results Early stents were complicated by an unacceptable rate of acute thrombosis, this problem is prevented by aggressive antithrombotic therapy (long-term aspirin plus clopidogrel with acute use of platelet glycoprotein IIb/IIIa inhibitors in high-risk patients Stents are now used in the majority of patients undergoing percutaneous revascularization 12/01/09
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Coronary Vasospasm & Angina with Normal Coronary Arteriograms Most symptoms of myocardial ischemia result from fixed stenosis of the coronary arteries or intraplaque hemorrhage or thrombosis at the site of lesions, some ischemic events may be precipitated or exacerbated by coronary vasoconstriction
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• Spasm of the large coronary arteries with resulting decreased coronary blood flow may occur spontaneously or may be induced by exposure to cold, emotional stress, or vasoconstricting medications, such as ergot derivative drugs • Spasm may occur both in normal and in stenosed coronary arteries and may be silent or result in angina
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Prinzmetal's (variant) angina • It is a clinical syndrome in which chest pain occurs without the usual precipitating factors and is associated with ST-segment elevation rather than depression • It often affects women under 50 years of age • It characteristically occurs in the early morning, awakening patients from sleep, tends to involve the right coronary artery, and is apt to be associated with arrhythmias or conduction defects • There may be no fixed stenoses • Ischemia usually results from coronary 12/01/09 vasoconstriction Free Template from www.brainybetty.com
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• Patients with this pattern of pain or any chest pain syndrome associated with ST-segment elevation should undergo coronary arteriography to determine whether fixed stenotic lesions are present • If they are, aggressive medical therapy or revascularization is indicated, since this may represent an unstable phase of the disease • If significant lesions are not seen and spasm is suspected, avoidance of precipitants such as cigarette smoking and cocaine is the top priority • Episodes of coronary spasm generally respond well to nitrates, and both nitrates and calcium channel blockers (including long-acting nifedipine, diltiazem, or amlopidine) are effective prophylactically
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Syndrome X There is a growing consensus that myocardial ischemia may also occur in patients with normal coronary arteries as a result of disease of the coronary microcirculation or abnormal vascular reactivity This has been termed "syndrome X.“
Cocaine It can induce myocardial ischemia and infarction by causing coronary artery vasoconstriction or by increasing myocardial energy requirements.
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Unstable Angina Unstable angina is characterized by • New-onset angina • Rapidly worsening angina (crescendo angina) • Angina on minimal exertion • Angina at rest
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Acute coronary syndrome • Unstable angina • Myocardial infarction • These entities comprise of a spectrum of diseases that encompasses ischemia with no myocardial damage, → ischemia with minimal myocardial
→ partial thickness( non-Q wave myocardial infarction → full thickness (Q-wave) damage,
myocardial infarction
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Culprit lesion of acute coronary syndrome It is usually an ulcerated or fissured atheromatous plaque with adherent platelet-rich thrombus and local coronary artery spasm
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Diagnosis • ECG will show ST/T wave changes including ST depression, transient ST elevation and T wave inversion • T wave changes are often prolonged
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Management • Patient should be admitted immediately as there is risk of AMI or death during the unstable phase • Appropriate treatment will reduce the incidence of adverse effects
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Initial management • Bed rest • Anti-platelet therapy with aspirin 300 mg followed by 75-325 mg daily and clopidogeral 300 mg followed by 75 mg daily for 12 months • Anticoagulation therapy with Unfractionated or Low-molecular weight heparin 12/01/09
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• β- Blocker (atenolol 50-199 mg daily or metoprolol 50-100 mg 12-hourly • Calcium channel blocker may be added to βblocker or replace it if β-blocker is contraindicated If pain persists or recurs then: • Infusion of intravenos nitrates are given (GTN 0.6-1.2 mg/hr or isosorbide dinitrate 1-2 mg/hr
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• Hemodynamically unstable patients will also be given glycoprotein IIb/IIIa receptor blockers ( abciximab, tirofiban), intra-aortic baloon pump or early coronary angiography with revascularization • If lesions are unsuited to PCI then urgent CABG should be considered
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