Atherosclerotic Coronary Artery Disease
5.1 Atherosclerosis
Nejm 2005;352:1685; Circ 2004;109:SuppIII; 2001;104:365
Cause: This fatty streak develops by early adulthood. It is caused by oxidation of lipids trapped in the extracellular matrix of the subendothelial space, leading to inflammation. Risk factors include advancing age, dyslipidemia, DM, HT, cigarette smoking, obesity, and some forms of psychological stress (Circ 1998;97: 1837; 1999;99:2192). Chlamydia pneumoniae and possibly CMV and herpes viruses have been found in atherosclerotic lesions; their role in development of ASHD is still unclear (Circ 1997; 96:4095; J Am Coll Cardiol 1998;31:1217; Clin Inf Dis 1998; 26:719).
Epidem
In U.S.pts, fatty streaks increase rapidly in prevalence and extent between ages 15 and 34; by ages 15-19, intimal lesions are present in the RCA in > 50% of subjects (Jama 1999;281:727). Risk factor reduction can account for about 50% of the decline in coronary mortality in the U.S. during 1980-1990, but > 70% of the decline occurred inpts who already had documented CAD.
Atherosclerosis risk is increased in diabetes, HT, obesity (Circ 1996;93:1372; Arch IM 1998;158:1855), dyslipidemia,
pseudoxanthoma elasticum, myotonic dystrophy, alkaptonuria, and ochronosis. In one study, children of parents with early CAD were overweight from childhood and developed adverse cardiovascular risk factor profiles at an increased rate (Jama 1997;278:1749). Poor fitness in young adults is associated with development of cardiac risk factors (Jama 2003;290:3092).
There is an association between glycemic control and risk for CAD in middle-aged and elderlypts with NIDDM (Ann IM 1996;124:127). Compared with nondiabetic PTCApts, diabeticpts have more extensive and diffuse atherosclerotic disease. Diabeticpts without MI have as high a risk of AMI as nondiabeticpts with prior MI (Nejm 1998;339:229). The 9-yr mortality was twice as high in diabeticpts and 9-yr rates of nonfatal MI, CABG, and repeat PTCA were higher in diabetics than in nondiabetics (Circ 1996;94:1818).
Low HDL with borderline/high triglycerides increases risk (Circ 1995;92:1430). In elderlypts, LDL level is more predictive than total HDL (Circ 1996;94:2381). Increased triglycerides levels, small LDL particle diameter, and decreased HDL levels are all associated with progression of ASHD; debate exists as to whether triglycerides and LDL size are independent risk factors (Jama 1996;276:875,882; Circ 1998;97:1029). Lp(a) may not be an independent risk factor but may increase risk in conjunction with other lipid factors (Circ 1997;96: 1390; J Am Coll Cardiol 1998;31:519; 1998;32:2035).
Up to 80% ofpts with unstable CAD have one or more risk factors (Jama 2003;290:898), as do 87-100% ofpts with fatal coronary events (Jama 2003;290:891).
Elevated homocysteine levels have been associated with increased risk of vascular disease (Arch IM 1997;159:2299; 1999;159:1077; Jama 1997;277:1775). Reduced red cell folate and vitamin B6 levels are also associated with increased risk (Circ 1998;97:437). In contrast to cross-sectional and
case-control studies, results of prospective studies have indicated less or no predictive ability for plasma homocysteine in ASHD (Arch IM 2000;160:422).
Estrogens convey a protective effect against ASHD (Nejm 1999;340:1801), although the HERS trial failed to demonstrate reduced CAD mortality with estrogen replacement. In women with ASHD, severity of disease at angiography is associated with polycystic ovary disease (Ann IM 1997;126:32). Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and MI in elderly women (Ann IM 2000;132:270).
Moderate alcohol consumption decreases risk (Circ 1996;94: 3023; Nejm 1997;337:1705; Ann IM 1997;126:372), as does regular exercise (Circ 1997;96:2534; Arch IM 1998;158:1633). Conversely, low fitness is an important precursor of mortality (Jama 1996;276:205).
Approximately 33% more deaths due to CAD occur in December-January than in June-September (Circ 1999;100:1630). Compared with the 1950-1969 reference period, the CAD death rate has been lower in subsequent decades, despite the lack of significant temporal changes in risks for recurrent MI or CHF (Framingham) (Circ 1999; 100:2054).
Pathophys
NO interferes with monocyte and leukocyte adhesion to the endothelium and with platelet-vessel wall interaction, decreases endothelial permeability, decreases the flux of lipoproteins into the vessel wall, and inhibits vascular smooth muscle cell proliferation. Major risk factors for atherosclerotic vascular disease (hypercholesterolemia, diabetes, HT, and smoking) are associated with impaired NO activity. Reduction
in NO synthesis is the primary process involved in endothelial dysfunction and is due to reduced availability of the NOS substrate L-arginine (Circ 1998;97:108).
Trapped LDL particles undergo progressive oxidation and are internalized by macrophages, facilitating the accumulation of cholesterol esters and resulting in the formation of foam cells. Injury increases the permeability and adhesiveness of the endothelium with respect to leukocytes and platelets. It also induces the endothelium to have procoagulant instead of anticoagulant properties.
Modified LDL is chemotactic for other monocytes and can upregulate the expression of genes for macrophage colony-stimulating factor and monocyte chemotactic protein. It can also expand the inflammatory response by stimulating replication of monocyte-derived macrophages and entry of new monocytes and specific subtypes of T lymphocytes into lesions.
Mediators of inflammation (tumor necrosis factor α, interleukin-1, macrophage colony-stimulating factor) increase binding of LDL to endothelium and smooth muscle and, in turn, increase the transcription of the LDL-receptor gene. Modified LDL initiates induction of urokinase and inflammatory cytokines such as interleukin-1. The inflammatory response stimulates migration and proliferation of smooth muscle cells.
Progression of lesions is also associated with activation of genes that induce arterial calcification, which in turn changes the mechanical characteristics of the artery wall and predisposes it to plaque rupture at sites of monocytic infiltration. Plaque rupture exposes blood to tissue factors in the lesion and induces thrombosis, which is the proximate cause of clinical events. Ruptured plaques may also heal slowly, producing plaque progression (J Am Coll Cardiol 2005;45:652).
Homocysteine is toxic to endothelium, is prothrombotic, increases collagen production, and decreases the availability of NO.
Hypertension increases the formation of hydrogen peroxide and free radicals in plasma, which in turn can reduce formation of NO by endothelium, increase leukocyte adhesion, and increase peripheral resistance. Angiotensin II is a potent vasoconstrictor that also stimulates growth of smooth muscle and increases oxidation of LDL (Circ 1995;91:2488; Nejm 1999;340:115).
Pts with DM have a reduced ability to develop collateral blood vessels in the presence of CAD (Circ 1999;99:2224).
Multiple metabolic risk factors tend to cluster, resulting in the metabolic syndrome (Circ 1997;95:1; 1997;96:3243; Jama 1997; 278:1759).
Persistent vasospasm may cause progression of atherosclerosis (Circ 1995;92:2446).
Sx: Atherosclerosis typically produces no symptoms until lesions become occlusive; “silent” ischemia can also occur (Cardiologia 1998;43:1159). Plaque rupture may occur with varying clinical presentations (Jama 2002;40:904).
Si: Arcus senilis; tendinous xanthomas in familial hypercholesterolemia; tuberoeruptive and planar xanthomas in familial dysbetalipoproteinemia
Crs: Progressive without intervention (Circ 1998;97:1876); possibly reversible with risk factor modification (Jama 1998;280:2001). Evidence exists for reduction in sequelae with smoking cessation (Nejm 1985;313:1511), hyperlipidemia (Lancet 1994;344:1383; Nejm 1995;333:1301; 1996;335:1001), and HT (Arch IM 1991;151:1277). There may also be an association between cessation of vasospastic activity and regression of atherosclerosis (Circ 1995;92:2446).
Lab: Measure fasting serum cholesterol: Pts with total cholesterol level > 200 mg/dL or who have hx of MI, angina, CABG, PTCA, TIA or known blockage of a carotid artery, abdominal aortic aneurysm, or ischemic peripheral arterial disease should have a complete lipid screen (NHLBI NIH Pub No 95-3045).
Elevated hsCRP level is an independent risk factor for CAD (Circ 2003;107:363; 2002;105:1135). Whether hsCRP contributes directly to the development of plaque remains uncertain (Nejm 2005;352:29).
X-ray: Studies listed under disease entries
Rx
Diet: Moderate restriction of dietary fat (Circ 1997;95:2701; Jama 1997;278:1509). One egg/day has little impact (Jama 1999;281:1387). Extreme restriction of fat intake offers little further advantage and may have potentially undesirable effects in hyperlipidemic subjects.
A high-fiber diet reduced CAD risk in middle-aged Finnish male smokers (Circ 1996;94:2720). Neither dietary fish consumption nor omega-3 fatty acid intake reduces the risk of MI, nonsudden cardiac death, or total CV mortality. Eating fish did reduce total mortality and risk of sudden cardiac death in men (Jama 1998;279:23); meta-analysis of 11 studies showed an inverse relationship between fish consumption and fatal CAD (Circ 2004;109:2705). The Mediterranean diet provides protection inpts with prior MI (Lancet 1994;343:1454; Circ 1999;99:779).
Physical exercise: There is a dose-response relationship between the amount of exercise performed per week and all-cause mortality and CVD mortality in middle-aged and elderly populations. The greatest potential for reduced mortality is in sedentary individuals who become moderately active (Circ 1996; 94:857). Exercise retards progression of CAD (Circ 1997; 96;2534). Women with ASHD who participate in cardiac
rehab programs showed greater lipid benefits than men (Circ 1995;92;773).
Smoking: The goal is complete cessation. There is a possible increased risk from exposure to second-hand smoke (Circ 1997;95:2374). Smoking cessation programs are cost-effective (Jama 1997;278:1759). Forpts with CAD, smoking cessation reduces the crude relative mortality risk by ˜36% (Jama 2003;290:86).
Lipid management: Goals as listed above. Statins have proven clinical benefit (Circ 1998;97:946). Fibrates lower triglycerides and usually raise HDL (Circ 1998;98:2088). Gemfibrozil may retard the progression of ASHD in men with low HDL cholesterol as their primary lipid abnormality (Circ 1997;96:2137). Administration of atorvastatin topts with ACS did not reduce frequence of recurrent events (Lancet 2003;361:809).
Diabetes: Inpts with NIDDM and microalbuminuria, multiple risk factor interventions reduce the risk of CAD events by 50% (Nejm 2003;348:383), and statin therapy reduces the risk of the first CAD event independent of LDL level (Lancet 2004;364:685; 2003;361:2005). Treatment with fenofibrate may slow the progression of plaque buildup (Lancet 2001; 357:905).
Antioxidants reduce the susceptibility of LDL to oxidation (J Am Coll Cardiol 1997;30:392). Vitamin E improves vasodilation inpts with coronary artery spasm (J Am Coll Cardiol 1998;32:1672) and improves relaxation in resistance vessels in smokers (J Am Coll Cardiol 1999;33:499), but meta-analysis of clinical trials did not show mortality reduction from vitamin E or β-carotene administration (Lancet 2003;361: 2017). AHA recommends that antioxidant vitamins be derived from foods (Circ 1996;94:1795). Pts with personal or family hx of premature ASHD, malnutrition, malabsorption syndromes, hypothyroidism, renal failure, or SLE and those taking nicotinic acid, theophylline, bile acid-binding resins,
methotrexate, and L-dopa might benefit from supplemental vitamins (0.4 mg folic acid, 2 mg vitamin B6, and 6 μg vitamin B12 with appropriate medical evaluation and monitoring (Circ 1999;99:178).
methotrexate, and L-dopa might benefit from supplemental vitamins (0.4 mg folic acid, 2 mg vitamin B6, and 6 μg vitamin B12 with appropriate medical evaluation and monitoring (Circ 1999;99:178).
Addressing multiple risk factors provides long-term continuing benefits (Circ 1996;94:946).
5.2 Stable Angina Pectoris
Circ 2003;107:149; 1999;99:2829
Cause: Imbalance between myocardial oxygen supply and perfusion pressure (aortic diastolic pressure), coronary artery tone and resistance, presence of epicardial coronary artery stenoses, and myocardial O2 demand. “Stable angina” by definition is a state in which this imbalance can be corrected.
In syndrome X,pts have angina and abnormal stress tests in the presence of angiographically normal coronary arteries.
Pathophys
Conditions that can increase O2 demand: Hyperthermia, hypothyroidism, cocaine use, HT, mental stress, AV fistula, hypertrophic or dilated cardiomyopathy, AS, tachycardia
Conditions that can decrease O2 supply: Anemia, hypoxemia (COPD, asthma, pneumonia, pulmonary HT, interstitial pulmonary fibrosis, obstructive sleep apnea), sickle cell disease, hyperviscosity (polycythemia, leukemia), AS, hypertrophic cardiomyopathy (J Am Coll Cardiol 1999;33:2092)
Mental stress: In the laboratory, ischemia is associated with peripheral vaoconstriction and increased afterload. During daily life, ischemia is accompanied by increased inotropy (J Am Coll Cardiol 1999;33:1476).
Syndrome Xpts may have a decreased coronary vasodilator capacity and microvascular dysfunction (CV Res 1998; 40:410; Am J Cardiol 1999;83:149).
Sx
Typical angina: Substernal chest discomfort with characteristic quality and duration, provoked by exertion/emotional stress, relieved by rest/TNG; atypical angina: Pain meeting 2 of preceding characteristics; noncardiac chest pain; Meets ≤ 1 of the typical angina characteristics (J Am Coll Cardiol 1983;1:574)
Functional status classification: Class I: Ordinary physical activity does not cause angina. Class II: Slight limitation of ordinary activity (climbing stairs rapidly or after meals or in cold). Class III: Marked limitations of ordinary physical activity (walking 1-2 blocks on level; climbing 1 flight of stairs at a normal pace). Class IV: Inability to carry on any physical activity without discomfort (Circ 1976;54:522).
Differential dx: Aortic dissection, pericarditis, pulmonary embolus, pneumothorax, pleuritis, esophageal spasm and reflux, cholecystitis, peptic ulcer disease, pancreatitis, chest wall pain, herpes zoster, panic disorder
Only 28% of diabeticpts with abnormal Tl stress tests reported exertional pain during the test; up to 75% of ischemic episodes (measured by AECG) inpts with stable angina are asymptomatic (Circ 1996;93:2089).
Si: During ischemia, may hear paradoxically split S2, transient S3 or S4, or murmur of MR
Crs: Average annual mortality inpts with CAD is 1-4%; about 1.5% for 1- and 2-vessel disease; and about 7% for 3-vessel disease (Circ 1994;90:2645). Risk stratification can also be based on noninvasive testing. Duke treadmill score (DTS) = exercise time − (5 × ST deviation) − (4 × exercise angina), with 0 = none, 1 = nonlimiting, and 2 = exercise-limiting (Circ 1998;98:1622). The 5-yr survival rates range from 95% forpts
with 1-vessel disease to 59% forpts with 3-vessel disease and severe proximal LAD stenosis (J Am Coll Cardiol 1996;27:964).
with 1-vessel disease to 59% forpts with 3-vessel disease and severe proximal LAD stenosis (J Am Coll Cardiol 1996;27:964).
Noninvasive Risk Stratification
High risk (greater than 3% annual mortality rate)
High-risk treadmill score (score ≤ −11)
Stress-induced large perfusion defect (particularly if anterior)
Stress-induced multiple perfusion defects of moderate size
Large, fixed perfusion defect with LV dilation or increased lung uptake (Tl-201)
Stress-induced moderate perfusion defect with LV dilation or increased lung uptake (Tl-201)
Echo wall motion abnormality (involving > 2 segments) developing with low-dose dobutamine (< 10 mg/kg/min) or at a low heart rate (< 120 beat/min)
Stress echo evidence of extensive ischemia
Intermediate risk (1-3% annual mortality rate)
Intermediate-risk treadmill score (−11 < score < +5)
Stress-induced moderate perfusion defect without LV dilation or increased lung intake (Tl-201)
Limited stress echo ischemia with a wall motion abnormality only at higher doses of dobutamine involving ≤ 2 segments
Low risk (less than 1% annual mortality rate)
Low-risk treadmill score (score ≥ +5)
Normal or small myocardial perfusion defect at rest or with stress
Normal stress echo wall motion or no change of limited resting wall motion abnormalities during stress
Although the published data are limited,pts with these findings will probably not be at low risk in the presence of either a high-risk treadmill score or severe resting LV dysfunction (LVEF < 35%) (J Am Coll Cardiol 1999;33:2092).
Exercise EKG without imaging: Forpts with an intermediate likelihood of CAD, including those with complete RBBB or < 1-mm resting ST depression, but not WPW, LBBB, digoxin rx, paced rhythm, > 1-mm resting ST depression
Absolute contraindications: Acute MI within 2 d, arrhythmias causing symptoms or hemodynamic compromise, symptomatic and severe AS, symptomatic CHF, acute pulmonary embolus or pulmonary infarction, acute myocarditis or pericarditis and acute aortic dissection
Relative contraindications: Left main coronary stenosis, moderate AS, electrolyte abnormalities, systolic HT > 200 mm Hg, diastolic BP > 110 mm Hg, tachyarrhythmia or bradyarrhythmia, hypertrophic cardiomyopathy and other forms of outflow tract obstruction, mental or physical impairment leading to an inability to exercise adequately, high-degree AV block
Exercise EKG with radionuclide or echo imaging: Forpts who have an abnormal rest EKG, who are using digoxin, or for whom PTCA is planned. Dipyridamole or adenosine myocardial perfusion or dobutamine echo are recommended forpts who are unable to exercise. Chemical stress with nuclear scanning is preferred forpts with LBBB or paced rhythm (see Chapter 4 on tests for the relevant protocols). Stress echo provides higher specificity, greater versatility, better convenience/efficacy/availability, and lower cost. Stress perfusion imaging has a higher technical success rate, higher sensitivity (especially for 1-vessel CAD), and better accuracy in evaluating possible ischemia when multiple rest LV wall
motion abnormalities are present, and it has a more extensive published database.
motion abnormalities are present, and it has a more extensive published database.
Echocardiogram: During chest pain, with murmur suggestive of AS, MR, or hypertrophic cardiomyopathy; echo or RVG forpts with h/o prior MI, pathological Q waves, or si/sx suggestive of CHF or with complex ventricular arrhythmia to assess LV function
Coronary angiography: Forpts with disabling (classes III/IV) chronic stable angina despite medical rx,pts with high-risk criteria on noninvasive testing regardless of anginal severity,pts with angina who have survived sudden cardiac death or serious ventricular arrhythmia or who have si/sx of CHF, andpts who have clinical characteristics that indicate a high likelihood of severe CAD; may also be used forpts with significant LV dysfunction (ejection fraction < 45%), class I/II angina, and demonstrable ischemia but less than high-risk criteria on noninvasive testing, and those with inadequate prognostic information after noninvasive testing
X-ray: CXR inpts with si/sx of CHF, valvular heart disease, pericardial disease, or aortic dissection/aneurysm
In a study of 3895 asymptomaticpts undergoing EBCT, no subject with a Ca++ score < 10 had an abnormal SPECT compared with 2.6% of those with scores of 11-100, 11.3% of those with scores 101-399, and 46% of those with scores > 400 (Circ 2000;101:244).
Rx: Medical: ASA; β-blockers; sl TNG or TNG spray; intermittent transdermal TNG rx increases exercise duration and maintains anti-ischemic effects for 12 hr after patch application without significant evidence of nitrate tolerance (Circ 1995;91:1368); calcium antagonists and/or long-acting nitrates when β-blockers are contraindicated, are not successful, or lead to unacceptable side effects (short-acting dihydropyridine calcium antagonists should be avoided); clopidogrel when ASA is absolutely contraindicated;
lipid-lowering therapy inpts with documented or suspected CAD and non-HDL cholesterol > 130 mg/dL with a target LDL < 100 mg/dL; ACEIs inpts with diabetes and/or LV systolic dysfunction; PEACE trial (8290pts) showed no reduction in CV death rate from ACEIs forpts with normal LV systolic function (Nejm 2004;351:20).
lipid-lowering therapy inpts with documented or suspected CAD and non-HDL cholesterol > 130 mg/dL with a target LDL < 100 mg/dL; ACEIs inpts with diabetes and/or LV systolic dysfunction; PEACE trial (8290pts) showed no reduction in CV death rate from ACEIs forpts with normal LV systolic function (Nejm 2004;351:20).
In low-riskpts with stable CAD, aggressive lipid-lowering rx was reported to be as effective as angioplasty and usual care in reducing the incidence of ischemic events (Nejm 1999;341:70).
In a meta-analysis, β-blockers provided similar clinical outcomes and were associated with fewer adverse events than Ca++ antagonists in randomized trials ofpts with stable angina (Jama 1999;281:1927).
The presence of other medical conditions may influence drug choice.
Enhanced external counterpulsation (EECP) reduces angina and extends time to exercise-induced ischemia inpts with symptomatic CAD (J Am Coll Cardiol 2003;41:1918; 1999; 33:1833).
Chelation rx has not been shown to have beneficial effects inpts with stable angina and a positive treadmill test (Jama 2002;287:481).
Revascularization: PTCA or other catheter-based techniques, CABG, laser surgical transmyocardial revascularization
CABG for significant left main CAD or left main equivalent (> 70% stenoses of proximal LAD and LCx), for 3-vessel disease (survival benefit greater inpts with abnormal LV function: ejection fraction < 40%), for 2-vessel disease with significant proximal LAD disease and either abnormal LV function (ejection fraction < 50%) or demonstrable ischemia on
noninvasive testing, for 1- or 2-vessel CAD without significant proximal left anterior descending CAD in survivors of sudden cardiac death or sustained VT, and for ongoing ischemia or hemodynamic compromise after failed PTCA
PTCA or CABG forpts (1) with 1- or 2-vessel CAD without significant proximal LAD disease but with a large area of viable myocardium and high-risk criteria on noninvasive testing; (2) with prior PTCA and recurrent stenosis associated with a large area of viable myocardium and/or high-risk criteria on noninvasive testing; or (3) who have not been successfully treated by medical rx and can undergo revascularization with acceptable risk
PTCA forpts with 2- or 3-vessel disease with significant proximal LAD disease, who have anatomy suitable for catheter-based rx and normal LV function, and who do not have treated diabetes
Evidence favors repeat CABG forpts with multiple saphenous vein graft stenoses and PTCA or CABG forpts with 1- or 2-vessel CAD without significant proximal LAD disease but with a moderate area of viable myocardium and demonstrable ischemia on noninvasive testing or with 1-vessel disease with significant proximal LAD disease.
Stents: Pts with multivessel CAD who receive stents have 3-yr survival rates without MI or CVA that are identical to the rates forpts who receive CABG (Circ 2004;109:1114), but 1-yr revascularization rates forpts with bare metal stents remain higher than forpts with CABG (Lancet 2002;360:965). Inpts with in-stent restenosis, brachytherapy (intra-coronary γ irradiation) reduced the 12-mon recurrence rate in saphenous vein grafts from 57% to 17%; however, restenosis after brachytherapy is common at 3 yr
(Circ 2003;107:2274,2283; Nejm 2002;346:1194). Compared with bare metal stents, stents containing sirolimus (rapamycin), an inhibitor of cytokine- and growth factor-mediated cell proliferation, reduced incidence of stent failure at 270 d from 21% to 8.6% (Jama 2005;293:165; Circ 2005;111:1040; Nejm 2003;349:1315); stents treated with paclitaxel reduced restenosis rates at 9 mon from 26.6% to 7.9% (Nejm 2004;350:221).
(Circ 2003;107:2274,2283; Nejm 2002;346:1194). Compared with bare metal stents, stents containing sirolimus (rapamycin), an inhibitor of cytokine- and growth factor-mediated cell proliferation, reduced incidence of stent failure at 270 d from 21% to 8.6% (Jama 2005;293:165; Circ 2005;111:1040; Nejm 2003;349:1315); stents treated with paclitaxel reduced restenosis rates at 9 mon from 26.6% to 7.9% (Nejm 2004;350:221).
Sex: Bypass graft surgery is associated with equally low mortality in women and men (1.4% vs 1.1%) (Circ 1995;92:80).
Age: Long-term results as measured by cumulative survival and cardiac event-free survival inpts who underwent CABG reoperation are good. The perioperative mortality rate for repeat CABG is reported to be 3%, with cumulative survival rates of 90.1%, 74%, and 63.4%. Cardiac event-free survival rates were 91.5%, 83.4%, and 67.8% at the 5-, 10-, and 15-yr follow-ups, respectively. Advanced age, HT, and a decreased LVEF significantly increase surgical risk (Chest 1999;115:1593). Cardiac mortality may be less than that expected in thesepts because of a high risk of noncardiac death (J Am Coll Cardiol 1997;30:881). Inpts > 80 yr old, survival at 1-5 yr was similar for medical or invasive rx (Circ 2004;110:1213; Jama 2003;289:1117). Pts > age 75 who had recurrent sx despite medical rx benefited from revascularization (Lancet 2001;358:951).
Functional status (BARI): Use of anti-ischemic medication was higher inpts post-PTCA than in those post-CABG. Amongpts who were angina-free at 5 yr, 52% ofpts who had PTCA required revascularization vs 6% ofpts who had CABG, but differences in angina-free rates betweenpts assigned to PTCA and CABG decreased from 73% vs 95% at 4-14 weeks to 79% vs 85% at 5 yr (Jama 1997;277:715).
CHF: Hx of CHF is associated with increased early and intermediate-term mortality inpts undergoing PTCA (J Am Coll Cardiol 1998;32:936).
Diabetes (BARI): Pts with diabetes have higher rates of revascularization and lower 1-yr survival rates than nondiabeticpts (J Am Coll Cardiol 2004;43:1348). The 5-yr cardiac mortality inpts with multivessel disease was greater after PTCA than CABG. No differences were found for the composite end point of cardiac mortality or MI between groups or for cardiac mortality in nondiabeticpts; a difference was found in diabeticpts on drug therapy (Circ 1997;96:2162). In diabetics, the better survival with CABG vs PTCA (5.8% vs 20.6%) was due to reduced cardiac mortality inpts receiving at least one LIMA graft (Circ 1997;96:1761). Pts with advanced 3-vessel CAD and IDDM should be revascularized by CABG. Diabeticpts (especially those taking oral hypoglycemic agents) with minimal multivessel disease could be considered for PTCA. Those with moderate ASHD, especiallypts requiring insulin, should be considered for surgery until the results of future trials are completed (Circ 1999;99:847).
Repeat surgery: In-hospital (11.5% vs 4.4%), 1-yr (19.3% vs 7.9%), and 3-yr mortality rates (28.8% vs 13.1%) after CABG were significantly higher inpts of age 80 yr compared with youngerpts. Although their initial surgical risk was high, octogenarians who underwent CABG had a long-term survival rate similar to that for the general U.S. octogenarian population (Circ 1995;92:85). The 10-yr patency for saphenous vein grafts is 61% vs 89% for LIMA grafts (J Am Coll Cardiol 2004;44:2149).
Risk factors: Treatment of HT according to Joint National Conference VI guidelines; smoking cessation therapy; management of diabetes and hyperlipidemia; exercise training programs; weight reduction in obesepts in the presence of HT, hyperlipidemia, or DM
Gemfibrozil produced a significant reduction in risk of major cardiovascular events inpts with CAD whose primary lipid abnormality was a low HDL cholesterol level (Nejm 1999;341:410).
Nicotine patches can also reduce the extent of exercise-induced myocardial ischemia as assessed by exercise Tl-201 SPECT (J Am Coll Cardiol 1997;30:125). All currently available nicotine replacement therapies appear to be equally efficacious, approximately doubling the quit rate compared with placebo. Concomitant behavioral rx increases quit rates, and combining the patch with nicotine gum or the patch with bupropion may increase the quit rate compared with any single rx (Jama 1999;81:72).
Under investigation: Folate supplementation, identification and appropriate treatment of clinical depression, and intervention directed at psychosocial stress reduction (J Am Coll Cardiol 1999;33: 2092; 1999;34:1262)
Inpts at high risk for cardiovascular events, rx with vitamin E had no apparent effect on cardiovascular outcomes (Nejm 2000;342:154).
In patients with angina refractory to medical rx and CAD that precluded CABG/PTCA, transmyocardial revascularization improved cardiac perfusion and clinical status over a 12-mon period (Nejm 1999;341:1021).
5.3 Acute Coronary Syndrome
(In older literature: Ustable angina and non-Q-wave MI)
Cause: Unstable angina results from an imbalance between myocardial O2 supply and demand. The most common cause is nonocclusive thrombus on a fissured or eroded nonocclusive plaque, but other causes include dynamic obstruction due to Prinzmetal angina (focal spasm of a segment of an epicardial coronary artery
with or without nonobstructive plaque); nonfocal constriction of arteries containing plaque that is caused by adrenergic stimuli, cold immersion, or cocaine; microcirculatory angina with constriction of small intramural coronary resistance vessels; progressive mechanical obstruction; inflammation and possibly infection; or extrinsic causes (eg, tachyarrhythmia, fever, thyrotoxicosis, hyperadrenergic states, HT or hypotension, aortic stenosis, anemia, hypoxemia).
with or without nonobstructive plaque); nonfocal constriction of arteries containing plaque that is caused by adrenergic stimuli, cold immersion, or cocaine; microcirculatory angina with constriction of small intramural coronary resistance vessels; progressive mechanical obstruction; inflammation and possibly infection; or extrinsic causes (eg, tachyarrhythmia, fever, thyrotoxicosis, hyperadrenergic states, HT or hypotension, aortic stenosis, anemia, hypoxemia).
Epidem: Similar to that for stable angina and AMI. In 1991, 570,000 hospitalizations for this principal diagnosis in the U.S. resulted in 3.1 million hospital days (AHCPR Pub 94-0602, 1994).
Elevated total homocysteine levels on admission predict late cardiac events in acute coronary syndromes (Circ 2000;102:605).
Pathophys: Inciting event is the rupture of an atherosclerotic plaque. Enzyme degradation and external mechanical shear forces in the artery rupture the fibrous cap and expose the underlying procoagulant atheromatous material. Macrophage deposition and infiltration ensue, with the release of enzymes resulting in digestion of the fibrous cap’s collagen and elastin. Cytokines enhance the plaque destabilization by inhibiting collagen synthesis. Circumferential stresses cause further plaque breakdown. The absence of Q waves is determined by the size of the infarct rather than the transmural extent (J Am Coll Cardiol 2004;44:554).
The ruptured plaque favors thrombus formation. Secretion of thromboxanes, serotonin, and other vasoactive substances promotes further platelet aggregation, and vasospasm contributes to both plaque rupture and thrombus formation.
Increasing severity of UA by Braunwald classification (see below) has been associated with increasing prevalence of thrombus, cellularity, atheroma, and neovasculature in plaque fragments (CV Res 1999;41:369).
Sx: Ischemic chest pain at rest, of new onset, or in a progressive pattern. Key elements: change in frequency, increase in severity or
duration of sx, occurrence of episodes lasting > 20 min, progression from effort or stress-related sx to sx at rest, new onset of nocturnal sx, decrease in amount of stress or effort necessary to provoke sx.
duration of sx, occurrence of episodes lasting > 20 min, progression from effort or stress-related sx to sx at rest, new onset of nocturnal sx, decrease in amount of stress or effort necessary to provoke sx.
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