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coronary artery disease; coronary atherosclerosis (CAD)

Atherosclerotic narrowing of the major epicardial coronary arteries. (A number of disease processes other than atherosclerosis can involve coronary arteries.) Etiology: (Risk factors)* 1) male age > 45 years 2) female age > 55 years 3) estrogen deficiency 4) elevated LDL cholesterol (> 160 mg/dL) 5) low HDL cholesterol (< 35 mg/dL) 6) smoking 7) hypertension 8) elevated homocysteine 9) elevated insulin 10) diabetes mellitus - much greater risk factor than hypertension or dyslipidemia [2] 11) non-coronary athersclerosis [4] 12) elevated C-reactive protein 13) sleep deprivation may play role [16] 14) radiation therapy to the thorax (Hodgkin's disease) [2] * also see cardiac risk factor Epidemiology: - declining rate of death from coronary artery disease due to primary prevention [10], secondary prevention [19] & in coronary care [19] - identified in 34% of mummies from 4 geographical regions, including ancient Egypt & Peru [24] - Tsimane, an indigenous group living a pre-industrial lifestyle in the Bolivian Amazon with low incidence of coronary artery disease [50] Pathology: - atherosclerosis with occlusion of coronary arteries - anatomic burden (degree of coronary artery occlusion) & LVEF better predict outcomes than ischemic burden (measured during stress testing) or initial treatment (medical therapy vs PCI) [29] - increased plasma levels of trimethylamine N-oxide associated with increased mortality in patients with stable CAD [45] - inflammation contributes to both the formation of arterial plaques & their destabilization [54] Genetics: - most cases NOT genetically determined [12] - implicated genes: TERT, ITGA2, ZC3H12A Laboratory: - lipid panel - coronary artery disease 23 mRNA expression analysis [43] - gene expression model not yet useful [17] - see ARUP consult [21] Special laboratory: 1) exercise tolerance testing* 2) dobutamine stress echocardiography* 3) 6 minute walk [20] 4) other tests may be useful a) exercise stress echocardiography b) dobutamine myocardial perfusion study c) coronary angiography - fractional flow reserve measurement during coronary angiography is superior to angiography alone for guiding percutaneous coronary intervention (PCI) in patients with severe but stable CAD [33] 3) insufficient evidence to recommend for or against screening in higher-risk patients [6] - routine screening in asymptomatic patients with diabetes mellitus does not reduce mortality [2] * see stress testing & imaging findings associated with poor prognosis # overall costs similar with imaging vs functional testing in patients with stable chest pain [40] Radiology: - cardiac CT angiography* may be best initial test [65] - other potentially useful tests a) coronary angiography b) cardiac magnetic resonance imaging* c) coronary artery calcium d) adenosine positron emission tomography e) myocardial perfusion study - myocardial perfusion scintigraphy - myocardial perfusion imaging with SPECT [31] - single-photon emission CT myocardial perfusion imaging (SPECT-MPI) * positive cardiac CT angiography in women more predictive of adverse cardiovascular events than in men [38] * cardiac CT angiography associated with lower risk for myocardial infarction but not mortality compared with exercise stress testing [54] * perivascular fat attenuation index measured with cardiac CT angiography may be useful for assessing coronary artery inflammation [54] * associated with fewer angiograms (RR=0.23) & revascularizations (RR=0.71), but similar rates of myocardial infarction (MI) & cardiovascular(CV)-related death, than direct referral for angiography [65] * cardiac CT angiography associated with fewer MI & CV-related deaths than exercise electrocardiography (RR=0.66) or SPECT-MPI (RR=0.64) but was associated with more revascularizations secondary to the index text than was exercise electrocardiography (RR=1.78) [65] * cardiac magnetic resonance imaging with better diagnostic accuracy than myocardial perfusion imaging with SPECT [39] * cardiac magnetic resonance imaging & myocardial perfusion scintigraphy may avoid unnecessary coronary angiography [42] Complications: - myocardial infarction (MI) - the majority of myocardial infarctions are associated with non-obstructive coronary artery disease [34] - extensive or obstructive subclinical atherosclerosis is associated with excess risk for myocardial infarction [63] - risk highest with extensive obstructive disease (RR=12) & obstructive but not extensive disease (RR=8) [63] - combined endpoint of death & MI more common among participants with extensive disease (RR=3) regardless of obstructive status [63] - fluctuations in body weight associated with increased risk of cardiovascular events in patients with CAD [51] - high & low systolic blood pressure (> 140 mm Hg or < 120 mm Hg) & high & low diastolic blood pressure (> 80 mm Hg or < 70 mm Hg) associated with increased cardiovascular risk in patients with stable coronary artery disease [44] - no increase in risk of stroke with low blood pressure - cognitive impairment - cognitive decline similar with CABG vs medical management [15] - cardiopulmonary bypass pump not a factor [32] - patients with LV ejection fraction > 50% more likely to die of cause other than sudden cardiac death due to arrhythmia [57] Management: 1) pharmacologic agents a) antihypertensive agents - goals - target BP of 140/90 mm Hg AHA/ACC/ASH [36], but may be lower in some patients [36] - target BP < 130/80 (AHA) [2] - avoid lowering diastolic BP < 70 mm Hg [2], < 60 mm Hg [36] - antihypertensives may benefit patients with normal BP (CAMELOT trial) - beta-blocker for HFrEF or angina pectoris [66] - target heart rate 55-60/min & ~75% of heart rate that produces angina pectoris on exertion [2] - does not reduce risk of cardiovascular events [22] - except after myocardial infarction - reduce risk of myocardial infarction, HF hospitalization & mortality [68] - nitrates - reduction in angina - increase in exercise tolerance - do not affect prognosis [68] - Ca+2 channel blockers - reactive airway disease intolerant to beta-blockers - brittle diabetic with episodes of severe hypoglycemia - patients in whom beta-blockers cause intolerable fatigue or depression - symptomatic relief only [68] - renin-angiotensin system inhibitors (ACE inhibitors/ARBs) - in patients with impaired left-ventricular function (LVEF < 35%) - may be beneficial for all patients with CAD (see EUROPA trial) - no added benefit for low-risk patients (PEACE trial) - no convincing evidence of benefit in patients with stable coronary artery disease without heart failure [58] b) antiplatelet agent(s) - aspirin 81-325 mg QD or 325 mg QOD may risk of cardiovascular events risk of cardiovascular events - reduces risk of myocardial infarction, ischemic stroke & mortality [68] - reduces risk of cardiac stent thrombosis [68] - P2Y12 inhibitors (clopidogrel) for aspirin failure - reduce risk of myocardial infarction, ischemic stroke & mortality [68] - reduce risk of cardiac stent thrombosis [68] - Aggrenox - addition of aspirin to warfarin may not reduce risk of myocardial infarction in patients with coronary artery disease [35] - no data after cororary revascularization - aspirin 100 mg QD + rivaroxaban 2.5 mg BID reduces risk of cardiovascular events (4.1% vs 5.4% for aspirin alone) [52] c) lipid-lowering agents (statins) - high-intensity statin (all patients <= 75 years of age) - reduce risk of myocardial infarction, ischemic stroke & mortality [68] - ezetimibe 10 plus moderate intensity statin (10 mg rosuvastatin) may be alternative in patients intolerant of high intensity statin [67] - add ezetimibe 10 mg or PCSK9 inhibitor to high intensity statin to achieve LDL cholesterol < 70 mg/dL [66] - MKSAP favors ezetimibe over PCSK9 inhibitor - ezetimibe reduces risk of myocardial infarction & ischemic stroke [68] - does not reduce mortality [68] - goal of LDL cholesterol < 100 mg/dL & < 70 mg/dL in high-risk patients [8] - intensive lipid-lowering therapy of LDL cholesterol to < 70 mg/dL slows atherosclerotic plaque progression assessed by CT angiography [46] - treat-to-target LDL cholesterol strategy of 50-70 mg/dL as the goal is noninferior to a high-intensity statin therapy for 3-year composite of death, myocardial infarction, stroke, or coronary revascularization [62] - intensive lipid-lowering therapy to very low LDL cholesterol levels is not associated with diminished mortality [47,48] - statin use associated with transformation of coronary atherosclerosis toward high-density calcification & slower plaque progression [61] d) SGLT-2 inhibitors for patients with diabetes mellitus type 2 or HFrEF [66] e) colchicine 0.5 mg/day FDA approved - may lower risk of cardiovascular events [60] at the cost of increased mortality - reduces cardiovascular mortality [64] f) ranolazine if other options exhausted [2] - symptomatic relief only [68] 2) revascularization procedures a) indications - impaired left ventricular function with > 50% stenosis in a major coronary vessel with evidence of myocardial viability in areas or reduced wall motion (by stress MIBI) - improves 10 year survival in patients with severe LV dysfunction [2] - normal left ventricular function with left main, 3 vessel or severe 2 vessel coronary disease - left main or multivessel disease with involvement of proximal left anterior descending artery & LV systolic dysfunction [2] - age is NOT a contraindication - revascularization improves morbidity & mortality at 6 months in patients > 75 years of age [5] - optimize medical therapy prior to consideration of revascularization [2] b) percutaneous coronary intervention (PCI) - improves symptoms of stable angina [2] - 5 year relief of angina with PCI somewhat < with CABG - does not improve survival or reduce future cardiovascular events [2] - stenting diminishes restenosis - may be preferable to CABG even in patients with diabetes [2] - for percutaneous coronary intervention in patients anticoagulated for atrial fibrillation or venous thromboembolism, dual antiplatelet therapy is recommended for only 1-4 weeks, followed by clopidogrel for 6 months [66] c) coronary artery bypass graft (CABG) - CABG comparable to PTCA except in diabetics - CABG preferable to PTCA in diabetics - preferable to PCI in patients with multi-vessel disease [2] d) see Bypass Angioplasty Revascularization Investivation (BARI) e) outcomes for PCI with coronary stenting similar to CABG for left main coronary artery disease [14] f) cardiac rehabilitation after revascularization or mypcardial infarction [66] 3) life style - a healthy life style can mitigate genetic risk factors [49] - Mediterranean diet is recommended to improve cardiovascular outcomes [66] - supplements including omega-3 fatty acids; vitamins A, C, D, or E; & calcium are not recommended to reduce cardiovascular risk [66] - exercise superior to angioplasty in patients with stable coronary artery disease - patients with highest level of activity with lowest 4 year mortality [55] 4) angioplasty with stenting no better than optimal medical therapy for coronary artery disease [13,59] with or without CKD 5) anemia - restrictive strategy for RBC transfusion - erythropoiesis-stimulating agent not recommended [28] 6) chelation therapy not recommended [23] (2014 ACC/AHA...) 7) see screening for coronary artery disease Notes: - lipid-lowering for secondary prevention in patients with cardiovascular disease much more effective than for primary prevention [2] - optimal medical therapy underutilized [18] - comprehensive guidelines for diagnosis & management of ischemic heart disease, including algorythms [23]

Interactions

disease interactions

Related

acute coronary syndrome; unstable angina (ACS) cardiovascular risk factor chronic stable angina coronary artery coronary stent/coronary stenting coronary syndrome X (microvascular angina) factors associated with poor prognosis in patients with CAD secondary prevention in patients with cardiovascular disease

Specific

angina & no obstructive coronary artery disease (ANOCA) angiographically significant coronary artery disease (CAD) coronary artery stenosis coronary thrombus inherited form of coronary artery disease left main coronary artery disease multivessel disease post cardiac transplant coronary artery disease Wellens' syndrome

General

atherosclerosis chronic heart disease coronary heart disease (CHD)

References

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