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Coronary artery
disease involves impairment of blood flow through the coronary arteries,
most commonly by atheromas. Clinical presentations include silent
ischemia, angina pectoris, acute coronary syndromes (unstable angina,
MI), and sudden cardiac death. Diagnosis is by symptoms, ECG, stress
testing, and sometimes coronary angiography. Prevention consists
of modifying reversible risk factors (eg, hypercholesterolemia, hypertension,
physical inactivity, obesity, and smoking). Treatment includes drugs
and procedures to reduce ischemia and restore or improve coronary
blood flow.
In developed countries, coronary artery disease (CAD) is the leading cause of death in both sexes, accounting for about 1⁄3 of all deaths. Mortality rate among white men is about 1/10,000 at ages 25 to 34 and nearly 1/100 at ages 55 to 64. Mortality rate among white men aged 35 to 44 is 6.1 times that among age-matched white women. For unknown reasons, the sex difference is less marked in nonwhites. Mortality rate among women increases after menopause and, by age 75, equals or even exceeds that of men.
Etiology
Usually, CAD is due to subintimal deposition of atheromas in large and medium-sized coronary arteries (atherosclerosis—see Arteriosclerosis). Less often, CAD is due to coronary spasm. Rare causes include coronary artery embolism, dissection, aneurysm (eg, in Kawasaki disease), and vasculitis (eg, in SLE, syphilis).
Pathophysiology
Coronary atherosclerosis is often irregularly distributed in different vessels but typically occurs at points of turbulence (eg, vessel bifurcations). As the atheromatous plaque grows, the arterial lumen progressively narrows, resulting in ischemia (often causing angina pectoris). The degree of stenosis required to produce ischemia varies with O2 demand.
Occasionally, an atheromatous plaque ruptures or splits. Reasons are unclear but probably relate to plaque morphology, plaque Ca content, and plaque softening due to an inflammatory process. Rupture exposes collagen and other thrombogenic material, which activates platelets and the coagulation cascade, resulting in an acute thrombus, which interrupts coronary blood flow and causes some degree of myocardial ischemia. The consequences of acute ischemia, collectively referred to as acute coronary syndromes (ACS), depend on the location and degree of obstruction and range from unstable angina to transmural infarction.
Coronary
artery spasm is a transient, focal increase in vascular tone, markedly narrowing the lumen and reducing blood flow; symptomatic ischemia (variant angina—see Coronary Artery Disease: Variant Angina) may result. Marked narrowing can trigger thrombus formation, causing infarction or life-threatening arrhythmia. Spasm can occur in arteries with or without atheroma. In arteries without atheroma, basal coronary artery tone is probably increased, and response to vasoconstricting stimuli is probably exaggerated. The exact mechanism is unclear but may involve abnormalities of nitric oxide production or an imbalance between endothelium-derived contracting and relaxing factors. In arteries with atheroma, the atheroma may cause local hypercontractility; proposed mechanisms include loss of sensitivity to intrinsic vasodilators (eg, acetylcholine) and increased production of vasoconstrictors (eg, angiotensin II, endothelin, leukotrienes, serotonin, thromboxane) in the area of the atheroma. Recurrent spasm may damage the intima, leading to atheroma formation. Use of vasoconstricting drugs (eg, cocaine, nicotine) and emotional stress also can trigger coronary spasm.
Risk
Factors
Risk factors for CAD are the same as those for atherosclerosis: high blood levels of low density lipoprotein (LDL) cholesterol and lipoprotein a, low blood levels of high-density lipoprotein (HDL) cholesterol, diabetes mellitus (particularly type 2), smoking, obesity, and physical inactivity. Smoking may be a stronger predictor of MI in women (especially those < 45). Genetic factors play a role, and several systemic disorders (eg, hypertension, hypothyroidism) and metabolic disorders (eg, hyperhomocysteinemia) contribute to risk. A high level of apoprotein B (apo B) is an important risk factor; it may identify increased risk when total cholesterol or LDL level is normal.
High blood levels of C-reactive protein indicate plaque instability and inflammation and may be a stronger predictor of risk of ischemic events than high levels of LDL. High blood levels of triglycerides and insulin (reflecting insulin resistance) may be risk factors, but data are less clear. CAD risk is increased by smoking; a diet high in fat and calories and low in phytochemicals (found in fruits and vegetables), fiber, and vitamins C and E; a diet relatively low in ω-3 (n-3) polyunsaturated fatty acids (PUFAs), at least in some people; and poor stress management.
Anatomy
The right and left coronary arteries arise from the right and left coronary sinuses in the root of the aorta just above the aortic valve orifice. The coronary arteries divide into large and medium-sized arteries that run along the heart's surface (epicardial coronary arteries) and subsequently send smaller arterioles into the myocardium. The left coronary artery begins as the left main artery and quickly divides into the left anterior descending (LAD) and circumflex arteries. The LAD artery usually follows the anterior interventricular groove and, in some people, continues over the apex. This artery supplies the anterior septum (including the proximal conduction system) and anterior free wall of the left ventricle (LV). The circumflex artery, which is usually smaller than the LAD artery, supplies the lateral LV free wall. Most people have right dominance: The right coronary artery passes along the atrioventricular (AV) groove over the right side of the heart; it supplies the sinus node (in 55%), right ventricle, and usually the AV node and inferior myocardial wall. About 10 to 15% of people have left dominance: The circumflex artery is larger and continues along the posterior AV groove to supply the posterior wall and AV node.
Treatment
Treatment generally aims to reduce cardiac workload, improve coronary artery blood flow, and, over the long term, halt and reverse the atherosclerotic process. Coronary blood flow can be improved by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). An acute coronary thrombosis may sometimes be dissolved by fibrinolytic drugs (see Coronary Artery Disease: Fibrinolytics).
PCI:
At first, PCI was performed with balloon angioplasty alone. However, roughly 50% of patients developed restenosis within 6 mo, and 1 in 3 ultimately required repeat angioplasty or CABG. Insertion of a bare-metal stent following angioplasty reduced the rate of restenosis, but many patients still required repeat treatment. Drug-eluting stents, which secrete an antiproliferative drug (eg, sirolimus , paclitaxel ) over a period of several weeks, have reduced the rate of restenosis to about 10%. Now, most PCI is done with stents, and about ¾ of all stents used in the US are drug-eluting stents. With the recent controversy over drug-eluting stents and abrupt restenosis, use of the new drug-eluting stents appears to be decreasing in most centers. Patients with acute stenoses (ie, with unstable angina or acute MI) seem to do better with bare-metal stents. Patients without significant infarct or complication may quickly return to work and usual activities, but strenuous activities should be avoided for 6 wk.
In-stent thrombosis occurs because of the inherent thrombogenicity of metallic stents. Most cases occur within the first 24 to 48 h. However, late stent thrombosis, occurring after 30 days and as late as ≥ 1 yr, can occur with both bare-metal and drug-eluting stents, especially after cessation of antiplatelet therapy. Progressive endothelialization of the bare-metal stent occurs within the first few months and reduces the risk of thrombosis. However, the antiproliferative drugs secreted by drug-eluting stents inhibit this process and prolong the risk of thrombosis. Thus, patients who undergo stent placement are treated with various antiplatelet drugs and anticoagulants (see Coronary Artery Disease: Antiplatelet drugs). The current standard regimen consists of aspirin given indefinitely, clopidogrel given for a variable period (1 mo for bare-metal stents and at least 12 mo for drug-eluting stents), glycoprotein IIb/IIIa inhibitors begun as early as possible after presentation and continued for 18 to 24 h after stent placement, and intraprocedural anticoagulation with heparin or a similar agent. After stent insertion, a HMG-CoA reductase inhibitor (statin) is added if one is not already being used.
Overall risk of PCI is comparable with that for CABG. Mortality rate is 1 to 3%; MI rate is 3 to 5%. In < 3%, intimal dissection causes obstruction requiring emergency CABG.
CABG:
CABG uses sections of autologous veins (eg, saphenous) or, preferably, arteries (eg, internal mammary, radial) to bypass diseased segments. At 1 yr, about 85% of venous bypass grafts are patent, but after 10 yr, as many as 97% of internal mammary artery grafts are patent. Arteries also hypertrophy to accommodate increased flow.
CABG is typically performed during cardiopulmonary bypass with the heart stopped; a bypass machine pumps and oxygenates blood. Risks of the procedure include stroke and MI. For patients with a normal-sized heart, no history of MI, good ventricular function, and no additional risk factors, risk is < 5% for perioperative MI, 2 to 3% for stroke, and ≤ 1% for mortality; risk increases with age and presence of underlying disease. Operative mortality rate is 3 to 5 times higher for a second bypass than for the first; thus, timing of the first bypass should be optimal.
After cardiopulmonary bypass, about 25 to 30% of patients develop cognitive dysfunction, possibly caused by microemboli originating in the bypass machine. Dysfunction ranges from mild to severe and may persist for weeks to years. To minimize this risk, some centers use a beating heart technique (ie, no cardiopulmonary bypass), in which a device mechanically stabilizes the part of the heart upon which the surgeon is working.
CAD may progress despite bypass surgery. Postoperatively, the rate of proximal obstruction of bypassed vessels increases. Vein grafts become obstructed early if thrombi form and later (several years) if atherosclerosis causes slow degeneration of the intima and media. Aspirin prolongs vein graft patency. Continued smoking has a profound adverse effect on patency.
Prevention
Prevention of CAD involves modifying atherosclerosis risk factors (see Arteriosclerosis: Treatment): smoking cessation, weight loss, a healthful diet, regular exercise, modification of serum lipids, and control of hypertension and diabetes. Antihypertensives should be used to achieve a goal blood pressure of < 130/80 mm Hg. Modification of serum lipids (particularly with statins) may slow or even partially reverse the progression of CAD. LDL targets are < 100 mg/dL (< 2.59 mmol/L) for those with known CAD or 70 to 80 mg/dL (1.81 to 2.07 mmol/L) for those with a history of ischemic event. Nicotinic acid or a fibrate should be added for those with an HDL < 40 mg/dL (< 1.03 mmol/L).
Last full review/revision December 2007 by James Wayne Warnica, MD
Content last modified December 2007
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