Overview of Coronary Artery Disease

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 cause ischemia varies with oxygen demand.

Occasionally, an atheromatous plaque ruptures or splits. Reasons are unclear but probably relate to plaque morphology, plaque calcium content, and plaque softening due to an inflammatory process. Rupture exposes collagen and other thrombogenic material, which activate platelets and the coagulation cascade (see figure Pathways in Blood Coagulation), 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, non–ST-segment elevation myocardial infarction (NSTEMI), to ST-segment elevation myocardial infarction (STEMI), which can result in transmural infarction, and other complications including malignant ventricular arrhythmias, conduction defects, heart failure, and sudden death.

Coronary artery spasm is a transient, focal increase in vascular tone, markedly narrowing the lumen and reducing blood flow; symptomatic ischemia (vasospastic 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 endothelial cell abnormalities of nitric oxide production or an imbalance between endothelium-derived contracting and relaxing factors.

• In arteries with atheroma, the atheroma causes endothelial dysfunction, possibly resulting in 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 substances (eg, cocaine, nicotine) and emotional stress also can trigger coronary spasm.

Coronary artery dissection is a rare, non-traumatic tear in the coronary intima with creation of a false lumen. Blood flowing through the false lumen expands it, which restricts blood flow through the true lumen sometimes causing coronary ischemia or infarction. Dissection may occur in atherosclerotic or non-atherosclerotic coronary arteries. Non-atherosclerotic dissection is more likely in pregnant or postpartum females and/or patients with fibromuscular dysplasia or other connective tissue disorders.

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4. 4. Ridker PM, Lei L, Louie MJ, et al. Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance. Circulation 2024;149(1):28-35. doi:10.1161/CIRCULATIONAHA.123.066213

(See also Medications for Acute Coronary Syndromes.)

Medical management of patients with CAD depends on symptoms, cardiac function, and the presence of other disorders. Recommended therapy includes

• Antiplatelet agents to prevent thrombus formation

• Statins to lower LDL cholesterol levels

• Beta-blockers to reduce symptoms of angina

Antiplatelet agents and statins improve short-term and long-term outcomes, probably by improving atheromatous plaque stability and endothelial function.

Beta-blockers reduce symptoms of angina by reducing heart rate and contractility and decreasing myocardial oxygen demand. Beta-blockers also reduce mortality post-infarction, especially in the presence of post-myocardial infarction (MI) LV dysfunction.

Calcium channel blockers are also helpful. They often are combined with beta-blockers in managing angina and hypertension but have not been proven to reduce mortality.

Nitrates modestly dilate coronary arteries and decrease venous return, decreasing cardiac work and relieving angina quickly. Longer acting nitrate formulations help decrease angina events but do not decrease mortality.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are most effective at reducing mortality post MI in CAD patients with LV dysfunction (1, 2).

Little evidence exists to guide therapy for patients with endothelial dysfunction. Treatment is generally similar to that for typical large-vessel atherosclerosis, and some evidence suggests that use of beta-blockers may enhance endothelial function (3).

(See Percutaneous Coronary Interventions.)

PCI is indicated for patients with acute coronary syndrome (ACS) or with stable ischemic heart disease who have angina despite optimal medical therapy.

Drug-eluting stents, which release an antiproliferative drug (eg, everolimus, zotarolimus) over a period of several weeks, have reduced the rate of restenosis lower than the rate with bare metal stents, to < 10% (4). Most PCI is done with stents, and most stents used in the United States are drug-eluting.

Patients without significant infarct or complications may return to work and usual activities usually within a few days after stent placement. However, cardiac rehabilitation is recommended for all patients.

In-stent thrombosis occurs because of the inherent thrombogenicity of metallic stents. Most cases occur within the first 24 to 48 hours. However, late stent thrombosis, occurring after 30 days and as late as ≥ 1 year (rarely), 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 released by drug-eluting stents inhibit this process and prolong the risk of thrombosis. Thus, patients who undergo stent placement are treated with various antiplatelet agents. The current standard regimen for patients with a bare-metal or drug-eluting stent consists of all of the following (5):

• Intraprocedural anticoagulation with heparin or a similar agent (eg, bivalirudin, particularly for those at high risk of bleeding)

• Aspirin given indefinitely

• Clopidogrel, prasugrel, or ticagrelor for at least 3 months and up to 12 months

Angioplasty Stent

Image

The best results are obtained when the newer antiplatelet agents (eg, ticagrelor or clopidogrel) are begun before the procedure.

Glycoprotein IIb/IIIa inhibitors are not routinely used in stable patients (ie, no comorbidities, no acute coronary syndrome) having elective stent placement. They may be beneficial in some patients with an acute coronary syndrome but should not be considered routine. It is unclear whether it is beneficial to give glycoprotein IIb/IIIa inhibitors before arrival in the cardiac catheterization laboratory, but most national organizations do not recommend their use in this situation (5).

A statin is started after stent insertion, if one is not already being used because PCI by itself does not cure or prevent the progression of CAD. Statin therapy has been shown to improve long-term event-free survival (6). Patients who receive a statin before the procedure have a lower risk of periprocedural MI.

Overall, risks of undergoing PCI are comparable to those of CABG. Overall mortality rate is < 1%, but varies based on individual risk factors and tends to be similar to that of CABG; Q wave MI rate is < 1%. In < 1% of patients, intimal dissection causes obstruction requiring emergency CABG. Risk of stroke with PCI is lower than with CABG. A meta-analysis of 19 randomized trials reported a higher risk of stroke in patients undergoing CABG (1.2%) than PCI (0.34%,) at 30 days (7). Risk of bleeding is 1 to 2%.

(See Coronary Artery Bypass Grafting.)

CABG uses arteries (eg, internal mammary, radial) whenever possible, and if necessary, sections of autologous veins (eg, saphenous) to bypass diseased segments of the coronary arteries. At 1 year, about 85% of venous bypass grafts are patent, and after 5 years, one third or more are completely blocked. However, after 10 years, as many as 97% of internal mammary artery grafts are patent (8). Arteries also hypertrophy to accommodate increased flow. CABG is superior to PCI in patients with diabetes and in patients with multivessel disease amenable to grafting.

Coronary artery bypass grafting is typically done 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, 1 to 2% for stroke, and ≤ 1% for mortality; risk increases with age, poor LV function, and presence of underlying disease. Operative mortality rate is 3 to 5 times higher for a second bypass than for the first.

After cardiopulmonary bypass, about 25 to 30% of patients develop cognitive dysfunction or behavioral changes, possibly caused by microemboli originating in the bypass machine (9). Cognitive or behavioral changes are more prevalent in older patients, prompting suspicion that these changes are most likely due to diminished "neuronal reserve," making older patients more susceptible to minor injuries incurred during cardiopulmonary bypass. Dysfunction ranges from mild to severe and may persist for weeks to years. To minimize this risk, some centers use a beating heart technique (off-pump CABG, which uses no cardiopulmonary bypass), in which a device mechanically stabilizes the part of the heart upon which the surgeon is working. However, long-term studies have failed to demonstrate lasting benefits of this approach in comparison to conventional on-pump CABG.

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. After CABG, a statin should be started or continued at maximally tolerated doses.

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3. 3. Peller M, Ozierański K, Balsam P, Grabowski M, Filipiak KJ, Opolski G. Influence of beta-blockers on endothelial function: A meta-analysis of randomized controlled trials. Cardiol J 2015;22(6):708-716. doi:10.5603/CJ.a2015.0042

4. 4. Bønaa KH, Mannsverk J, Wiseth R, et al. Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease. N Engl J Med 2016;375(13):1242-1252. doi:10.1056/NEJMoa1607991

5. 5. Writing Committee Members, Lawton JS, Tamis-Holland JE, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol 2022 Apr 19;79(15):1547]. J Am Coll Cardiol 2022;79(2):e21-e129. doi:10.1016/j.jacc.2021.09.006

6. 6. Grundy SM, Stone NJ, Bailey AL, et al: 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Circulation 2019 Jun 18;139(25):e1182-e1186] [published correction appears in Circulation 2023 Aug 15;148(7):e5]. Circulation 139(25):e1082–e1143, 2019. doi:10.1161/CIR.0000000000000625

7. 7. Palmerini T, Biondi-Zoccai G, Reggiani LB, et al: Risk of stroke with coronary artery bypass graft surgery compared with percutaneous coronary intervention. J Am Coll Cardiol 60(9):798–805, 2012. doi:10.1016/j.jacc.2011.10.912

8. 8. Hillis LD, Smith PK, Anderson JL, et al: 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation 2011 Dec 20;124(25):e957]. Circulation 124(23):e652–e735, 2011. doi:10.1161/CIR.0b013e31823c074e

9. 9. Kulik A, Ruel M, Jneid H, et al: Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American Heart Association. Circulation 131(10):927–964, 2015. doi:10.1161/CIR.0000000000000182

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2. 2. Whelton PB, Carey RM, Aronow WS, et al: ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 71:e127–e248, 2018. doi: 10.1161/HYP.0000000000000066

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4. 4. US Preventive Services Task Force, Davidson KW, Barry MJ, et al: Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA 327(16):1577–1584, 2022. doi:10.1001/jama.2022.4983