The term coronary artery disease (CAD) is generally used to refer to a pathologic process affecting the coronary arteries (usually atherosclerosis).
Arterio (athero) sclerosis progressively blocks coronary arteries and their branches.
- Leading cause of death in the US and Europe
- Predominant sex: Male > Female
- Predominant age for peak clinical manifestations:
- Men: 50–60 years
- Women: 60–70 years
- In postmenopausal women, the risk for incident coronary disease is tripled compared with premenopausal women.
- Mortality from coronary heart disease (CHD) has fallen over the past four decades
- Framingham data suggest that the age-adjusted annual incidence for men aged 35–64 is 12 per 1,000 per year, and for women, 5 per 1,000 per year. For men >65, the incidence is 27 per 1,000 per year, and for women, 16 per 1,000 per year.
- For persons aged 40 years, the lifetime risk of developing CHD is 49% in men and 32% in women. For those reaching age 70 years, the lifetime risk is 35% in men and 24% in women.
The 2010 Heart Disease and Stroke Statistics update of the American Heart Association reported that 17.6 million persons in the US have CHD, including 8.5 million with myocardial infarction (MI) and 10.2 million with angina pectoris.
- Primary risk factors:
- Diabetes mellitus
- Male age >45; female >55
- Family history of premature CHD (1st-degree relative: Male <55 years; female <65 years)
- Blood pressure >140/90
- Active cigarette abuse
- High-density lipoprotein (HDL) cholesterol <40 mg/dL (HDL >60 mg/dL is a protective factor)
- Elevated low-density lipoprotein (LDL) cholesterol
- Secondary risk factors:
- Mild renal insufficiency
- Estrogen deficiency
- Depression and stress
Family history is an independent risk factor.
- Lifestyle changes are indicated when lifestyle-related factors (obesity, physical inactivity, increased triglycerides, decreased HDL, or metabolic syndrome are present), regardless of LDL.
- HDL has antiatherogenic properties.
- Atherosclerosis, inflammation, including autoimmunity
- Embolism compromising coronary arteries
- Subintimal atheromas in large and medium vessels
Commonly Associated Conditions
Cerebrovascular disease (ischemic stroke); peripheral arterial disease (claudication); aortic atherosclerosis (abdominal aortic aneurysm); metabolic syndrome
- Clinical manifestations:
- Substernal chest pain, diaphoresis, palpitations
- Exertional dyspnea
- Paroxysmal nocturnal dyspnea
- Cardiac arrhythmias
- Pedal edema/fluid overload
Advanced obstructive CHD can exist with minimal or no symptoms, and can progress rapidly.
Focus on stigmata of vascular disease and manifestations of heart failure.
Diagnostic Tests & Interpretation
- ECG: Variable; may be normal or may see ST-segment elevation/depression and/or T-wave inversion, or Q waves from old infarction. 10–20% of acute MI have initially normal ECG.
- Exercise ECG testing is the most commonly used noninvasive test because it is simple and inexpensive, but sensitivity no better than 60–70%. Specificity is much higher.
- Stress testing (exercise, pharmacologic), with or without radionuclide or ECG imaging
- Echocardiography using either exercise or pharmacologic (dobutamine or dipyridamole) stress.
- Radionuclide myocardial perfusion imaging using either exercise or pharmacologic stress improves sensitivity somewhat (70–80%).
- Positron emission tomography
- Coronary artery calcium as measured by electron beam and multidetector row computed tomography and histologic, ultrasonographic, and angiographic measures of coronary disease.
- Cardiac computed tomography angiography is an emerging technique for examining coronary anatomy noninvasively.
- Fasting lipid profile.
- hs-CRP may be useful as an independent marker of prognosis in patients with stable CHD or in ACS.
Follow-Up & Special Considerations
- Specific changes in diet may reduce serum CRP.
- Hormone replacement therapy raises serum CRP in postmenopausal women.
- Angiography: Narrowed coronary arteries
- Echocardiography: Possible wall-motion abnormalities
- Focal thickening of the intima with an increase in smooth muscle cells and extracellular matrix
- Accumulation of intracellular lipid deposits or extracellular lipids or both, which produce the fatty streak
- Development of fibrous plaques
- Advanced lesions become revascularized from both the luminal and medial aspects.
The use of aspirin for primary prevention is controversial because of the difficulty determining benefits and risk for a given individual. Benefits in terms of reduction in risk of stroke and MI must be balanced against risk of hemorrhage:
- AHA: For men with >10%, 10-year risk of symptomatic CHD (Framingham risk score) (AHA) (1), consider 75–160 mg aspirin per day. A risk calculator is available online at http://hp2010.nhlbihin.net/atpiii/calculator.asp
- Low-risk diabetics (those aged <50 years with 1 or fewer additional risk factors) may not benefit from aspirin (AHA/ADA) for primary prevention.
- For high-risk women, aspirin (75–160 mg/dl) should be used unless contraindicated (AHA) (2)[A]. If intolerant of aspirin, clopidogrel should be substituted (2)[B].
- Women aged ≥65 years: Consider aspirin therapy (81 mg daily or 100 mg every other day) if blood pressure is controlled and benefit for ischemic stroke and MI prevention likely to outweigh risk of gastrointestinal bleeding and hemorrhagic stroke (2)[B]. Stroke risk calculator available at http://www.westernstroke.org/personalstrokerisk1.xls
- Consider in most diabetics aged >50 years with one or more additional risk factors (cigarette smoking, hypertension, obesity, albuminuria, hyperlipidemia, or family history of CHD) (3)[C]. Recent trials failed to show a significant reduction in CVD end points (4).
- The 2009 USPTF statement on the use of aspirin for the prevention of cardiovascular disease:
- In women aged 55–79 years, when the potential benefit of a reduction in ischemic stroke outweighs the risk of an increase in gastrointestinal hemorrhage (5).
- In men aged 45–79, when the potential benefit of a reduction in the rate of MI outweighs the risk of an increase in gastrointestinal hemorrhage (6). This occurs with 10-year MI risk of 10–20% in patients with average risk of GI bleeding.
- Aspirin is recommended for secondary prevention of CVD after acute MI and unstable angina, occlusive stroke, transient ischemic attack, stable angina, and coronary artery bypass surgery to reduce risk of MI, stroke and vascular death (7)[A].
- In secondary prevention, the absolute benefit is large compared to the absolute risk of major bleeding.
- Primary prevention: Benefit depends more on overall risk than cholesterol levels
- Statins may reduce incidence of cardiovascular death, myocardial infarction and stroke in patients without cardiovascular disease, but number needed to treat is high and use is increasingly controversial, especially since it is not clear that statins decrease overall death in primary prevention (8)[B].
- WHO Cooperative Trial (clofibrate), Lipid Research Clinics Coronary Primary Prevention Trial (cholestyramine), and the Helsinki Heart Study (gemfibrozil) did not demonstrate a reduction in coronary mortality.
- The ASCOT-LLA trial (atorvastatin) did not show statistically significant reductions in cardiovascular mortality.
- Statins reduce mortality and myocardial infarction in adults with coronary heart disease (7) (SOR)[A].
- Lipid-lowering therapy (primarily with statins) is recommended for most patients with diabetes (SOR) (3)[A].
- For established CAD: Aspirin/ASA: 75–160 mg/day; clopidogrel 75 mg PO daily, if ASA is contraindicated.
- Angiotensin-converting enzyme (ACE) inhibitors in all with increased risk factors, diabetes mellitus (DM), or known CAD
- Beta blockers for post-MI patients
- Cholesterol-lowering agents:
- Data for mortality reduction best for HMG-CoA reductase inhibitor statins. Atorvastatin (10–80 mg PO once daily), initial dose 10–20 mg/d; fluvastatin (20–80 mg/d), initial dose 20–40 mg/dL; lovastatin (10–80 mg/d), initial dose 10–20 mg/dL; pravastatin (maintenance 10–80 mg/d), initial dose 40 mg/dL; simvastatin (20–40 mg once daily), maintenance 5–80 mg/dL; rosuvastatin (5–40 mg once daily), initial dose 10–20 mg/dL
- Statins also have anti-inflammatory and immunomodulatory effects, and effects on vascular tone and thrombogenicity.
- Average reduction % in LDL is dose-dependent: Atorvastatin 35–60%, fluvastatin 22–35%, lovastatin 21–42%; pravastatin 22–37%, rosuvastatin 45–63%, simvastatin 26–47%.
- Fish oil and other γ-3 acid ethyl esters: 3 standard fish oil capsules daily supply approximately 1 g of EPA + DHA.
- To increase HDL cholesterol (no proven benefit):
- Niacin: 2–6 g/d in divided doses
- Gemfibrozil: 600 mg 2 b.i.d.
- Fenofibrate: 67–200 mg/d
- Probucol: 500 mg 2 b.i.d.
- Colesevelam: 3.75–4.375 g/d
- Average reduction % in triglyceride from baseline:
- Bile acid sequestrant: Cholestyramine 11–28%; colesevelam (no effect); colestipol 12–15%
- Fibric acid: Fenofibrate 28.9%; gemfibrozil 31%; niacin E 16–31%, niacin IR 18%
- Statin: Baseline TG levels >250 mg/dl 35–45%; baseline TG levels <250 mg/dl><25%
- Average increase % in HDL from baseline:
- Bile-acid sequestrant: Cholestyramine 4–8%; coleselevam 3–8%; colestipol, no effect
- Ezetimibe 3.5%
- Fibric acid: fenofibrate 1%; gemfibrozil: 6%
- Niacin ER 20–40%; Niacin IR 17%
- Statins: 5–10%
Antiplatelet activity: Ticlopidine, dipyridamole, clopidogrel
- Known CHD or CHD-risk equivalent (10-year risk >20%) has a LDL-C goal <100 mg/dL
- Prevention of further disease progression:
- Smoking cessation, treatment of hypercholesterolemia (diet, drugs); increase HDL (diet, exercise); control of BP (<140/90; if DM or renal disease, <130/80); diabetes mellitus, exercise 30–40 minutes 5 times/week, moderate alcohol consumption, stress reduction, treatment of depression, diet changes, weight loss (body mass index <25).
For patients with type 2 diabetes taking statins, routine monitoring of liver function test or muscle enzymes is not recommended.
- Monitor lipid panel.
- Preventive programs (weight loss, smoking cessation, diabetes nutritional education)
- Low fat: 20–30 g/d, and eliminate or reduce trans fats
- Weight loss diet if obesity a problem
- Increase soluble fiber and plant stanols.
- Reduce consumption of red meat; increase fish, olive oil, and nuts.
- Individuals who consume a healthy diet have significantly lower risks of CVD, including both CHD and stroke:
American Heart Association, 7320 Greenville Avenue, Dallas, TX 75231, (214) 373-6300.
- In population studies, for every 10% reduction in serum cholesterol, CHD was reduced by 15%; and total mortality risk, by 11%
- The incidence of a MI is increased 6-fold in women and 3-fold in men who smoke at least 20 cigarettes per day.
- Current smoking was associated with a 50% increase in the progression of atherosclerosis versus nonsmokers.
- Ventricular fibrillation
- Angina pectoris
- Sudden cardiac death
1. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprenhensive Risk Reduction for Adult Patients Without Coronary of Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinated Committee. Circulation. 2002;106(3):388–91.
2. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007;115(11):1481–501.
3. Standards of Medical Care in diabetes. Diabetes Care. 2010;33(Suppl 1):S11–S61.
4. Belch J, MaqcCuish A, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomized placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:1840.
5. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Tasks Force recommendation statement. Ann Intern Med. 2009;150(6):396–404.
6. Wolff T, Miller T, Ko S. Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;150(6):405–10.
7. Becker RC, Meade T, et al. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.2008;133:776S.
8. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. 2008;52(22):1469–81.
Aspirin for the prevention of cardiovascular disease. U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(6):396–404.
Framingham risk estimates: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
See Also (Topic, Algorithm, Electronic Media Element)
Angina; Atherosclerosis; Myocardial Infarction, ST-Segment Elevation (STEMI)
Algorithm: Chest_Pain/Acute Coronary Syndrome
414.00 Coronary atherosclerosis of unspecified type of vessel, native or graft
53741008 Coronary arteriosclerosis (disorder)
- Net benefit of aspirin increases with increasing cardiovascular risk.
- Insufficient evidence to recommend for or against aspirin for low-risk patients.
- Aspirin significantly reduced the relative risk of subsequent vascular events (nonfatal MI, nonfatal stroke, and vascular death) by approximately 22%.
- The CHD death rate increases at higher plasma concentrations of total and LDL-cholesterol, and statins for patients with known CAD reduce morbidity and mortality.