Overview and Risk Factors
Coronary heart disease (CHD) is the most common cause of death for both men and women in Western countries and is increasingly prevalent in developing countries. Also called coronary artery disease, this atherosclerotic process includes injury to arterial endothelium, fatty streaks due to macrophage ingestion of LDL cholesterol at the damaged site, platelet aggregation, and fibrosis. These events contribute to plaque formation in the intimal layer of medium and large arteries. Progressive arterial narrowing causes ischemia, which occurs initially with exertion, but may eventually occur at rest.
Atherosclerosis normally begins in childhood and slowly progresses throughout life. However, rapid progression may occur by the third decade of life. Symptoms often do not present until late stages. Angina pectoris is frequently the main presenting symptom. It results from ischemia due to the narrowing of one or more coronary arteries. Angina is typically described as substernal pressure, and it can radiate to the neck, arms, back, and upper abdomen. Stable angina tends to occur regularly or predictably with exertion, whereas unstable angina occurs unpredictably, often with minimal exertion or at rest.
When atherosclerotic plaques rupture, vasoconstriction and clot formation can lead to complete occlusion of a coronary artery, causing myocardial infarction (MI). MI may be silent, or it may be signaled by prolonged pain or discomfort similar to that associated with simple angina. Compared with men (who are more likely to experience crushing substernal chest pain), women are more likely to experience shortness of breath, jaw or back pain, and nausea/vomiting. Further, care is sometimes delayed for women because caregivers and patients may believe that women are not at significant risk for cardiac disease.
Atherosclerosis of the extremities -ie, peripheral vascular disease- often presents as claudication, in which calf, thigh, or hip pain is associated with activity and relieved with rest. Other signs of peripheral vascular disease include underdeveloped calf muscles, hairless shiny skin on the lower extremities, dystrophic toenails, bruits over the femoral, iliac, or popliteal arteries, and decreased peripheral pulses.
- Increasing age.
- Male gender.
- Family history.
- Cigarette smoking.
- Sedentary lifestyle.
In addition, psychological stress and socioeconomic status have been correlated with CHD risk, perhaps because they contribute to other risk factors.
Diagnosis of atherosclerosis and CHD is based on knowledge of a patient's individual risk factors, along with a careful medical history, physical exam, and diagnostic tests.
No blood test can definitively diagnose atherosclerosis. However, epidemiological studies have found fibrinogen,1 white blood cell counts,2 cholesterol, C-reactive protein, and homocysteine concentrations associated with plaque formation and heart disease risk. For MI, a number of laboratory tests are available, but none is completely sensitive or specific. Correlation with patient symptoms, electrocardiograms, and angiographic studies is crucial.
Creatine kinase-MB fraction (CK-MB). CK-MB is a specific marker for acute myocardial injury. The serum concentration rises within 2 to 8 hours of the onset of acute MI. Serial measurements every 2 to 4 hours (for about 12 hours) help determine the extent and time frame of myocardial injury. CK-MB is also useful for the determination of reinfarction, or extension of myocardial injury. Concentrations normally decrease after 1 to 3 days, so subsequent elevations or plateaus indicate another myocardial infarction.
Troponins. These are proteins that combine with calcium to facilitate cardiac muscle cell contraction through actin-myosin interaction. Troponins are released into the bloodstream during myocardial injury. Troponin T lacks specificity for myocardial injury, because it is also present in skeletal muscle cells. Troponin I is more specific for myocardial injury than troponin T or CK-MB.
Levels of both tropinin I and CK-MB increase during the early course of a myocardial infarction. Because troponin I remains elevated for 5 to 14 days, it has greater sensitivity than CK-MB and LDH as a marker for diagnosing recent MI. However, this prolonged elevation may mask reinfarction or extension of infarction in the early days after an initial event.
Cholesterol. Elevated total and low-density lipoprotein (LDL) cholesterol concentrations, and low high-density lipoprotein (HDL) cholesterol concentrations (less than 50 mg/dL in women and 40 mg/dL in men), increase the risks for atherosclerosis and CHD events. Although the National Cholesterol Education Program defines elevated total cholesterol concentration as above 200 mg/dl and elevated LDL cholesterol concentration as above 100 mg/dL (with higher thresholds for some groups), evidence indicates a significant benefit for maintaining lower levels.3 In epidemiologic studies and clinical trials, CHD event risk continually decreases until total cholesterol is below about 150 mg/dL. Many experts now call for LDL cholesterol concentrations below 70 mg/dL for high-risk patients or for secondary prevention, and CHD risk continuously decreases until LDL is below 40 mg/dL.4
Triglycerides. Elevated concentrations (above 150 mg/dL) increase risk for heart disease.
Homocysteine. Elevated levels (above 12 µmol/L) may cause damage to arterial walls, thus increasing the risk for plaque formation. Men normally have a slightly higher homocysteine concentration than women. Levels tend to increase with age. Although homocysteine levels have been correlated with CHD risk, neither a cause-effect relationship nor a treatment outcomes benefit has been established in clinical trials.5
C-reactive protein (CRP). CRP is an acute phase marker of inflammation, nonspecific for etiology and location other than in clinical context. High sensitivity-CRP (hs-CRP) has been found to be associated with increased risk of cardiac events, with levels greater than 3 mg/dL associated with greatest risk.6 However, hs-CRP has not reliably been shown to have a cause-effect relationship or a treatment outcome benefit in cardiovascular disease. The usefulness of CRP and many other inflammatory and acute phase reactants as screening measures or therapeutic targets in cardiovascular disease remains unproven,7-10 pending the results of additional clinical trials. The NIH-funded Atherosclerosis Risk in Communities Study (ARIC) concluded that routine measurement of CRP, homocysteine and 17 other novel risk markers is not warranted, and reinforced the utility of standard risk factor assessment and management.11
EKG. Findings may include ST elevation (acute myocardial injury or infarction) or depression (myocardial ischemia), T wave inversion (myocardial ischemia or MI), and ventricular premature complexes.
Stress tests. Methods include treadmill or bicycle exercise stress tests (EST), and EST or pharmacologic stress tests combined with nuclear imaging or echocardiography. These tests may be used for CHD diagnosis, risk stratification, and prognosis, and often help determine the advisability for cardiac catheterization and revascularization.
EKG changes and symptoms (eg, exertional chest pain) are monitored during stress tests, providing both determinants of CHD presence and severity, and indications for test termination. Pharmacologic stress modalities are typically used when an exercise stress test is inappropriate or inconclusive. Pharmacologic stress agents include coronary vasodilators, such as dipyridamole and adenosine, and cardiac inotropes, such as dobutamine and (less commonly) arbutamine.
Other Imaging Tests
Cardiac catheterization with coronary angiography. A catheter is inserted into a peripheral artery (usually a femoral artery) and advanced under fluoroscopic guidance to the coronary artery ostia. A radiopaque dye is then injected to identify the locations and severities of coronary blockages. This invasive procedure is performed when coronary artery stenosis is known or suspected, and the need for coronary artery angioplasty, stent placement, or bypass surgery is anticipated.
Intravascular ultrasound (IVUS). IVUS is highly sensitive to the presence and composition of coronary artery plaques. Its 2 major uses currently are to clarify the severity of stenoses identified on angiography, and to assess the deployment of coronary artery stents.
Computed tomography (CT). Electron beam tomography (EBT) accurately identifies and quantifies coronary artery calcification. This test has several applications in CHD, including diagnosis, disease distribution, risk stratification, prognosis, and treatment decisions. EBT is a helpful screening method in specific patient populations, but has limited value for low-risk, asymptomatic patients.
CT angiography (CTA) uses intravenous contrast to obtain noninvasive coronary angiograms. Technical advances such as 64-slice scanners can produce angiograms that rival invasive coronary angiography, and the entire approach to CHD diagnosis and risk stratification may change as this technology continues to improve.
Magnetic resonance imaging (MRI). Cardiac MRI has historically been best suited for evaluation of cardiac chambers, pericardium, thoracic vessels, and congenital heart disease. However, technical advances to minimize the effects of cardiac motion have expanded MRI applications to include CHD evaluation. Such applications overlap substantially with CTA, and the role for MRI in CHD remains uncertain.
Diet and lifestyle changes to modify risk factors (eg, smoking, obesity, hypertension, lack of physical activity, and dyslipidemia) are the cornerstone of treatment, with medications playing an adjunctive role. Unfortunately, counseling of patients regarding the importance of diet and exercise in the prevention of heart disease remains suboptimal.12
Important preventive steps include the following:
- Blood pressure control. (See Hypertension.)
- Reduction of plasma lipids. (See Hyperlipidemia.)
- Smoking cessation.
- Dietary change. (See Nutritional Considerations.)
Drugs are used to reduce the symptoms of angina, as well to control specific risk factors.
Nitrates (sublingual nitroglycerin vs. oral forms) are vasodilators, and provide greatest benefit through decreased preload (venodilation).
Beta-blockers (eg, propranolol, atenolol, metoprolol) decrease myocardial oxygen demand by decreasing contractility and heart rate.
Calcium-channel blockers (diltiazem, verapamil, nifedipine, amlodipine) relax arterial smooth muscle, resulting in decreased afterload.
Antiplatelet therapy. For those who can tolerate aspirin, 81 mg to 325 mg daily is prescribed to decrease CHD event risk. Clopidogrel 75 mg daily is an alternative for persons unable to tolerate aspirin, or for those who have had CHD events despite aspirin. Clopidogrel may also be combined with low-dose aspirin (81 mg daily) for high-risk patients and aspirin failures, and after stent placement.
Lipid-lowering agents, such as the following, may also be prescribed. (See Hyperlipidemia.)
- HMG CoA reductase inhibitors (statins).
- Cholesterol absorption inhibitors (ezetimibe, colesevelam).
- Bile acid sequestrants (cholestyramine, colestipol).
- Fibrinates (gemfibrozil, fenofibrate).
- Nicotinic acid.
Surgery and Other Mechanical Interventions
For high-risk CHD patients, including those with prominent symptoms, severe multivessel coronary artery disease (CAD), acute coronary syndromes, or MI, coronary revascularization may be achieved with percutaneous transluminal coronary angioplasty, intracoronary stent placement, or coronary artery bypass graft (CABG) surgery. For most categories of patients, stenting and CABG have similar success rates for relief of symptoms and control of CHD event risk. The need for subsequent revascularization is usually lower after CABG than after angioplasty or stent placement.
The role of diet in coronary heart disease is evident from its pathological process, which involves the formation of arterial plaques, alterations in endothelial function (which, in turn, influence blood pressure), heightened risk for thrombosis, and inflammatory processes. Diet plays a role through the regulation of blood lipids and by influencing endothelial function and the underlying inflammation that causes disease progression. A modified diet, particularly if combined with regular exercise, can prevent, delay, or reverse the progression of atherosclerosis and development of CHD, with subsequent reduction in cardiovascular events.
The primary goals of dietary intervention are described below.
Controlling Blood Lipid Concentrations
Saturated fats and cholesterol in the diet increase levels of blood lipids, particularly LDL cholesterol, while soluble fiber tends to reduce them. Controlling blood lipoprotein concentrations with a combination of diet, exercise, and medication, if necessary, is a cornerstone of treatment for most CHD patients, as described in more detail in the Hyperlipidemia chapter.
Decreasing dietary saturated fat and cholesterol. Following diets low in saturated fat and cholesterol can help reduce progression of atherosclerosis.13 The National Cholesterol Education Program has recommended moderate reductions in total fat (≤ 30% of energy), saturated fat (≤ 7% of energy), and cholesterol (< 200 mg/day) intake. In clinical trials, such changes reduce plasma LDL cholesterol concentration about 5%.14 Studies suggest that low-fat vegetarian and vegan regimens are significantly more effective, reducing LDL cholesterol approximately 15% to 30%.15-16 Because such regimens have also been shown to reduce body weight and blood pressure and to be useful in programs for reversing atherosclerosis, they may be preferable to many patients, provided they are prescribed along with basic diet instruction.17
Increasing dietary fiber. Soluble fiber, as is found in oats, barley, and beans, is particularly helpful in this regard. (See Hyperlipidemia for more information.)Sources of soluble dietary fiber and pectin, found mainly in fruits and vegetables, have also reduced atherosclerotic progression.18
Consuming soy products. Both epidemiologic19 and clinical20 studies have shown that soy foods (eg, soymilk and meat substitutes) may reduce CHD risk. In addition to reducing blood lipids, soy has cardioprotective effects, such as lowering oxidized LDL, homocysteine, and blood pressure.
Clinical trials have combined these lipid-lowering strategies. A vegetarian diet emphasizing cholesterol-lowering foods (including oats, soy foods, nuts, and sterol/stanol margarines) appears to be particularly effective, lowering LDL cholesterol concentration approximately 30%, an effect similar to that of treatment with lovastatin.20
Improving Antioxidant Status and Endothelial Function
Dietary antioxidants, folate, magnesium, and other substances in foods may reduce the burden of oxidized LDL and improve endothelial function through increased availability of nitric oxide. Diet-related improvements in endothelial function may also reduce blood pressure.
Fruits and vegetables can help reduce atherosclerosis and lower risk for CHD, particularly if the diet is low in saturated fat.21 However, the benefits of these foods go beyond their having no cholesterol, very little saturated fat, and abundant fiber. Among their cardioactive components are vitamin C,22 antioxidant flavonoids,23 and folic acid.24
Several studies have shown that higher dietary intakes of carotenoid-containing fruits and vegetables are associated with a decreased risk of coronary artery disease.25 Others have found an inverse relationship between lower blood levels of carotenoids and higher risk for cardiovascular events.26
The role of inflammatory processes in atherosclerosis is increasingly apparent. Loss of excess body fat reduces the inflammation that acts as both a promoter of atherosclerosis progression and a trigger for cardiovascular events. In addition, shifting the balance of dietary fat away from saturated fats toward omega-3 fatty acids appears to reduce atherosclerosis and may help lower coronary risk, presumably by reducing inflammatory processes. This balance can be altered by the elimination of animal products, tropical oils (the leading sources of saturated fats), and partially hydrogenated vegetable oils (trans fats).
Some investigators have further adjusted this balance in clinical studies by the addition of omega-3 fatty acids in either foods or supplements. And several researchers have found an anti-atherosclerotic effect from both alpha-linolenic acid27 and long-chain omega-3 fats.28 Cardioprotective properties of these fatty acids include reduction of blood viscosity and triglyceride-lowering, antiplatelet, antidysrhythmic, and anti-inflammatory effects.29
There are 3 important caveats to such studies. First, benefits of omega-3 fatty acids have generally been demonstrated in individuals following less than optimal diets, rather than in vegetarians or individuals following very low-fat diets. Second, while many studies have used fish oils, some evidence indicates that diets rich in plant sources of omega-3 fatty acids are associated with a similar reduction in heart disease risk.30 Walnuts, flaxseed, flaxseed oil, and canola oil are rich sources of alpha-linolenic acid and lack the cholesterol of nonplant sources of omega-3 fatty acids. Third, fats or oils that provide omega-3 fatty acids are as energy dense as any other fats and are mixtures of various fat types. Fish oils, for example, include significant amounts of saturated fat (15%-30% of total fat content) and cholesterol. Patients who include fatty fish in their diets as a means of increasing omega-3 intake will also increase total and saturated fat intake, and may experience elevated cholesterol and weight gain.
In addition to the above considerations, evidence suggests that other dietary factors may be helpful, as described below.
In epidemiological studies, whole grain consumption is associated with a lower risk of heart disease,31 as is frequent consumption of nuts.32 In addition to providing the lipid-lowering benefit of dietary fiber, these foods provide magnesium and vitamin E, both of which are inversely related to coronary heart disease occurrence or mortality.33-34 Nuts are high in fat and calories, however, and may influence body weight.
The role of alcohol remains controversial. No controlled clinical trials have examined the effect of alcohol intake on cardiovascular endpoints. Nevertheless, moderate alcohol consumption (1-2 drinks/day) may reduce cardiovascular disease risk through several mechanisms: increasing blood concentrations of HDL cholesterol, plasminogen, and tissue plasminogen activator; improving endothelial function; and decreasing platelet aggregation, fibrinogen, and lipoprotein (a).35 However, regular alcohol consumption also contributes to several medical conditions, including serious diseases of the liver, pancreas, central nervous system, and cardiovascular system. Alcohol also increases the risks for some cancers, notably gastrointestinal and breast cancers.36
Control of Major CHD Risk Factors
Coronary heart disease risk is significantly influenced by the development of comorbid diet-related conditions, including abdominal obesity, high blood pressure, and elevated blood glucose concentrations. A combination of these conditions (along with elevated triglycerides and/or low HDL) is known as metabolic syndrome. The presence of metabolic syndrome predicts CHD more strongly than its individual components do.37
Preventing excess weight gain can lower the risk for coronary artery disease. Accumulation of abdominal fat in particular is associated with the severity of coronary atherosclerosis.38 Studies have shown that obesity is a predictor of acute coronary events.39 Loss of excess body weight also reduces the inflammatory marker C-reactive protein and the proinflammatory cytokine interleukin 6, both of which have been correlated with CHD risk.40,41
Blood pressure. Reductions in blood pressure to optimal levels prevent an estimated 37% of CHD events in men and 56% in women.42 (See Hypertension.)
Blood glucose concentrations. Chronically elevated blood glucose increases risk for coronary disease.43 Even in persons without diabetes, impaired glucose tolerance is predictive of greater risk for cardiovascular morbidity,44 and normalization of postprandial hyperglycemia reduces cardiovascular events in these patients.45
Exercise. Regular exercise reduces cardiovascular mortality in patients with established coronary heart disease,46 particularly if the activity is sufficiently intense.47 Current recommendations suggest a minimum of 30 minutes of moderately vigorous physical activity every day. Before a CHD patient starts an exercise regimen, however, a physical examination is essential, with particular attention to cardiac function, joints, and feet.
Survival and Prognosis after Coronary Events
A low-fat vegetarian diet reduces the risk for repeated coronary events. Individuals who adhered to a low-fat (< 10% of energy) vegetarian diet as part of treatment for pre-existing heart disease had an absence of coronary events in a 12-year study.16 Diet interventions that have also included exercise, stress reduction, and smoking cessation appear to cause regression of atherosclerotic lesions.15
Mediterranean-style diets also decrease the risk for repeated cardiovascular events. The combination of known protective nutrients found in the plant based Mediterranean diet significantly reduced cardiac death, nonfatal MI, unstable angina, stroke, heart failure, and pulmonary or peripheral embolism when compared with a Western diet.48 However, Mediterranean diets are higher in fat (25%-35%) than low-fat vegetarian diets, and are therefore not likely to be as effective for weight loss or regression of atherosclerotic lesions.
Vegetarian diet, non-dairy, low-fat
Nutrition consultation to advise patient regarding the above diet and arrange follow-up.
Exercise prescription: Patient must be screened to ensure safe initiation of an exercise program and slowly work toward a goal of 30 minutes daily of aerobic semivigorous activity. Exercise physiology and physical therapy consultation as appropriate.
What to Tell the Family
Atherosclerosis and coronary heart disease are preventable, treatable, and in some cases possibly reversible. Diet therapy and exercise are fundamental for these aims, and many patients are eventually able to reduce or eliminate previously required medications. Vegetarian diets are particularly effective and appear to be as acceptable to patients as other regimens. Because such diets usually require learning new cooking techniques and acquiring new tastes, families play an important role in joining the patient in the process of dietary change. Family members can support the heart disease patient by following a similar diet and exercise regimen, which will likely benefit their health as well.
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