Coronary heart disease (CHD), also known as ischemic heart disease, is a leading cause of death in Western countries and is increasingly common in developing countries. The atherosclerotic process includes injury to arterial endothelium, fatty streaks due to macrophage ingestion of oxidized low-density lipoprotein (LDL) cholesterol at the damaged site, platelet aggregation, and fibrosis. These events contribute to plaque formation in the intimal layer of medium- and large-sized arteries. Progressive arterial narrowing causes ischemia (supply-demand mismatch), which occurs initially with exertion but may eventually occur at rest.
Atherosclerosis commonly begins in early childhood (perhaps even during fetal development in some cases) and slowly progresses throughout life. Rapid progression may occur by the third decade of life. Symptoms often do not present until later stages. Angina pectorisis 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 but may manifest as shortness of breath or chest aching. Stable angina tends to occur predictably with exertion, whereas unstable angina occurs unpredictably, often with minimal exertion or at rest, and may be a sign of dangerous instability in the plaques.
When atherosclerotic plaques rupture, vasoconstriction and clot formation can lead to complete occlusion of a coronary artery, causing a myocardial infarction (MI). An MI may be silent, or it may be signaled by prolonged pain or discomfort similar to that associated with simple angina. Individuals with diabetes are at higher risk of having silent ischemia. 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, i.e., 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. A common manifestation of peripheral vascular disease in men is erectile dysfunction.
Diabetes. Hyperinsulinemia or impaired glucose tolerance, without a diagnosis of diabetes, also raises the risk for CHD.
Dyslipidemia, including elevated serum lipoprotein (a).
Family history. First-degree relatives with MI before age 55 (men) or 65 (women).
Obesity. Excess weight is associated with several risk factors for CHD (see Obesity chapter).
Chronic kidney disease and microalbuminuria.
Inflammation. Elevated inflammatory markers, such as CRP, are associated with risk of CHD. This may occur in the context of many autoimmune diseases.
Diagnosis of atherosclerosis and CHD is based on a patient’s individual risk factors, along with a careful medical history, physical exam, and diagnostic tests. Stress tests and imaging studies are generally not advised for asymptomatic individuals, except when certain or multiple CHD risk factors exist, or when vigorous exercise is planned.
No blood test definitively diagnoses the presence or extent of atherosclerosis. However, several tests can help predict long-term risk of future cardiovascular events. Diagnosis of an acute myocardial infarction is more straightforward, as laboratory tests, combined with symptoms and electrocardiographic and angiographic findings, are sensitive and specific.
Creatine kinase-MB fraction (CK-MB). CK-MB is a specific marker for acute myocardial injury. It has largely been replaced by cardiac troponin, which is now preferred in diagnosing injury or reinfarction.
Troponins. Cardiac troponin proteins combine with calcium to facilitate cardiac muscle cell contraction through actin-myosin interaction. Troponins are released into the bloodstream during myocardial injury with an identifiable rise 2-3 hours post insult. Although troponin I is more specific for myocardial injury than troponin T, these markers are equally useful for diagnosing acute MI.
Levels of both CK-MB and troponin increase during the early course of a MI. However, troponin is more sensitive and specific. Because troponin remains elevated for 5-14 days, it can be used to diagnose late MI. Recent data suggest that troponin rises quickly, even from an abnormal baseline, and is now preferred over CK-MB for diagnosis of reinfarction.
Cholesterol. Elevated total and LDL cholesterol concentrations and low high-density lipoprotein (HDL) cholesterol concentrations (less than 50 mg/dL in women and 40 mg/dL in men) are associated with increased risk for atherosclerosis and CHD events. Previously, the National Cholesterol Education Program defined 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. In epidemiologic studies and clinical trials, CHD event risk decreases until total cholesterol is below about 150 mg/dL and until LDL is below 40 mg/dL.
New guidelines from the American College of Cardiology and the American Heart Association no longer put emphasis on specific LDL cholesterol levels. Current guidelines use lipid levels along with blood pressure, age, race, sex, and smoking status to estimate 10-year risk of a cardiovascular disease event (heart attack or stroke). These guidelines designate 4 treatment groups which gain the most benefit from pharmacologic cholesterol-lowering: those between ages 40-75 with known atherosclerotic disease, those with LDL cholesterol >190mg/dL, those with diabetes, and patients 40-75 years old with a 10-year risk of an atherosclerotic disease related event of ≥7.5% (based on pooled cohort equations).
Although individuals with higher plasma HDL cholesterol concentrations have been shown to have modest reductions in cardiovascular risk, HDL elevation is no longer a clinical goal. In controlled trials, treatment-induced HDL cholesterol elevations have not reduced the risk of coronary heart disease events, coronary disease mortality, or total mortality. The LDL/HDL ratio has not been shown to be a better predictor of cardiovascular outcomes than LDL cholesterol alone. For more details, see the Dyslipidemia chapter.
Low HDL cholesterol levels are common in populations that follow low-fat, plant-based diets and have low coronary risk, and they appear to be the result of decreased transport rather than an increase in HDL catabolism common to individuals eating a high-fat Western diet.
Triglycerides. Elevated concentrations (above 150 mg/dL) are independently associated with CHD risk.
Homocysteine. This amino acid is atherogenic, is known to cause vascular intimal thickening and platelet aggregation and promotes platelet rich thrombi. 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-outcome benefit has been established in clinical trials. Therefore, it is not commonly used in clinical practice. Optimal homocysteine metabolism requires adequate amounts of vitamin B12, vitamin B6, and folic acid. A diet rich in fruits and vegetables and low in total and saturated fat can lower serum homocysteine levels.
C-reactive protein (CRP). CRP is an acute phase marker of inflammation. High sensitivity-CRP (hs-CRP) is associated with increased risk of cardiac events, with levels greater than 3 mg/dL associated with greatest risk. 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, pending the results of additional clinical trials. , , , The 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. The Centers for Disease Control and Prevention and the American Heart Association have issued a statement that patients considered to be at intermediate risk for CHD, based on Framingham scores, could be further risk-stratified based on CRP levels, if treating physicians deem it appropriate.
Interleukin-6 (IL-6). IL-6 is a pro- and anti-inflammatory cytokine that has the ability to activate B cells, T cells, and macrophages. It is also the major inducer of acute phase reactants, including CRP and various other inflammatory cytokines. In contrast to CRP, IL-6 appears to have a direct causal role in CHD development. While not currently used in clinical practice, IL-6 may be a therapeutic target in the future.
Leukocyte myeloperoxidase. This enzyme, released by white blood cells during inflammation, promotes the oxidation of lipoproteins and is associated with presence of CHD and risk for future events, independently of other cardiac risk factors., Currently, this test has little clinical utility.
Lipoprotein (a).This is a type of low-density lipoprotein. Elevated levels promote atherosclerosis and are associated with increased risk for CHD. Levels are not routinely checked for screening, and excess is genetically determined. Clinical trials are needed to determine appropriate treatment, but aggressive LDL cholesterol lowering with maximal dose statin and the addition of a PCSK9 inhibitor, nicotinic acid, or ezetimibe has been suggested.
Other biomarkers of inflammation have been associated with CHD risk, including IL-18, ESR, WBC count, and TNF- α, but these tests are not typically used in clinical practice.
EKG. Findings may include ST elevation (acute myocardial injury or infarction) or depression (myocardial ischemia), T wave inversion (myocardial ischemia or MI), new left bundle branch block (acute 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 they often help determine the advisability for cardiac catheterization and revascularization.
EKG changes and symptoms (e.g., 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, most commonly, regadenoson, and less often, dipyridamole and adenosine, and cardiac inotropes, such as dobutamine.
Cardiac catheterization with coronary angiography. A catheter is inserted into a peripheral artery (either radial artery or 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). This method is highly sensitive to the presence and composition of coronary artery plaques. Its three major uses currently are to clarify the severity of stenosis identified on angiography, to characterize the composition of and degree of calcification within plaques, and to assess the deployment of coronary artery stents.
Computed tomography (CT). Coronary artery calcification (CAC) is correlated with CHD events. Multidetector CT accurately identifies and quantifies coronary artery calcification. This test has several applications in CHD, including diagnosis, disease distribution, risk stratification, prognosis, and treatment decisions. CAC scoring is a helpful screening method in specific patient populations but has limited value for low-risk, asymptomatic patients. In 2010, the American College of Cardiology/American Heart Association (ACC/AHA) suggested that screening for coronary artery disease by measurement of CAC is reasonable for CVD risk assessment in asymptomatic adults at Framingham intermediate risk (10-20%, 10-year risk). This screening is not recommended for patients at low or high risk.
Coronary CT angiography (CCTA) uses intravenous contrast to obtain noninvasive coronary angiograms. Technical advances such as 64-slice scanners can produce angiograms that rival invasive coronary angiography. CCTA is not recommended as a general screening tool but may be useful in specific patient populations, such as those with equivocal stress test results or those who are unable to perform any type of stress test. This modality continues to have limitations, but the entire approach to CHD diagnosis and risk stratification may change as this technology advances.
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 (e.g., 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.
Important preventive steps include the following:
Drugs are used to reduce the symptoms of angina, as well to control specific risk factors.
Nitrates (sublingual nitroglycerin versus oral forms) are vasodilators and provide greatest benefit through decreased preload (venodilation).
Beta-blockers (e.g., 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, 81-325 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 (and newer, similar medications, such as ticagrelor and prasugrel) 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 Dyslipidemias chapter.)
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.
Stents and CABG do not arrest the disease process—they simply treat the most focally severe areas of a systemic disease process.
Regular exercise is effective in primary and secondary cardiovascular risk reduction, including in patients who are post-MI. Current guidelines recommend exercise intensity be aimed at achieving a heart rate of 50-90% of maximal heart rate, based on age. However, growing evidence suggests that high intensity aerobic training, with heart rate maintained at 85-95% of maximal is safe and may confer additional long-term benefits for CHD patients participating in organized cardiac rehab programs, beginning cautiously with appropriate supervision., In addition to aerobic training, studies indicate that resistance exercise may reduce CHD risk by lowering blood pressure, lowering LDL cholesterol, reducing body fat, and improving insulin resistance.
Current recommendations from the 2013 ACC/AHA Statement on Lifestyle therapy suggest physical activity be performed 3-4 sessions a week, lasting on average 40 minutes per session and involving moderate-to-vigorous intensity.
Post-MI patients and patients with established CHD should be referred, if possible, to an outpatient cardiac rehab team who can adequately evaluate risk and develop individual exercise plans that are safe and effective. Patients at risk for CHD should always have a thorough clinical examination with appropriate ancillary testing before starting an exercise program. High-risk patients should not attempt vigorous exercise without the supervision of a trained medical professional.
More recently, intensive cardiac rehabilitation is covered by Centers for Medicare and Medicaid Services as well as most private health insurers and includes 72 hours of intensive lifestyle modification highlighting a plant-based diet, exercise, stress relief, connection and support.
Many post-MI patients develop symptoms of depression, and nearly 1 in 5 meets the criteria for major depressive disorder, which is associated with poor therapy compliance and poor outcomes. Post-MI care should include screening for and treating depression with stress reduction therapy, physical activity and medication, if needed.,
Dietary factors are central to the CHD pathogenesis, and diet changes are integral to its prevention and treatment. The role of diet in CHD is evident from its pathological process, which involves the formation of arterial plaques, alterations in endothelial function, 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. Diets promoting cardiovascular health should begin as early as possible because the atherosclerosis that contributes to coronary artery disease begins in childhood.
Pioneering studies by Dean Ornish, MD, Caldwell Esselstyn Jr., MD, and others have shown that a low-fat plant-based diet, combined with regular exercise and a healthful overall lifestyle, can prevent, delay, and reverse the progression of atherosclerosis, with subsequent reduction in cardiovascular events.
The primary goals of dietary intervention are described below.
Controlling blood lipid concentrations. Saturated fats, trans fats, and cholesterol in the diet increase concentrations 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 Dyslipidemias chapter. The Lifestyle Heard Trial conducted by Dean Ornish resulted in a 37% reduction in LDL cholesterol with a vegetarian diet that focused on fruits, vegetables, soy, and no vegetable oils. Nonfat milk and yogurt were allowed, and total fat intake was less than 10% of the total calories. These results are significantly more dramatic than the five percent LDL reduction from the American Heart Association (AHA) diet. This diet does advocate for an increase in vegetables, fruit, and whole grains. However, the diet allows small amounts of cholesterol and saturated fat from animal products, which most likely moderates the cholesterol lowering affects.
Reducing blood pressure. Hypertension is a major risk factor for CHD. The same dietary and lifestyle changes that reduce total and LDL cholesterol can also significantly reduce blood pressure and lower the risk of a cardiac event.
Controlling blood sugar levels. Diabetes is a major contributor to coronary disease and, in turn, CHD is a leading cause of death for people with diabetes. Dietary interventions can increase insulin sensitivity for individuals with type 2 diabetes and improve blood glucose control for individuals with type 1 or type 2 diabetes.
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.
Reducing inflammation. The role of inflammatory processes in atherosclerosis is increasingly apparent. Loss of excess body fat reduces C-reactive protein, an indicator of inflammation.
The following dietary steps help patients in achieving these goals:
Avoiding animal-derived food products. Dairy products, meat, and eggs are the primary sources of saturated fat and cholesterol. Following diets low in saturated fat and cholesterol can help reduce progression of atherosclerosis.
The National Cholesterol Education Program has recommended moderate reductions in total fat (≤30% of energy), saturated fat (≤7% of energy), and cholesterol (< 200 mg/d) intake. In clinical trials, such changes reduce plasma LDL cholesterol concentration about 5%. Low-fat, plant-based (vegetarian and vegan) regimens are significantly more effective, reducing LDL cholesterol approximately 15-30%.,, Such regimens have also been shown to reduce body weight and blood pressure and to be useful in programs for reversing atherosclerosis.
Low-fat plant-based diets are also highly acceptable to patients, provided they are prescribed along with basic diet instruction and support. Combining daily aerobic exercise with a healthful diet adds to its benefit, particularly with regard to weight and blood glucose control.
Avoiding hydrogenated and partially hydrogenated oils. These products contain trans fats that increase LDL cholesterol and can reduce HDL cholesterol.,, Trans fatty acids also have pro-inflammatory effects similar to those of saturated fat and adversely affect vascular reactivity, reducing arterial flow-mediated dilation (a direct measure of vascular endothelial function).
Increasing fiber-containing whole plant foods. Soluble fiber, as is found in oats, barley, and beans, is particularly cardioprotective. Fruits and vegetables are also sources of soluble dietary fiber and pectin and are associated with reduced atherosclerotic progression. Most Americans do not consume adequate fiber, but large studies have shown that individuals following plant-based diets typically have fiber intakes that meet or exceed recommendations.,
Consuming soy and other legumes. Both epidemiologic and clinical studies have shown that soy products (e.g., soymilk and meat substitutes) may reduce CHD risk., In addition to reducing blood lipids, soy has cardioprotective effects, such as lowering oxidized LDL and blood pressure. Other legumes have also lowered total and LDL cholesterol in randomized controlled trials.
Clinical trials have combined these dietary lipid-lowering strategies. A vegetarian diet emphasizing specific cholesterol-lowering foods appears to be particularly effective, lowering LDL cholesterol concentration by 33%+4%, P< .001 in 2 weeks, an effect similar to that of statin drugs. In addition to excluding animal products, subjects consumed at least 600 grams (equivalent to 4 cups) of green leafy vegetables (cabbage, bok choy, chard, spinach, brussels sprouts, leeks, broccoli, and cauliflower), 500 grams (2 ½ cups) peas, sweet yellow corn, and eggplant, and 60-120 grams of peanuts, almonds, cashews, or avocado (½ cup to ¾ cup) per day. The vegetables were steamed or boiled. The diet included soymilk and fruit. The bulk of starch came from peas and corn. Reductions in cholesterol appeared to correlate with soluble fiber and vegetable protein intake. Diet analysis reported the subjects consumed 72 g of vegetable protein and 64 g of fiber (18 g soluble, 45 g insoluble) per day.
Increasing fruits and vegetables. Fruits and vegetables can help reduce atherosclerosis and lower risk for CHD, particularly if the diet is low in saturated fat. However, the benefits of these foods go beyond their having no cholesterol, very little saturated fat, and abundant fiber. Among their active components are vitamin C, antioxidant flavonoids, and folic acid.,,
Several studies have shown that higher dietary intakes of carotenoid-containing fruits and vegetables are associated with a decreased risk of coronary artery disease. Others have found an inverse relationship between lower blood levels of carotenoids and higher risk for cardiovascular events.
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, as is frequent consumption of nuts., 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., Nuts are high in fat and calories, however, and may influence body weight.
Other dietary factors under consideration:
Fish, fish oil, and omega-3 supplements are unproven. Although some studies have suggested that omega-3 polyunsaturated fatty acids in fish reduce the incidence of heart disease, the overall evidence does not support the addition of fish or omega-3 supplements to an otherwise plant-focused diet to reduce cardiovascular disease risk.,,,,,
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. However, even modest levels of alcohol consumption contribute to several medical conditions, including gastrointestinal and breast cancers, diseases of the liver, pancreas, central nervous system, and cardiovascular system, and more than moderate drinking is associated with increased cardiac mortality.,
A low-fat vegetarian diet reduces the risk for repeated coronary events. In a 12-year study, 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. Diet interventions that have also included exercise, stress reduction, and smoking cessation appear to cause regression of atherosclerotic lesions.
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, and a composite of endpoints, including unstable angina, stroke, heart failure, and pulmonary or peripheral embolism, when compared with a Western diet. However, Mediterranean diets are higher in fat (25-25%) than low-fat vegetarian diets and are therefore not likely to be as effective for weight loss or regression of atherosclerotic lesions.
Nutrition consultation to advise patient regarding the above diet and arrange follow-up.
Referral to a cardiac rehabilitation program.
Physical therapy and psychiatry or social support referrals as appropriate.
Atherosclerosis and coronary heart disease are preventable, treatable, and in some cases reversible. Low-fat, plant-based diets, along with other healthful lifestyle changes, 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.