Angina Pectoris
- Pathophysioilogy
- Management & Establishing the Cause
- Treatment
- Prevention
- Prognosis
- Clinical Case Study
- Study Questions
Coronary artery disease (atherosclerosis) jeopardizes cardiac function by causing an imbalance between the myocardial energy/oxygen supply and demand.
Ischemic muscle cells are electrically irritable and unstable, and the danger of developing cardiac arrhythmias and fibrillation is enhanced.
During ischemia, the normal cardiac electrical excitation pathways may be altered and often ectopic pacemaker foci develop. Electrocardiographic manifestations of myocardial ischemia can be observed in individuals with coronary artery disease during exercise stress tests. In addition, there is evidence that platelet aggregation and clotting function may be abnormal in atherosclerotic coronary arteries and the danger of thrombus or emboli formation is enhanced. It appears that certain platelet suppressants or anticoagulants such as aspirin may be beneficial in the treatment of this consequence of coronary artery disease.
elicit an increase in sympathetic tone that increases myocardial oxygen consumption. Myocardial ischemia and chest pain will result if coronary blood flow cannot keep pace with the increase in myocardial metabolism.
Because myocardial ischemia is produced by an imbalance between myocardial oxygen supply and demand, in general, treatment consists of increasing supply or reducing demand—or both.
It is important to eliminate any aggravating factors that could increase myocardial oxygen demand or reduce coronary artery flow.
Factors that Can Aggravate Myocardial Ischemia
Increased myocardial oxygen demand |
Tachycardia Hypertension Thyrotoxicosis Heart failure Valvular heart disease Catecholamine analogues (eg, bronchodilators, tricyclic antidepressants, cocaine) |
Reduced myocardial oxygen supply |
Anemia Hypoxia Carbon monoxide poisoning Hypotension Tachycardia |
Hypertension and tachyarrhythmias are obvious factors that need to be controlled. Thyrotoxicosis leads to tachycardia and increases in myocardial oxygen demand. Anemia is a common problem that increases myocardial oxygen demand because of reflex tachycardia; it reduces oxygen supply by decreasing the oxygen-carrying capacity of the blood. Similarly, hypoxia from pulmonary disease reduces oxygen delivery to the heart. Heart failure increases angina because it often results in left ventricular dilatation, which increases wall stress, and in excess catecholamine tone, which increases contractility and produces tachycardia.
Heart Rate Control
Heart rate is a major determinant of myocardial oxygen demand, and attention to its control is imperative. Any treatment that accelerates heart rate is generally not going to be efficacious in preventing myocardial ischemia.
Therefore, care must be taken with potent vasodilator drugs, such as hydralazine, which may lower blood pressure and induce reflex tachycardia.
Furthermore, because most coronary blood flow occurs during diastole, the longer the diastole, the greater the coronary blood flow; and the faster the heart rate, the shorter the diastole.
Blood Pressure Control
Increases in blood pressure raise myocardial oxygen demand by elevating left ventricular wall tension, and blood pressure is the driving pressure for coronary perfusion. A critical blood pressure is required that does not excessively increase demand, yet keeps coronary perfusion pressure across stenotic lesions optimal. Unfortunately, determining what this level of blood pressure should be in any given patient is difficult, and a trial-and-error approach is often needed to achieve the right balance. Consequently, it is prudent to reduce blood pressure when it is very high, and it may be important to allow it to increase when it is very low. It is not uncommon to encounter patients whose myocardial ischemia has been so vigorously treated with a combination of pharmacologic agents that their blood pressure is too low to be compatible with adequate coronary perfusion. In such patients, withholding some of their medications may actually improve their symptoms. Although myocardial contractility and left ventricular volume also contribute to myocardial oxygen demand, they are less important than heart rate and blood pressure. Myocardial contractility usually parallels heart rate. Attention should be paid to reducing left ventricular volume in anyone with a dilated heart, but not at the expense of excessive hypotension or tachycardia because these factors are more important than volume for determining myocardial oxygen demand.
Blood pressure should be reduced to below 120/85 mm Hg if possible,
and a moderate-to-high-intensity statin (that reduces low-density lipoprotein [LDL] cholesterol levels by >30% from pretreatment levels) should be used.
Changes in lifestyle behaviors should also be recommended. These changes include weight loss in overweight or obese patients, dietary changes to reduce fat and sugar intake, and smoking cessation.
Antianginal therapy should be initiated as soon as the diagnosis is suspected. In patients with stable angina, beta-blockers, calcium-channel blockers, and long-acting nitrates reduce angina similarly and appear to have a similar safety profile (except for short-acting calcium-channel blockers).
Aspirin
In patients in whom stable angina is suspected, preventive therapies, including aspirin, should be started immediately if they are not already in use.
PCSK9 antibodies for cardiovascular risk reduction
●In patients at very high risk for cardiovascular disease events (expected 10-year event rate of greater than 25 percent), such as those in the proposed NCEP guidelines, use high-intensity statin therapy plus a PCSK9-ab rather than targeting a goal LDL-C1 (Grade 2B).
In higher-risk patients who do not tolerate any statin regimen, we suggest treatment with a PCSK9-ab (Grade 2B). In very high-risk patients who do not tolerate any statin regimen, we recommend treatment with a PCSK9-ab (Grade 1B).
Monoclonal antibodies that inhibit proprotein convertase subtilisin kexin 9 (PCSK9-abs) reduce LDL-cholesterol levels by as much as 70 percent. Randomized trials with small numbers of events and limited follow-up suggest that at least two of these agents, alirocumab and evolocumab, substantially reduce cardiovascular events and mortality when used for secondary prevention, both as monotherapy and in combination with statin therapy [1,2]. (See "Lipid lowering with drugs other than statins and fibrates", section on 'PCSK9 inhibitors'.)
PCSK9-abs are becoming available for clinical use. The agents require subcutaneous injection every two to four weeks and are very expensive. While awaiting greater experience with these agents, we would use them in situations where the expected reductions in cardiovascular events are likely to outweigh any as yet unknown adverse events from a new therapy. These include using them in combination with statin therapy in very high-risk patients such as those in the proposed NCEP guidelines (table 1), and as monotherapy in high-risk and very high-risk patients who are intolerant of statin therapy. (See "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease", section on 'Stable CVD'.)
What are some of the newer medical therapies for chronic angina?
A. Ranolazine is a metabolic antianginal agent that is approved for the treatment of chronic angina. It diminishes myocardial ischemia by reducing calcium overload caused by inhibition of the late sodium current. It does not affect heart rate or blood pressure and thus may be considered as a first-line agent for patients with slow heart rate or low blood pressure. It has been evaluated in two studies of outcomes in patients with angina, with mixed results. Ranolazine prolongs the QT interval in a dose-dependent manner; however, no increase in significant arrhythmias has been observed with its use in multiple safety studies. Still, caution is warranted regarding prescription of other drugs that cause QT-interval prolongation, as well as regarding other drug–drug interactions. Ivabradine is a selective heart-rate–lowering (physiological) agent that inhibits the If current in the pacemaker cells in the sinoatrial node. It is approved for treatment of heart failure with a goal of preventing hospitalization in patients who have an increased heart rate despite adequate beta-blocker therapy. It has also been reported to be effective in improving exercise duration in patients with chronic angina who are not receiving background therapy. However, the results of a large randomized trial involving patients who had both stable coronary artery disease without heart failure and a resting heart rate of 70 beats per minute or more have aroused concern about the use of ivabradine for chronic angina. Ivabradine should not be used to treat angina in the absence of heart failure.
When would you consider revascularization for a patient with chronic stable angina?
A. The decision regarding whether and how to revascularize (with percutaneous coronary intervention [PCI] or coronary-artery bypass grafting [CABG]) or whether to continue medical therapy should ideally involve a heart-team approach incorporating input from interventional cardiologists and cardiothoracic surgeons. The decision should take into account clinical risk factors, characteristics of the lesion, and hemodynamic factors, and it may be informed by the use of validated risk scores to refine the selection of patients for PCI versus CABG. Randomized trials involving patients who were eligible for either medical therapy or revascularization have shown that PCI is effective in reducing angina in patients with chronic angina, but it does not result in a lower risk of death or myocardial infarction than that with medical therapy. These observations suggest that medical therapy alone is a reasonable starting point if it has an acceptable side-effect profile. Revascularization should be considered for patients who have ongoing angina despite adequate medical therapy; this group includes as many as 50% of patients with chronic angina.
Primary Prevention
Patients with and without coronary heart disease should be advised to
Stop smoking
Maintain normal blood pressure
Main normal cholesterol levels
Exercise
Achieve or maintain a normal weight
Control diabetes mellitus if present.
Moderate-intensity statin therapy includes daily treatment with:
●Lovastatin 40 mg
●Pravastatin 40 mg
●Simvastatin 40 mg
●Atorvastatin 10 to 20 mg
●Rosuvastatin 5 to 10 mg
High-intensity statin therapy includes daily treatment with:
●Atorvastatin 40 to 80 mg
●Rosuvastatin 20 to 40 mg
Secondary Prevention
Patients with known cardiovascular disease (CVD) are at high risk for CV events. Treatment in such patients, as well as in other patients known to have a similar risk of CV events, is discussed as secondary prevention. In secondary prevention, statins have been shown in multiple large trials to reduce CV events and to reduce all-cause mortality. Meta-analysis of fairly short-term clinical trials in high-risk patients found that proprotein convertase subtilisin kexin 9 antibodies (PCSK9-abs) also appear to decrease CV events and mortality. Trials of other lipid-lowering agents have generally only shown reductions in CV events.
Trials of statins, and other medications used in combination with statins, have provided additional information that is related to the appropriate serum low-density lipoprotein cholesterol (LDL-C) target in patients being treated for secondary prevention. However, the results of these trials are open to various interpretations and the ideal target LDL-C level has not been completely defined.
This topic will review the evidence for LDL-C goals in patients treated with statins for secondary prevention of CHD, as well as the evidence for using agents other than statins in patients who are unable to tolerate statins or who do not achieve LDL-C goals with statins alone. The general approach to lipid lowering therapy for secondary prevention and in patients with an acute coronary syndrome, as well as an overview of the treatment of hypercholesterolemia, are discussed separately. (See "Secondary prevention of cardiovascular disease", section on 'Dyslipidemia' and "Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome" and "Treatment of lipids (including hypercholesterolemia) in secondary prevention".)
Risk factors for coronary artery disease.
Nonmodifiable/Uncontrollable Male sex Age: men ≥45 years old women ≥55 years old or postmenopausal Positive family history of CAD |
|
| Modifiable with Demonstrated Morbidity and Mortality Benefits | |
Hypertension Left ventricle hypertrophy Dyslipidemia HDL <35 mg/dL LDL >130 mg/dL Diabetes mellitus |
Overweight and obesity Physical inactivity Smoking (risk abates after 3 years’ quit) Low fruit and vegetable intake Excessive alcohol intakea |
| Potentially Modifiable but without Demonstrated Mortality and Morbidity Effects | |
Stress Depression Hypertriglyceridemia Hyperhomocysteinemia Hyperreninemia |
Elevated uric acid Lipoprotein(a) Fibrinogen Elevated high-sensitivity C-reactive protein |
Several tests that are used to diagnose coronary artery disease can also provide prognostic information. The standard exercise ECG stress test is the least sensitive test for coronary artery disease and cannot define its extent, but the duration of exercise, presence of ST-segment changes, and occurrence of angina confer prognostic information. As compared with the routine exercise ECG stress test, stress tests that involve imaging typically have a superior ability to detect coronary artery disease without an appreciable loss of specificity. The exercise ejection fraction is one of the most important prognostic variables in patients with coronary artery disease. Imaging stress tests allow evaluation of left ventricular performance and assessment of the extent of ischemia during stress.
A 53-year-old male with a history of hypertension and smoking, but no family history of cardiac disease, presents to your office complaining of a chest pain. The pain is substernal, radiates to his left arm, and is associated with exertion. The patient notes that this same pain has been going on for the last 6 months and has not changed at all in duration, intensity, or characteristic. It generally lasts 5 minutes or so and resolves with rest.
You tell the patient that:
A) Without doing any test, you know that the probability that this pain is cardiac is greater than 85%.
B) If his ECG in the office is normal, his pain is unlikely to represent cardiac disease.
C) Even with risk factors, his probability of having CAD with “typical angina” is still only 50% or so.
D) The only intervention indicated at this point are life style modifications (e.g., stop smoking) and addressing his cholesterol and hypertension.
E) It is likely that he has unstable angina.
Answer Click Here
A 55-year-old man presents to the clinic with complaints of chest pain. He states that for the past 5 months he has noted intermittent substernal chest pressure radiating to the left arm. The pain occurs primarily when exercising vigorously and is relieved with rest. He denies associated shortness of breath, nausea, vomiting, or diaphoresis. He has a medical history significant for hypertension and hyperlipidemia. He is taking atenolol for his high blood pressure and is eating a low-cholesterol diet. His family history is notable for a father who died of myocardial infarction at age 56 years. He has a 50-pack-year smoking history and is currently trying to quit. His physical examination is within normal limits with the exception of his blood pressure, which is 145/95 mm Hg, with a heart rate of 75 bpm.
Questions
A. The most likely diagnosis in this patient is coronary artery disease, specifically angina pectoris. Because the symptoms are exertional only and have been stable for several months, this patient would be classified as having stable angina. If the pain occurred at rest, with less and less activity, or more frequently or for a longer duration despite similar activity levels, he would be classified as having unstable angina.
B. By far the most common cause of coronary artery disease is atherosclerosis of the large epicardial arteries, and this is the most likely cause in this patient. A less common cause is coronary artery vasospasm, found more commonly in Japanese individuals. Vasospastic angina is most often nonexertional. Rare causes include emboli and congenital abnormalities.
C. This patient has several cardiac risk factors, including male gender, a family history of coronary artery disease, hyperlipidemia, smoking, and hypertension.
D. The mechanism by which atherosclerotic plaques form remains unclear and is the subject of much debate. It appears that atherosclerosis starts early in life, when the endothelial linings of the blood vessels are exposed to shear stress. The injury that results causes the endothelial cells to release vascular cell adhesion molecules to which monocytes become attached and enter the subendothelium, where they engulf oxidized low-density lipoprotein (LDL), forming foam cells. The injured endothelium, in combination with the foam cells, forms the fatty streak characteristic of atherosclerosis. Oxidized LDL causes the release of cytokines and inhibition of NO. Vascular smooth muscle moves from the media to the intima, where they proliferate, laying down collagen and matrix and taking up oxidized LDL to form more foam cells. T cells also accumulate in the growing plaque. T cells, smooth muscle cells, and endothelial cells produce various cytokines and growth factors responsible for further cell migration and proliferation. Ultimately, the thickened and distorted artery wall takes up calcium, creating a brittle plaque.
E. Chest pain is due to myocardial ischemia, which occurs when cardiac oxygen demand exceeds supply. In the case of stable angina, fixed narrowing of one or more coronary arteries by atherosclerotic plaque occurs. When the patient exercises, cardiac oxygen demand increases. However, because of the decreased diameter of the coronary arteries, insufficient blood flow, and, therefore, insufficient oxygen, is supplied to the heart. Chest pain has been attributed to this ischemia; however, it has been shown that up to 80% of all ischemic episodes are asymptomatic. When present, chest pain is thought to be triggered by adenosine release, causing stimulation of the sympathetic afferent fibers that innervate the atrium and ventricle. These fibers then traverse the sympathetic ganglia and five upper thoracic dorsal roots of the spinal cord. These fibers converge with fibers from other structures in the spinal cord, which accounts for the frequent sensation of pain in the chest wall, back, and arm.
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A 45-year-old man began having chest pressure with exertion that was relieved with rest. He did not have diabetes, high blood pressure, or high cholesterol, and had never had a myocardial infarction. His examination and resting ECG were normal. On the basis of the testing modalities available, he was scheduled for exercise stress testing. After a positive test, he underwent coronary angiography that demonstrated a significant stenosis in the left coronary artery. He underwent a stenting procedure and was placed on aspirin and cholesterol-lowering medication.
Coronary arteriogram demonstrating severe stenosis (white arrow) in the left coronary artery. Note that the circumflex artery (CX) is patent.
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