Angina

Japanese: 狭心症

Definition/Concept Angina pectoris is a clinical syndrome characterized by a characteristic discomfort in the chest and adjacent areas (angina pain) caused by transient myocardial ischemia, or oxygen deficiency, due to coronary artery disease. Transient myocardial ischemia occurs when the myocardial demand for oxygen increases or decreases due to coronary artery disease, or when both mechanisms are combined.
Classification Angina pectoris is classified based on the mechanism of onset, triggers of attacks, and course of the attack (Table 5-7-2).
1) Classification based on onset mechanism:
It is classified into organic angina caused by organic stenosis, vasospastic angina caused by spasm of the coronary arteries (coronary spasm), and coronary thrombotic angina. Although it is normally diagnosed based on coronary angiography findings, in most cases it can be diagnosed through medical interview.
2) Classification based on triggers of attacks:
It is classified as exertional angina, rest angina, and exertional and rest angina. Even exertional angina can be caused by organic stenosis or exertion-induced coronary spasm.
3) Classification based on progression:
It is classified as stable angina or unstable angina. Stable angina is angina caused by exertion above a certain level, and refers to stable exertional angina. Unstable angina is an attack that occurs with increasing frequency and intensity, and can lead to acute myocardial infarction or sudden death, and is classified as an acute coronary syndrome.
4) Silent myocardial ischemia:
A condition in which myocardial ischemia occurs without angina or similar symptoms is called asymptomatic myocardial ischemia or silent myocardial ischemia (SMI), and was already listed as an item of painless ischemic heart disease in the 1962 WHO classification. In actual clinical practice, it is often discovered when long-term electrocardiograms or stress tests are performed for some reason, such as preoperative examinations of high-risk patients, or in patients who have been treated for diabetes for a long time, it is often discovered during exercise stress tests to screen for ischemia, even though they have no symptoms. It often occurs in elderly people and diabetic patients. Painless attacks are also frequently experienced by symptomatic angina patients. [⇨5-7-3)]
5) Microvascular angina:
This refers to angina that occurs during exertion or at rest, but in which there is no clear organic stenosis or coronary spasm on coronary angiography. It is thought to be caused by stenosis or spasm at the microvascular level that cannot be seen on coronary angiography. It is often seen in women middle-aged or older, and is believed to be caused by endothelial dysfunction.
Causes and etiology: With the Westernization of diet and changes in lifestyle, interest in ischemic heart disease (angina pectoris, myocardial infarction), a typical form of arteriosclerosis, is increasing. Causes include coronary artery risk factors and the Westernization of lifestyle, but chronic inflammation is drawing attention as a cause of the disease.
1) Coronary artery risk factors:
Modifiable risk factors include dyslipidemia, hypertension, smoking, diabetes, obesity, and hyperuricemia, while uncontrollable factors include age, sex (male), family history, and race.
2) Lifestyle habits:
Smoking, occupation (stress), personality, etc. are related to the progression of arteriosclerosis. Excessive calorie intake, excessive lipid intake, and lack of exercise are major factors in obesity and impaired glucose tolerance, and promote the progression of arteriosclerosis.
3) Chronic inflammation:
Coronary arteriosclerosis is often caused by atherosclerosis, and much research has been done into its progression based on Russell Ross's theory of impaired vascular response. Currently, arteriosclerosis is generally considered to be a chronic inflammatory disease of the blood vessels.
According to the 2008 patient survey conducted by the Ministry of Health , Labor and Welfare, the total number of patients with ischemic heart disease (myocardial infarction and angina pectoris) is 800,000, of which 460,000 were male and 340,000 were female, of which approximately 600,000 had angina pectoris.
Pathophysiology Angina pectoris is primarily caused by transient myocardial ischemia, which can result from either increased myocardial oxygen demand or decreased supply due to coronary artery disease, or from a combination of both mechanisms. The three main factors that determine myocardial oxygen demand are the force of myocardial contraction, heart rate, and ventricular wall tension during systole. Ventricular wall tension during systole (afterload) is expressed as the product of ventricular volume and systolic ventricular pressure, so clinically the product of heart rate and systolic blood pressure is called the rate-pressure product or double product and is used as an indicator of myocardial oxygen demand.
The coronary circulation is responsible for the supply of oxygen to the myocardium, which is expressed as the product of the difference in oxygen content between the coronary artery and vein and the coronary blood flow rate. In the coronary circulation, the myocardial oxygen uptake rate is extremely high, with the difference in oxygen content between the coronary artery and vein reaching 70-75% even at rest, and it rarely increases further even if the myocardial oxygen demand increases. Therefore, the supply of oxygen to the myocardium is actually controlled by the coronary blood flow rate. Myocardial ischemia is a condition in which the amount of blood required for the metabolism of the myocardium is not supplied in sufficient quantity, and is accompanied by the accumulation of metabolic products due to reduced perfusion. The mechanisms of myocardial ischemia include when the oxygen supply cannot keep up with the increased oxygen demand of the myocardium (relative oxygen deficiency) and when the oxygen supply itself is reduced (absolute oxygen deficiency) (Figure 5-7-5). Therefore, there are two major mechanisms that can be considered for the development of angina pectoris. One type is organic angina, which occurs when myocardial ischemia occurs because the myocardium does not receive the oxygen it needs when myocardial oxygen demand increases during exercise or mental excitement due to severe organic stenosis of the coronary arteries. The other type is coronary spastic angina (or vasospastic angina), which occurs when the oxygen supply to the myocardium is reduced due to spasms in the coronary arteries.
1) Coronary artery sclerosis:
Coronary artery sclerosis does not immediately lead to coronary artery stenosis, and not all coronary artery stenosis leads to myocardial ischemia. When lipid-laden plaque (atheroma) accumulates in coronary artery stenosis, the blood vessel diameter actually expands to a certain extent (positive remodeling), but as the stenosis progresses, the lumen narrows (negative remodeling). The relationship between coronary artery stenosis and blood flow is not linear; blood flow begins to decrease at rest when the coronary artery is stenotic to 80%, and the maximum blood flow equivalent to exercise begins to decrease when the stenosis is 50% or more. In other words, coronary artery stenosis that causes angina pain (significant stenosis) only becomes noticeable as a symptom of exertional angina once the condition has progressed to a certain extent.
Cardiovascular events associated with acute coronary syndromes, such as unstable angina and acute myocardial infarction, occur when plaque rupture leads to vascular occlusion caused by thrombus formation. Plaque rupture depends on the size of the lipid core, the thinness of the plaque capsule, and the degree of inflammatory cell infiltration, and is also thought to be influenced by changes in circulatory dynamics such as blood pressure and blood flow, as well as systemic factors.
2) Coronary spasm:
Vasospastic angina is caused by excessive contraction of the coronary artery (coronary spasm), which leads to myocardial ischemia; however, complete occlusion causes transmural ischemia in the perfused area, resulting in angina accompanied by ST-segment elevation on the electrocardiogram, i.e., variant angina. When the coronary artery is incompletely occluded or diffusely narrowed due to spasm, non-transmural ischemia occurs, resulting in angina accompanied by ST-segment depression. Coronary spasm tends to occur at rest from the night to early morning, and presents with the clinical picture of rest angina. Coronary spasm can also be induced by exertion, but is more likely to occur in the morning, and multivessel coronary spasm has high disease activity and is prone to producing severe symptoms.
3) Vascular endothelial function:
Vascular endothelium regulates vascular tone by producing and releasing three main types of endothelium-derived relaxing factors (EDRFs): nitric oxide (NO), prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). The most important of the EDRFs is NO. NO induces relaxation of vascular smooth muscle by increasing cyclic GMP through activation of guanylate cyclase (Figure 5-7-6).
Clinical manifestations
1) Symptoms:
Anginal pain, a symptom of an angina attack, is typically described as a feeling of tightness or pressure in the chest, such as a "squeezing" or "compression" in the anterior chest, or a burning sensation in the chest, such as a "burning" or "hot" feeling. The area of anginal pain is vague, usually extending beyond the palm of the hand, and it may also be felt in places other than the anterior chest, such as the shoulders, neck, back of the head, teeth, back, upper limbs, or epigastric region (radiating pain). The pain usually disappears within a few minutes. Exertion-induced anginal pain usually disappears within 1-2 minutes with rest. If chest pain persists for 30 minutes or more, acute myocardial infarction should be suspected. Attacks of exertional angina usually disappear within 2-3 minutes with rest or sublingual administration of nitroglycerin, but up to three tablets of nitroglycerin may be required to relieve severe angina attacks. If there is no response to nitroglycerin, it is important to consider the possibility of acute coronary syndrome, such as unstable angina or acute myocardial infarction, which may progress to acute myocardial infarction, or the possibility of a disease other than ischemic heart disease. Furthermore, attacks of exertional angina are characterized by being always precipitated by a certain level of exertion or rate-pressure product, and always disappearing with rest. For this reason, attacks often occur during the day when exertion is high. Furthermore, important symptoms of angina pectoris include shortness of breath and difficulty breathing during an attack. This is thought to be due to impaired left ventricular function, such as increased left ventricular end-diastolic pressure and decreased ejection fraction caused by myocardial ischemia.
The characteristics of angina pain caused by vasospastic angina are no different from exertional angina, but whereas attacks of exertional angina often occur during the day when people are more active, vasospastic angina is particularly likely to occur when resting from the night through to the early morning, and while it can be precipitated by mild exertion in the morning, it is often not precipitated even by considerable exertion from the afternoon onwards. In other words, there is a marked diurnal variation in attacks and in the exercise threshold required to cause an attack. This is because coronary artery tonus is increased from the night through to the early morning, making coronary artery spasm (coronary spasm) more likely to occur during these times.
2) Objective findings:
No special findings are observed when there is no attack. Examination should focus on the presence or absence of coronary risk factors such as hypertension, obesity, and dyslipidemia, as well as findings suggesting xanthomas, thickening of the Achilles tendon, diabetes, or smoking. During an attack, the third and fourth sounds may be heard as a sign of transient left ventricular dysfunction. Transient papillary muscle ischemia may also cause mitral regurgitation, resulting in a systolic murmur. Blood pressure generally rises during an attack, but may decrease in cases of severe myocardial ischemia. Heart rate usually increases, but often decreases in cases of ischemia of the inferior wall of the left ventricle. In vasospastic angina, the pulse and blood pressure are normal or tend to be bradycardia and blood pressure tends to decrease.
Test results
1) Electrocardiogram [⇨5-5-1)]: No characteristic findings are observed on an electrocardiogram when not at attack, except in special cases such as immediately after a severe ischemic attack. Electrocardiogram changes occur only during attacks. If an electrocardiogram is not obtained during an attack, an exercise or drug stress test is performed to make a diagnosis. In particular, with regard to vasospastic angina, if symptoms occur frequently, a definitive diagnosis can be made by recording a 12-lead electrocardiogram during attacks and when not at attack. Since coronary spasm occurs in the relatively large coronary arteries on the surface of the heart, it is accompanied by ST elevation, but when it is incompletely blocked or diffusely narrowed, angina attacks accompanied by ST depression occur. The variant angina reported by Prinzmetal et al. is considered to be one type of vasospastic angina accompanied by ST elevation at rest.
2) Holter ECG : A method for recording electrocardiogram changes during spontaneous attacks. In organic angina, ST depression occurs when the heart rate increases, while in vasospastic angina, ST depression or elevation occurs at night or early in the morning.
3) Stress electrocardiogram:
a) Exercise stress test: A method to induce an ischemic attack by increasing myocardial oxygen consumption through exercise stress. The rate-pressure product (RPP), which is heart rate x systolic blood pressure, is used as an index of myocardial oxygen consumption. i) Master stress test: This is useful as a screening test, but the sensitivity of detecting myocardial ischemia is low because the stress is light. ii) Multistage exercise stress test: Using an ergometer or treadmill, the stress is increased stepwise until angina pain, dyspnea, leg fatigue, etc. appear under electrocardiogram monitoring, or until the target heart rate is reached. Maximum or submaximal exercise stress tests are preferable. In organic angina, a positive result is considered when horizontal or downsloping type ST depression is observed on the electrocardiogram during exercise stress, which is 0.1 mV or more above the isoelectric line, i.e., the PR segment, and lasts for 0.08 seconds or more above the J point (Figure 5-7-7).
ST depression indicates subendocardial myocardial ischemia, while ST elevation indicates more severe transmural myocardial ischemia. Transient ST elevation attacks are associated with coronary artery spasm (Figure 5-7-8).
The appearance of transient negative U waves indicates myocardial ischemia during an exercise-induced attack of organic angina or during an attack of vasospastic angina (Figure 5-7-9).
b) Hyperventilation stress test: In order to induce coronary spasm, hyperventilation (approximately 25 times per minute or more) is performed for six minutes while the patient is at rest in the early morning. The mechanism by which coronary spasm occurs is that the Na ⁺ H ⁺ exchange system, an ion exchange system, works to correct the respiratory alkalosis caused by hyperventilation, pumping out H ⁺ from within cells (endothelium and smooth muscle cells). In exchange, Na ⁺ ions enter the cells. It is speculated that the Na ⁺ /Ca ² ⁺ exchange system then works, causing Ca ²⁺ ions to flow into the cells, which is why coronary spasm occurs. The resulting increase in Ca ²⁺ concentration in the endothelium and smooth muscle cells is similar to the effect of acetylcholine, and it has also been shown that when coronary spasm occurs, smooth muscle cells are highly sensitive to Ca ²⁺ .
4) Coronary angiography:
It is performed to evaluate organic stenotic lesions and coronary spasm.
a) Organic angina: Coronary angiography is performed to determine whether or not there is an organic lesion in the coronary artery, and if so, what extent and extent of the lesion, and whether or not revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery is indicated. Left ventriculography is performed at the same time as coronary angiography and is useful for evaluating left ventricular function.
Figure 5-7-10 shows coronary angiography images taken from the right anterior oblique RAO direction and the left anterior oblique LAO direction. Since the degree of stenosis may appear different depending on the direction of angiography, it is important to change the angle of angiography.
b) Vasospastic angina: A pharmacologic provocation test for coronary spasm is performed by administering acetylcholine or ergonovine into the coronary artery. Acetylcholine has the effect of releasing NO from the endothelium to dilate blood vessels, but at the same time it also exerts a strong vascular smooth muscle contracting effect. In cases of vasospastic angina, the production and release of NO from the coronary artery endothelium is reduced, and vascular tone is increased. It is believed that the reason why acetylcholine, an endothelium-dependent vasorelaxant, induces coronary spasm is due to impaired release of NO from the endothelium by acetylcholine and excessive contraction of vascular smooth muscle. Since the half-life of acetylcholine is very short, it spontaneously resolves, unlike spasms caused by ergonovine. In other words, it is useful for diagnosing multivessel coronary spasm because it does not require nitrates. Multivessel coronary spasm attacks are often severe and are one of the prognostic factors for vasospastic angina. In the case shown in Figure 5-7-11, coronary spasm occurred in both the left and right coronary arteries during the acetylcholine loading test (this is called multivessel coronary spasm).
5) Echocardiogram:
During an attack, abnormalities in the wall motion of ischemic myocardium can be observed. If dobutamine stress echocardiography reveals significant organic stenosis in the coronary arteries, myocardial ischemia is induced and wall motion abnormalities can be evaluated. Coronary artery stenosis can also be estimated by coronary artery echocardiography, which depicts coronary blood flow at rest using color Doppler and measures and analyzes the coronary blood flow velocity using pulsed Doppler.
6) Biochemical tests:
The ischemia of angina pectoris is transient and the myocardium is not in necrosis, so there is no increase in myocardial enzymes such as serum CK (creatine kinase), CK-MB, an isoenzyme with high myocardial specificity, and cardiac troponin T and I. Coronary risk factors include diabetes, dyslipidemia, hyperuricemia, and hyperhomocystinemia.
7) Nuclear medicine examinations:
Using myocardial perfusion agents thallium ( ^201Tl ) or technetium ( ^99mTc ), a relative decrease in blood flow to ischemic areas of the myocardium, abnormal wall motion of the ischemic myocardium, and decreased ejection fraction are detected through exercise stress or drug stress (intravenous adenosine injection). In stress ^201Tl myocardial scintigraphy, the nuclide is injected intravenously during maximum exercise stress, and the patient is placed at rest for a few minutes before scanning. The image shows the distribution of blood flow during stress, and blood flow defects indicate transient blood flow disorders or myocardial infarction. If the defects have disappeared in the resting image 2 to 4 hours later, this indicates transient myocardial ischemia, and if the defects remain, this indicates myocardial infarction. Currently, electrocardiogram-gated SPECT (single-photon emission computed tomography) is the most commonly used method in clinical practice. In the case shown in Figure 5-7-12, redistribution findings are observed from the anterior septum to the apex.
8) Cardiac CT : Multislice CT makes it possible to take images of the beating organ, the heart, and the increased number of detectors has enhanced the functionality of the device. It is useful for coronary artery disease unless there is severe calcification, and is excellent not only for evaluating coronary artery stenosis, but also for evaluating the properties of atherosclerotic plaque. An example is shown in Figure 5-7-13.
9) Cardiac MR : Not only is it useful for MRA (MR angiography) to evaluate coronary artery stenosis, but it is also useful for diagnosing cardiac function and regional wall motion using cine MRI, evaluating myocardial infarction and myocardial viability using delayed contrast MRI, and diagnosing myocardial ischemia using stress myocardial perfusion MRI. It is useful as a non-invasive test in cases where CT is difficult, such as cases of reduced renal function, severe coronary artery calcification, and cases where radiation exposure should be avoided.
Diagnosis 1: Correctly understand anginal pain through interview. If an electrocardiogram is recorded during an attack, the diagnosis is almost certain. Attacks quickly disappear with sublingual administration of nitroglycerin. To objectively prove the occurrence of transient myocardial ischemia, attacks are induced through exercise or drug loading and an electrocardiogram is recorded. Stress testing is contraindicated for unstable angina. If attacks of chest tightness occur during daytime exertion and disappear with rest, it is organic angina, and if chest tightness occurs while resting from late at night to early in the morning, it is vasospastic angina.
② If the electrocardiogram shows left bundle branch block or WPW syndrome, making it difficult to determine myocardial ischemia on the electrocardiogram, ^201Tl myocardial scintigraphy should be used to prove myocardial ischemia.
③The Canadian Cardiovascular Society severity classification (CCSC) (Table 5-7-3) is used to diagnose severity, and for unstable angina, the Braunwald classification (Table 5-7-4) is used.
④If chest pain is severe and persistent, serum creatine kinase (CK), CK isoenzyme (CK-MB), troponin T, troponin I, etc. should be measured to differentiate it from acute myocardial infarction.
⑤ Diagnosis of severity based on coronary artery disease: Multivessel disease is more severe than single-vessel disease, proximal stenosis is more severe than distal stenosis, and diffuse disease is more severe than focal disease. In terms of stenosis type, eccentric stenosis accompanied by thrombus and diffuse irregular disease are more severe.
⑥ Assessment of coronary risk factors: Evaluate coronary risk factors such as hypertension, smoking, dyslipidemia, diabetes, obesity, ischemic heart disease, family history of sudden death, personality, and stress.
⑦It can be difficult to make a definitive diagnosis of vasospastic angina, so guidelines outlining diagnostic key points have been created and a diagnostic flowchart has been included (Figure 5-7-14).
Differential diagnosis: Diseases that cause chest pain are subject to differential diagnosis, and include the following:
1) Heart disease:
a) Acute myocardial infarction: Compared to angina pectoris, the attacks are more intense and last longer (more than 30 minutes, often more than 1 hour), are ineffective against sublingual administration of nitroglycerin, and serum creatine kinase (CK), CK isoenzyme (CK-MB), troponin T, troponin I, etc. are elevated. Acute myocardial infarction is divided into ST-segment elevation acute myocardial infarction and non-ST-segment elevation acute myocardial infarction, and is categorized as an acute coronary syndrome along with unstable angina and sudden cardiac death. When electrocardiogram changes other than ST-segment elevation acute myocardial infarction are unclear, the difference between unstable angina pectoris and non-ST-segment elevation acute myocardial infarction is determined by the presence or absence of elevation of myocardial injury markers, i.e., the degree of ischemic injury, but they are considered to be pathological conditions on the same continuous disease spectrum, and have a very wide spectrum of severity, ranging from relatively mild cases that can be treated with drug therapy alone to cases requiring immediate revascularization, making early diagnosis and differentiation important.
b) Acute pericarditis, acute myocarditis: These are often accompanied by inflammatory symptoms such as fever, and electrocardiograms show widespread ST elevation that does not correspond to the coronary artery supply. Pericardial rub sound may also be heard. c) Cardiomyopathy: Patients with hypertrophic cardiomyopathy may sometimes complain of transient chest pain.
2) Pulmonary pleural disease:
a) Pulmonary embolism: Patients often complain of sudden chest pain and shortness of breath. Lung perfusion scans show defects corresponding to segments or lobes. Contrast CT is relatively simple and has a high diagnostic ability.
b) Pneumonia, pleurisy, pneumothorax, etc.
3) Aortic disease:
a) Aortic dissection: Symptoms include severe chest pain. If the lesion does not extend to the ostium of the coronary artery, no obvious ischemic changes will be seen on the electrocardiogram. A chest X-ray will show a marked enlargement of the aortic diameter, and a definitive diagnosis will be made by contrast CT scan.
4) Chest wall disease:
Intercostal neuralgia, costochondral fracture, chest muscle pain, etc.
5) Esophageal diseases:
Esophagitis, hiatal hernia, esophageal spasm, etc.
6) Digestive disorders:
Gastroduodenal ulcers, cholelithiasis, pancreatitis, etc. A particularly important point in differentiating between these conditions is whether or not the chest pain is relieved by sublingual administration of nitroglycerin. In the case of angina pectoris, the attack usually resolves within 2 to 3 minutes after sublingual administration.
The goal of treatment is to alleviate attacks, prevent myocardial infarction, and improve life prognosis. The aim is to prevent myocardial oxygen deprivation by increasing the oxygen supply to the myocardium, or by decreasing the myocardial oxygen demand, or both, in response to transient myocardial oxygen deprivation. In the case of exertional angina, triggers of attacks are avoided, and drug therapy is used to suppress the increase in myocardial oxygen demand. If this is insufficient, coronary artery bypass surgery or percutaneous coronary intervention (PCI) is performed to increase coronary blood flow, and therefore the supply of oxygen.
1) General treatment
a) Elimination or control of triggers of attacks: Physical exertion, mental excitement, cold, excessive drinking and eating increase oxygen consumption in the myocardium and can trigger exertional angina, so they must be avoided.
b) Removal or control of risk factors for atherosclerosis: Most coronary artery stenosis is caused by atherosclerosis, and it is necessary to remove or control risk factors that promote atherosclerosis, such as hypertension, dyslipidemia, smoking, diabetes, and obesity.
2) Drug therapy:
a) Organic angina:
i) Treatment of attacks: Nitroglycerin is highly effective. As soon as an attack occurs, one tablet (0.3 mg) is placed under the tongue and allowed to dissolve. The effect usually appears within 2 to 3 minutes. If the attack worsens or does not subside after 5 minutes, one more tablet should be added. If symptoms do not subside after 3 to 4 tablets are administered sublingually, the patient should be transferred to a coronary care unit (CCU) or equivalent facility where monitoring can be performed and treatment should be provided.
Nitrates such as nitroglycerin dilate the venous system, reducing the amount of blood returning to the heart, thereby decreasing the volume of the ventricle, lowering tension in the ventricular wall, and reducing the oxygen demand of the myocardium. At the same time, they dilate the large parts of the coronary arteries. Due to this mechanism of action, they eliminate attacks of exertional angina by reducing the oxygen demand of the myocardium.
ii) Medications for angina pectoris: Sublingual administration of nitroglycerin is short-lived, and drugs that are effective for a long time are required to prevent attacks. ① β-blockers: β-blockers are widely used to treat exertional angina, as they reduce myocardial oxygen demand by lowering heart rate, blood pressure, and myocardial contractility. ② Antiplatelet drugs: Aspirin is used unless contraindicated. After coronary intervention, aspirin and a thienopyridine antiplatelet drug are used in combination to prevent thrombosis. ③ Long-acting nitrates: These are effective by reducing tension in the ventricular wall and dilating the coronary arteries, but resistance has been reported. To prevent this, it is preferable not to maintain blood concentrations at a continuously high level, but to avoid administration during times when attacks are not occurring. ④ Calcium antagonists: Calcium antagonists are the first choice for vasospastic angina, but they dilate peripheral blood vessels to lower blood pressure, and some types also reduce heart rate, reducing myocardial oxygen demand and are effective for exertional angina.
iii) Percutaneous coronary intervention (PCI): 1) Plain old balloon angioplasty (POBA): Balloon angioplasty, first performed by Gruentzig in 1977, is less invasive than surgical procedures and has a high success rate, so it has been widely used for organic angina and coronary thrombotic angina. However, problems arose with acute occlusion and dissection of the dilated coronary artery and a high rate of restenosis, which led to the development of the following stents. 2) Coronary stent implantation (Figure 5-7-15): This method involves placing a special cylindrical metal wire (stent) in the coronary artery, and has rapidly become popular. Stent implantation reduces acute coronary occlusion, and the restenosis rate, while better than balloon dilation, was still only 20-30%. Since then, drug-eluting stents (DES), which are stents coated with immunosuppressants or anticancer drugs, have shown dramatic effects on restenosis, but there are concerns about the occurrence of late thrombosis and very late stent thrombosis (VLST), which can occur even after one year, and this is a topic of ongoing debate. Furthermore, there is no proof that DES improves life prognosis. 3) High-speed rotational atherectomy 4. Excimer laser coronary angioplasty: This is a system in which a 308 nm laser beam is irradiated onto the stenosed or blocked lesion tissue via an excimer laser angioplasty laser catheter that is percutaneously inserted into the lesion in the coronary artery, vaporizing and removing the lesion and expanding the blood vessel lumen. In Japan, this system has been recognized as advanced medical care and has recently been covered by insurance.
iv) Surgery (coronary artery bypass surgery: CABG): Most can be controlled by drug therapy or catheter therapy, but in some cases, there are cases where it cannot be controlled by medical treatment, and in such cases coronary artery bypass surgery (AC bypass) is considered. If there is a stenosis in the main trunk of the left coronary artery or a stenosis of 75% or more on three branches, and the periphery of the stenosis is sufficiently thick, it is considered to be an indication for surgery. The blood vessels used for bypass include the internal thoracic artery, the great saphenous vein, the radial artery, and the gastro-omental artery.
b) Coronary spasm angina:
i) Treatment during seizures: Nitroglycerin is significantly effective in the same way as exerted angina pectoris.
ii) Treatment drugs:
(1) Ca antagonists: Ca antagonists that suppress intravascular smooth muscle cells Ca influx have a high antispasm effect and are the most appropriate agent for coronary spasm angina pectoris.
(2) Beta-blockers: It is relatively dominant in alpha receptors, which promotes vasoconstriction, exacerbate coronary spasm angina pectoris, and worsens prognosis. If β-blockers are necessary because organic stenosis is present, it is recommended to use a Ca antagonist or nitrate drug in combination.
(3) Persistent nitrate drugs: It compensates for the decline in NO activity due to impaired coronary endothelial function, and is effective in coronary spasms with a different mechanism of action than Ca antagonists, and is important to use differently depending on the combination with Ca antagonists and case studies.
(4) Nicolanzil: A derivative of nicotinamide and has selective coronary artery dilation and inhibitory coronary spasm. Due to its mechanism of action different from Ca antagonists, it may be used in drug-resistant cases.
c) Angina pectoris with organic stenosis added to organic stenosis: Organic and coronary spasm angina pectoris do not exist independently, but organic stenosis and spasm may be involved in various degrees, so it is important to treat the patient while considering the degree of involvement of both.
d) Angiogenesis: In severe cases where coronary revascularization is not applicable, cells with differentiation and inducing angiogenesis can be directly implanted into blood vessels, or exogenous administration of cytokines with angiogenesis promoter effects can be used to neovascularize capillaries, promote collateral circulation, and improve cardiac function decline and subjective symptoms associated with ischemia.
Course and prognosis The course and prognosis of angina pectoris is dependent on the pathology, severity, whether or not there has been a history of myocardial infarction, left ventricular function, complications (diabetes, left ventricular hypertrophy), etc.
1) Organic angina:
Multi-branch lesions, left coronary artery main lesions, and cases of impaired left ventricular function have a poor prognosis (Figure 5-7-16). Unstable angina pectoris, where the frequency, intensity, and duration of seizures gradually worsen, is at a high risk of acute myocardial infarction and sudden death.
2) Coronary spasm angina:
The prognosis has been relatively good due to the emergence of Ca antagonists, but if the spasms do not localize only to one branch and appear in multiple branches, it may cause fatal arrhythmias during seizures, and it is necessary to continue taking oral care. [Ogawa Hisao and Masamoto Seiji]
■ References
Braunwald E ed: Heart Disease: A Textbook of Cardiovascular Medicine, 3rd ed, Saunders, Philadelphia, 1988.
Yamagishi Masakazu, et al: Guidelines on the selection criteria for the diagnosis and understanding of chronic ischemic heart disease (revised edition 2010).
Guidelines for Diagnosis and Treatment of Cardiovascular Diseases (Report of the 2009 Joint Research Group), Japanese Society of Cardiovascular Sciences, 2010. http://www.j-circ.or.jp/guideline/pdf/JCS2010_yamagishi_h.pdf
Ogawa Hisao, et al: Guidelines for the diagnosis and treatment of coronary spasm angina pectoris. Guidelines for the diagnosis and treatment of cardiovascular disease (Reporting the Joint Research Group 2006-2007)
Circulation Journal, 72, Suppl Ⅳ, 1195-1238, 2008．

Table 5-7-2
Classification of angina pectoris ">

Table 5-7-2

Table 5-7-3
"Canadian Cardiovascular Society Classifi cation, Circulation, '76"" >

Table 5-7-3

Table 5-7-4
Classification of unstable angina pectoris (Braunwald, 1988) ">

Table 5-7-4

Figure 5-7-5
Myocardial ischemia and pathology ">

Figure 5-7-5

Figure 5-7-6
Endothelial-derived relaxation factor EDRF ">

Figure 5-7-6

Figure 5-7-8
Electrocardiogram in patients with coronary spasm angina pectoris ">

Figure 5-7-8

Figure 5-7-9
Negative U wave ">

Figure 5-7-9

Figure 5-7-14
Diagnosis flow chart for coronary spasm angina pectoris (CSA) ">

Figure 5-7-14

Figure 5-7-16
Prognosis from the viewpoint of the number of affected branches and left ventricular ejection fraction ">

Figure 5-7-16

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

定義・概念
　狭心症とは，冠動脈病変により，心筋が一過性に虚血，つまり酸素欠乏に陥ったために生じる特有な胸部およびその隣接部の不快感（狭心痛）を主症状とする臨床症候群である．一過性心筋虚血の発生機序としては，冠動脈病変を基盤として心筋の酸素需要が増加するか，供給が減少するか，あるいは両方の機序の組み合わせにより生じる．
分類
　狭心症は，発症機序，発作の誘因，経過の観点から分類される（表5-7-2）．
1）発症機序からみた分類：
器質的狭窄による器質性狭心症，冠動脈の攣縮（冠攣縮：スパズム）による冠攣縮性狭心症，そして冠血栓性狭心症に分類される．本来は冠動脈造影所見に基づいて診断されるが，多くは問診から診断可能である．
2）発作の誘因からみた分類：
労作性狭心症，安静時狭心症，労作兼安静狭心症に分類される．労作性であっても器質的狭窄によることもあれば，労作により誘発された冠攣縮によることもある．
3）経過からみた分類：
安定狭心症，不安定狭心症に分類される．安定狭心症はある一定以上の労作によって生じる狭心症で，安定労作性狭心症を意味する．不安定狭心症は発作の頻度，強度が増加してくるもので急性心筋梗塞や突然死に至る可能性があり急性冠症候群として包括される．
4）無症候性心筋虚血：
心筋虚血を生じているにもかかわらず狭心痛あるいはそれに類似する症状を伴わない病態を無症候性心筋虚血（asymptomatic myocardial ischemia），あるいは無痛性心筋虚血（silent myocardial ischemia：SMI）とよび，1962年のWHO分類ですでに無痛性虚血性心疾患の項目として記載されている．実臨床では，たとえば高リスク患者に対する手術前検査など何らかの理由で長時間心電図や負荷試験などを行った際に発見されるとか，糖尿病を長期加療された患者が，症状はないものの虚血スクリーニング目的の運動負荷試験で見つかることも多い．高齢者や糖尿病患者に生じることが多い．また，有症状の狭心症患者でも無痛性の発作を高頻度に生じている．【⇨5-7-3）】
5）微小血管性狭心症：
労作時や安静時に狭心症を生じるが冠動脈造影上明らかな器質的狭窄も冠攣縮もないものを指す．冠動脈造影で見えない微小血管レベルでの狭窄や攣縮が原因であると考えられている．中年以降の女性にみられることが多く，内皮機能障害が原因とされている．
原因・病因
　食生活の欧米化と生活習慣の変化に伴って動脈硬化性疾患の典型である虚血性心疾患（狭心症，心筋梗塞）に対する関心は高まっている．原因としては冠動脈危険因子や生活習慣の欧米化があるが，病因として慢性炎症が注目されている．
1）冠動脈危険因子：
改善しうる危険因子として，脂質異常症，高血圧，喫煙，糖尿病，肥満，高尿酸血症などがあり，制御できない因子として，年齢，性（男性），家族歴，人種があげられる．
2）生活習慣様式：
喫煙，職業（ストレス），性格など動脈硬化の進展と関連する．カロリー過多，脂質過剰摂取，運動不足は肥満，耐糖能異常の大きな要因となり動脈硬化の進展を促進する．
3）慢性炎症：
冠動脈硬化は多くは粥状動脈硬化によるが，その進展にはRussell Rossの血管反応障害説を基礎として多くの研究がなされ，現在では動脈硬化症は血管の慢性炎症性疾患との概念が一般的である．
疫学
　厚生労働省の平成20年患者調査によると，虚血性心疾患（心筋梗塞，狭心症）の総患者数は80万人，性別にみると，男性46万人，女性34万人であり，うち狭心症は約60万人とされる．
病態生理
　狭心症は，一過性の心筋虚血が本体であるが，冠動脈病変を基盤として心筋の酸素需要が増加するか，供給が減少するか，あるいは両方の機序の組み合わせによって生じる．　心筋の酸素需要を規定する3つのおもな因子は，心筋の収縮力と心拍数および収縮期の心室壁の張力である．収縮期の心室壁の張力（後負荷）は，心室の容積と収縮期心室圧の積で表されるので，臨床的には心拍数と収縮期血圧の積がrate-pressure productまたはdouble productとよばれて心筋の酸素需要量の指標として用いられている．
　心筋への酸素の供給を司っているのが冠循環であり，心筋への酸素の供給は冠動静脈の酸素含有量の較差と冠血流量の積で表されるが，冠循環においては心筋の酸素摂取率はきわめて高く冠動静脈の酸素含有量の較差は，安静時でも70〜75％に達しており，心筋の酸素需要が増加しても，さらに増加することは少ない．したがって，心筋への酸素の供給は実際上，冠血流量によって支配される．心筋虚血とは，心筋の代謝に必要な十分量の血液が供給されない状態であり，灌流低下のために代謝産物の蓄積を伴う．心筋虚血の機序としては，心筋の酸素需要の増大に酸素供給が追いつかなくなる場合（相対的酸素不足）と，酸素供給自体が減少する場合（絶対的酸素不足），がある（図5-7-5）．　したがって，狭心症の発生には大きく２つの機序が考えられる．１つは冠動脈の器質的狭窄が強いために運動や精神的興奮時などの心筋酸素需要量が増加したときに心筋に必要な酸素が供給されずに心筋虚血が生じる器質性狭心症，もう1つは冠動脈に攣縮（スパズム）が生じることにより心筋への酸素供給量が減少することによる冠攣縮性狭心症（coronary spastic anginaあるいはvasospastic angina）である．
1）冠動脈硬化：
冠動脈硬化症が冠動脈狭窄に直ちに連続するものではなく，また冠動脈狭窄がすべて心筋虚血をきたすのではない．冠動脈狭窄は脂質の蓄積したプラーク（粥腫）が蓄積してもある程度まではむしろ血管径は拡大する方向に変形し（positive remodeling），進行すると内腔の狭窄（negative remodeling）が始まる．冠動脈の狭窄と血流の関係は直線的ではなく，安静時で血流が低下し始める冠動脈の狭窄は80％以上であり，運動時に相当する最大血流量が減少し始めるのは50％以上からである．つまり，狭心痛を起こす冠動脈狭窄（有意狭窄）はある程度進行した状態となってはじめて労作性狭心症の症状を自覚する．
　不安定狭心症，急性心筋梗塞などの急性冠症候群の心血管イベントは，プラーク破綻に伴う血栓形成から血管閉塞を生じ発症する．プラークの破綻は脂質コアの大きさ，プラーク皮膜の薄さ，炎症細胞浸潤，などの程度に左右され，また，血圧，血流などの循環動態の変化，さらに全身性の因子によっても影響されると考えられている．
2）冠攣縮：
冠攣縮性狭心症は冠動脈の過剰収縮（冠攣縮：スパスム）により心筋虚血をきたすが，完全に閉塞されると，その灌流域に貫壁性虚血を生じ，その結果，心電図上ST上昇を伴った狭心症，すなわち異型狭心症が起こる．冠動脈が攣縮により不完全に閉塞されるか，またはびまん性に狭小化される場合，非貫壁性虚血を生じST低下を伴った狭心症が起こる．冠攣縮は夜間から早朝にかけて安静時に生じやすく，安静狭心症の臨床像を呈する．冠攣縮は労作によっても誘発されるが，午前中に起こりやすく，多枝冠攣縮はdisease activityが高く重篤な症候が出現しやすい．
3）血管内皮機能：
血管内皮は，一酸化窒素（NO），プロスタグランジンI2（PGI2），内皮由来過分極因子（endothelium-derived hyperpolarizing factor：EDHF）の主として3種類の内皮由来弛緩因子（endothelium-derived relaxing factor：EDRF）を産生，遊離して，血管トーヌスの調節を行っている．EDRFの中で最も重要なものはNOである．NOはグアニル酸シクラーゼ活性化によるサイクリックGMPの増加により血管平滑筋の弛緩を惹起する（図5-7-6）．
臨床症状
1）自覚症状：
狭心症の発作時の症状である狭心痛（anginal pain）は，典型的には前胸部が“絞めつけられる”“圧迫される”などの胸部絞扼感や胸部圧迫感として，また，胸が“焼ける”“熱くなる”などの胸部灼熱感として訴えられる．狭心痛の範囲は漠然としており，手のひら以上の広がりをもつことが普通で，前胸部以外の場所で，肩，首，後頭部，歯，背中，上肢，心窩部などに狭心痛を感じることもある（放散痛）．痛みは通常数分以内に消失する．労作によって誘発される狭心痛は安静によって通常1～2分で消失する．胸痛が30分以上持続する場合には急性心筋梗塞を疑う．労作性狭心症の発作は安静あるいはニトログリセリンの舌下投与により，通常2～3分以内に消失するが，重症の狭心症発作消失にニトログリセリンが3錠ぐらいまで必要となることもある．ニトログリセリンに反応しない場合は急性心筋梗塞に移行する可能性のある不安定狭心症または急性心筋梗塞などの急性冠症候群の発症，あるいは虚血性心疾患以外の病気である可能性を考慮する．また，労作性狭心症の発作は一定以上の労作またはrate-pressure productにより必ず誘発され，安静により必ず消失するのを特徴とする．そのため，発作は労作の多い日中に生じることが多い．さらに，狭心症の症状として重要なものに，発作時の息切れ，呼吸困難がある．これは心筋の虚血に起因する左室拡張終期圧の上昇，駆出率の低下など左心室機能の障害によるものと思われる．
　冠攣縮性狭心症による狭心痛の性状は，労作性狭心症と変わらないが，労作性狭心症の発作が活動の多い日中に生じることが多いのに対し，特に夜間から早朝にかけての安静時に出現しやすく，午前中には軽度の労作によっても誘発されるが，午後からはかなりの労作によっても誘発されない場合が多い．つまり発作の著明な日内変動および発作を引き起こすのに要する運動閾値の著明な日内変動が認められる．これは冠動脈のトーヌスが夜間から早朝にかけて亢進しており，この時間帯には冠動脈の攣縮（冠攣縮）が出現しやすいことによる．
2）他覚所見：
非発作時には特別な所見は認められない．冠危険因子である高血圧，肥満，脂質異常症の有無，を疑わせる黄色腫やアキレス腱の肥厚，糖尿病，喫煙を示唆する所見がないかに注意をして診察する．発作時には一過性の左心室機能障害のあらわれとして，Ⅲ音やⅣ音が聴取されることがある．また一過性の乳頭筋虚血により僧帽弁閉鎖不全症をきたし，そのため収縮期雑音を聴取することがある．血圧は一般には発作時に上昇するが，強い心筋虚血の場合は低下することがある．心拍数は通常増加するが左室下壁の虚血の場合は減少することが多い．冠攣縮性狭心症では，脈拍，血圧は正常かむしろ徐脈，血圧低下傾向となる．
検査成績
1）心電図
【⇨5-5-1）】：非発作時の心電図では，高度の虚血発作直後など特別な場合を除いて特徴的な所見はない．発作時にのみ心電図変化を生じる．発作時の心電図がとらえられていないときは，診断をするために運動あるいは薬物での負荷検査を行う．特に冠攣縮性狭心症に関しては，症状が頻繁に発生している場合は，発作時と非発作時の12誘導心電図を記録することで確定診断がつく．冠攣縮は心臓表面の比較的太い冠動脈に起きるのでST上昇を伴うが，不完全に閉塞されるか，びまん性に狭小化されるときは，ST下降を伴った狭心症発作が起きる．Prinzmetalらが報告した異型狭心症は安静時にST上昇を伴う冠攣縮性狭心症の１つと考えられる．
2）Holter心電図
：自然発作時の心電図変化を記録する方法．器質性狭心症では心拍数増加時にST低下が，冠攣縮性狭心症では夜間から早朝にST低下あるいは上昇が記録される．
3）負荷心電図：
a）運動負荷試験：運動負荷により心筋酸素消費量を増加して虚血発作を誘発する方法．心筋酸素消費量の指標として，心拍数×収縮期血圧のrate-pressure product（RPP）が使用される．　ⅰ）マスター負荷試験：スクリーニング検査として有用であるが，負荷量が軽度なため心筋虚血検出の感度は低い．　ⅱ）多段階運動負荷試験：エルゴメーターやトレッドミルを用い，心電図モニター下に狭心痛や呼吸困難，下肢疲労などが出現するまで，または目標心拍数に達するまで負荷を段階的に増加する．最大運動負荷または亜最大運動負荷試験が望ましい．器質性狭心症では，運動負荷で心電図上，水平型（horizontal type）または右下がり型（downsloping type）のST下降が，等電位線すなわち，PR segmentより0.1 mV以上あり，しかもJ点より0.08秒以上持続する場合を陽性とする（図5-7-7）．
　ST下降は心内膜下の心筋虚血を表し，ST上昇はより強度の貫壁性の心筋虚血を表す．一過性のST上昇発作は冠動脈攣縮が関与している（図5-7-8）．
　一過性の陰性U波の出現は器質性狭心症における運動負荷時の発作時でも，冠攣縮性狭心症の発作時でも心筋の虚血を表す（図5-7-9）．
b）過換気負荷テスト：冠攣縮誘発を目的として早朝安静時に，過換気（25回/分以上を目安として）を6分間行う．冠攣縮の起きる機序として，過換気による呼吸性アルカローシスを補正するために，イオン交換系であるNa^＋H^＋交換系が働き，細胞内（内皮および平滑筋細胞）H^＋をくみ出す．それと交換にNa^＋イオンが細胞内に入ってくる．するとNa^＋/Ca²^＋交換系が働いてCa^2＋イオンが細胞内に流入し，そのために冠攣縮が起きると推測されている．結果的に内皮および平滑筋細胞のCa^2＋濃度が上昇することはアセチルコリンによる作用と同様であり，冠攣縮を起こす場合平滑筋細胞がCa^2＋に対して感受性が高くなっていることも明らかにされている．
4）冠動脈造影検査：
器質的狭窄病変や冠攣縮の評価を目的として行われる．
a）器質性狭心症：冠動脈に器質的病変が存在するかどうか，存在するとすればどの程度，どの範囲であるか，経皮的冠動脈インターベンション（percutaneous coronary intervention：PCI）や冠動脈バイパス手術による血行再建術の適応はあるかなどを決めるために冠動脈造影法を行う．左室造影法は冠動脈造影法を行うときに施行し，左心室の機能を評価するのに有用である．
　図5-7-10に，冠動脈造影の右前斜位RAO方向，左前斜位LAO方向からの像を示す．造影の方向によっては狭窄の程度が違って見えることがあるので角度をかえて造影することが重要である．
b）冠攣縮性狭心症：冠攣縮薬物誘発試験は，アセチルコリンあるいはエルゴノビンの冠動脈内投与により施行される．アセチルコリンは内皮よりNOを放出させて血管を拡張する作用を有するが，同時に強力な血管平滑筋収縮作用も示す．冠攣縮狭心症例では冠動脈内皮からのNOの産生，放出が低下し，血管トーヌスが亢進しており，内皮依存性血管弛緩物質であるアセチルコリンにより冠攣縮が惹起されるのは，アセチルコリンによる内皮からのNOの放出障害と血管平滑筋の過収縮によると考えられている．アセチルコリンの半減期は非常に短いためエルゴノビンによる攣縮とは異なり，自然寛解する．つまり，硝酸薬を必要としないため多枝冠攣縮の診断に有用である．多枝冠攣縮発作はしばしば重篤で冠攣縮性狭心症の予後規定因子の1つである．図5-7-11の症例はアセチルコリン負荷試験にて左右の冠動脈に冠攣縮を生じた（これを多枝冠攣縮という）．
5）心エコー図：
発作時に虚血心筋部の壁運動の異常が観察される．ドブタミン負荷心エコーで冠動脈に器質的な有意狭窄がある場合には心筋虚血が誘発され壁運動異常を評価できる．また，安静時のカラードプラ法で冠血流を描出しパルスドプラ法でその冠血流速度を計測・分析する冠動脈エコーにより，冠動脈狭窄を推定できる．
6）生化学的検査：
狭心症の虚血は一過性であり，心筋は壊死に陥っていないので，血清CK（クレアチンキナーゼ），心筋特異性の高いアイソザイムであるCK-MB，心筋トロポニンTやIなどの心筋由来の酵素は上昇しない．冠危険因子として，糖尿病，脂質異常症，高尿酸血症，高ホモシスチン血症などが認められる．
7）核医学的検査法：
心筋血流製剤のタリウム（²⁰¹Tl）やテクネシウム（^99mTc）を用いて，運動負荷や薬物負荷（アデノシン静注法）により，心筋の虚血部位への血流の相対的減少や虚血部心筋の壁運動の異常，駆出率の低下などを検出する．負荷²⁰¹Tl心筋シンチグラフィにおいては，最大運動負荷時に核種を静注して数分後に患者を安静にして撮影を行う．その像は，負荷時の血流分布を示し，血流欠損像は一過性の血流障害か心筋梗塞を表す．2〜4時間後の安静時像で欠損が消失していれば一過性心筋虚血を意味し，欠損像が残存していれば心筋梗塞を表す．現在臨床で汎用されてるのは，心電図同期SPECT法（single-photon emission computed tomography）である．図5-7-12の症例は，前壁中隔〜心尖部に再分布所見を認める．
8）心臓CT法
：マルチスライスCTにより，拍動する臓器である心臓が撮影可能となり，検出器の増加によって装置の機能が充実した．高度石灰化病変でなければ冠動脈疾患にとって有用で，冠動脈狭窄の評価のみならず，動脈硬化性プラークの性状評価にもすぐれている．図5-7-13に症例を示す．
9）心臓MR法
：冠動脈狭窄評価のためのMRA（MR angiography）のみでなく，シネMRIによる心機能と局所壁運動の診断，遅延造影MRIによる心筋梗塞と心筋バイアビリティの評価，負荷心筋パーフュージョンMRIによる心筋虚血の診断などに有用である．腎機能低下症例，冠動脈の高度石灰化症例，放射線被曝を避けたい症例などCT施行が困難な場合の非侵襲的検査として有用である．
診断
①問診にて狭心痛を正しく把握する．発作時の心電図が記録されれば診断はほぼ確定される．発作はニトログリセリンの舌下投与により速やかに消失する．一過性心筋虚血の出現を客観的に証明するために，運動負荷や薬剤負荷により発作を誘発して心電図を記録する．不安定狭心症に対して負荷試験は禁忌である．日中労作時に胸部圧迫感の発作があり，安静にて消失すれば器質性狭心症であり，深夜から早朝の安静時に胸部圧迫感が出現すれば冠攣縮性狭心症である．
②心電図に左脚ブロックやWPW症候群などがあり，心電図上の心筋虚血の判定が困難な場合には²⁰¹Tl心筋シンチグラフィを用いて心筋虚血を証明する．
③重症度診断として，Canadian Cardiovascular Societyの重症度分類（CCSC）が（表5-7-3），不安定狭心症では，Braunwaldの分類（表5-7-4）が用いられる．
④胸痛が強度で持続するとき，急性心筋梗塞と鑑別するために血清クレアチンキナーゼ（CK），CKアイソエンザイム（CK-MB），トロポニンT，トロポニンIなどを測定する．
⑤冠動脈病変による重症度診断：1枝病変より，多枝病変が，遠位部狭窄より近位部狭窄が，限局性病変よりびまん性病変が重症である．狭窄形態としては，血栓を伴う偏心性狭窄やびまん性不規則病変が重症である．
⑥冠危険因子の評価：高血圧，喫煙，脂質異常症，糖尿病，肥満，虚血性心疾患，突然死の家族歴，性格，ストレスなどの冠危険因子を評価する．
⑦冠攣縮性狭心症に対しては確定診断が難しい場合もあり，診断のポイントを示したガイドラインが作成され，診断のフローチャートが記載されている（図5-7-14）．
鑑別診断
　胸痛をきたす疾患は鑑別診断の対象となり，以下のような疾患があげられる．
1）心疾患：
　a）急性心筋梗塞：発作が狭心症のそれに比べると，より強度で持続時間も長く（30分以上，多くは1時間以上），ニトログリセリンの舌下投与に対しても無効であり，さらに血清クレアチンキナーゼ（CK），CKアイソエンザイム（CK-MB），トロポニンT，トロポニンIなどが上昇する．急性心筋梗塞はST上昇型急性心筋梗塞と非ST上昇型急性心筋梗塞に分けられ，不安定狭心症，心臓突然死とともに急性冠症候群として包括される．ST上昇型急性心筋梗塞ではない心電図変化のはっきりしない場合の，不安定狭心症と非ST上昇型急性心筋梗塞の違いは，心筋傷害マーカー上昇の有無，つまり虚血傷害の程度で決まってくるが，連続した同一疾患スペクトル上の病態としてとらえられ，薬物療法のみで治療可能な比較的軽症のものから早急な血行再建を要するものまで重症度のスペクトルが非常に広い特徴を有し，初期診断鑑別が重要になってくる．　
b）急性心外膜炎，急性心筋炎：発熱などの炎症所見を伴うことが多く，心電図上，冠動脈支配に一致しない広範囲のST上昇を認める．心膜摩擦音を聴取することもある．　c）心筋症：肥大型心筋症においてときに一過性に胸痛を訴えることがある．
2）肺胸膜疾患：
a）肺塞栓症：突然の胸痛と呼吸困難を訴えることが多い．肺血流シンチグラムでは区域または肺葉に一致する欠損をみる．造影CTは比較的簡便で診断能は高い．
b）肺炎，胸膜炎，気胸など
3）大動脈疾患：
a）大動脈解離：激しい胸痛で発症する．冠動脈入口部まで病変が及んでいなければ心電図には明らかな虚血性変化は生じない．胸部X線写真で大動脈径の著明な拡大を認め，造影CT検査で確定診断を行う．
4）胸壁疾患：
肋間神経痛，肋軟骨骨折，胸部筋肉痛など
5）食道疾患：
食道炎，食道裂孔ヘルニア，食道痙攣など
6）消化器疾患：
胃十二指腸潰瘍，胆石症，膵炎など
　鑑別点として特に重要なのは，ニトログリセリンの舌下投与により胸痛が消失するか否かということである．狭心症の場合，舌下投与後2〜３分以内で発作が消失するのがほとんどである．
治療
　目標は発作の寛解と心筋梗塞を予防し生命予後を改善すること．　心筋の一過性酸素欠乏に対し，心筋への酸素供給を増加させるか，または心筋の酸素需要を減少させる，あるいはこの両方により心筋の酸素欠乏を防ぐことが目的である．　労作性狭心症の場合は，発作の誘因を避けるとともに，薬物療法によって，心筋の酸素需要の増加を抑制する．　不十分ならば冠動脈バイパス手術や経皮的冠動脈インターベンション（PCI）を行い，冠血流量，つまり酸素の供給を増加するようにする．
1）一般療法
a）発作の誘因の除去ないし制御：身体的労作，精神的興奮，寒冷，過飲，過食などは心筋の酸素消費量を増加させ，労作性狭心症の誘因となるので避ける必要がある．
b）動脈硬化の危険因子の除去ないし制御：冠動脈狭窄病変はほとんどが動脈硬化に基づくものであり，高血圧，脂質異常症，喫煙，糖尿病および肥満など，動脈硬化を促進する危険因子の除去ないし制御が必要である．
2）薬物療法：
a）器質性狭心症：
　ⅰ）発作時の治療：ニトログリセリンが著効を呈する．発作が出現するとすぐに1錠（0.3 mg）を舌下に入れて溶解させる．通常2〜3分以内に効果があらわれる．発作が増強していく場合や5分を経過しても発作が消失しない場合には，さらにもう1錠追加する．3〜４錠の舌下投与後も症状の消失しない場合には，モニター可能な冠疾患集中治療室（coronary care unit：CCU）あるいはそれに準じた施設に移して治療を行う．
　ニトログリセリンなどの硝酸薬は静脈系を拡張して心臓へ還る血液量を減少させ，したがって心室の容積を減少させて心室壁の張力を低下させ，心筋の酸素需要量を減少させる．これと同時に冠動脈の太い部分を拡張させる．これらの作用機序のために，労作性狭心症に対しては心筋の酸素需要を減少させることにより発作を消失させる．
　ⅱ）狭心症の治療薬：ニトログリセリン舌下投与の持続時間は短く，発作の予防のためには長時間有効な薬剤が必要とされる．①β遮断薬：β遮断薬は，心拍数，血圧および心筋の収縮性を低下させることによって心筋の酸素需要を減少させるので広く労作性狭心症の治療に使用されている．②抗血小板薬：禁忌でなければアスピリンを使用する．冠動脈インターベンション後は血栓症予防としてアスピリンとチエノピリジン系抗血小板薬の2剤を併用する．③持続性硝酸薬：心室壁の張力の低下と冠動脈の拡張により有効であるが，耐性の出現が指摘されており，その予防のためには血中濃度を持続的に高レベルに保つのではなく，発作の起こらない時間帯は投与しないことが好ましい．④Ca拮抗薬：Ca拮抗薬は冠攣縮性狭心症に対し第一選択薬であるが，末梢血管を拡張して血圧を低下させ，また種類によっては心拍数も減少させるので心筋の酸素需要を減少させ，労作性狭心症に対しても有効である．
　ⅲ）経皮的冠動脈インターベンション（percutaneous coronary intervention：PCI）：①バルーン拡張術（plain old balloon angioplasty：POBA）：1977年にはじめてGruentzigにより行われたバルーン拡張術は，外科手術に比し侵襲が少なく，成功率も高いので器質性狭心症や冠血栓性狭心症に広く適用されたが，拡張部冠動脈の急性閉塞や解離および高い再狭窄率が問題となり次のステントが登場した．②冠動脈ステント留置術（coronary stent implantation（図5-7-15）：特殊な筒状の金属製のワイヤー（ステント）を冠動脈内に留置する方法で急速に普及した．ステント留置により急性冠閉塞が減少し，再狭窄率はバルーン拡張術よりは良好であったが20〜30％であった．その後，免疫抑制薬や抗癌薬でコーティングしたステントdrug-eluting stents（DES；薬剤溶出性ステント）は再狭窄には劇的な効果があるが，遅発性血栓症（late thrombosis）の発生，さらには1年以後にも生じるvery late stent thrombosis（VLST）が懸念されており議論が続いている．また，DESでも生命予後の改善は証明されていない．③高速回転式粥腫切除術（rotational atherectomy）ロータブレーター：ダイアモンド粒子でコーティングされたカテーテルの先端チップが高速回転することにより冠動脈の病変を切削する方法で，高度石灰化病変に有効である．④エキシマレーザ冠動脈形成術：308 nmのレーザ光を，経皮的に冠動脈内病変部に挿入されたエキシマレーザ血管形成用レーザカテーテルを介して狭窄，閉塞病変組織に照射することにより，病変部を蒸散，除去し，血管内腔を拡大するシステムでわが国では先進医療から，最近保険診療として認められた．
　ⅳ）外科手術（冠動脈バイパス術，coronary artery bypass graft surgery ：CABG）：大部分は，薬物療法，カテーテル治療によってコントロール可能であるが，中には内科的治療でコントロールしえない症例もあり，このような場合には冠動脈バイパス手術（A-Cバイパス術）が考慮される．左冠動脈主幹部の狭窄，または3枝に内径75％以上の狭窄があり，しかも狭窄の末梢が十分に太ければ，手術の適応となると考えられる．バイパスに使われる血管としては内胸動脈，大伏在静脈，橈骨動脈，胃大網動脈がある．
b）冠攣縮性狭心症:
　ⅰ）発作時の治療：ニトログリセリンが著効するのは労作性狭心症と同じである．
　ⅱ）治療薬：
　（1）Ca拮抗薬：血管平滑筋細胞内Ca流入を抑制するCa拮抗薬は，高い抗攣縮作用を有し，冠攣縮性狭心症に対する最も適切な薬剤である．
　（2）β遮断薬：相対的にα受容体優位となり血管収縮を助長し冠攣縮性狭心症を増悪させ予後を悪化させる．器質的狭窄が併存するためβ遮断薬を使う必要がある場合は，Ca拮抗薬や硝酸薬を併用することが推奨される．
　（3）持続性硝酸薬：冠動脈内皮機能の障害によるNO活性の低下を補い，Ca拮抗薬とは異なる作用機序で冠攣縮に有効であり，Ca拮抗薬との併用や症例により使い分けることが重要である．
　（4）ニコランジル：ニコチン酸アミドの誘導体であり選択的な冠動脈拡張作用と冠攣縮抑制作用を有する．Ca拮抗薬と異なる作用機序のため，薬剤抵抗性の症例に併用されることがある．
c）器質的狭窄に攣縮が加わった狭心症：器質性と冠攣縮性の狭心症は独立して存在するのではなく，器質的狭窄と攣縮がさまざまの程度で関与していることがあり，両方の関与の程度を考えながら治療することが重要である．
d）血管新生療法：冠血行再建術が適応とならない重症例において，血管への分化能や血管新生誘導能をもつ細胞を直接移植したり，血管新生促進作用を有するサイトカインを外因性に投与することによって，毛細血管を新生し側副血行路を促進させ，虚血に伴う心機能低下や自覚症状を改善させる．
経過・予後
　狭心症の経過と予後は，病態，重症度，心筋梗塞既往の有無，左心機能，合併症（糖尿病，左室肥大）などに左右される．
1）器質性狭心症：
多枝病変，左冠動脈主幹部病変，左室機能低下例は予後が悪い（図5-7-16）．発作の頻度，強度，持続時間が次第に増悪してくる不安定狭心症は，急性心筋梗塞や突然死に至る危険が大きい．
2）冠攣縮性狭心症：
Ca拮抗薬の出現により，予後は比較的良好となってきたが，器質的狭窄合併例，攣縮が1枝のみに限局せず，多枝に出現する場合は，発作時に致死的な不整脈を生じ突然死する可能性もあり，確実な内服継続が必要である．［小川久雄・掃本誠治］
■文献
Braunwald E ed: Heart Disease: A Textbook of Cardiovascular Medicine, 3rd ed, Saunders, Philadelphia, 1988.
山岸正和，他：慢性虚血性心疾患の診断と病態把握のための検査法の選択基準に関するガイドライン（2010 年改訂版）．
循環器病の診断と治療に関するガイドライン（2009 年度合同研究班報告），日本循環器学会，2010. http://www.j-circ.or.jp/guideline/pdf/JCS2010_yamagishi_h.pdf
小川久雄，他：冠攣縮性狭心症の診断と治療に関するガイドライン．循環器病の診断と治療に関するガイドライン（2006 - 2007 年度合同研究班報告）
Circulation Journal, 72, Suppl Ⅳ, 1195-1238, 2008．

表5-7-2
狭心症の分類">

表5-7-2

表5-7-3
"狭心症重症度分類（Canadian Cardiovascular Society Classifi cation, Circulation, '76）"">

表5-7-3

表5-7-4
不安定狭心症の分類(Braunwald，1988）">

表5-7-4

図5-7-5
心筋虚血発生と病態">

図5-7-5

図5-7-6
内皮由来弛緩因子EDRF">

図5-7-6

図5-7-8
冠攣縮性狭心症患者の心電図">

図5-7-8