Ischemic heart disease: Stable Angina pectoris – clinical features, treatment

01Definition and overview

Angina pectoris is discomfort in the chest, or nearby, caused by myocardial ischaemia: a supply of oxygen too small for the heart's demand. Stable angina is angina whose pattern has not changed for weeks: it comes on with a predictable level of effort or emotion and goes within minutes of rest or a nitrate.

European guidance places stable angina within the chronic coronary syndromes, the presentations of coronary disease outside an acute event. They include:

• suspected coronary disease with stable angina or breathlessness;
• coronary disease after an acute coronary syndrome or revascularisation;
• heart failure or left ventricular dysfunction caused by coronary disease;
• angina or ischaemia with non-obstructive coronary arteries (ANOCA or INOCA), caused by vasospasm or by dysfunction of the small vessels.

Unstable angina, which is new and severe, rapidly worsening, or occurs at rest or on minimal effort, is an acute coronary syndrome and is managed differently.

02Etiology and pathophysiology

Causes

• Atherosclerosis of the large epicardial coronary arteries, by far the commonest.
• Coronary vasospasm, in vasospastic (variant, or Prinzmetal) angina, which comes at rest, often at night or early morning, with transient ST elevation.
• Coronary microvascular dysfunction, in which the small vessels fail to dilate or constrict abnormally; more common in women and in diabetes.
• Causes outside the arteries that raise demand or lower supply: aortic stenosis, hypertrophic cardiomyopathy, severe hypertension, tachyarrhythmias, anaemia and thyrotoxicosis.

The risk factors for coronary atherosclerosis are age, male sex, a family history of premature coronary disease, raised LDL cholesterol and lipoprotein(a), smoking, hypertension, diabetes, obesity, physical inactivity, chronic kidney disease and chronic inflammatory diseases.

Why the pain comes with effort

Atheroma begins with damage to the endothelium, which lets LDL into the vessel wall. Macrophages take up the oxidised LDL and become foam cells (the fatty streak), smooth muscle cells migrate and lay down collagen, and a plaque forms with a lipid core and a fibrous cap. A stable plaque grows slowly and narrows the lumen.

At rest the flow through a narrowed artery is kept up because the small vessels beyond it dilate. On exertion the demand rises with the heart rate, the contractility and the wall stress, but the dilated small vessels have no reserve left, so the flow cannot rise enough once the narrowing is severe, usually more than about 50 to 70 per cent of the diameter. The subendocardium suffers first, because it is compressed during systole and perfused mainly in diastole, which shortens as the heart speeds up.

1. 1

   Demand outstrips supply

   Exertion, cold or emotion raises the heart rate and blood pressure; the narrowed artery cannot deliver more blood.
2. 2

   Metabolism shifts

   The myocardium beyond the narrowing turns to anaerobic metabolism and releases lactate, adenosine and bradykinin.
3. 3

   Function fails

   Relaxation is impaired first, then contraction of the ischaemic segment, which shows as a wall motion abnormality.
4. 4

   The ECG changes

   ST depression appears; unlike ST elevation, it does not show which artery is involved.
5. 5

   Pain

   Adenosine and bradykinin stimulate cardiac sympathetic afferents entering the spinal cord at C7 to T4, so the pain is felt in the chest, arms, neck and jaw. Rest lowers the demand and the pain goes within minutes.

This sequence, the ischaemic cascade, explains why pain is a late sign, why some patients, especially older people and those with diabetes, have ischaemia without pain, and why imaging of perfusion or wall motion is more sensitive than the ECG.

Nitrates relieve angina mainly by dilating the veins, which reduces the preload and the wall stress, and also dilate the coronary arteries and relieve spasm. Beta-blockers and rate-limiting calcium channel blockers lower the demand by slowing the heart, which also lengthens diastole.

03Clinical features

The history

Angina has three typical features:

1. a constricting, heavy or tight discomfort in the front of the chest, or in the neck, jaw, shoulder or arm;
2. brought on by physical exertion or emotional stress;
3. relieved by rest or a nitrate within 5 minutes.

Pain with all three is typical angina, with two atypical, and with one or none non-anginal. These labels are less useful than they seem: most patients describe their symptoms in less classic terms, and some have only breathlessness on exertion (an angina equivalent), fatigue or epigastric discomfort, especially women, older people and people with diabetes. Angina is worse in the cold, after a heavy meal and in the morning.

Pain that is sharp, lasts seconds, can be pointed to with one finger, changes with breathing, movement or pressure on the chest, or lasts for hours without other findings is unlikely to be angina. The differential diagnosis includes oesophageal reflux and spasm, musculoskeletal pain, pericarditis, pleurisy, pulmonary embolism, biliary pain and anxiety.

Examination

Examination is usually normal. It looks for the causes and the risk factors (raised blood pressure, xanthelasma, arcus and tendon xanthomas, signs of anaemia or thyrotoxicosis), the murmur of aortic stenosis or obstructive cardiomyopathy, signs of heart failure, and disease elsewhere in the arteries (carotid bruits, weak foot pulses).

04Diagnosis and management

Tests

European guidance works in four steps: a clinical evaluation with an ECG and blood tests, echocardiography with an estimate of the likelihood of coronary disease, diagnostic testing chosen by that likelihood, and treatment.

• ECG at rest, often normal; it may show Q waves of an old infarction, left ventricular hypertrophy, left bundle branch block or ST and T changes. An ECG during pain is very useful.
• Echocardiography at rest: left ventricular function, wall motion, valves (aortic stenosis) and hypertrophy.
• Blood tests: full blood count, creatinine, glucose and HbA1c, a lipid profile, lipoprotein(a) once, and thyroid function at least once. Troponin only if an acute coronary syndrome is suspected.
• A chest X-ray in selected patients, when heart failure or lung disease is possible.

The likelihood of obstructive coronary disease is then estimated from age, sex, the symptoms and the number of risk factors, and it can be refined by a coronary calcium score or other findings:

• CT coronary angiography shows the arteries without a catheter. Its strength is ruling out disease, and finding plaque leads to preventive treatment: in a large trial, adding it to usual care reduced coronary death or myocardial infarction over 5 years from 3.9 to 2.3 per cent, probably because more patients were started on preventive treatment.
• Functional tests show ischaemia and its extent, which links the symptoms to a particular artery and guides revascularisation.
• Invasive coronary angiography is used when the likelihood or the risk is very high, when non-invasive tests are inconclusive, or when revascularisation is planned. The functional significance of an intermediate narrowing is measured with a pressure wire: a fractional flow reserve of 0.80 or less, or an instantaneous wave-free ratio of 0.89 or less, means it limits flow.
• An exercise ECG alone is no longer recommended for diagnosis, because it misses and mislabels too many patients, but it still shows exercise capacity, symptoms and the blood pressure response.
• When angina persists with no obstructive narrowing, invasive testing of coronary function (acetylcholine for spasm, measures of microvascular resistance and flow reserve) can define the cause.

Treatment that prevents events

The core measures, lifestyle, a statin and an antiplatelet drug, are given to every patient with coronary disease and reduce myocardial infarction and death. The others are added for chosen patients:

• Lifestyle: stopping smoking, a Mediterranean-style diet, at least 150 minutes of moderate exercise a week, weight loss, little alcohol, and control of blood pressure and diabetes. An exercise-based cardiac rehabilitation programme, especially after an event.
• Statins at high intensity, to an LDL cholesterol below 1.4 mmol/L and a fall of at least 50 per cent, adding ezetimibe and then a PCSK9 inhibitor if the target is not reached.
• Aspirin 75 to 100 mg daily, or clopidogrel 75 mg daily as an alternative. After a stent in stable disease, aspirin and clopidogrel together for usually 6 months (1 to 3 months if the bleeding risk is high), then one drug for life. A second antithrombotic drug long term is considered for patients at high risk of events and low risk of bleeding.
• Low-dose colchicine, 0.5 mg daily, can be considered: in a large trial it reduced myocardial infarction, stroke and revascularisation by about 30 per cent, but not deaths.
• An ACE inhibitor (or ARB) for patients with hypertension, diabetes, chronic kidney disease or a reduced ejection fraction.
• In diabetes, an SGLT2 inhibitor or a GLP-1 receptor agonist with proven cardiovascular benefit; with overweight or obesity (a body mass index over 27) without diabetes, semaglutide can be considered.
• Annual influenza vaccination, and vaccination against pneumococcus and COVID-19.

Treatment that relieves angina

Antianginal drugs are chosen to suit the patient's heart rate, blood pressure, ventricular function and other diseases, and are often combined:

Vasospastic angina is treated with a calcium channel blocker, adding a long-acting nitrate if needed; a beta-blocker alone is avoided because it can worsen spasm. Microvascular angina is treated with the usual antianginal drugs, often a beta-blocker first, together with the statin and an ACE inhibitor.

When a patient is still limited after two drugs, revascularisation is discussed.

Revascularisation

Percutaneous coronary intervention (balloon angioplasty with a drug-eluting stent, through the radial artery) and coronary artery bypass grafting (internal mammary artery to the left anterior descending artery, with arterial or vein grafts to the others) are decided by a heart team.

• For symptoms: angina that limits the patient despite drugs. In a trial with a placebo procedure, stenting relieved angina in patients with proven ischaemia who took few antianginal drugs.
• For prognosis: a significant left main stem narrowing, three-vessel disease and narrowing of the proximal left anterior descending artery that limit flow. Added to drugs, revascularisation improves survival in left main disease and reduces cardiovascular death or myocardial infarction over the long term in the others. With multivessel disease and an ejection fraction of 35 per cent or less, bypass surgery improves survival.
• In other patients with stable disease and normal ventricular function, a large trial of patients with moderate or severe ischaemia found that early revascularisation did not reduce death or myocardial infarction over about 3 years compared with drugs alone, although angina improved more. So drugs come first, and revascularisation is added for symptoms or for the high-risk anatomy above.
• Bypass surgery is preferred over stenting for complex multivessel disease, particularly with diabetes; stenting suits simpler disease of one or two vessels.

Refractory angina, persisting despite full drug treatment and when revascularisation is not possible, is managed in specialist clinics with pain programmes and newer techniques.

05Epidemiology

Coronary heart disease is the commonest cause of death in the world. Angina becomes more common with age: in Europe about 5 to 7 per cent of women aged 45 to 64 have it and 10 to 12 per cent of those aged 65 to 84, and about 4 to 7 per cent and 12 to 14 per cent of men. Men develop obstructive coronary disease about ten years earlier than women; women more often have angina with non-obstructive arteries. Among patients now referred with suspected angina, most have a low likelihood of obstructive disease. Up to 70 per cent of patients with angina who undergo angiography, more often women, have no obstructive narrowing, and most of them have spasm or microvascular dysfunction. The age-adjusted rates of coronary death have fallen steadily in Western Europe with prevention and treatment.

06Prognosis

Most patients with stable angina do well: in older series about 1 to 2 per cent died each year, and about as many had a non-fatal myocardial infarction, and modern prevention has lowered these rates further. The risk is higher with a reduced ejection fraction (the strongest predictor), extensive or left main disease, ischaemia at a low workload, diabetes, kidney disease and persisting smoking. Angina with non-obstructive arteries is not benign: it carries a higher risk of events than normal arteries without angina, and the symptoms are often persistent and disabling.

Any change in the pattern, with pain more frequent, more easily provoked or at rest, signals an unstable plaque and needs urgent assessment, because a plaque that ruptures causes an acute coronary syndrome.