Coronary Artery Disease

Coronary artery disease is atherosclerotic narrowing of the epicardial coronary arteries, causing a mismatch between myocardial oxygen supply and demand. It is the leading cause of death worldwide. This article addresses the chronic phase (chronic coronary syndromes), as distinct from acute presentations.

Epidemiology and risk

• Prevalence of angina is about 3 to 5% in middle-aged adults and rises with age. Lifetime risk after age 40 is about 1 in 2 in men and 1 in 3 in women.
• Modifiable risk factors are smoking, hypertension, dyslipidaemia (raised LDL cholesterol, lipoprotein(a)), diabetes, obesity, physical inactivity and chronic kidney disease.
• Non-modifiable factors are age, male sex, premature family history (first-degree male relative under 55 or female relative under 65), and familial hypercholesterolaemia.
• Other contributors include chronic inflammatory disease, HIV, prior chest radiotherapy, and premature menopause.

Pathophysiology

• Lipid deposition and inflammation in the intima produce a plaque with a necrotic core and fibrous cap. Stable plaques narrow the lumen, and flow limitation appears at about 70% diameter stenosis at rest-adjusted demand.
• Vulnerable plaques with thin caps rupture or erode, which precipitates acute coronary syndromes. Most infarcts arise from plaques that were less than 70% stenotic.
• Non-obstructive mechanisms include microvascular dysfunction (INOCA), vasospastic angina and myocardial bridging.

Clinical syndromes within chronic coronary disease

• Stable exertional angina from obstructive epicardial disease.
• Angina with non-obstructive arteries: microvascular and vasospastic angina.
• Ischaemic cardiomyopathy and silent ischaemia.
• Asymptomatic disease detected on imaging, or stable symptoms after an acute event or revascularisation.

Anatomical burden determines prognosis. Left main stenosis of 50% or more, proximal LAD disease, three vessel disease and reduced ejection fraction carry the highest risk.

Typical angina has all three of these features

• Retrosternal chest pressure, tightness or heaviness, which may radiate to the left arm, neck, jaw or back.
• Provoked by exertion or emotional stress.
• Relieved within 5 minutes by rest or sublingual nitroglycerin.

Two of three features is atypical, and one or none is non-anginal chest pain. Women, older adults and patients with diabetes often present with dyspnoea, fatigue, epigastric discomfort or nausea. Angina equivalents include exertional breathlessness and arm or jaw pain.

Grading and variants

• Canadian Cardiovascular Society class I (strenuous activity only) to IV (symptoms at rest or with any activity).
• Decubitus angina occurs on lying flat. Walk-through angina fades with continued exercise. Postprandial angina follows meals.
• Vasospastic (Prinzmetal) angina occurs at rest, often at night or early morning, in younger patients and smokers, with transient ST elevation.
• Microvascular angina occurs in women with exertional symptoms and prolonged episodes.

Examination is often normal. Look for xanthelasma, tendon xanthomata, hypertensive retinopathy, a fourth heart sound, mitral regurgitation murmur during ischaemia, aortic stenosis, and signs of peripheral or carotid arterial disease.

Red flags

• New onset, crescendo, rest or prolonged angina, which indicate unstable angina and need emergency assessment.
• Syncope with exertion, heart failure symptoms, and ventricular arrhythmia.
• Chest pain with tearing quality, pleuritic or positional features, which suggest dissection, pulmonary embolism or pericarditis.

Differential diagnosis includes gastro-oesophageal reflux, oesophageal spasm, musculoskeletal pain, aortic stenosis, hypertrophic cardiomyopathy, pericarditis, anaemia, thyrotoxicosis, anxiety, and cocaine-induced ischaemia.

Estimate pretest probability from age, sex and symptom type. Investigate according to this probability.

Baseline tests

• Resting ECG (often normal, may show old infarction, ST-T changes or left ventricular hypertrophy).
• Fasting lipids including lipoprotein(a) once, HbA1c, creatinine and eGFR, CBC, TSH, and high sensitivity troponin if symptoms are recent or progressive.
• Resting echocardiography for ventricular function, wall motion abnormality, valve disease and hypertrophy.
• Chest radiograph when heart failure or pulmonary disease is suspected.

Selecting the diagnostic test

• Low to intermediate probability: coronary CT angiography is the preferred first test. It has a high negative predictive value (about 95 to 99%). A calcium score of zero carries a very low event rate in low-risk patients.
• Intermediate to high probability, known disease, or CT unsuitable (heavy calcification, arrhythmia, stent): functional imaging, which includes stress echocardiography, stress cardiac MRI, SPECT or PET myocardial perfusion.
• Very high probability with severe symptoms despite therapy, or high-risk features: invasive coronary angiography.
• Exercise ECG is limited by lower sensitivity (about 68%) and specificity (about 77%), but gives functional capacity. It is not useful in left bundle branch block, paced rhythm or resting ST depression of 1 mm or more.
• Pharmacological stress with dobutamine (up to 40 micrograms/kg/min) or vasodilators (adenosine 140 micrograms/kg/min, regadenoson 0.4 mg bolus) for patients unable to exercise.

High-risk findings: ischaemia over 10% of the myocardium (or 3 or more segments), ejection fraction under 40%, left main or proximal LAD stenosis, three vessel disease, and extensive wall motion abnormality.

Invasive physiology guides revascularisation in intermediate stenoses (40 to 90%)

• Fractional flow reserve of 0.80 or less is significant. Instantaneous wave-free ratio of 0.89 or less is significant.
• Provocative testing with intracoronary acetylcholine and coronary flow reserve for suspected vasospasm or microvascular disease (flow reserve under 2.0, index of microcirculatory resistance of 25 or more).

Prognostic work-up includes coronary artery calcium scoring in the asymptomatic intermediate-risk person (score above 100, or above the 75th percentile, favours statins).

Treatment has three goals: relieve symptoms, prevent myocardial infarction and death, and improve quality of life. Optimal medical therapy is the foundation for all patients.

Lifestyle

• Smoking cessation, with varenicline (0.5 mg daily days 1 to 3, 0.5 mg twice daily days 4 to 7, then 1 mg twice daily for 12 weeks) or bupropion SR 150 mg daily for 3 days then twice daily.
• Mediterranean pattern diet, sodium under 2 g/day, alcohol limited, weight loss, and at least 150 minutes per week of moderate aerobic exercise. Cardiac rehabilitation reduces cardiovascular mortality.
• Annual influenza vaccination and pneumococcal vaccination.

Secondary prevention

• Antiplatelet: aspirin 75 to 100 mg daily lifelong, or clopidogrel 75 mg daily in aspirin intolerance. After a recent myocardial infarction or PCI, dual therapy with aspirin and clopidogrel 75 mg is used for 6 to 12 months (1 to 3 months if bleeding risk is high), then single therapy.
• Rivaroxaban 2.5 mg twice daily plus aspirin 100 mg in stable disease with high ischaemic risk and low bleeding risk (reduces major cardiovascular events but increases bleeding).
• Lipids: high-intensity statin with atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg daily. Target LDL cholesterol under 55 mg/dL (1.4 mmol/L) with at least 50% reduction. Add ezetimibe 10 mg daily, then bempedoic acid 180 mg daily or a PCSK9 inhibitor (evolocumab 140 mg SC every 2 weeks or 420 mg monthly, alirocumab 75 to 150 mg every 2 weeks, or inclisiran 284 mg SC at day 0, 3 months, then every 6 months).
• ACE inhibitor (ramipril 5 to 10 mg daily, perindopril 8 to 10 mg daily) for hypertension, diabetes, heart failure, left ventricular dysfunction or chronic kidney disease. Use an ARB if intolerant (losartan 50 to 100 mg daily).
• Beta blocker (bisoprolol 2.5 to 10 mg daily, metoprolol succinate 50 to 200 mg daily) after myocardial infarction, in heart failure with reduced ejection fraction, and for angina.
• Diabetes: SGLT2 inhibitor (empagliflozin 10 mg daily or dapagliflozin 10 mg daily) and GLP-1 receptor agonist (semaglutide up to 1 mg weekly) for cardiovascular benefit. Metformin remains first line for glucose control.
• Anti-inflammatory: colchicine 0.5 mg daily has reduced events in stable disease, with gastrointestinal effects and interaction with strong CYP3A4 and P-glycoprotein inhibitors.
• Blood pressure target below 130/80 mmHg.
• Add omeprazole 20 mg daily or pantoprazole 40 mg daily for patients on dual antiplatelet therapy or at high gastrointestinal bleeding risk.

Anti-anginal therapy

• Sublingual nitroglycerin 0.4 mg (tablet or spray) for acute attacks, repeated every 5 minutes up to three doses. Warn about hypotension and absolute contraindication to concurrent phosphodiesterase-5 inhibitors (sildenafil within 24 hours, tadalafil within 48 hours) and riociguat.
• First line: beta blocker or a rate-limiting calcium channel blocker (diltiazem ER 180 to 360 mg daily, verapamil SR 120 to 480 mg daily). Do not combine these two. Dihydropyridines (amlodipine 5 to 10 mg daily, nifedipine ER 30 to 90 mg daily) combine with beta blockers.
• Long-acting nitrate: isosorbide mononitrate ER 30 to 120 mg once daily, with a nitrate-free interval of 10 to 14 hours (for example, no dose at night) to prevent tolerance.
• Second line add-ons: ranolazine 375 to 500 mg twice daily increasing to 750 to 1000 mg twice daily (QT prolongation, interaction with simvastatin above 20 mg), ivabradine 5 mg twice daily increasing to 7.5 mg twice daily (heart rate above 70 in sinus rhythm), trimetazidine 35 mg modified release twice daily, and nicorandil 10 to 20 mg twice daily.
• Vasospastic angina: amlodipine or diltiazem, with nitrates. Avoid beta blockers and aspirin dose escalation.
• Microvascular angina: beta blocker, calcium channel blocker, ranolazine, ACE inhibitor and statin.
• Refractory angina: enhanced external counterpulsation, spinal cord stimulation, coronary sinus reducer, and cardiac rehabilitation.

Revascularisation Indications for improving prognosis

• Left main stenosis of 50% or more.
• Proximal LAD stenosis with multivessel disease.
• Three vessel disease, particularly with diabetes or reduced left ventricular function (ejection fraction 35% or less).
• Large ischaemic territory (over 10% of myocardium) in the remaining patent artery.

Revascularisation also relieves symptoms in patients with persistent angina despite maximal therapy. In stable disease without these features, an initial invasive strategy does not reduce death or infarction compared with medical therapy.

Choice of method uses the SYNTAX score and the Heart Team

• PCI with drug-eluting stents: suitable for low to intermediate anatomical complexity (SYNTAX 22 or less), single vessel or two vessel disease, and high surgical risk. Left main PCI is an alternative to surgery with low to intermediate SYNTAX.
• Coronary artery bypass grafting: favoured in multivessel disease with diabetes, high SYNTAX score (33 or more), left main disease with complex anatomy, and reduced ejection fraction.

Follow-up

• Review at least annually: symptoms, adherence, blood pressure, lipids, HbA1c, renal function and weight. Repeat ECG and echocardiography when clinical status changes.
• Treat depression and anxiety, which are common and worsen outcomes. Sertraline 50 to 100 mg daily is the best studied antidepressant after infarction.
• Counsel on sexual activity resumption and driving after events. Avoid NSAIDs.