Coronary artery disease

Coronary artery disease (CAD), also known as coronary heart disease (CHD) or ischemic heart disease (IHD), is a condition in which the coronary arteries that supply blood, oxygen, and nutrients to the heart muscle become narrowed or blocked, most commonly as a result of atherosclerosis. It is the most common type of cardiovascular disease and a leading cause of death worldwide. CAD can manifest as stable angina, acute coronary syndromes (including myocardial infarction), heart failure, or sudden cardiac death. Its development is driven by a complex interplay of genetic, metabolic, and lifestyle factors, and modern management integrates lifestyle modification, pharmacotherapy, and revascularization procedures.

Signs and symptoms

The clinical presentation of coronary artery disease ranges from asymptomatic to life-threatening events. The hallmark symptom is angina pectoris, typically described as pressure, heaviness, squeezing, or burning in the chest, often radiating to the left arm, neck, jaw, or back. Stable angina occurs predictably with exertion or emotional stress and is relieved by rest or nitroglycerin. Unstable angina refers to new-onset, worsening, or rest angina and is part of the acute coronary syndrome spectrum.

Some individuals, particularly women, older adults, and those with diabetes, may present with atypical symptoms such as dyspnea, fatigue, nausea, epigastric discomfort, or syncope. Silent ischemia, in which objective evidence of myocardial ischemia occurs without any symptoms, is common and particularly dangerous because it delays diagnosis. A myocardial infarction (heart attack) is often the first recognized manifestation, presenting with severe, prolonged chest pain, diaphoresis, shortness of breath, and frequently hemodynamic instability. Arrhythmias and sudden cardiac arrest can be the initial and terminal events in CAD.

Risk factors

Coronary artery disease is multifactorial, with risk factors classified as modifiable and non-modifiable. Non-modifiable factors include advanced age, male sex, and a family history of premature CAD (myocardial infarction or coronary revascularization in a first-degree male relative before age 55 or female relative before age 65). Certain genetic polymorphisms also contribute to baseline risk.

Modifiable risk factors form the foundation of preventive strategies. They include:

• Dyslipidemia: elevated low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol, and elevated triglycerides.
• Hypertension: sustained blood pressure ≥130/80 mmHg increases shear stress on endothelium and accelerates atherosclerosis.
• Cigarette smoking: both active and passive smoking damage vascular endothelium, increase thrombogenicity, and lower HDL.
• Diabetes mellitus: insulin resistance and hyperglycemia promote endothelial dysfunction, inflammation, and advanced glycation end-product formation.
• Obesity and physical inactivity: visceral adiposity contributes to metabolic syndrome, while regular exercise improves lipid profiles and endothelial function.
• Unhealthy diet: diets high in saturated fats, trans fats, sodium, and refined sugars, and low in fruits, vegetables, and fiber are atherogenic.
• Psychosocial factors: chronic stress, depression, anxiety, and social isolation are associated with neurohormonal changes that promote CAD.

Emerging risk factors include elevated lipoprotein(a), C-reactive protein as a marker of systemic inflammation, and chronic kidney disease. Many patients have multiple coexisting risk factors that multiply their total cardiovascular risk.

Pathophysiology

The underlying pathological process in most cases of CAD is atherosclerosis, a chronic inflammatory disease of the arterial wall. It begins with endothelial dysfunction, often triggered by risk factors such as hyperlipidemia, hypertension, smoking, or disturbed shear stress. This dysfunction leads to increased permeability to lipoproteins, particularly LDL, which accumulates in the intima and becomes oxidized. Oxidized LDL triggers an inflammatory response, recruiting monocytes that differentiate into macrophages and ingest lipids to become foam cells. These foam cells form the earliest visible lesion, the fatty streak.

Over time, smooth muscle cells migrate from the media to the intima, proliferate, and produce extracellular matrix components such as collagen, forming a fibrous cap over a lipid-rich necrotic core. This fibroatheroma can progressively narrow the lumen, causing flow-limiting stenosis. When myocardial oxygen demand exceeds the ability of the narrowed artery to deliver oxygen, ischemia develops, manifesting as stable angina.

Acute coronary syndromes result from plaque disruption—rupture, erosion, or fissure—exposing thrombogenic material to the bloodstream. This triggers platelet adhesion, activation, and aggregation, as well as activation of the coagulation cascade, leading to thrombus formation. A partially occlusive thrombus may cause unstable angina or non-ST-elevation myocardial infarction (NSTEMI), while a completely occlusive thrombus typically causes ST-elevation myocardial infarction (STEMI). The extent of myocardial necrosis depends on the duration of occlusion, collateral circulation, and metabolic demand.

Other less common mechanisms of myocardial ischemia in CAD include epicardial coronary artery spasm (Prinzmetal angina), microvascular dysfunction, and spontaneous coronary artery dissection.

Diagnosis

Diagnosis of CAD is based on clinical history, risk factor assessment, and a variety of diagnostic tests. The initial evaluation includes a thorough history, physical examination, resting electrocardiogram (ECG), and laboratory studies (lipid profile, blood glucose, cardiac biomarkers if acute syndrome is suspected).

For patients with stable symptoms suggestive of ischemia, non-invasive stress testing is often used to provoke and detect ischemia. Exercise ECG stress testing examines ST-segment changes and symptoms during treadmill or bicycle exercise. When the baseline ECG is abnormal or exercise capacity is limited, imaging stress tests are preferred: stress echocardiography evaluates regional wall motion abnormalities; myocardial perfusion imaging with single-photon emission computed tomography (SPECT) or positron emission tomography (PET) assesses relative perfusion defects at rest and under stress. Stress can be induced with exercise or pharmacological agents (dobutamine, adenosine, regadenoson).

Coronary computed tomographic angiography (CCTA) is a non-invasive anatomical test that directly visualizes coronary artery stenosis and plaque burden. It has high sensitivity for excluding significant CAD and has been increasingly used as a first-line test in low-to-intermediate risk patients. Coronary artery calcium scoring via non-contrast CT provides a quantitative marker of calcified plaque burden and strong prognostic information.

The gold standard for diagnosing epicardial CAD is invasive coronary angiography, which allows direct visualization of the coronary lumen and enables immediate percutaneous coronary intervention if indicated. Fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) can be measured during angiography to assess the functional significance of intermediate stenoses. Intravascular imaging modalities such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) provide detailed plaque characterization and guide optimal stent deployment.

For acute coronary syndromes, diagnosis relies on ECG findings (ST-segment elevation or depression, T-wave inversion, new left bundle branch block) and elevated levels of high-sensitivity cardiac troponins.

Prevention

Prevention of CAD is divided into primordial, primary, and secondary strategies. Primordial prevention aims to prevent the development of risk factors themselves by promoting healthy lifestyle choices from childhood: maintaining a healthy weight, regular physical activity, a heart-healthy diet (rich in vegetables, fruits, whole grains, and unsaturated fats; low in sodium, sugar, and saturated and trans fats), and avoiding tobacco.

Primary prevention targets individuals with one or more risk factors but without established CAD. It focuses on risk factor modification through lifestyle changes and, when appropriate, pharmacotherapy. Statins are the cornerstone for LDL-cholesterol lowering in individuals at elevated 10-year risk, as determined by risk estimation systems such as the Pooled Cohort Equation or SCORE2. Blood pressure control is achieved with lifestyle and antihypertensive medications, and diabetes management aims for glycemic control alongside cardiovascular risk reduction with agents such as SGLT2 inhibitors or GLP-1 receptor agonists that have proven cardiovascular benefit. Low-dose aspirin is no longer routinely recommended for primary prevention due to its bleeding risk, but may be considered in selected high-risk individuals.

Secondary prevention applies to patients with established CAD. It includes antiplatelet therapy (aspirin with or without a P2Y12 inhibitor for a period after acute events or stenting), high-intensity statin therapy to achieve LDL-cholesterol goals, beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in post-myocardial infarction or left ventricular dysfunction, and aggressive management of all modifiable risk factors. Cardiac rehabilitation programs improve exercise capacity, adherence to therapy, and quality of life.

Treatment

Treatment of CAD depends on the clinical presentation—chronic stable angina or acute coronary syndrome—and the extent and severity of disease.

Lifestyle and medical therapy are universal. All patients should receive counseling on smoking cessation, a Mediterranean-style diet, regular exercise, and weight management. Anti-anginal medications for symptom control include beta-blockers (first-line), calcium channel blockers, and long-acting nitrates. Ranolazine, ivabradine, and trimetazidine are second-line options. All CAD patients benefit from antiplatelet therapy (usually aspirin) and statins. In the setting of an acute coronary syndrome, dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor such as ticagrelor, prasugrel, or clopidogrel) is administered for at least 6–12 months, along with an anticoagulant during the acute phase.

Revascularization is indicated for patients with significant obstructive CAD who have refractory symptoms despite optimal medical therapy, high-risk anatomy (left main disease, proximal left anterior descending artery stenosis, multivessel disease), or large areas of ischemia. Options include:

• Percutaneous coronary intervention (PCI): balloon angioplasty with stent implantation, performed via radial or femoral access. Drug-eluting stents are standard to reduce restenosis. PCI is the preferred revascularization strategy for acute STEMI and many cases of unstable angina/NSTEMI.
• Coronary artery bypass grafting (CABG): surgical revascularization using arterial grafts (internal mammary artery, radial artery) and saphenous vein grafts. CABG is recommended over PCI in patients with complex multivessel disease, diabetes, and left ventricular dysfunction, as it often provides more durable long-term outcomes.

In patients with advanced heart failure or intractable angina who are not candidates for revascularization, spinal cord stimulation, enhanced external counterpulsation, or stem cell therapy have been explored. Refractory end-stage CAD may require heart transplantation.

Complication management includes anti-arrhythmic drugs or implantable cardioverter-defibrillators for malignant arrhythmias and treatment of heart failure according to guidelines.

Epidemiology

Coronary artery disease is the leading cause of death globally, responsible for an estimated 9 million deaths annually. The burden is shifting predominantly to low- and middle-income countries, which account for over 80% of cardiovascular deaths. In higher-income countries, age-standardized mortality rates have declined over recent decades due to improved prevention, acute management, and secondary prevention, although the absolute number of cases continues to rise with population aging.

Prevalence increases with age, and men are affected at earlier ages than women, although the gender gap narrows after menopause. Marked geographical variations exist, with the highest rates observed in Eastern Europe and Central Asia. Socioeconomic disparities influence both incidence and outcomes, with poorer populations experiencing higher risk factor burdens and worse access to care.

History

Descriptions of angina and its association with sudden death date back to ancient times, but the modern understanding of CAD emerged in the 18th and 19th centuries. William Heberden delivered his classic description of angina pectoris in 1768. Edward Jenner and Caleb Hillier Parry linked angina to coronary artery calcification. In the early 20th century, James B. Herrick elucidated the pathophysiology of myocardial infarction and the role of coronary thrombosis. The Framingham Heart Study, launched in 1948, identified the major cardiovascular risk factors and transformed the concept of preventive cardiology. The development of coronary angiography by Mason Sones in 1958, followed by coronary angioplasty by Andreas Grüntzig in 1977, and the first coronary artery bypass surgery by René Favaloro in 1967, revolutionized treatment. The introduction of statins in the 1980s and drug-eluting stents in the 2000s further dramatically improved patient outcomes.

Society and culture

The pervasive impact of CAD has shaped public health policy, diet, and lifestyle recommendations globally. Awareness campaigns such as the American Heart Association’s “Go Red for Women” have highlighted sex-specific differences in symptom recognition and treatment. Depictions in film and literature often portray the classic “clutching of the chest” during a heart attack, contributing to public recognition but also common misconceptions. Workplace wellness programs, urban design promoting walkability, and legislation to reduce trans fats or require calorie labeling reflect the societal response to the CAD epidemic. Advances in genetics and big data analytics are increasingly driving precision medicine approaches to CAD prevention and treatment, and research continues into novel anti-inflammatory therapies and regenerative strategies for damaged myocardium.