Coronary artery disease (CAD) typically refers to progressive atherosclerosis within the coronary arteries, ultimately diminishing blood flow to the myocardium. Less common causes for coronary artery obstruction exist (eg, dissections, vasospasm, vasculitis) and result in variants of the disease. In the early stages, patients are asymptomatic, and CAD may be undetected or incidentally identified, such as by visualization of coronary artery calcification indicative of atherosclerosis on a chest CT. Symptoms (angina) ultimately develop due to ischemia, insufficient blood flow to meet metabolic demand of the myocardium, which may occur in an acute or chronic fashion. Acute ischemia due to plaque rupture and coronary thrombosis results in an acute coronary syndrome (ACS), which is classified as unstable angina, non ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI), depending on severity and clinical features. These acute events are covered separately. Chronic, gradual progression generally results in stable angina, in which symptoms occur during periods of higher metabolic demand, such as physical exertion, and resolve with rest.

Inflammation is important in the pathogenesis of atherosclerosis. Endothelial cell dysfunction leads to macrophage and low-density lipoprotein (LDL) accumulations, causing foam cell formation and fatty streaks. This results in smooth muscle cell migration, proliferation, and extracellular matrix deposition, defined as a fibrous plaque. As the disease progresses, the fibrous plaque worsens and will eventually form a complex atheroma.

The hallmark symptom of ischemia is retrosternal chest pain / discomfort that may radiate to the neck, jaw, or left arm. Often, patients with this condition rest to ease the discomfort. The pain also generally improves with use of nitroglycerin. The pain is short-lived and starts gradually, rising to a maximum intensity within minutes, often described as "crescendo angina." Chest pain that reaches a peak within seconds should raise the possibility of an alternative diagnosis, notably aortic dissection. Other common symptoms include palpitations, nausea or heartburn-like symptoms, and hypotension. Atypical symptoms, such as dyspnea or syncope, are seen more often in women, elderly patients, and diabetic patients. Women tend to develop heart disease at a later age compared with men, with diabetes / insulin resistance, hypertension, obesity, and smoking being the strongest risk factors for early-onset CAD in women. There also appears to be an independent association between both hypertensive disorders during pregnancy and low birth weight with development of atherosclerotic cardiovascular disease.

Modifiable risk factors for development of CAD include smoking, hypertension, hyperlipidemia, type 2 diabetes mellitus, high glycemic index and glycemic load, obesity, and a sedentary lifestyle. Increased urinary sodium is associated with increased risk. Nonmodifiable risk factors include increasing age, male sex, postmenopausal status in women, and family history of CAD. Multiple forms of predominantly air pollution are risk factors for CAD.