Coronary Artery Disease Etiologies and Mechanisms

Introduction to CAD Etiologies

The American Heart Association acknowledges that the three main etiologies of CAD are atherosclerotic plaque formation, coronary microvascular dysfunction, and epicardial coronary vasospasm 1, 2, 3

Atherosclerosis is the predominant cause of CAD, characterized by inflammatory plaque accumulation in epicardial coronary arteries, according to the American College of Cardiology 4, 5, 6
The pathological process begins with endothelial dysfunction, followed by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation in the arterial wall, as stated by the European Society of Cardiology 1
Plaques prone to rupture typically contain a large lipid core, low smooth muscle cell density, high macrophage density, and thin fibrous cap, as described by the American Heart Association 1
Three distinct thrombotic mechanisms cause acute coronary syndromes: plaque rupture, plaque erosion, and calcified nodules, with plaque rupture being more common in men and plaque erosion more common in women, as reported by the American College of Cardiology 1
Atherosclerotic CAD is the leading cause of sudden cardiac death and acute myocardial infarction in adults over age 30-40 years, according to the American Heart Association 4, 5, 6

Microvascular dysfunction affects the coronary microvasculature and causes ischemia even without obstructive epicardial disease, representing a prevalent mechanism across the entire CAD spectrum, as stated by the European Society of Cardiology 2
Microvascular angina results from structural or functional changes in the coronary microvasculature leading to impaired coronary flow reserve and/or reduced microcirculatory conductance, as described by the American College of Cardiology 2
CMD prevalence ranges from 26% to 54% in patients with non-obstructive CAD, depending on assessment technique, according to the European Heart Journal 2
Risk factors for CMD include smoking, age, diabetes, hypertension, dyslipidemia, and inflammatory conditions, as reported by the American Heart Association 2

Vasospastic angina is caused by abnormal vasoconstriction of epicardial coronary arteries leading to dynamic coronary obstruction, which can occur with or without underlying atherosclerosis, as stated by the American College of Cardiology 4, 5, 6, 2
Epicardial vasospasm can cause transient ischemia even without significant fixed stenosis, according to the European Society of Cardiology 3
Vasospasm prevalence varies by ethnicity, with Japanese populations showing higher rates than Western populations, as reported by the European Heart Journal 2
Microvascular angina and epicardial vasospasm frequently co-exist, which is associated with worse prognosis, according to the American College of Cardiology 2

Spontaneous coronary artery dissection (SCAD) accounts for 87-95% of cases in women with mean presentation age 44-53 years, and is responsible for 5-17% of all SCAD cases and up to 43% of ACS cases in pregnancy, as reported by the American Heart Association 1
Myocardial bridging, congenital coronary anomalies, Kawasaki disease, vasculitis, and cardiac transplant vasculopathy represent additional etiologies, according to the American College of Cardiology 4, 7, 5, 6

Different ischemic mechanisms frequently act concomitantly in the same patient, requiring comprehensive evaluation beyond simple angiographic assessment, as stated by the European Society of Cardiology 2
CAD should be viewed as a dynamic, progressive condition that may destabilize at any moment throughout a patient's lifetime, according to the American Heart Association 3
Risk factors for epicardial atherosclerosis also promote endothelial dysfunction and abnormal vasomotion throughout the entire coronary tree, as reported by the American College of Cardiology 3

The European Society of Cardiology recommends that stable plaque is characterized by a thick fibrous cap, small lipid core, producing fixed stenosis causing effort-induced angina, as stated by the European Heart Journal 8, 9
Chronic stable angina is caused by fixed stenosis >70% which leads to demand-supply mismatch during exertion, according to the European Heart Journal 8, 9

The American Heart Association notes that smoking is a common trigger for coronary vasospasm, as reported in Circulation 10
Cold exposure, hyperventilation, and emotional stress can also trigger vasospasm, as stated in Circulation 10
Vasospasm can occur in normal arteries, non-obstructive CAD, or at sites of atherosclerotic plaque, according to the European Heart Journal and Circulation 8, 10

The American College of Cardiology states that spontaneous lysis can occur, leading to transient symptoms, possible MINOCA, as reported in Arteriosclerosis, Thrombosis, and Vascular Biology 11