Three Main Etiologies of Coronary Artery Disease
The three main etiologies of CAD are: (1) atherosclerotic plaque formation causing obstructive disease, (2) coronary microvascular dysfunction, and (3) epicardial coronary vasospasm. 1, 2
1. Atherosclerotic Obstructive CAD
Atherosclerosis is the predominant cause of CAD, characterized by inflammatory plaque accumulation in epicardial coronary arteries that leads to flow-limiting stenoses. 1, 2
The pathological process begins with endothelial dysfunction, followed by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation in the arterial wall. 2
Plaques prone to rupture typically contain a large lipid core, low smooth muscle cell density, high macrophage density, and thin fibrous cap. 2
Three distinct thrombotic mechanisms cause acute coronary syndromes: plaque rupture (more common in men at 71% vs 33% in women), plaque erosion (more common in women at 58% vs 24% in men), and calcified nodules. 1
Atherosclerotic CAD is the leading cause of sudden cardiac death and acute myocardial infarction in adults over age 30-40 years. 1
2. Coronary Microvascular Dysfunction (CMD)
Microvascular dysfunction affects the coronary microvasculature and causes ischemia even without obstructive epicardial disease, representing a prevalent mechanism across the entire CAD spectrum. 1, 2
Microvascular angina results from structural or functional changes in the coronary microvasculature leading to impaired coronary flow reserve (CFR ≤2.0-2.5) and/or reduced microcirculatory conductance. 1
CMD prevalence ranges from 26% to 54% in patients with non-obstructive CAD, depending on assessment technique (PET, CMR, thermodilution, or Doppler). 1
Risk factors include smoking, age, diabetes, hypertension, dyslipidemia, and inflammatory conditions such as systemic lupus erythematosus and rheumatoid arthritis. 1
Functional and structural microcirculatory abnormalities can cause angina and ischemia independently of epicardial disease status. 1, 2
3. Epicardial Coronary Vasospasm
Vasospastic angina is caused by abnormal vasoconstriction of epicardial coronary arteries leading to dynamic coronary obstruction, which can occur with or without underlying atherosclerosis. 1, 2
Epicardial vasospasm can cause transient ischemia even without significant fixed stenosis. 2
Vasospasm prevalence varies by ethnicity: Japanese populations show higher rates than Western populations, with multiple coronary spasms (≥2 arteries) occurring in 24.3% of Japanese, 19.3% of Taiwanese, but only 7.5% of Caucasians. 1
Microvascular angina and epicardial vasospasm frequently co-exist, which is associated with worse prognosis. 1
Concomitant endothelial dysfunction is prevalent in most patients with inducible coronary artery spasm and/or impaired adenosine-mediated vasodilation. 1
Additional Non-Atherosclerotic Causes
While less common than the three main etiologies, other coronary conditions can cause acute cardiac events:
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. 1
Myocardial bridging, congenital coronary anomalies, Kawasaki disease, vasculitis, and cardiac transplant vasculopathy represent additional etiologies. 1
Clinical Integration
Different ischemic mechanisms frequently act concomitantly in the same patient, requiring comprehensive evaluation beyond simple angiographic assessment. 1, 2