Etiologies and Pathogenic Mechanisms of Coronary Artery Disease

Primary Etiologies of CAD

The American College of Cardiology and other guideline societies acknowledge that atherosclerotic plaque formation in epicardial arteries, coronary microvascular dysfunction, and epicardial coronary vasospasm are the three main etiologies of CAD 1
Atherosclerosis is the predominant cause of CAD worldwide, accounting for the vast majority of cases, and is associated with classic risk factors including smoking, diabetes mellitus, hypertension, hyperlipidemia, family history of premature CAD, and postmenopausal state, as stated by the American Heart Association 2, 3, 1
The American College of Radiology notes that atherosclerotic CAD is the leading cause of sudden cardiac death and acute myocardial infarction in adults over age 30-40 years 1

The atherosclerotic process begins with endothelial dysfunction, followed by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation in the arterial wall, according to the American College of Cardiology 1, 4
Plaques prone to rupture 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, 4

Functional and structural microcirculatory abnormalities cause angina and ischemia through impaired coronary flow reserve and reduced microcirculatory conductance, even with non-obstructive epicardial disease, as noted by the American College of Cardiology 1, 4
Endothelial dysfunction leads to impaired flow-mediated vasodilation in both epicardial arteries and microcirculation, according to the American College of Cardiology 4

Myocardial ischemia results from an imbalance between myocardial oxygen demand and coronary blood flow, influenced by both coronary factors and systemic conditions, as stated by the Journal of the American College of Radiology and the American College of Cardiology 3, 4
Anemia, tachycardia, and blood pressure changes contribute to myocardial ischemia by altering the supply-demand balance, according to the American College of Cardiology 4

Spontaneous coronary artery dissection (SCAD) accounts for 87-95% of cases in women with mean presentation age 44-53 years, responsible for up to 43% of acute coronary syndrome cases in pregnancy, as noted by the American College of Cardiology 1
Congenital coronary anomalies, myocardial bridging, Kawasaki disease, vasculitis, and cardiac transplant vasculopathy represent additional etiologies, according to the American Heart Association and the American College of Cardiology 2, 1

Different ischemic mechanisms frequently act concomitantly in the same patient, requiring comprehensive evaluation beyond simple angiographic assessment, as stated by the American College of Cardiology 1, 4
Women with CAD more often have non-obstructive disease, coronary vasospasm, and abnormal vasodilator reserve compared to men, with up to 37% showing non-obstructive CAD on angiography despite positive biomarkers, according to the Journal of the American College of Cardiology 6
In patients with congenital heart disease, abnormal glucose metabolism and diabetes mellitus prevalence is significant, with at least 1 in 5 adults with congenital heart disease affected, representing a special population at increased risk for premature CAD, as noted by the American Heart Association 5