Pathophysiology of Coronary Artery Disease

Introduction to CAD Pathophysiology

Coronary artery disease involves complex structural and functional alterations in both macro- and microvascular compartments of the coronary tree, leading to myocardial demand-supply mismatch and ischemia 1
The European Society of Cardiology recognizes CAD as an inflammatory disorder with multiple pathophysiological mechanisms affecting both epicardial arteries and microcirculation 1

Atherosclerotic plaque accumulation in epicardial arteries is the fundamental pathological process in CAD, according to the European Heart Journal 1, 2
Plaque formation begins with endothelial dysfunction, followed by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation, as stated by the European Heart Journal 3
Plaques prone to rupture typically have a large lipid core, low smooth muscle cell density, high macrophage density, and thin fibrous cap, as described by the European Heart Journal 3

Coronary microvascular dysfunction is increasingly recognized as a prevalent factor across the entire spectrum of CAD, affecting patients with and without obstructive epicardial disease, as noted by the European Heart Journal 1, 2
Functional and structural microcirculatory abnormalities can cause angina and ischemia even with non-obstructive epicardial disease, as reported by the European Heart Journal 1, 2
Risk factors for epicardial atherosclerosis also promote endothelial dysfunction and abnormal vasomotion in the entire coronary tree, according to the European Heart Journal 1

Epicardial vasospasm can cause transient ischemia even without significant fixed stenosis, as stated by the European Heart Journal 1, 2
Endothelial dysfunction leads to impaired flow-mediated vasodilation in epicardial arteries, as described by the European Heart Journal 1
Macro- and microcirculatory vasoconstriction can occur due to endothelial dysfunction, as noted by the European Heart Journal 1

Anemia, tachycardia, and blood pressure changes can contribute to myocardial ischemia, as reported by the European Heart Journal 1, 2
Myocardial hypertrophy and fibrosis increase oxygen demand and contribute to ischemia, according to the European Heart Journal 1, 2
Hypertension increases LV output impedance and intramyocardial wall tension, raising myocardial oxygen demand, as stated by the American Heart Association 6
Systolic hypertension and wide pulse pressure increase aortic impedance and central systolic pressure augmentation, as described by the American Heart Association 6

CAD should be viewed as a dynamic, progressive condition that may destabilize at any moment, as noted by the European Heart Journal 1, 2
Different mechanisms of ischemia may act concomitantly in the same patient, as reported by the European Heart Journal 1
Patients may transition between different types of chronic coronary syndromes and acute coronary syndromes throughout their lifetime, according to the European Heart Journal 1, 7