What is coronary artery disease?

What is Coronary Artery Disease?

Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial coronary arteries, combined with structural and functional abnormalities in both the macrovascular and microvascular coronary circulation, leading to myocardial ischemia when oxygen demand exceeds supply. 1, 2

Core Pathological Process

Atherosclerosis is the fundamental disease mechanism, beginning with endothelial dysfunction and progressing through distinct stages 2, 3:

• Initial endothelial injury occurs before any visible plaque formation 2
• Lipid accumulation in the arterial subintima creates early fatty streaks 2
• Inflammatory cells infiltrate and smooth muscle cells proliferate, forming complex plaques 3
• Fibrous cap develops over a lipid-rich core, which may thin and rupture 2, 3
• Plaque disruption triggers acute thrombosis, causing acute coronary syndromes 2

CAD is now understood as an inflammatory disorder, not simply cholesterol storage disease, fundamentally changing how we approach treatment 3, 4

Expanded Pathophysiology: Beyond Simple Blockages

The modern understanding has evolved from viewing CAD as fixed stenoses to recognizing multiple dynamic mechanisms 1, 2:

Macrovascular Abnormalities

• Fixed flow-limiting stenoses in large epicardial arteries remain important but are not the only mechanism 2, 3
• Diffuse atherosclerosis without visible narrowing can cause ischemia during stress 2
• Epicardial vasospasm produces transient ischemia even without significant stenosis 2, 3
• Structural anomalies like myocardial bridging contribute to symptoms 2

Microvascular Dysfunction

Coronary microvascular dysfunction (CMD) is increasingly recognized as prevalent across the entire CAD spectrum, affecting patients with and without obstructive disease 2, 3:

• Functional and structural microcirculatory abnormalities cause angina even with non-obstructive epicardial disease (ANOCA/INOCA) 2, 3
• Capillary rarefaction reduces myocardial perfusion capacity 2
• Risk factors promoting epicardial atherosclerosis simultaneously damage the entire coronary tree, including resistance arterioles 2, 3

Systemic Contributors

• Anemia, tachycardia, and blood pressure fluctuations create oxygen supply-demand mismatch 2, 3
• Myocardial hypertrophy and fibrosis increase oxygen requirements 2, 3
• Hypertension raises left ventricular wall tension and impedance 3

Multiple ischemic mechanisms frequently coexist in individual patients, making CAD a complex, multifactorial disease 2, 3

Major Risk Factors Driving Disease Development

Modifiable Risk Factors

These factors directly accelerate atherosclerosis and should be aggressively targeted 2, 5:

• Hypertension accelerates endothelial injury and plaque formation 2
• Elevated LDL cholesterol is a major driver of plaque accumulation 2, 5
• Diabetes mellitus significantly increases risk and is considered a CAD risk equivalent 2, 5
• Cigarette smoking causes direct vascular injury through oxidative stress 2
• Low HDL cholesterol independently predicts cardiovascular events 2, 5
• Physical inactivity substantially increases risk 2, 5
• Obesity affects blood pressure, lipid metabolism, and glucose tolerance 2, 5
• Atherogenic diet high in saturated fats and low in fruits/vegetables 2, 5

Non-Modifiable Risk Factors

• Advancing age reflects cumulative atherosclerosis burden 5
• Genetic predisposition involves at least 60 independent loci, though each contributes small individual effects 2
• Male sex increases risk, though women have worse outcomes after acute events 1

Emerging Risk Factors

• Left ventricular hypertrophy increases sudden cardiac death risk (HR 1.45 per 50 g/m² increment) 5
• Elevated resting heart rate predicts sudden cardiac death 5
• Socioeconomic and psychosocial stress independently contribute 2, 5

Persons with multiple risk factors face exponentially higher risk than those with single factors 5

Clinical Manifestations

CAD presents across a spectrum from stable chronic syndromes to life-threatening acute events 1:

Chronic Coronary Syndromes

• Stable angina provoked by exertion, emotion, or stress 1
• Dyspnea as an anginal equivalent 1
• Asymptomatic ischemia detected on screening 1

Acute Coronary Syndromes

For many adults, sudden cardiac death or acute myocardial infarction is the first manifestation, because most acute events result from rupture of previously non-obstructive plaques 1:

• Type 1 myocardial infarction from atherosclerotic plaque rupture with thrombosis 1
• Type 2 myocardial infarction from supply-demand mismatch without plaque rupture 1
• Myocardial infarction with non-obstructive coronary arteries (MINOCA), more common in women 1

Critical Clinical Considerations

CAD is a dynamic, progressive disease that may destabilize at any moment, not a static condition 1, 3. Patients transition between chronic and acute phases throughout their lifetime 3.

Women present differently than men 1:

• Higher proportion of plaque erosion, microvascular dysfunction, and vasospasm rather than classic plaque rupture 1
• Less obstructive disease on angiography but worse outcomes 1
• More likely to present late and in heart failure 1
• Pregnancy-related hypertensive disorders increase lifetime CAD risk 1

Vigorous exercise transiently increases risk of sudden cardiac death and myocardial infarction in both healthy individuals and those with known CAD 1