36. Coronary artery disease – definition, types, pathogenesis.

Coronary artery disease – etiology, pathogenesis, types

• ⭐ Coronary artery disease or coronary heart disease (CHD) - heart disease caused by impaired coronary blood flow
• ❏ This results in damage to the myocardium due to an imbalance of myocardial blood supply and demand

Coronary circulation

• ❏ The coronary arteries are also called the epicardial arteries → run along the outer surface of the heart on the epicardium
• ❏ The main ones are the left coronary artery and the right coronary artery
• ❏ The left coronary artery divides into the left anterior descending and the left circumflex arteries
• ❏ The right coronary artery gives rise to the posterior descending artery along the back surface of the heart

Etiology of CHD

• ❏ Atherosclerosis is the most important factor
• ❏ Atherosclerosis is by far the most common cause of CHD, and atherosclerotic plaque disruption the most frequent cause of MI and sudden cardiac death
• ❏ Risk factors for atherosclerosis:

1. Modifiable - hyperlipidemia, hypertension, cigarette smoking, diabetes (endothelial cells have glut 1 transport which is insulin independent → high glucose levels can enter cells uninterrupted)
2. Non-modifiable - age, male gender, family history, genetic abnormalities, obesity

Pathogenesis of CHD

• ❏ Atherosclerosis can affect one or all three of the major epicardial coronary arteries and their branches
• ❏ Clinically significant lesions may be located anywhere in these vessels but tend to predominate in the first several centimetres of the left anterior descending and left circumflex or the entire length of the right coronary artery
• ❏ There are two types of atherosclerotic lesions:

1. The fixed or stable plaque → obstructs blood flow
2. The unstable or vulnerable plaque → can rupture and cause platelet adhesion and thrombus formation

• ❏ Atherosclerotic plaques are made up of a soft lipid-rich core with a fibrous cap
• ❏ Plaques with a thin fibrous cap and large lipid core are at greatest risk for rupture
• ❏ Plaque disruption may occur with or without thrombosis
• ❏ Platelets play a major role in linking plaque disruption to acute CHD
• ❏ As a part of the response to plaque disruption, platelets aggregate and release substances that further propagate platelet aggregation, vasoconstriction and thrombus formation
• ❏ Mechanism of atherosclerotic plaque formation:

1. Damaged endothelium → platelet aggregation + LDL accumulation
2. Macrophages are attracted to the site → combine with LDL to form foam cells
3. Smooth muscle cells migrate to the site forming an extracellular matrix
4. ECM + foam cells form fatty streaks
5. Fibrous plaque
6. Calcification