Atherosclerosis and Cardiovascular Disease
Describe the mechanisms leading to atherosclerosis., What are the key inflammatory and lipid-related processes involved in the formation of atherosclerotic plaques, and how do these plaques contribute to the development of ischemic heart disease? What are the primary risk factors for atherosclerosis, and how do lifestyle modifications, pharmacological interventions (such as statins), and emerging therapies (such as PCSK9 inhibitors) help reduce cardiovascular risk? How does the rupture of an atherosclerotic plaque lead to acute coronary syndromes, and what are the treatment options available to restore coronary perfusion?
Mechanisms Leading to Atherosclerosis
Atherosclerosis is a complex disease characterized by the buildup of fatty deposits (plaques) within arterial walls, leading to narrowing and hardening of the arteries.
Key Mechanisms
- Endothelial Injury:
- Damage to the endothelium (the inner lining of blood vessels) can result from hypertension, smoking, diabetes, and high cholesterol. This injury increases permeability and promotes the adhesion of leukocytes and platelets.
- Lipid Accumulation:
- Low-density lipoprotein (LDL) cholesterol penetrates the damaged endothelium and becomes oxidized. Oxidized LDL triggers inflammatory responses and attracts monocytes, which differentiate into macrophages.
- Inflammation:
- Activated macrophages engulf oxidized LDL, transforming into foam cells. This accumulation of foam cells leads to the formation of fatty streaks, which develop into larger plaques over time.
- Cytokines and growth factors released during inflammation promote the recruitment of smooth muscle cells to the intima (inner layer of the artery), contributing to plaque growth.
- Plaque Formation:
- Over time, plaques grow and can become calcified, fibrotic, and necrotic. A fibrous cap forms over the lipid core, stabilizing the plaque.
Role of Atherosclerotic Plaques in Ischemic Heart Disease
Atherosclerotic plaques contribute to ischemic heart disease (IHD) by narrowing coronary arteries, reducing blood flow to the heart muscle. This can lead to:
- Angina: Chest pain due to insufficient blood flow during exertion or stress.
- Myocardial Infarction: Complete blockage of blood flow can cause heart tissue death.
Primary Risk Factors for Atherosclerosis
- Modifiable Risk Factors:
- Hyperlipidemia: Elevated LDL cholesterol and triglycerides.
- Hypertension: High blood pressure contributes to endothelial damage. APA