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Atherosclerosis for USMLE Step 1

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Atherosclerosis for the USMLE Step 1 Exam
Atherosclerosis
  • Definition:
    • Atherosclerosis is a chronic disease involving plaque buildup within the arterial walls, leading to narrowed vessels and reduced blood flow.
    • Plaques are composed of lipids, cholesterol, calcium, and inflammatory cells, contributing to progressive vessel obstruction and increasing the risk of ischemic events like myocardial infarction (MI) and stroke.
Atherosclerotic plaque
  • Risk Factors:
    • Non-modifiable: Age, male gender, and family history.
    • Modifiable:
    • Hyperlipidemia: Elevated LDL cholesterol promotes plaque formation.
    • Hypertension: Increases endothelial injury, promoting plaque development.
    • Smoking: Causes endothelial dysfunction and oxidative damage.
    • Diabetes: Accelerates atherosclerosis through vascular inflammation and endothelial injury.
    • Obesity and Sedentary Lifestyle: Associated with metabolic syndrome, which includes hypertension, insulin resistance, and dyslipidemia.
Pathophysiology
  • Endothelial Injury and Dysfunction:
    • Initiated by factors such as hypertension, smoking, and high LDL levels, leading to increased vascular permeability and inflammation.
    • Endothelial dysfunction reduces nitric oxide (NO) production, impairing vasodilation and promoting leukocyte adhesion to the endothelium.
  • Lipoprotein Infiltration and Oxidation:
    • LDL particles enter the intimal layer of the artery and undergo oxidative modification to become oxidized LDL (oxLDL).
    • oxLDL attracts monocytes, which differentiate into macrophages that internalize oxLDL and form lipid-laden foam cells.
  • Foam Cell Formation and Fatty Streaks:
    • Accumulation of foam cells forms “fatty streaks,” the earliest visible lesion of atherosclerosis, which can be seen in young adults.
  • Plaque Progression:
    • Chronic inflammation stimulates smooth muscle cell migration and proliferation from the media into the intima, where they secrete extracellular matrix proteins like collagen.
    • The result is a fibrous cap over a lipid core, forming a mature atherosclerotic plaque.
  • Plaque Stability and Rupture:
    • Stable Plaques: Thick fibrous cap, less prone to rupture; causes slow narrowing and symptoms like stable angina.
    • Vulnerable Plaques: Thin fibrous caps and large lipid cores make them prone to rupture, exposing thrombogenic material that can trigger clot formation and acute coronary syndrome (ACS).
Clinical Manifestations
  • Coronary Artery Disease (CAD):
    • Atherosclerosis in coronary arteries presents as angina or MI.
    • Stable angina is predictable and occurs with exertion; MI or unstable angina may follow plaque rupture and thrombosis.
  • Peripheral Artery Disease (PAD):
    • Involves atherosclerosis in peripheral vessels, especially in the lower limbs, causing intermittent claudication, ischemic pain at rest, or non-healing ulcers.
  • Cerebrovascular Disease:
    • Atherosclerosis in the carotid or cerebral arteries leads to transient ischemic attacks (TIA) or ischemic stroke.
Diagnosis
  • Laboratory Tests:
    • Lipid Profile: Elevated LDL and decreased HDL levels.
    • Inflammatory Markers: High-sensitivity C-reactive protein (hs-CRP) may be elevated, indicating inflammation.
  • Imaging:
    • Coronary Angiography: Direct visualization of coronary artery narrowing.
    • Ankle-Brachial Index (ABI): Used to assess the severity of PAD.
    • Ultrasound: Commonly used to assess carotid artery stenosis in cerebrovascular disease.
Management
  • Lifestyle Modifications:
    • Diet: Low in saturated fats, high in fruits and vegetables.
    • Exercise: Regular physical activity improves lipid profiles and cardiovascular health.
    • Smoking Cessation: Reduces oxidative stress and improves endothelial function.
  • Pharmacologic Therapy:
    • Statins: First-line agents for reducing LDL levels and stabilizing plaques.
    • Antiplatelet Therapy: Aspirin is used to prevent thrombotic events, especially in CAD or following TIA.
    • Antihypertensive Agents: ACE inhibitors or beta-blockers are often used to control blood pressure and prevent endothelial damage.
    • Diabetes Control: Optimizing blood glucose levels reduces cardiovascular risk in diabetics.
Key Points
  • Atherosclerosis:
    • Chronic disease marked by plaque buildup in the arterial wall, leading to conditions like CAD, PAD, and stroke.
    • Major risk factors include hyperlipidemia, hypertension, smoking, and diabetes.
  • Pathogenesis:
    • Begins with endothelial injury, LDL infiltration, and inflammation, leading to foam cell formation and plaque buildup.
    • Plaque rupture may lead to thrombosis and ischemic events like MI.
  • Diagnosis and Management:
    • Diagnosis involves lipid profiling and imaging to detect vascular blockages.
    • Management includes lifestyle changes, statin therapy, antihypertensive medications, and antiplatelet agents to reduce cardiovascular risk.

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