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Atherosclerosis for USMLE Step 3

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Atherosclerosis for the USMLE Step 3 Exam
Atherosclerosis
  • Definition:
    • Atherosclerosis is a chronic, progressive disease of the arterial wall characterized by plaque formation, which narrows the vessel lumen and restricts blood flow.
    • Plaques are made up of lipids, cholesterol, calcium, and inflammatory cells, predisposing patients to ischemic events, including myocardial infarction (MI) and stroke.
Atherosclerotic plaque
  • Risk Factors:
    • Non-modifiable: Age, male sex, and family history of cardiovascular disease.
    • Modifiable:
    • Hyperlipidemia: Elevated LDL cholesterol and low HDL are directly linked to plaque formation.
    • Hypertension: Contributes to endothelial injury, which promotes plaque development.
    • Smoking: Damages the endothelium, increasing oxidative stress and promoting inflammation.
    • Diabetes Mellitus: Enhances vascular inflammation and plaque formation through hyperglycemia.
    • Obesity and Sedentary Lifestyle: Linked to insulin resistance and hypertension, key components of metabolic syndrome.
Pathophysiology
  • Endothelial Injury and Dysfunction:
    • Endothelial damage is the first step in atherosclerosis, often due to hypertension, smoking, or high LDL, leading to increased permeability and inflammatory cell recruitment.
    • Endothelial dysfunction reduces nitric oxide (NO) production, which impairs vasodilation and enhances leukocyte adhesion.
  • Lipoprotein Infiltration and Oxidation:
    • LDL particles migrate into the arterial intima and undergo oxidation, becoming oxidized LDL (oxLDL), which is highly atherogenic.
    • oxLDL attracts monocytes that differentiate into macrophages, which then internalize oxLDL and form foam cells.
  • Foam Cell Formation and Fatty Streaks:
    • Foam cells accumulate in the intima, forming fatty streaks, the earliest visible lesion in atherosclerosis. These lesions may progress or stabilize.
  • Plaque Formation:
    • Chronic inflammation triggers smooth muscle cell migration to the intima, where they proliferate and secrete extracellular matrix proteins (e.g., collagen), forming a fibrous cap over a lipid core.
    • This fibrous cap stabilizes the plaque, but it can also become thin and rupture if inflammation persists.
  • Plaque Rupture and Thrombosis:
    • Stable Plaques: Have thick fibrous caps and less lipid content, leading to chronic luminal narrowing (e.g., stable angina).
    • Vulnerable Plaques: Thin fibrous caps and large lipid cores are prone to rupture, exposing thrombogenic material that triggers acute clot formation, leading to ischemic events like MI.
Clinical Manifestations
  • Coronary Artery Disease (CAD):
    • Plaque formation in coronary arteries causes CAD, which can present as stable angina, unstable angina, or MI.
    • Stable angina is predictable and occurs with exertion, while unstable angina or MI results from plaque rupture and thrombus formation.
  • Peripheral Artery Disease (PAD):
    • Atherosclerosis in peripheral arteries, especially in the lower limbs, leads to intermittent claudication, rest pain, and, in severe cases, ischemic ulcers or gangrene.
  • Cerebrovascular Disease:
    • Plaque formation in carotid or cerebral arteries can cause transient ischemic attacks (TIA) or ischemic stroke.
Diagnosis
  • Laboratory Testing:
    • Lipid Profile: Elevated LDL and low HDL levels are common.
    • Inflammatory Markers: High-sensitivity C-reactive protein (hs-CRP) may be elevated, indicating increased inflammation.
  • Imaging:
    • Coronary Angiography: Gold standard for evaluating coronary artery blockages.
    • Ankle-Brachial Index (ABI): Assesses PAD severity by comparing ankle and brachial blood pressure.
    • Carotid Ultrasound: Detects carotid artery stenosis in patients at risk for stroke.
Management
  • Lifestyle Modifications:
    • Diet and Exercise: A low-saturated-fat, high-fiber diet, combined with regular exercise, improves lipid profiles and cardiovascular health.
    • Smoking Cessation: Reduces endothelial damage and oxidative stress, helping to prevent plaque progression.
  • Pharmacologic Therapy:
    • Statins: First-line agents for lowering LDL and stabilizing plaques, with significant evidence in reducing MI and stroke risk.
    • Antiplatelet Therapy: Aspirin or clopidogrel is recommended to prevent thrombotic events in patients with CAD or following TIA.
    • Antihypertensive Therapy: ACE inhibitors, ARBs, and beta-blockers lower blood pressure and reduce cardiovascular risk.
    • Diabetes Control: Optimizing blood glucose levels, often with metformin or SGLT2 inhibitors, reduces cardiovascular complications in diabetes.
Key Points
  • Atherosclerosis:
    • A chronic arterial disease marked by plaque buildup, leading to ischemic complications like CAD, PAD, and stroke.
    • Main risk factors include hyperlipidemia, hypertension, smoking, diabetes, and a sedentary lifestyle.
  • Pathogenesis:
    • Begins with endothelial injury, followed by LDL infiltration and foam cell formation, leading to plaque progression.
    • Plaque rupture can cause thrombotic events, resulting in MI, stroke, or acute limb ischemia.
  • Diagnosis and Management:
    • Diagnosis includes lipid profile evaluation and imaging (e.g., angiography, ABI, ultrasound).
    • Treatment includes lifestyle changes, statins, antihypertensives, antiplatelet agents, and diabetes management to reduce cardiovascular risk.

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