Back
ditki Logo
medical & biological sciences

Atherosclerosis for USMLE Step 2

Start your One-Week Free Trial
Already subscribed? Log in »
Atherosclerosis for the USMLE Step 2 Exam
Atherosclerosis
  • Definition:
    • Atherosclerosis is a chronic, progressive disease involving the formation of plaques within the arterial wall, leading to vessel narrowing and reduced blood flow.
    • Plaques consist of lipids, cholesterol, calcium, and inflammatory cells, creating a pro-thrombotic environment and increasing the risk for ischemic events, including myocardial infarction (MI) and stroke.
Atherosclerotic plaque
  • Risk Factors:
    • Non-modifiable: Age, male gender, and family history.
    • Modifiable:
    • Hyperlipidemia: Elevated LDL cholesterol is directly linked to plaque formation.
    • Hypertension: Causes endothelial injury, accelerating atherosclerosis.
    • Smoking: Induces oxidative stress, damages endothelium, and promotes inflammation.
    • Diabetes Mellitus: Contributes to plaque formation through hyperglycemia and vascular inflammation.
    • Obesity and Sedentary Lifestyle: Associated with metabolic syndrome, which includes hypertension, insulin resistance, and dyslipidemia.
Pathophysiology
  • Endothelial Injury and Dysfunction:
    • Atherosclerosis begins with endothelial cell injury due to factors like hypertension, smoking, and high LDL levels, which increase vascular permeability and promote inflammatory cell recruitment.
    • Endothelial dysfunction impairs nitric oxide (NO) production, limiting vasodilation and enhancing leukocyte adhesion to the endothelium.
  • Lipoprotein Infiltration and Oxidation:
    • LDL particles infiltrate the subendothelial space and become oxidized, forming oxidized LDL (oxLDL), which attracts monocytes.
    • Monocytes differentiate into macrophages that internalize oxLDL, forming lipid-laden foam cells.
  • Foam Cell Formation and Fatty Streaks:
    • Foam cell accumulation leads to the formation of fatty streaks, the earliest detectable lesions of atherosclerosis.
    • These fatty streaks can progress to more advanced lesions over time.
  • Plaque Formation:
    • Inflammatory signaling promotes smooth muscle cell migration from the media to the intima, where they produce extracellular matrix proteins, such as collagen.
    • A fibrous cap forms over the lipid-rich core, creating a mature atherosclerotic plaque.
  • Plaque Stability and Complications:
    • Stable Plaques: Characterized by thick fibrous caps and low lipid content, leading to gradual luminal narrowing and stable angina.
    • Vulnerable Plaques: Thin fibrous caps and large lipid cores make them prone to rupture, triggering acute thrombosis and ischemic events like MI.
Clinical Manifestations
  • Coronary Artery Disease (CAD):
    • CAD, due to atherosclerosis in coronary arteries, presents as stable angina, unstable angina, or myocardial infarction.
    • Stable angina is predictable and occurs with exertion, while MI and unstable angina follow plaque rupture and thrombosis.
  • Peripheral Artery Disease (PAD):
    • Atherosclerosis in peripheral vessels, commonly in the lower extremities, leads to intermittent claudication (pain on exertion), ischemic rest pain, or ulcers in severe cases.
  • Cerebrovascular Disease:
    • Carotid or intracranial artery atherosclerosis leads to transient ischemic attacks (TIA) or ischemic strokes, depending on the area of vascular obstruction.
Diagnosis
  • Laboratory Tests:
    • Lipid Profile: Elevated LDL and low HDL levels indicate increased atherosclerosis risk.
    • Inflammatory Markers: High-sensitivity C-reactive protein (hs-CRP) may be elevated, signifying inflammation.
  • Imaging:
    • Coronary Angiography: Direct visualization of coronary artery stenosis.
    • Ankle-Brachial Index (ABI): A measure used to diagnose PAD.
    • Carotid Ultrasound: Used to detect carotid artery stenosis in patients at risk for stroke.
Management
  • Lifestyle Modifications:
    • Diet and Exercise: A diet low in saturated fats and high in fiber, combined with regular exercise, improves cardiovascular health.
    • Smoking Cessation: Reduces oxidative stress and helps prevent further plaque formation.
  • Pharmacologic Therapy:
    • Statins: First-line therapy for lowering LDL and stabilizing plaques, reducing the risk of MI and stroke.
    • Antiplatelet Therapy: Aspirin or clopidogrel is used to prevent thrombotic events, especially in CAD or post-TIA.
    • Antihypertensive Therapy: ACE inhibitors, ARBs, and beta-blockers are commonly used to reduce blood pressure and protect against further vascular damage.
    • Diabetes Control: Optimizing blood glucose levels with medications (e.g., metformin, SGLT2 inhibitors) lowers cardiovascular risk in diabetics.
Key Points
  • Atherosclerosis:
    • A chronic disease involving plaque buildup in arterial walls, leading to ischemic complications such as CAD, PAD, and stroke.
    • Major risk factors include hyperlipidemia, hypertension, smoking, diabetes, and obesity.
  • Pathogenesis:
    • Triggered by endothelial injury, LDL infiltration, and inflammation, which lead to foam cell formation and plaque progression.
    • Plaque rupture is the main cause of thrombotic events, including MI and stroke.
  • Diagnosis and Management:
    • Diagnosis includes lipid profile evaluation and imaging (e.g., angiography, ABI, ultrasound).
    • Management centers on lifestyle changes, statin therapy, antiplatelet agents, and blood pressure and glucose control to lower cardiovascular risk.

Related Tutorials