Atherosclerosis for ABIM
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Atherosclerosis for the American Board of Internal Medicine Exam
Atherosclerosis
- Definition:
- Atherosclerosis is a chronic inflammatory condition characterized by the buildup of plaque within the arterial walls, leading to narrowed arteries and reduced blood flow.
- Plaques consist of lipids, cholesterol, calcium, and inflammatory cells, which progressively obstruct the vascular lumen and increase the risk of ischemic events.
- Epidemiology:
- A leading cause of cardiovascular morbidity and mortality worldwide, responsible for coronary artery disease (CAD), stroke, and peripheral artery disease (PAD).
- Risk increases with age and is more common in males and postmenopausal females.
- Risk Factors:
- Non-modifiable: Age, male gender, and family history of premature atherosclerosis.
- Modifiable:
- Hyperlipidemia: Elevated low-density lipoprotein (LDL) cholesterol promotes plaque formation.
- Hypertension: Increases endothelial injury, which predisposes to plaque formation.
- Smoking: Contributes to oxidative stress, endothelial dysfunction, and inflammation.
- Diabetes Mellitus: Accelerates atherosclerosis through mechanisms including glycation of proteins and increased oxidative stress.
- Obesity and Sedentary Lifestyle: Associated with insulin resistance, hypertension, and dyslipidemia.
- Emerging Risk Factors:
- Inflammatory Markers: Elevated C-reactive protein (CRP) has been linked to increased atherosclerosis risk.
- Homocysteine Levels: Elevated homocysteine may impair endothelial function and promote thrombosis.
- Metabolic Syndrome: A constellation of abdominal obesity, hypertension, hyperglycemia, and dyslipidemia that raises cardiovascular risk.
Pathophysiology
- Endothelial Injury and Dysfunction:
- Endothelial injury from factors like hypertension, hyperlipidemia, and smoking initiates atherosclerosis by increasing vascular permeability and attracting inflammatory cells.
- Endothelial dysfunction reduces nitric oxide (NO) production, which impairs vasodilation and promotes leukocyte adhesion.
- Lipoprotein Infiltration and Oxidation:
- LDL particles enter the subendothelial space, where they undergo oxidative modification, becoming oxidized LDL (oxLDL).
- oxLDL is highly atherogenic, attracting monocytes that differentiate into macrophages and internalize oxLDL, forming “foam cells.”
- Foam Cell Formation and Fatty Streaks:
- Foam cells accumulate within the intima, creating fatty streaks, the earliest visible lesion in atherosclerosis.
- Fatty streaks are typically seen in young adults and may progress or remain stable.
- Plaque Progression:
- Continued inflammation stimulates smooth muscle cell migration and proliferation from the media to the intima, leading to extracellular matrix (ECM) production.
- Over time, ECM and collagen deposition create a fibrous cap over the lipid core, forming a mature atherosclerotic plaque.
- Plaque Stability and Complications:
- Stable Plaques: Thick fibrous caps and less lipid content, leading to gradual luminal narrowing and stable angina.
- Vulnerable Plaques: Thin fibrous caps, large lipid cores, and high inflammatory cell content. These plaques are prone to rupture, leading to thrombosis and acute coronary syndromes (ACS).
- Plaque Rupture and Thrombosis: Rupture exposes thrombogenic material, activating the coagulation cascade and platelet aggregation, which can obstruct blood flow, causing ischemic events.
Clinical Manifestations
- Coronary Artery Disease (CAD):
- Atherosclerosis in coronary arteries leads to ischemic heart disease, presenting as stable angina, unstable angina, myocardial infarction (MI), or sudden cardiac death.
- Stable angina is predictable and triggered by exertion, while unstable angina and MI result from plaque rupture and thrombosis.
- Cerebrovascular Disease:
- Carotid and cerebral artery atherosclerosis can lead to transient ischemic attacks (TIA) or ischemic stroke, with symptoms depending on the area of brain involvement.
- Strokes from atherosclerosis often involve large vessels, such as the internal carotid artery or middle cerebral artery.
- Peripheral Artery Disease (PAD):
- Atherosclerosis in peripheral arteries, especially in the lower extremities, causes PAD, presenting as intermittent claudication, resting pain, or non-healing ulcers.
- Severe PAD may lead to critical limb ischemia and necessitate revascularization or amputation.
- Aortic Aneurysm and Dissection:
- Atherosclerosis weakens the aortic wall, increasing susceptibility to aneurysm formation, particularly in the abdominal aorta.
- Dissections are less directly linked to atherosclerosis but can occur when the aorta is weakened by the disease.
Diagnosis
- Physical Examination:
- May reveal signs such as diminished pulses (in PAD), carotid bruits (suggesting carotid artery stenosis), or signs of ischemia (e.g., angina, TIA).
- Elevated blood pressure, xanthomas, or other signs of dyslipidemia may indicate underlying risk.
- Laboratory Tests:
- Lipid Profile: Elevated LDL and low high-density lipoprotein (HDL) levels are typical.
- Inflammatory Markers: High-sensitivity CRP can be an additional risk indicator.
- Blood Glucose and HbA1c: Important in patients with diabetes or suspected insulin resistance.
- Imaging:
- Coronary Angiography: Gold standard for CAD, allowing direct visualization of coronary artery blockages.
- Carotid Ultrasound: Used for detecting carotid artery stenosis in patients with TIA or stroke risk factors.
- Ankle-Brachial Index (ABI): Measures the ratio of ankle to brachial systolic blood pressure to assess PAD severity.
- CT Angiography and Magnetic Resonance Angiography (MRA): Non-invasive options to visualize plaque and vascular lumen in multiple arterial territories.
Management
- Lifestyle Modifications:
- Smoking Cessation: Crucial to reduce further plaque development and risk of ischemic events.
- Diet and Exercise: A heart-healthy diet (low in saturated fats, rich in fruits and vegetables) and regular exercise improve lipid profiles and cardiovascular health.
- Weight Management: Reduces risk by lowering blood pressure and improving insulin sensitivity.
- Pharmacologic Therapy:
- Statins: First-line agents to reduce LDL and stabilize plaques; evidence shows reduced mortality in atherosclerosis.
- Antiplatelet Therapy: Aspirin or clopidogrel reduces the risk of thrombotic events, particularly in CAD or after stroke.
- Antihypertensive Agents: ACE inhibitors, angiotensin II receptor blockers (ARBs), or beta-blockers to reduce blood pressure and prevent endothelial injury.
- Diabetes Control: Optimizing glucose levels in diabetics through lifestyle changes and medications (e.g., metformin, SGLT2 inhibitors) reduces atherosclerotic progression.
- Revascularization:
- Percutaneous Coronary Intervention (PCI): Stenting for obstructive CAD to restore blood flow.
- Carotid Endarterectomy or Stenting: Indicated for symptomatic carotid stenosis or high-grade asymptomatic lesions in selected patients.
- Surgical Bypass for PAD: For patients with severe or disabling PAD not responsive to conservative measures.
Key Points
- Atherosclerosis:
- A chronic inflammatory disease characterized by plaque buildup in the arterial walls, leading to ischemic complications like CAD, PAD, and stroke.
- Risk factors include hyperlipidemia, hypertension, diabetes, smoking, and genetic predisposition.
- Pathogenesis:
- Initiated by endothelial injury and LDL infiltration, leading to foam cell formation, fatty streaks, and fibrous plaque formation.
- Plaque rupture can result in acute thrombosis and ischemic events such as MI or stroke.
- Clinical Manifestations:
- Includes stable and unstable angina, MI, TIA/stroke, and claudication in PAD.
- Diagnosis and Management:
- Diagnosis relies on clinical history, physical examination, imaging, and laboratory tests (e.g., lipid profile).
- Management includes lifestyle modifications, statins, antihypertensive agents, and antiplatelet therapy, with revascularization for symptomatic CAD or PAD.