ABIM - Hyperlipidemia Pathophysiology

Here are key facts for ABIM from the Hyperlipidemia Pathophysiology tutorial, as well as points of interest at the end that are not directly addressed in this tutorial but should help you prepare for the boards.

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1. Classification systems: The older scheme, which focuses on inherited lipidemias, is called the Fredrickson Classification system. The newer system divides lipidemias according to primary (aka, genetic) or secondary (aka, acquired) causes 2. Disease association: Hyperlipidemia is often asymptomatic, but it significantly increases one's risk for cardiovascular diseases, especially atherosclerosis 3. Diagnostic criteria: Hypercholesterolemia is often defined as: Total cholesterol > 200 mg/dL, Low-Density Lipoproteins > 130 mg/dL, High-Density Lipoproteins < 40 mg/dL. Hypertriglyceridemia = levels above 150 mg/dL 1. Lipoprotein components: Comprise proteins and phospholipids that transport cholesterol and triglycerides in the body 2. Chylomicrons: Deliver dietary triglycerides and cholesterol to the liver and peripheral tissues 3. VLDL: Very Low Density Lipoproteins are made in the liver, and are rich in triglycerides 4. IDL: Intermediate Density Lipoproteins are produced when triglycerides are removed from VLDL; thus, like the chylomicron remnants, they are rich in cholesterol 5. LDL: Low Density Lipoproteins are produced after even more triglycerides are removed from the Very Low Density Lipoproteins and their remnants; thus, LDL is very rich in cholesterol, which it carries to the peripheral tissues 6. HDL: High Density Lipoproteins, which are part of the reverse cholesterol transport pathway, carry cholesterol from the peripheral tissues to the liver 1. Xanthomas definition: These are created by lipid deposits in the skin associated with foam cells (macrophages that have ingested lipids) 2. Tuberous xanthomas: Form small to large bulges in the skin over the joints, particularly the elbows and knees 3. Eruptive xanthomas: Are erythematous bumps that tend to appear on the buttocks, shoulders, and extensor surfaces 4. Plane xanthomas: Are thin yellow plaques. Xanthelasma is characterized by plaques around the eyelids 5. Palmar xanthomas: Are characterized by yellow plaques that form along the creases of the palm of the hands 6. Tendinous xanthomas: Are bumps that form over the tendons or ligaments. The Achilles tendon at the posterior ankle is a common site for these xanthomas

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1. Type I (Hyperchylomicronemia): Occurs when there is a deficiency in lipoprotein lipase or an alteration in apolipoprotein C-II, which activates lipoprotein lipase. These deficiencies cause elevated chylomicrons and triglyceride levels exceeding 500 mg/dL. This disorder is associated with acute pancreatitis, eruptive xanthomas, and, when triglyceride levels are exceedingly high, lipemia retinalis 2. Type IIa (Hypercholesterinemia): Occurs when LDL receptors are deficient. Results in elevated Low-Density Lipoproteins and cholesterol. There are heterozygous and homozygous forms. Patients are at increased risk of premature Atherosclerotic Cardiovascular Disease (ASCVD), tendinous xanthomas, and, corneal arcus, which is a whitish ring around the iris 3. Type IIb (Hyperlipidemia): Occurs when there is a reduction in LDL receptors or increased apolipoprotein B. Characterized by elevated Low Density Lipoproteins and Very Low Density Lipoproteins. Both triglycerides and cholesterol are also elevated. Patients are at increased risk of premature ASCVD and may have tendinous xanthomas. This is the most common inherited dyslipidemia 4. Type III (Dysbetalipoproteinemia): Occurs when apolipoprotein E-2 is defective. The disorder is characterized by elevated chylomicron remnants and Intermediate Density Lipoproteins (hence, this disorder is sometimes called Remnant Removal Disease). Both triglyceride and cholesterol levels are elevated. Patients are at increased risk of ASCVD, and may have palmar xanthoma and/or tuberoeruptive xanthomas of the elbows and knees 5. Type IV (Hypertriglyceridemia): Characterized by increased production and decreased secretion of Very Low Density Lipoproteins. Elevated levels of triglycerides. Patients are at increased risk for acute pancreatitis and ASCVD. Type IV is another relatively common inherited hyperlipidemia 6. Type V (Mixed hypertriglyceridemia): Associated with increased Very Low Density Lipoprotein production and decreased Low Density Lipoprotein production. Characterized by elevations in chylomicron remnants and VLDL. Increased triglyceride and cholesterol levels. Patients are at risk for acute pancreatitis, eruptive xanthomas, and ASCVD 1. Dietary factors: The most significant contributors in the United States are diets high in saturated fats, cholesterol, and trans fats, coupled with sedentary lifestyles 2. Alcohol consumption: High levels of alcohol consumption also elevate lipid levels 3. Medical conditions: Several other disorders may contribute to hyperlipidemia, including: diabetes mellitus, chronic kidney disease, nephrotic syndrome, hypothyroidism, cholestatic liver diseases, and Cushing syndrome 4. Medication-induced: Several drugs can cause hyperlipidemia, including oral contraceptives, diuretics, beta-blockers, and antiretroviral agents

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1. ASCVD risk calculators: Using pooled cohort equations for 10-year risk estimation 2. Primary prevention strategies: Statin benefit groups and intensity selection 3. Secondary prevention protocols: Management post-cardiovascular events 1. Apolipoprotein B: More accurate predictor of cardiovascular risk than LDL-C 2. Lipoprotein(a): Independent genetic risk factor for ASCVD 3. LDL particle number: More precise marker in discordant lipid profiles 1. Familial hypercholesterolemia: Cascade screening and aggressive treatment 2. Severe hypertriglyceridemia: Management to prevent pancreatitis 3. Statin intolerance: Alternative therapies and rechallenge protocols 4. Special populations: Elderly, chronic kidney disease, diabetes, liver disease 5. Emerging therapies: PCSK9 inhibitors, bempedoic acid, inclisiran