Hyperlipidemia for ABIM
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Hyperlipidemia for the American Board of Internal Medicine Exam
Hyperlipidemia, characterized by elevated levels of lipids in the blood, is a major risk factor for atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD), stroke, and peripheral artery disease (PAD). The primary focus of hyperlipidemia management is to reduce LDL cholesterol (LDL-C) levels, as high LDL-C is strongly associated with an increased risk of cardiovascular events.
Classification of Hyperlipidemia
Hyperlipidemia is typically classified based on lipid profiles:
- Primary Hyperlipidemia: Genetic disorders affecting lipid metabolism.
- Familial Hypercholesterolemia: High LDL-C due to defective LDL receptors or apolipoprotein B.
- Familial Combined Hyperlipidemia: Elevations in LDL-C and triglycerides.
- Polygenic Hypercholesterolemia: Multiple genes contribute to moderately elevated LDL-C.
- Secondary Hyperlipidemia: Secondary to lifestyle factors or medical conditions.
- Diet and Lifestyle: High intake of saturated and trans fats, obesity, sedentary lifestyle, and excessive alcohol consumption.
- Medical Conditions: Diabetes, hypothyroidism, chronic kidney disease, and liver disease.
- Medications: Glucocorticoids, antipsychotics, thiazide diuretics, and certain beta-blockers.
Lipoprotein Types and Their Roles
- Low-Density Lipoprotein (LDL): Known as "bad cholesterol," LDL transports cholesterol to cells, contributing to plaque formation and ASCVD risk. Lowering LDL is the primary target of therapy.
- High-Density Lipoprotein (HDL): Known as "good cholesterol," HDL helps remove cholesterol from the bloodstream and may be protective against ASCVD.
- Triglycerides (TG): High levels are associated with pancreatitis and may contribute to ASCVD, especially in combination with high LDL-C or low HDL-C.
- Non-HDL Cholesterol: Includes all atherogenic particles (LDL, VLDL, IDL); used as an alternative target in patients with high triglycerides.
Screening Guidelines
- General Adult Population:
- Baseline Screening: Begin lipid screening at age 20 in low-risk individuals, with more frequent screening in those with risk factors or a family history of premature ASCVD.
- Risk-Based Screening: Repeat every 4–6 years for individuals aged 40–75 with no known ASCVD to assess ASCVD risk.
- High-Risk Populations:
- Diabetes: Screen annually.
- Family History of Early ASCVD: Initiate screening earlier, especially in cases of familial hyperlipidemia.
- High-Risk Conditions: Screen more frequently in patients with conditions like CKD, metabolic syndrome, or chronic inflammatory diseases.
ASCVD Risk Assessment
The 10-year ASCVD risk score, calculated using factors such as age, sex, race, BP, cholesterol levels, smoking status, and diabetes, guides the intensity of lipid-lowering therapy.
- Low Risk (<5%): Lifestyle modifications are the primary intervention.
- Borderline Risk (5–7.4%): Lifestyle changes; consider moderate-intensity statin if additional risk factors are present.
- Intermediate Risk (7.5–19.9%): Lifestyle changes and moderate- to high-intensity statin therapy.
- High Risk (≥20%): Lifestyle modifications and high-intensity statin therapy.
Treatment of Hyperlipidemia
Lifestyle Modifications
- Diet: Focus on a heart-healthy diet, such as the Mediterranean or DASH diet.
- Saturated Fats: Limit intake, replacing them with monounsaturated and polyunsaturated fats.
- Dietary Cholesterol: Moderate restriction, though recent guidelines place more emphasis on saturated fats.
- Fiber: Soluble fiber from sources like oats, barley, and legumes can help lower LDL-C.
- Physical Activity: Engage in moderate-intensity aerobic exercise for at least 150 minutes per week to improve lipid levels and cardiovascular health.
- Weight Loss: Achieving and maintaining a healthy weight can improve lipid levels, particularly triglycerides.
- Smoking Cessation: Reduces cardiovascular risk and improves HDL-C.
Pharmacologic Therapy
Statins
- Mechanism of Action: Inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, leading to upregulation of LDL receptors and increased clearance of LDL-C.
- Indications:
- Primary Prevention: For patients with an elevated ASCVD risk score.
- Secondary Prevention: For patients with known ASCVD, irrespective of baseline LDL-C levels.
- Intensity:
- High-Intensity Statins: Atorvastatin (40–80 mg) and rosuvastatin (20–40 mg) are used to achieve ≥50% reduction in LDL-C.
- Moderate-Intensity Statins: Atorvastatin (10–20 mg) or rosuvastatin (5–10 mg) for patients with lower ASCVD risk or who cannot tolerate high doses.
- Side Effects: Myalgia, myopathy, and elevated liver enzymes; monitor liver function and creatine kinase if symptoms arise.
Ezetimibe
- Mechanism: Inhibits cholesterol absorption in the intestine, reducing hepatic cholesterol stores and circulating LDL-C.
- Use: Added to statin therapy in patients who do not achieve LDL-C goals with statins alone or cannot tolerate high-intensity statins.
PCSK9 Inhibitors
- Mechanism: Monoclonal antibodies (e.g., evolocumab, alirocumab) that inhibit PCSK9, a protein that degrades LDL receptors, thus enhancing LDL clearance.
- Use: Primarily for patients with familial hypercholesterolemia or those with ASCVD who require further LDL-C reduction despite maximally tolerated statins and ezetimibe.
- Administration: Subcutaneous injection every 2–4 weeks.
Bile Acid Sequestrants
- Mechanism: Bind bile acids in the intestine, promoting conversion of cholesterol to bile acids and reducing LDL-C.
- Use: Used as an adjunct in patients who cannot tolerate statins or in combination with other agents for additional LDL-C reduction.
- Side Effects: Gastrointestinal side effects such as constipation and bloating; may interfere with absorption of other medications.
Fibrates
- Mechanism: Activate peroxisome proliferator-activated receptor alpha (PPAR-α), enhancing lipoprotein lipase activity and reducing triglycerides.
- Use: Primarily for hypertriglyceridemia, particularly if triglycerides exceed 500 mg/dL to reduce the risk of pancreatitis.
- Side Effects: Myopathy (especially if combined with statins), liver enzyme elevation, and increased risk of gallstones.
Niacin (Nicotinic Acid)
- Mechanism: Decreases hepatic VLDL synthesis, lowering triglycerides and increasing HDL-C.
- Use: Limited use due to adverse effects; occasionally considered in patients with low HDL-C or high triglycerides who cannot tolerate other therapies.
- Side Effects: Flushing, pruritus, hyperglycemia, and hepatotoxicity.
Monitoring and Follow-Up
- Lipid Panel: Re-evaluate 4–12 weeks after initiation or change in therapy, then every 3–12 months based on patient stability.
- Liver Enzymes: Routine monitoring is not required unless symptoms arise, but baseline liver function tests are recommended before starting statins.
- CK Levels: Checked if patients develop muscle pain or weakness while on statins.
Special Populations
- Diabetes: Patients aged 40–75 with diabetes are candidates for moderate- to high-intensity statins regardless of baseline LDL-C.
- Elderly: Treatment should be individualized, weighing benefits versus risks of statins, especially in those over 75 years.
- Familial Hypercholesterolemia: Often requires aggressive therapy with high-intensity statins, ezetimibe, and PCSK9 inhibitors.
Key Points
- Primary vs. Secondary Prevention: Statins are used for both, with high-intensity statins for patients with high ASCVD risk or known ASCVD.
- Lifestyle Modifications: Essential for all patients, focusing on diet, exercise, and smoking cessation.
- Statins: First-line therapy for LDL-C reduction; high-intensity statins aim for ≥50% LDL reduction.
- Non-Statin Options: Ezetimibe and PCSK9 inhibitors are added for further LDL-C lowering if statins alone are insufficient.
- Triglyceride Management: Fibrates are indicated for severe hypertriglyceridemia (>500 mg/dL) to reduce pancreatitis risk.
- Monitoring: Lipid levels reassessed 4–12 weeks after therapy initiation or adjustment, then every 3–12 months.
- Risk Assessment: 10-year ASCVD risk score guides treatment intensity and decision-making in primary prevention.