Management of Genetic Disorders of Lipid Metabolism

Initial Assessment and Therapy

• A complete lipid profile, including LDL-C, HDL-C, triglycerides, and total cholesterol, is recommended as part of the initial assessment, along with liver function tests and creatine kinase for baseline, by the American Heart Association 1
• Statins are the cornerstone of treatment for elevated LDL cholesterol, with high-intensity statins recommended for significant LDL reduction, as suggested by the American College of Cardiology 2, 3

Target Lipid Levels

• Target LDL-C levels are <70 mg/dL for adults with coronary heart disease or diabetes, and <100 mg/dL for adults without coronary heart disease, as recommended by the American Heart Association 2, 3
• Target triglyceride levels are <150 mg/dL, as recommended by the American Heart Association and American College of Cardiology 4, 5, 6
• Target non-HDL cholesterol or apolipoprotein B levels may be considered for mixed dyslipidemias, as recommended by the American Heart Association 2, 3

Pharmacological Interventions

• Statin therapy is recommended as the primary pharmacological approach when LDL-C is elevated, with the choice of statin based on required LDL-C reduction percentage, as suggested by the American College of Cardiology and European Society of Cardiology 4, 7
• Fibrates are recommended as first-line pharmacological therapy for severe hypertriglyceridemia, according to the American Academy of Family Physicians 5
• Omega-3 fatty acids can be used as monotherapy or in combination for triglyceride reduction, at a dose of 1-4 g/day, as suggested by the American Heart Association and American Academy of Family Physicians 5, 8, 9, 10
• Niacin is considered effective for both triglyceride reduction and HDL-C elevation, and can be used for combined dyslipidemia, at a dose of 500-2000 mg/day, as recommended by the American College of Cardiology and American Diabetes Association 4, 11
• PCSK9 inhibitors are recommended for patients with heterozygous or homozygous familial hypercholesterolemia who are not at target LDL-C levels, as suggested by the American College of Cardiology 12

Lifestyle Modifications

• Lifestyle modifications, including weight loss, exercise, and dietary changes, are recommended as the first line of treatment, according to the American Heart Association and American Academy of Family Physicians 4, 5, 6
• Dietary recommendations include reducing simple carbohydrate intake, limiting dietary cholesterol to <200 mg/day, increasing consumption of omega-3 fatty acids (2-4 g/day), soluble fiber (10-25 g/day), and plant stanols/sterols (2 g/day), as recommended by the American College of Cardiology and American Heart Association 5, 13, 8
• Limiting trans fat to <1% of total caloric intake and saturated fat to <7% of total calories is also recommended, as suggested by the American Heart Association 8
• Engaging in at least 30-60 minutes of moderate-intensity aerobic activity on most days of the week is recommended, as suggested by the American College of Cardiology 13
• Aim for a healthy BMI of 18.5-24.9 kg/m² and target waist circumference <40 inches in men and <35 inches in women, as recommended by the American College of Cardiology 13

Safety Monitoring

• Recheck lipid profile in 4-12 weeks after initiating therapy, and once target levels are achieved, monitor every 6-12 months, as recommended by the American Diabetes Association and American College of Cardiology 14, 15
• Monitor for muscle symptoms, especially with combination therapy, as recommended by the American Heart Association and European Society of Cardiology 8, 1
• Evaluate total cardiovascular risk using validated risk calculators (Pooled Cohort Equations) to determine the risk level and guide treatment decisions, as recommended by the American College of Cardiology 16
• Assess lipid profiles, including triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol, to identify lipid abnormalities and guide treatment, as recommended by the American Heart Association, American Diabetes Association, and American College of Cardiology 17, 14, 6, 18, 19, 20, 21, 22
• Lipid profiles can be classified based on the following table:

Pediatric Management

• Early identification and treatment of genetic lipid disorders in children is recommended, with dietary therapy as the first-line approach, and consideration of drug therapy if dietary therapy alone is unsuccessful in lowering LDL-C levels to <130 mg/dL, as recommended by the American Academy of Pediatrics 2
• Statins are recommended as the primary pharmacological therapy for children with genetic lipid disorders, as suggested by the American Heart Association 2

Additional Recommendations

• Complete smoking cessation is recommended to improve cardiovascular health, as advised by the American Heart Association 23, 24
• Moderate alcohol consumption or abstinence, especially with high triglycerides, is suggested to reduce the risk of cardiovascular disease, as recommended by the American Heart Association 8, 17, 14
• Aim to reduce body weight by 10% in the first year for overweight/obese individuals to improve cardiovascular health, as recommended by the American Heart Association 25, 9, 10