Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 40-17: Familial Hypercholesterolemia + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Elevated serum total cholesterol and low-density lipoprotein (LDL) cholesterol Autosomal dominant inheritance Mutation in LRL, PCSK9, or APOB +++ General Considerations ++ A group of autosomal dominant conditions that result in elevated LDL levels in the blood High LDL predisposes to atherosclerosis, which leads to premature myocardial infarction or stroke The incidence of these serious complications increases with age and when associated with the other common predispositions to atherosclerosis, such as smoking and hypertension +++ Demographics ++ About 1 in 500 people in the United States have familial hypercholesterolemia Worldwide prevalence is about 10 million Familial hypercholesterolemia is diagnosed in only about 15% of people; even fewer are treated effectively + Clinical Findings Download Section PDF Listen +++ ++ Yellow lipid deposits appear on tendons, especially the Achilles (tendon xanthoma) + Diagnosis Download Section PDF Listen +++ ++ Elevated total serum cholesterol with the LDL component particularly high Detailed family history and genetic testing should be done in persons Younger than 40 years with an LDL level > 200 mg/mL Older than 40 years with a level > 250 mg/mL + Treatment Download Section PDF Listen +++ ++ Statins, usually at high doses, can reduce LDL levels (Table 28–3) The younger the treatment is begun, the better the outcome in reducing mortality from atherosclerosis In homozygous familial hypercholesterolemia, if high-dose statins do not reduce LDL sufficiently, treatment with a monoclonal antibody (e.g. alirocumab and evolocumab) that blocks the action of the PCSK9 enzyme (which inactivates hepatic receptors that transport LDL into the liver for metabolism) can be an expensive adjunct to standard therapy If all else fails, then plasmapheresis to reduce LDL is needed ++Table Graphic Jump LocationTable 28–3.Effects of selected lipid-modifying drugs (listed alphabetically).View Table||Download (.pdf) Table 28–3. Effects of selected lipid-modifying drugs (listed alphabetically). Drug Lipid-Modifying Effects Triglyceride Initial Daily Dose Maximum Daily Dose Cost for 30 Days of Treatment with Dose Listed1 LDL HDL Alirocumab (Praluent) –45 to –60% ± ± 75 mg once every 2 weeks 150 mg once every 2 weeks $540.00 (75 mg every 2 weeks) Atorvastatin (Lipitor) –25 to –40% +5 to 10% ↓↓ 10 mg once 80 mg once $15.60 (20 mg once) Cholestyramine (Questran, others) –15 to –25% +5% ± 4 g twice a day 24 g divided $84.00 (8 g divided) Colesevelam (WelChol) –10 to –20% +10% ± 625 mg, 6–7 tablets once 625 mg, 6–7 tablets once $673.20 (6 tablets once) Colestipol (Colestid) –15 to –60% +5% ± 5 g twice a day 30 g divided $141.00 (10 g divided) Evolocumab (Repatha) –50 to –60% ± ± 140 mg once every 2 weeks 420 mg once monthly $540.00 (140 mg every 2 weeks) Ezetimibe (Zetia) –20% +5% ± 10 mg once 10 mg once $308.43 (10 mg once) Fenofibrate (Tricor, others) –10 to –15% +15 to 25% ↓↓ 48 mg once 145 mg once $33.60 (145 mg once) Fenofibric acid (Trilipix) –10 to –15% +15 to 25% ↓↓ 45 mg once 135 mg once $160.20 (135 mg once) Fluvastatin (Lescol) –20 to –30% +5 to 10% ↓ 20 mg once 40 mg once $113.40 (20 mg once) Gemfibrozil (Lopid, others) –10 to –15% +15 to 20% ↓↓ 600 mg once 1200 mg divided $58.20 (600 mg twice a day) Lomitapide (Juxtapid)2,3 –40 to –50%4 –7%4 ↓↓ 5 mg once 60 mg once $53,656.24 (any dose) Lovastatin (Mevacor, others) –25 to –40% +5 to 10% ↓ 10 mg once 80 mg divided $63.00 (20 mg once) Mipomersen (Kynamro)2,3 –20 to –25%5 +11%5 ↓ 200 mg subcutaneously once weekly 200 mg subcutaneously once weekly $36,532.96 (200 mg weekly) Niacin (OTC, Niaspan) –15 to –25% +25 to 35% ↓↓ 100 mg once 3–4.5 g divided $5.40 (1.5 g twice a day, OTC) $282.60 (2 g Niaspan) Omega-3 fatty acid ethyl esters (Lovaza) ↓↓ 4 g once 4 g once $248.40 (4 g daily) Omega-3 fatty acid icosapent ethyl (Vascepa) ↓↓ 2 g twice 2 g twice $397.20 (2 g twice day) Pitavastatin (Livalo, Zypitamag) –30 to 40% +10 to 25% ↓↓ 2 mg once 4 mg once $279.00 (2 mg once) Pravastatin (Pravachol) –25 to –40% +5 to 10% ↓ 20 mg once 80 mg once $75.00 (20 mg once) Rosuvastatin (Crestor) –40 to –50% +10 to 15% ↓↓ 10 mg once 40 mg once $43.20 (20 mg once) Simvastatin (Zocor, others) –25 to –40% +5 to 10% ↓↓ 5 mg once 80 mg once $1.95 (10 mg once) 1Average wholesale price (AWP, for AB-rated generic when available) for quantity listed. Source: IBM Micromedex Red Book (electronic version) IBM Watson Health, Greenwood Village, CO, USA. Available at https://www.micromedexsolutions.com (cited April 12, 2020). AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions.2Restricted to patients with homozygous familial hypercholesterolemia.3FDA Black Box warning regarding hepatotoxicity.462% of patients also received plasma lipoprotein apheresis.5No plasma lipoprotein apheresis allowed in clinical trial.HDL, high-density lipoprotein; LDL, low-density lipoprotein; ± variable, if any; others, indicates availability of less expensive generic preparations; OTC, over the counter. + Outcome Download Section PDF Listen +++ +++ Prevention ++ Screening relatives who are at risk by measuring LDL levels and by identifying the mutation in the family and using that for screening +++ When to Refer ++ For comprehensive evaluation of infants for their lipid profile For genetic counseling of the patient, his or her parents, siblings, and offspring For signs of atherosclerotic cardiovascular disease +++ When to Admit ++ For signs or symptoms of acute arterial occlusive events + References Download Section PDF Listen +++ + +Ajufo E et al. Recent advances in the pharmacological management of hypercholesterolaemia. Lancet Diabetes Endocrinol. 2016 May;4(5):436–46. [PubMed: 27012540] + +Kramer AI et al. Estimating the prevalence of familial hypercholesterolemia in acute coronary syndrome: systematic review and meta-analysis. Can J Cardiol. 2019 Oct;35(10):1322–31. [PubMed: 31500889] + +Louter L et al. Cascade screening for familial hypercholesterolemia: practical consequences. Atheroscler Suppl. 2017 Nov;30:77–85. [PubMed: 29096865] + +Rosenson RS. CETP inhibition improves the lipid profile but has no effect on clinical cardiovascular outcomes in high-risk patients. Evid Based Med. 2017 Oct;22(5):184–5. [PubMed: 28844064] + +Sabatine MS. PCSK9 inhibitors: clinical evidence and implementation. Nat Rev Cardiol. 2019 Mar;16(3):155–65. [PubMed: 30420622]