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Guidelines

Guidelines Summary

A 2017 consensus statement on pediatric familial hypercholesterolemia from a joint working group of the Japan Pediatric Society and the Japan Atherosclerosis Society included the following key points^[55]:

A family history of FH and the presence of premature CAD are important diagnostic factors in FH
Because plasma LDLc levels fluctuate in children, multiple measurements of this value should be taken
Following diagnosis of FH, the patient’s family should be screened for the disease
Regular examination for CAD is recommended in those pediatric patients with heterozygous FH who have Achilles tendon thickening or carotid artery atherosclerosis
Pediatric patients with homozygous FH should undergo regular, systemic exams, performed by specialists, for atherosclerotic CVD
Fat should account for 20-25% of the energy obtained from food, and carbohydrates should account for 50-60%; less than 7% of energy should be obtained from saturated fatty acids, and less than 200 mg of cholesterol should be consumed per day
In pediatric patients with heterozygous FH, an LDLc level of 180 mg/dL or above from age 10 should prompt the initiation of drug therapy
Statin therapy, initiated at a low dose, is the first choice for drug treatment in pediatric heterozygous FH; liver function tests should be carried out after one month and then, once a stable medication dose has been achieved, about once every 3-4 months; patients should undergo continuous monitoring for adverse effects and for abnormalities in growth and secondary sexual characteristics
At initial diagnosis of pediatric homozygous FH, treatment with lifestyle interventions and maximally tolerated statin therapy should be instituted; children with homozygous FH frequently need treatment with a combination of lipid-lowering drugs, including ezetimibe
Weekly or biweekly lipoprotein apheresis should be initiated in homozygous FH patients if target LDLc levels cannot be reached with statin therapy

Medication

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Pisciotta L, Priore Oliva C, Pes GM, Di Scala L, Bellocchio A, Fresa R, et al. Autosomal recessive hypercholesterolemia (ARH) and homozygous familial hypercholesterolemia (FH): a phenotypic comparison. Atherosclerosis. 2006 Oct. 188(2):398-405. [QxMD MEDLINE Link].
Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993 Jul 15. 72(2):171-6. [QxMD MEDLINE Link].
Patel MD, Thompson PD. Phytosterols and vascular disease. Atherosclerosis. 2006 May. 186(1):12-9.
[Guideline] Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1. 41 (1):111-88. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18. 139 (25):e1082-143. [QxMD MEDLINE Link]. [Full Text].
Raal FJ, Hovingh GK, Catapano AL. Familial hypercholesterolemia treatments: guidelines and new therapies. Atherosclerosis. 2018 Oct. 277:483-92. [QxMD MEDLINE Link]. [Full Text].
Richter WO, Donner MG, Hofling B, Schwandt P. Long-term effect of low-density lipoprotein apheresis on plasma lipoproteins and coronary heart disease in native vessels and coronary bypass in severe heterozygous familial hypercholesterolemia. Metabolism. 47(7):863-8. [QxMD MEDLINE Link].
Thompsen J, Thompson PD. A systematic review of LDL apheresis in the treatment of cardiovascular disease. Atherosclerosis. 2006 Mar 16. [Epub ahead of print].
Drouin-Chartier JP, Tremblay AJ, Bergeron J, Lamarche B, Couture P. High serum triglyceride concentrations in patients with homozygous familial hypercholesterolemia attenuate the efficacy of lipoprotein apheresis by dextran sulfate adsorption. Atherosclerosis. 2018 Mar. 270:26-32. [QxMD MEDLINE Link].
Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16. 372 (16):1500-9. [QxMD MEDLINE Link]. [Full Text].
Koren MJ, Giugliano RP, Raal FJ, Sullivan D, Bolognese M, Langslet G, et al. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation. 2014 Jan 14. 129 (2):234-43. [QxMD MEDLINE Link]. [Full Text].
Langslet G, Emery M, Wasserman SM. Evolocumab (AMG 145) for primary hypercholesterolemia. Expert Rev Cardiovasc Ther. 2015 May. 13 (5):477-88. [QxMD MEDLINE Link].
Raal FJ, Hovingh GK, Blom D, Santos RD, Harada-Shiba M, Bruckert E, et al. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017 Apr. 5 (4):280-290. [QxMD MEDLINE Link].
Blom DJ, Harada-Shiba M, Rubba P, et al. Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial. J Am Coll Cardiol. 2020 Jul 14. 76 (2):131-42. [QxMD MEDLINE Link]. [Full Text].
Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2012 Nov 1. [QxMD MEDLINE Link].
Liu X, Men P, Wang Y, Zhai S, Zhao Z, Liu G. Efficacy and safety of lomitapide in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Mar 2. [QxMD MEDLINE Link].
Raal FJ, Rosenson RS, Reeskamp LF, et al. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Aug 20. 383 (8):711-20. [QxMD MEDLINE Link]. [Full Text].
Kane JP, Malloy MJ, Tun P, Phillips NR, Freedman DD, Williams ML, et al. Normalization of low-density-lipoprotein levels in heterozygous familial hypercholesterolemia with a combined drug regimen. N Engl J Med. 1981 Jan 29. 304(5):251-8. [QxMD MEDLINE Link].
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O'Riordan M. Rosuvastatin slows atherosclerosis in FH kids. Heartwire. June 6, 2014. [Full Text].
Braamskamp M, Langslet G, McCrindle BW, et al. Efficacy and safety of rosuvastatin in children aged 6–17 years with familial hypercholesterolemia: findings from the CHARON study (abstract M140). Presented at EAS 2014: The 82nd European Atherosclerosis Society Congress; June 2, 2014; Madrid, Spain.
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Ray KK, Bays HE, Catapano AL, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019 Mar 14. 380 (11):1022-32. [QxMD MEDLINE Link]. [Full Text].
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Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2019 Jul 29. 2047487319864671. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

Metacarpophalangeal joint tendon xanthomas in a 45-year-old man with heterozygous familial hypercholesterolemia.

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Table 1. LDLc Target levels and levels Indicating Therapeutic Lifestyle Changes (TLC) and Drug Therapy

Risk Category

LDLc Target level,

mg/dL

LDLc level Indicating TLC,

mg/dL

LDLc level for Considering Drug Therapy,

mg/dL*

High risk:

CHD or CHD risk equivalent

(10-y risk >20%)

< 100

Optional goal < 70

>100

Moderately high risk:

More than 2 risk factors

(10-y risk 10-20%)

130

Optional goal < 100

>130

(100-129 may consider drug options)

Moderate risk:

More than 2 risk factors

(10-y risk 10%)

< 130

>130

>160

Lower risk:

0-1 risk factor

< 160

>160

>190

(160-189 LDL-lowering drug optional)

*The 2004 update recommended that when statin therapy is initiated in patients at high or moderately high risk, a dose and strength should be chosen that achieves at least a 30-40% LDLc reduction (see Table 3).

Table 2. Recommended Dietary Intake

Food Category	Typical US Diet	NCEP Diet	Diet for FH
Cholesterol, mg/d	500	< 200	100
Total fat, % energy (calories)	40	25-35	20
Saturated fat, % energy (calories)	14	< 7	< 6
Carbohydrate, % energy (calories)	45	50-60	65
Protein, % energy (calories)	Approximately 15	15	N/A

Table 3. Statin and Statin Combination Approved Doses, Expected LDLc Decrease, and Dose Required for 30-40% LDLc Reduction

Statin	FDA-Approved Dose	Expected LDLc Decrease	Dose Required for 30-40% LDLc Reduction
Atorvastatin	10-80 mg daily	35-60%	10 mg
Fluvastatin	20-40 mg at bedtime	20-30%	40 mg qd/bid
Fluvastatin	40 mg bid	35%	40 mg bid
Extended-release fluvastatin (Lescol XL)	80 mg at bedtime	35-38%	80 mg at bedtime
Lovastatin	20-80 mg at supper	25-48%	40 mg at dinner
Extended-release lovastatin (Altoprev)	20-60 mg at bedtime	25-45%	60 mg at bedtime
Pravastatin	40-80 mg at bedtime	30-40%	40 mg at bedtime
Rosuvastatin	10-40 mg daily	40-60%	5 mg daily
Simvastatin	20-80 mg daily at bedtime	35-50%	20 mg at bedtime
Simvastatin + ezetimibe (Vytorin)	10/20 mg 10/40 mg 10/80 mg at bedtime	50-60%	10/20 mg at bedtime

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Author

Mose July, MD, CCD Endocrinologist and Certified Clinical Densitometrist, Kymera Independent Physicians

Mose July, MD, CCD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Coauthor(s)

Omolola Bolaji Olajide, MD, FACE Associate Professor, Consultant, Department of Internal Medicine, Program Director, Fellowship Program, Section of Endocrinology, Joan C Edwards School of Medicine at Marshall University

Omolola Bolaji Olajide, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Gregory William Rutecki, MD Professor of Medicine, Fellow of The Center for Bioethics and Human Dignity, University of South Alabama College of Medicine

Gregory William Rutecki, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Nephrology, National Kidney Foundation, Society of General Internal Medicine

Disclosure: Nothing to disclose.

Sections Familial Hypercholesterolemia
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Guidelines
Medication
Follow-up
Questions & Answers
Tables
References

Familial Hypercholesterolemia Guidelines

Guidelines Summary

References

Tables

Contributor Information and Disclosures

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