Familial Hypercholesterolemia Differential Diagnoses

  • Author: Elena Citkowitz, MD, PhD, FACP; Chief Editor: George T Griffing, MD   more...
 
Updated: Jan 12, 2012
 
 

Differential Diagnoses

  • Dysbetahyperlipoproteinemia (type III hyperlipidemia)
  • Familial ligand defective apoB-100, familial defective apoB-100
  • Homozygous autosomal recessive hypercholesterolemia
  • Sitosterolemia (Phytosterolemia)
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Contributor Information and Disclosures
Author

Elena Citkowitz, MD, PhD, FACP  Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael

Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Gregory William Rutecki  MD, Professor of Medicine, University of South Alabama Medical School

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

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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 Research, and Endocrine Society

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

  1. Goldstein JL, Hobbs HH, Brown, MS. Familial Hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:2863-2913.

  2. Illingworth DR, Duell PB, Connor WE. Disorders of lipid metabolism. In: Felig P, Baxter JD, Frohmin LA, eds. Endocrinology and Metabolism. 1315-1403.

  3. Ueda M. Familial hypercholesterolemia. Mol Genet Metab. Dec 2005;86(4):423-6. [Medline].

  4. Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. May 2003;168(1):1-14. [Medline].

  5. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. Sep 1 2004;160(5):421-9. [Medline].

  6. Sibley C, Stone NJ. Familial hypercholesterolemia: a challenge of diagnosis and therapy. Cleve Clin J Med. Jan 2006;73(1):57-64. [Medline].

  7. Bjorkhem I, Boberg KM. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:2073-2099.

  8. Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. May 18 2001;292(5520):1394-8. [Medline].

  9. Kane JP, Havel RJ. Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:2717-2752.

  10. Goldstein JL, Brown MS. Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis. Circulation. Sep 1987;76(3):504-7. [Medline].

  11. Goldstein JL, Brown MS. Molecular medicine. The cholesterol quartet. Science. May 18 2001;292(5520):1310-2. [Medline].

  12. Khachadurian AK, Uthman SM. Experiences with the homozygous cases of familial hypercholesterolemia. A report of 52 patients. Nutr Metab. 1973;15(1):132-40. [Medline].

  13. 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. Oct 2006;188(2):398-405. [Medline].

  14. Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. Jul 15 1993;72(2):171-6. [Medline].

  15. Patel MD, Thompson PD. Phytosterols and vascular disease. Atherosclerosis. May 2006;186(1):12-9.

  16. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97. [Medline].

  17. National Cholesterol Education Program Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. The Expert Panel. Arch Intern Med. Jan 1988;148(1):36-69. [Medline].

  18. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. Jul 13 2004;110(2):227-39. [Medline].

  19. [Guideline] Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. Jul 2011;217(1):3-46. [Medline].

  20. Connor WE, Connor SL. Dietary treatment of familial hypercholesterolemia. Arteriosclerosis. Jan-Feb 1989;9(1 Suppl):I91-105. [Medline].

  21. Illingworth DR. Management of hypercholesterolemia. Med Clin North Am. Jan 2000;84(1):23-42. [Medline].

  22. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. Nov 29 2001;345(22):1583-92. [Medline].

  23. 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. [Medline].

  24. Thompsen J, Thompson PD. A systematic review of LDL apheresis in the treatment of cardiovascular disease. Atherosclerosis. Mar 16 2006;[Epub ahead of print].

  25. 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. Jan 29 1981;304(5):251-8. [Medline].

  26. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. Jun 22 2011;305(24):2556-64. [Medline].

  27. Cohen DE, Anania FA, Chalasani N,. An assessment of statin safety by hepatologists. Am J Cardiol. Apr 17 2006;97(8A):77C-81C. [Medline].

  28. Scandinavian Simvastatin Survival Study. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. Nov 19 1994;344(8934):1383-9. [Medline].

  29. Jones PH, Davidson MH, Stein EA. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. Jul 15 2003;92(2):152-60. [Medline].

  30. Thompson PD, Clarkson PM, Rosenson RS, National Lipid Association Statin Safety Task Force Liver Exert Panel. An assessment of statin safety by muscle experts. Am J Cardiol. Apr 17 2006;97(8A):69C-76C.

  31. Bulbulia R, Bowman L, Wallendszus K, et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet. Dec 10 2011;378(9808):2013-20. [Medline]. [Full Text].

  32. McKenney JM, Davidson MH, Jacobson TA, Guyton JR, National Lipid Association Statin Safety Task Force Liver Expert Panel. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. Apr 17 2006;97(8A):89C-94C.

  33. Amundsen AL, Khoury J, Iversen PO, Bergei C, Ose L, Tonstad S. Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia. Atherosclerosis. Feb 6 2006;[Epub ahead of print].

  34. Buchwald H, Matts JP, Fitch LL, Campos CT, Sanmarco ME, Amplatz K, et al. Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group. JAMA. Sep 16 1992;268(11):1429-33. [Medline].

  35. Rader DJ, Cohen J, Hobbs HH,. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest. 2003;111:1795-1803.

  36. Zuliani G, Vigna GB, Corsini A, Maioli M, Romagnoni F, Fellin R. Severe hypercholesterolaemia: unusual inheritance in an Italian pedigree. Eur J Clin Invest. May 1995;25(5):322-31. [Medline].

 
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Metacarpophalangeal joint tendon xanthomas in a 45-year-old man with heterozygous familial hypercholesterolemia.
Table 1. LDLc Target levels and levels Indicating Therapeutic Lifestyle Changes (TLC) and Drug Therapy
Risk CategoryLDLc 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>100
Moderately high risk:



More than 2 risk factors



(10-y risk 10-20%)



130



Optional goal < 100



>130>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 CategoryTypical US DietNCEP DietDiet for FH
Cholesterol, mg/d500< 200100
Total fat, % energy (calories)4025-3520
Saturated fat, % energy (calories)14< 7< 6
Carbohydrate, % energy (calories)4550-6065
Protein, % energy (calories)Approximately 1515N/A
Table 3. Statin and Statin Combination Approved Doses, Expected LDLc Decrease, and Dose Required for 30-40% LDLc Reduction
StatinFDA-Approved DoseExpected LDLc DecreaseDose Required for 30-40% LDLc Reduction
Atorvastatin10-80 mg daily35-60%10 mg
Fluvastatin20-40 mg at bedtime20-30%40 mg qd/bid
40 mg bid35%40 mg bid
Extended-release fluvastatin



(Lescol XL)



80 mg at bedtime35-38%80 mg at bedtime
Lovastatin20-80 mg at supper25-48%40 mg at dinner
Extended-release lovastatin



(Altoprev)



20-60 mg at bedtime25-45%60 mg at bedtime
Pravastatin40-80 mg at bedtime30-40%40 mg at bedtime
Rosuvastatin10-40 mg daily40-60%5 mg daily
Simvastatin20-80 mg daily at bedtime35-50%20 mg at bedtime
Lovastatin + extended-release niacin



(Advicor)



20/500 mg



20/1000 mg



at bedtime



25-40%40/2000 mg at bedtime*
Simvastatin + ezetimibe



(Vytorin)



10/20 mg



10/40 mg



10/80 mg



at bedtime



50-60%10/20 mg at bedtime
*Start with 20/500 mg and increase monthly by 20/500.
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