318
Views
0
CrossRef citations to date
0
Altmetric
Reviews

Current challenges in the management of patients with familial hypercholesterolemia

, &
Pages 217-229 | Published online: 18 Jan 2017

References

  • Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: The Metabolic and Molecular Bases of Inherited Disease. Scriver CR, Beaudet AL, Sly WS et al. (Eds). McGraw-Hill, NY, USA, 2863–2913 (2001).
  • Slack J. Risks of ischaemic heart-disease in familial hyperlipoproteinaemic states. Lancet 1380–1382 (1969).
  • Stone NJ, Levy RI, Fredrickson DS, Verter J. Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circulation 49, 476–488 (1974).
  • Sijbrands EJ, Westendorp RG, Defesche JC, de Meier PH, Smelt AH, Kastelein JJ. Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study. BMJ 322, 1019–1023 (2001).
  • Versmissen J, Oosterveer DM, Yazdanpanah M et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 337, a2423 (2008). One of the best descriptions of the effectiveness of statins in patients with familial hypercholesterolemia (FH).
  • Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis 168, 1–14 (2003).
  • Scientific Steering Committee on behalf of the Simon Broome Register Group. Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Atherosclerosis 142, 105–112 (1999).
  • Sjouke B, Kusters DM, Kastelein JJP, Hovingh GK. Familial hypercholesterolemia: present and future management. Curr. Cardiol. Rep. 13, 527–536 (2011).
  • Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J. Clin. Invest. 111, 1795–1803 (2003).
  • Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J. Clin. Endocrin. Metab. 97, 3956–3964 (2012). The authors estimated the prevalence of FH in a large population by applying the Dutch lipid clinic criteria in combination with molecular screening of most common Danish causative mutations. They demonstrated that the prevalence of FH may be higher than expected.
  • Kessling AM, Seed M, Taylor R, Wynn V, Humphries SE. Rising cholesterol levels in children with familial hypercholesterolaemia. Biomed. Pharmacother. 44, 373–379 (1990).
  • Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ 303, 893–896 (1991).
  • Williams RR, Hunt SC, Schumacher C et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am. J. Cardiol. 72, 171–176 (1993).
  • Goldberg AC, Hopkins PN, Toth PP et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J. Clin. Lipidol. 5(Suppl. 3), S1–S8 (2011).
  • Reiner Z, Catapano AL, 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). Eur. Heart J. 32, 1769–1818 (2011).
  • Clarke RE, Padayachee ST, Preston R et al. Effectiveness of alternative strategies to define index case phenotypes to aid genetic diagnosis of familial hypercholesterolaemia. Heart 99, 175–180 (2013).
  • Lambert H, Humphries SE, Neil HA. Screening for hypercholesterolemia versus case finding for familial hypercholesterolaemia: systematic review and cost effectiveness analysis. Health Technol. Assess. 4, 1–123 (2000).
  • Betard C, Kessling AM, Roy M et al. Molecular genetic evidence for a founder effect in familial hypercholesterolemia among French Canadians. Hum. Genet. 88, 529–536 (1992).
  • Abifadel M, Varret M, Rabes JP et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 2, 154–156 (2003).
  • Benjannet S, Rhainds D, Essalmani R et al. NARC:1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J. Biol. Chem. 47, 48865–48875 (2004).
  • Marduel M, Carrié A, Sassolas A et al. Molecular spectrum of autosomal dominant hypercholesterolemia in France. Hum. Mutat. 31, e1811–e1824 (2010).
  • Marks D, Wonderling D, Thorogood M et al. Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia. BMJ 324, 1303–1308 (2002).
  • Sharma P, Boyers D, Boachie C et al. Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolaemia: a systematic review and economic evaluation. Health Technol. Assess. 16, 1–266 (2012).
  • Marks D, Thorogood M, Neil SM, Humphries SE, Neil HAW. Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programs. J. Med. Screen 13, 156–159 (2006).
  • Umans-Eckenhausen MA, Defesche JC, Sijbrands EJ et al. Review of first 5 years of screening for familial hypercholesterolaemia in The Netherlands. Lancet 357, 165–168 (2001). Reports the results of a national program dedicated to the identification of FH.
  • Leren TP, Finborud TH, Manshaus TE, Ose L, Berge KE. Diagnosis of familial hypercholesterolemia ingeneral practice using clinical diagnostic criteriaor genetic testing as part of cascade geneticscreening. Community Genet. 11, 26–35 (2008).
  • Marteau T, Senior V, Humphries SE et al. Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial. Am. J. Med. Genet. A 128A, 285–293 (2004).
  • Huijgen R, Kindt I, Verhoeven SB et al. Two years after molecular diagnosis of familial hypercholesterolemia: majority on cholesterol-lowering treatment but a minority reaches treatment goal. PLoS ONE 5, e9220 (2010).
  • Neil HA, Hammond T, Huxley R et al. Extent of underdiagnosis of familial hypercholesterolaemia in routine practice: prospective registry study. BMJ 321, 148 (2000).
  • Qureshi N, Humphries SE, Seed M, Rowlands P, Minhas R. Identification and management of familial hypercholesterolaemia: what does it mean to primary care? Br. J. Gen. Pract. 59, 773–776 (2009).
  • Mant D. Commentary: what’s so special about familial hypercholesterolaemia? Br. J. Gen. Pract. 59, 777–778 (2009).
  • Jones PH, Davidson MH, Stein EA et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am. J. Cardiol. 92, 152–160 (2003).
  • Neil A, Cooper J, Betteridge J et al. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur. Heart J. 29, 2625–2633 (2008).
  • Smilde TJ, van Wissen S, Wollersheim H et al. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomized, double-blind trial. Lancet 357, 577–581 (2001).
  • Pijlman AH, Huijgen R, Verhagen SN et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis 209, 189–194 (2010).
  • Mata N, Alonso R, Badimon L et al. Clinical characteristics and evaluation of LDL Cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART). Lipids Health Dis. 10, 94 (2011). Offers a clear demonstration that patients with FH are suboptimally treated in clinical practice.
  • Leren TP, Berge KE. Subjects with molecularly defined familial hypercholesterolemia or familial defective apoB100 are not being adequately treated. PLoS ONE 6, e16721 (2011).
  • Stein EA, Strutt K, Southworth H et al. Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia. Am. J. Cardiol. 92, 1287–1293 (2003).
  • Kawashiri MA, Nohara A, Noguchi T et al. Efficacy and safety of coadministration of rosuvastatin, ezetimibe, and colestimide in heterozygous familial hypercholesterolemia. Am. J. Cardiol. 109, 364–369 (2012).
  • Kastelein JJ, Akdim F, Stroes ES et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N. Engl. J. Med. 358, 1431–1443 (2008).
  • Thompson GR; HEART-UK LDL Apheresis Working Group. Recommendations for the use of LDL apheresis. Atherosclerosis 198, 247–255 (2008).
  • Mabuchi H, Koizumi J, Shimizu M et al. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Am. J. Cardiol. 82, 1489–1495 (1998).
  • Cummings MH, Watts GF, Umpleby M et al. Increased hepatic secretion of very-lowdensity-lipoprotein apolipoprotein B-100 in heterozygous familial hypercholesterolaemia: a stable isotope study. Atherosclerosis 113, 79–89 (1995).
  • Sundaram M, Yao Z. Recent progress in understanding protein and lipid factors affecting hepatic VLDL assembly and secretion. Nutr. Metab. (Lond.) 7, 35 (2010).
  • Ito MK. ISIS 301012 gene therapy for hypercholesterolemia: sense, antisense, or nonsense? Ann. Pharmacother. 41, 1669–1678 (2007).
  • Raal FJ, Santos RD, Blom DJ et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomized, double blind, placebo-controlled trial. Lancet 375, 998–1006 (2010). First to report the impressive results of the treatment with mipomersen of patients with homozygous FH.
  • Akdim F, Visser ME, Tribble DL et al. Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am. J. Cardiol. 105, 1413–1419 (2010).
  • Stein EA, Dufour R, Gagne C et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 126, 2283–2292 (2012).
  • Visser ME, Akdim F, Tribble DL et al. Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J. Lipid Res. 51, 1057–1062 (2010).
  • Burnett JR, Watts GF. MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty promises? Expert Opin. Ther. Targets 11, 181–189 (2007).
  • Cuchel M, Bloedon LT, Szapary PO et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N. Engl. J. Med. 356, 148–156 (2007).
  • Cuchel M, Meagher EA, du Toit Theron H 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 381, 40–46 (2013). This very recent trial extends to a longer follow-up of the evaluation of the effects of lomitapide in patients with homozygous FH.
  • Lindholm MW, Elmén J, Fisker N et al. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates. Mol. Ther. 20(2), 376–381 (2012).
  • Liang H, Chaparro-Rigger J, Strop P et al. Proprotein convertase substillisin/kexin type 9 reduces LDL cholesterol in statin-treated hypercholesterolemic nonhuman primates. J. Pharmacol. Exp. Ther. 340, 228–236 (2012).
  • Stein EA, Mellis S, Yancopoulos GD et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N. Engl. J. Med. 366, 1108–1118 (2012).
  • Stein EA, Gipe D, Bergeron J et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a Phase 2 randomised controlled trial. Lancet 380, 29–36 (2012).
  • Raal F, Scott R, Somaratne R et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the reduction of LDL C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder (Rutherford) randomized trial. Circulation 126, 2408–2417 (2012). Largest trial employing a PCSK9 inhibitor in FH carried out so far.
  • Vuorio A, Kuoppala J, Kovanen PT et al. Statins for children with familial hypercholesterolemia. Cochrane Database Syst. Rev. 7, CD006401 (2010).
  • Avis HJ, Hutten BA, Gagné C et al. Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. J. Am. Coll Cardiol. 55(11), 1121–1126 (2010).
  • Rodenburg J, Vissers MN, Wiegman A et al. Statin treatment in children with familial hypercholesterolemia; the younger, the better. Circulation 116, 664–668 (2007).
  • Goldberg AC, Hopkins PN, Toth PP et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients. J. Clin. Lipidol. 5(Suppl. 3), S1–S8 (2011).
  • Daniels SR, Greer FR. Lipid screening and cardiovascular health in children. Pediatrics 122, 198–208 (2008).
  • Avis HJ, Vissers MN, Stein EA et al. A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 27(8), 1803–1810 (2007).
  • Watts GF, Sullivan DR, Poplawski N et al.; Familial Hypercholesterolaemia Australasia Network Consensus Group (Australian Atherosclerosis Society). Familial hypercholesterolaemia: a model of care for Australasia. Atheroscler. Suppl. 12, 221–263 (2011).
  • Descamps OS, Tenoutassa S, Stephenne X et al. Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization. Atherosclerosis 218, 272–280 (2011).
  • McCrindle BW, Urbina EM, Dennison BA et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension and Obesity Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation 115, 1948–1967 (2007).
  • Raitakari OT, Juonala M, Kähönen M et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA 290, 2277–2283 (2003).
  • Wiegman A, de Groot E, Hutten BA et al. Arterial intima–media thickness in children heterozygous for familial hypercholesterolaemia. Lancet 363, 369–370 (2004).
  • Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J. Lipid Res. 50(Suppl.), S172–S177 (2009).
  • Vuorio A, Docherty KF, Humphries SE, Kuoppala J, Kovanen PT. Statin treatment of children with familial hypercholesterolemia. Trying to balance incomplete evidence of long-term safety and clinical accountability: are we approaching a consensus? Atherosclerosis 226(2), 315–320 (2012). Evaluates all evidence supporting the use of statins in children with FH.
  • Wiegman A, Hutten BA, de Groot E et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. JAMA 292, 331–337 (2004).
  • Kusters DM, Homsma SJ, Hutten BA et al. Dilemmas in treatment of women with familial hypercholesterolaemia during pregnancy. Neth. J. Med. 68, 299–303 (2010).
  • Amundsen AL, Khoury J, Iversen PO et al. Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia. Atherosclerosis 189(2), 451–457 (2006).
  • Palinski W, Napoli C. The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis. FASEB J. 16, 1348–1360 (2002).
  • Alkemade FE, Gittenberger-de Groot AC, Schiel AE et al. Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life. Arterioscler. Thromb. Vasc. Biol. 27, 2228–2223 (2007).
  • Thorogood M, Seed M, De Mott K. Management of fertility in women with familial hypercholesterolaemia: summary of NICE guidance. BJOG 116, 478–479 (2009).
  • Kusters DM, Lahsinoui HH, van de Post JA et al. Statin use during pregnancy: a systematic review and meta-analysis. Expert Rev. Cardiovasc Ther. 10, 363–378 (2012).
  • Tardif JC, McGowan M, Ceska R et al. Apolipoprotein B synthesis inhibition by mipomersen reduces low-density lipoprotein cholesterol when added to maximally tolerated lipid-lowering medication in patients with severe heterozygous hypercholesterolemia free. J. Am. Coll. Cardiol. 57(14), e492 (2011).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.