Homozygous familial hypercholesterolaemia: New insights and guidance for clinicians to improve detection and clinical management. A position paper fromthe Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Marina Cuchel, Eric Bruckert, Henry N. Ginsberg, Frederick J. Raal, Raul D. Santos, Robert A. Hegele, Jan Albert Kuivenhoven, Børge G. Nordestgaard, Olivier S. Descamps, Elisabeth Steinhagen-Thiessen, Anne Tybjærg-Hansen, Gerald F. Watts, Maurizio Averna, Catherine Boileau, Jan Borén, Alberico L. Catapano, Joep C. Defesche, G. Kees Hovingh, Steve E. Humphries, Petri T. KovanenLuis Masana, Päivi Pajukanta, Klaus G. Parhofer, Kausik K. Ray, Anton F H Stalenhoef, Erik Stroes, Marja Riitta Taskinen, Albert Wiegman, Olov Wiklund, M. John Chapman

Research output: Contribution to journalArticle

Abstract

Aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results: Early diagnosis ofHoFHand prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH.We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensiveACVDevaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. Conclusion: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.

Original languageEnglish
Pages (from-to)2146-2157
Number of pages12
JournalEuropean Heart Journal
Volume35
Issue number32
DOIs
Publication statusPublished - Aug 21 2014

Fingerprint

Hyperlipoproteinemia Type II
Consensus
LDL Cholesterol
Therapeutics
Cardiovascular Diseases
Lipids
Xanthomatosis
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Blood Component Removal
Genetic Heterogeneity
Genetic Testing
Coronary Angiography
Tendons
Lipoproteins
Aorta
Life Style
Early Diagnosis
Atherosclerosis
Referral and Consultation
Parents

Keywords

  • Diagnosis
  • Ezetimibe
  • Genetics
  • Homozygous familial hypercholesterolaemia
  • Lipoprotein apheresis
  • Lomitapide
  • Mipomersen
  • Phenotypic heterogeneity
  • Statins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Homozygous familial hypercholesterolaemia : New insights and guidance for clinicians to improve detection and clinical management. A position paper fromthe Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. / Cuchel, Marina; Bruckert, Eric; Ginsberg, Henry N.; Raal, Frederick J.; Santos, Raul D.; Hegele, Robert A.; Kuivenhoven, Jan Albert; Nordestgaard, Børge G.; Descamps, Olivier S.; Steinhagen-Thiessen, Elisabeth; Tybjærg-Hansen, Anne; Watts, Gerald F.; Averna, Maurizio; Boileau, Catherine; Borén, Jan; Catapano, Alberico L.; Defesche, Joep C.; Hovingh, G. Kees; Humphries, Steve E.; Kovanen, Petri T.; Masana, Luis; Pajukanta, Päivi; Parhofer, Klaus G.; Ray, Kausik K.; Stalenhoef, Anton F H; Stroes, Erik; Taskinen, Marja Riitta; Wiegman, Albert; Wiklund, Olov; Chapman, M. John.

In: European Heart Journal, Vol. 35, No. 32, 21.08.2014, p. 2146-2157.

Research output: Contribution to journalArticle

Cuchel, M, Bruckert, E, Ginsberg, HN, Raal, FJ, Santos, RD, Hegele, RA, Kuivenhoven, JA, Nordestgaard, BG, Descamps, OS, Steinhagen-Thiessen, E, Tybjærg-Hansen, A, Watts, GF, Averna, M, Boileau, C, Borén, J, Catapano, AL, Defesche, JC, Hovingh, GK, Humphries, SE, Kovanen, PT, Masana, L, Pajukanta, P, Parhofer, KG, Ray, KK, Stalenhoef, AFH, Stroes, E, Taskinen, MR, Wiegman, A, Wiklund, O & Chapman, MJ 2014, 'Homozygous familial hypercholesterolaemia: New insights and guidance for clinicians to improve detection and clinical management. A position paper fromthe Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society', European Heart Journal, vol. 35, no. 32, pp. 2146-2157. https://doi.org/10.1093/eurheartj/ehu274
Cuchel, Marina ; Bruckert, Eric ; Ginsberg, Henry N. ; Raal, Frederick J. ; Santos, Raul D. ; Hegele, Robert A. ; Kuivenhoven, Jan Albert ; Nordestgaard, Børge G. ; Descamps, Olivier S. ; Steinhagen-Thiessen, Elisabeth ; Tybjærg-Hansen, Anne ; Watts, Gerald F. ; Averna, Maurizio ; Boileau, Catherine ; Borén, Jan ; Catapano, Alberico L. ; Defesche, Joep C. ; Hovingh, G. Kees ; Humphries, Steve E. ; Kovanen, Petri T. ; Masana, Luis ; Pajukanta, Päivi ; Parhofer, Klaus G. ; Ray, Kausik K. ; Stalenhoef, Anton F H ; Stroes, Erik ; Taskinen, Marja Riitta ; Wiegman, Albert ; Wiklund, Olov ; Chapman, M. John. / Homozygous familial hypercholesterolaemia : New insights and guidance for clinicians to improve detection and clinical management. A position paper fromthe Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. In: European Heart Journal. 2014 ; Vol. 35, No. 32. pp. 2146-2157.
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abstract = "Aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results: Early diagnosis ofHoFHand prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH.We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensiveACVDevaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. Conclusion: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.",
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author = "Marina Cuchel and Eric Bruckert and Ginsberg, {Henry N.} and Raal, {Frederick J.} and Santos, {Raul D.} and Hegele, {Robert A.} and Kuivenhoven, {Jan Albert} and Nordestgaard, {B{\o}rge G.} and Descamps, {Olivier S.} and Elisabeth Steinhagen-Thiessen and Anne Tybj{\ae}rg-Hansen and Watts, {Gerald F.} and Maurizio Averna and Catherine Boileau and Jan Bor{\'e}n and Catapano, {Alberico L.} and Defesche, {Joep C.} and Hovingh, {G. Kees} and Humphries, {Steve E.} and Kovanen, {Petri T.} and Luis Masana and P{\"a}ivi Pajukanta and Parhofer, {Klaus G.} and Ray, {Kausik K.} and Stalenhoef, {Anton F H} and Erik Stroes and Taskinen, {Marja Riitta} and Albert Wiegman and Olov Wiklund and Chapman, {M. John}",
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TY - JOUR

T1 - Homozygous familial hypercholesterolaemia

T2 - New insights and guidance for clinicians to improve detection and clinical management. A position paper fromthe Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

AU - Cuchel, Marina

AU - Bruckert, Eric

AU - Ginsberg, Henry N.

AU - Raal, Frederick J.

AU - Santos, Raul D.

AU - Hegele, Robert A.

AU - Kuivenhoven, Jan Albert

AU - Nordestgaard, Børge G.

AU - Descamps, Olivier S.

AU - Steinhagen-Thiessen, Elisabeth

AU - Tybjærg-Hansen, Anne

AU - Watts, Gerald F.

AU - Averna, Maurizio

AU - Boileau, Catherine

AU - Borén, Jan

AU - Catapano, Alberico L.

AU - Defesche, Joep C.

AU - Hovingh, G. Kees

AU - Humphries, Steve E.

AU - Kovanen, Petri T.

AU - Masana, Luis

AU - Pajukanta, Päivi

AU - Parhofer, Klaus G.

AU - Ray, Kausik K.

AU - Stalenhoef, Anton F H

AU - Stroes, Erik

AU - Taskinen, Marja Riitta

AU - Wiegman, Albert

AU - Wiklund, Olov

AU - Chapman, M. John

PY - 2014/8/21

Y1 - 2014/8/21

N2 - Aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results: Early diagnosis ofHoFHand prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH.We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensiveACVDevaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. Conclusion: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.

AB - Aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. Methods and results: Early diagnosis ofHoFHand prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH.We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensiveACVDevaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. Conclusion: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.

KW - Diagnosis

KW - Ezetimibe

KW - Genetics

KW - Homozygous familial hypercholesterolaemia

KW - Lipoprotein apheresis

KW - Lomitapide

KW - Mipomersen

KW - Phenotypic heterogeneity

KW - Statins

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