Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the 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 Kovanen; Luis 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; European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia

doi:10.1093/eurheartj/ehu274

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

Department of Clinical Medicine

555 Citations (Scopus)

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 of HoFH and 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 comprehensive ACVD evaluation 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 language	English
Journal	European Heart Journal
Volume	35
Issue number	32
Pages (from-to)	2146-2157
Number of pages	12
ISSN	0195-668X
DOIs	https://doi.org/10.1093/eurheartj/ehu274
Publication status	Published - 21 Aug 2014

Keywords

Anticholesteremic Agents
Arcus Senilis
Atherosclerosis
Blood Component Removal
Cardiovascular Diseases
Cholesterol, LDL
Diagnosis, Differential
Early Diagnosis
Gene Frequency
Genetic Heterogeneity
Homozygote
Humans
Hyperlipoproteinemia Type II
Liver Transplantation
Mutation
Pedigree
Phenotype
Practice Guidelines as Topic
Xanthomatosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/eurheartj/ehu274

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Cuchel, M., Bruckert, E., Ginsberg, H. N., Raal, F. J., Santos, R. D., Hegele, R. A., Kuivenhoven, J. A., Nordestgaard, B. G., Descamps, O. S., Steinhagen-Thiessen, E., Tybjærg-Hansen, A., Watts, G. F., Averna, M., Boileau, C., Borén, J., Catapano, A. L., Defesche, J. C., Hovingh, G. K., Humphries, S. E., ... European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia (2014). Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society . European Heart Journal, 35(32), 2146-2157. https://doi.org/10.1093/eurheartj/ehu274

Homozygous familial hypercholesterolaemia : new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society . / Cuchel, Marina; Bruckert, Eric; Ginsberg, Henry N et al.

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

Research output: Contribution to journal › Journal article › Research › peer-review

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, M-R, Wiegman, A, Wiklund, O, Chapman, MJ & European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia 2014, 'Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the 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 M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society . European Heart Journal. 2014 Aug 21;35(32):2146-2157. doi: 10.1093/eurheartj/ehu274

Cuchel, Marina ; Bruckert, Eric ; Ginsberg, Henry N et al. / Homozygous familial hypercholesterolaemia : new insights and guidance for clinicians to improve detection and clinical management. A position paper from the 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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title = "Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society ",

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 of HoFH and 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 comprehensive ACVD evaluation 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.",

keywords = "Anticholesteremic Agents, Arcus Senilis, Atherosclerosis, Blood Component Removal, Cardiovascular Diseases, Cholesterol, LDL, Diagnosis, Differential, Early Diagnosis, Gene Frequency, Genetic Heterogeneity, Homozygote, Humans, Hyperlipoproteinemia Type II, Liver Transplantation, Mutation, Pedigree, Phenotype, Practice Guidelines as Topic, Xanthomatosis",

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 Marja-Riitta Taskinen and Albert Wiegman and Olov Wiklund and Chapman, {M John} and {European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia}",

note = "{\textcopyright} The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2014",

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doi = "10.1093/eurheartj/ehu274",

language = "English",

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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 from the 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

AU - European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia

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 of HoFH and 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 comprehensive ACVD evaluation 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 of HoFH and 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 comprehensive ACVD evaluation 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 - Anticholesteremic Agents

KW - Arcus Senilis

KW - Atherosclerosis

KW - Blood Component Removal

KW - Cardiovascular Diseases

KW - Cholesterol, LDL

KW - Diagnosis, Differential

KW - Early Diagnosis

KW - Gene Frequency

KW - Genetic Heterogeneity

KW - Homozygote

KW - Humans

KW - Hyperlipoproteinemia Type II

KW - Liver Transplantation

KW - Mutation

KW - Pedigree

KW - Phenotype

KW - Practice Guidelines as Topic

KW - Xanthomatosis

U2 - 10.1093/eurheartj/ehu274

DO - 10.1093/eurheartj/ehu274

M3 - Journal article

C2 - 25053660

SN - 0195-668X

VL - 35

SP - 2146

EP - 2157

JO - European Heart Journal

JF - European Heart Journal

IS - 32

ER -