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
N1 - © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.
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 -
