Статья

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

M. CuchelInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA [email protected]Éric BruckertInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAH. N. GinsbergInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAF. J. RaalInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAR. D. SantosInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USARobert A. HegeleInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAJan Albert KuivenhovenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USABørge G. NordestgaardInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAOlivier DescampsInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAE. Steinhagen-ThiessenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAAnne Tybjærg‐HansenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAGerald F. WattsInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAMaurizio AvernaInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USACathérine BoileauInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAJan BorénInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAAlberico L. CatapanoInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAJoep C. DefescheInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAG. Kees HovinghInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USASteve E. HumphriesInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAPetri T. KovanenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAL. MasanaInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAP. PajukantaInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAKlaus G. ParhoferInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAKausik K. RayInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAAnton F. H. StalenhoefInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAErik S.G. StroesInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAMarja‐Riitta TaskinenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAAlbert WiegmanInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAOlov WiklundUniversity of PennsylvaniaM. John ChapmanInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAfor the European Atherosclerosis Society Consensus Panel on Familial HypercholesterolaemiaInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAM. CuchelInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA [email protected]O. S. DescampsInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAH. N. GinsbergInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAB. G. NordestgaardInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAF. J. RaalInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAR. D. SantosInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAE. Steinhagen-ThiessenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAAnne Tybjærg‐HansenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAHenry N. GinsbergInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAJ. BorenInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAG. K. HovinghInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAP. PajukantaInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USAAnton F. H. StalenhoefInstitute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA

2014en

ABI

Аннотация

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.

Перевод пока недоступен

Идентификаторы

DOI: 10.1093/eurheartj/ehu274

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar