Turk Kardiyol Dern Ars. 2015; 43(1): 1-14 | 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
Institute for Translational Medicine and Therapy, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA

OBJECTIVE
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
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: Homozygous familial hypercholesterolaemia, Diagnosis, Genetics, Phenotypic heterogeneity, Statins, Ezetimibe, Lipoprotein apheresis, Lomitapide, Mipomersen

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