TY - JOUR
T1 - Defining severe familial hypercholesterolaemia and the implications for clinical management
T2 - a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel
AU - Santos, Raul D.
AU - Gidding, Samuel S.
AU - Hegele, Robert A.
AU - Cuchel, Marina A.
AU - Barter, Philip J.
AU - Watts, Gerald F.
AU - Baum, Seth J.
AU - Catapano, Alberico L.
AU - Chapman, M. John
AU - Defesche, Joep C.
AU - Folco, Emanuela
AU - Freiberger, Tomas
AU - Genest, Jacques
AU - Hovingh, G. Kees
AU - Harada-Shiba, Mariko
AU - Humphries, Steve E.
AU - Jackson, Ann S.
AU - Mata, Pedro
AU - Moriarty, Patrick M.
AU - Raal, Frederick J.
AU - Al-Rasadi, Khalid
AU - Ray, Kausik K.
AU - Reiner, Zelijko
AU - Sijbrands, Eric J.G.
AU - Yamashita, Shizuya
N1 - Funding Information:
KA-R has received grants from Pfizer; advisory board fees from Sanofi; and speaker's honoraria from AstraZeneca, Pfizer, and Sanofi. PJB has received personal fees from Amgen, Sanofi-Regeneron, Pfizer, and Merck; and grants from Pfizer. SJB has received advisory board fees from Aegerion, Merck, and Sanofi-Regeneron; speaker's honoraria from Aegerion, Amgen, and Merck; and consulting fees from Amgen. MJC has received honoraria for service on advisory boards, speaker's honoraria, and research funding from Amgen, AstraZeneca, CSL, Kowa, Sanofi-Regeneron, and Unilever. MAC has received grants from the National Heart, Lung, and Blood Institute (P01-HL-0594-07-14), Regeneron Pharmaceuticals, Sanofi-Aventis, and Aegerion; and personal fees from Sanofi-Aventis and Aegerion. ALC has received grants from Amgen, Pfizer, and Sanofi; and personal fees from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Mediolanum, Merck, Pfizer, Recordati, Rottapharm, and Sanofi. EF and ASJ are executive directors of the International Atherosclerosis Society. TF has received speaker's honoraria from Amgen, Sanofi, and Pfizer. JG has received grants from Amgen, Sanofi, Pfizer, and Aegerion. SSG is a member of the scientific advisory board of the FH Foundation. MH-S has received grants from the Japanese Ministry of Health and Welfare, the Japan Agency of Medical Research and Development, Astellas Pharma, and Kaneka Medix; and personal fees from Sanofi, Astellas Pharma, Kowa, Astellas Amgen, AstraZeneca, Boehringer Ingelheim, BML, Bayer, MSD, and Aegerion. RAH has received grants and personal fees from Aegerion, Amgen, Pfizer, Sanofi, and Valeant; grants from the Canadian Institutes of Health Research. the Heart and Stroke Foundation of Canada, and Ionis; and personal fees from Tribute Pharma. GKH has received honoraria directly or to his institution for consultancy, advisory board membership, and conduct of clinical trials from Amgen, Aegerion, Pfizer, AstraZeneca, Sanofi, Regeneron, Kowa, Ionis Pharmaceuticals, Cerenis, and Synageva. SEH has received grants from the British Heart Foundation. PM has received grants and personal fees from Amgen; and grants from Sanofi. PMM has received grants from Catabasis, Pfizer, Novartis, Kaneka, and the US National Institutes of Health; grants and advisory board fees from ISIS/Akcea Therapeutics; grants and honoraria from Amgen, Genzyme, Regeneron, and Sanofi; consulting fees from Duke and Cymabay Therapeutics; advisory board fees and speaker honoraria from Aegerion; speaker honoraria from Alexion (formerly Synageva); and advisory board fees from Esperion. FJR has received grants from the University of Witwatersrand; and personal fees and non-financial support from AstraZeneca, Pfizer, Merck, Amgen, and Sanofi. KKR has received grants from Pfizer, Amgen, MSD, Sanofi, and Regeneron; and personal fees from Amgen, Sanofi, Regeneron, Pfizer, AstraZeneca, Kowa, Aegerion, MedCo, MSD, ISIS, Cerenis, and Lilly. ZR has received personal fees from Sanofi, Amgen, and Synageva. EJGS has received sponsorship from the International FH Foundation for the Rotterdam meeting of the FH CTA Consortium; a travel grant from the FH Foundation; grants from the Diabetes Fund, Erasmus MC, Masqueliers, and Novartis; and speaker honoraria from Astellos, Boehringer Ingelheim, MSD, and Novartis. RDS has received personal fees from Amgen, Aegerion, AstraZeneca, Akcea, Biolab, Boehringer-Ingelheim, Cerenis, Eli-Lilly, Genzyme, Kowa, Merck, Pfizer, Sanofi-Regeneron, Torrent, and Unilever. GFW has received grants and personal fees from Sanofi and Amgen. SY has received grants from Boehringer Ingelheim, Otsuka, the National Institute of Biomedical Innovation, Japan Tobacco, Kyowa Medex, Ono Pharmaceutical, Astellas, Daiichi-Sankyo, Mochida, AstraZeneca, Izumisano City, Kaizuka City, Hayashibara, Teijin, and Kaken; grants and personal fees from Shionogi, Bayer, MSD, Takeda, Sanwa Kagaku Kenkyusho, and Kowa; personal fees from Medical Review and Skylight Biotec; and has a patent pending with Fujirebio, unrelated to this Review. JCD declares no competing interests.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Familial hypercholesterolaemia is common in individuals who had a myocardial infarction at a young age. As many as one in 200 people could have heterozygous familial hypercholesterolaemia, and up to one in 300 000 individuals could be homozygous. The phenotypes of heterozygous and homozygous familial hypercholesterolaemia overlap considerably; the response to treatment is also heterogeneous. In this Review, we aim to define a phenotype for severe familial hypercholesterolaemia and identify people at highest risk for cardiovascular disease, based on the concentration of LDL cholesterol in blood and individuals' responsiveness to conventional lipid-lowering treatment. We assess the importance of molecular characterisation and define the role of other cardiovascular risk factors and advanced subclinical coronary atherosclerosis in risk stratification. Individuals with severe familial hypercholesterolaemia might benefit in particular from early and more aggressive cholesterol-lowering treatment (eg, with PCSK9 inhibitors). In addition to better tailored therapy, more precise characterisation of individuals with severe familial hypercholesterolaemia could improve resource use.
AB - Familial hypercholesterolaemia is common in individuals who had a myocardial infarction at a young age. As many as one in 200 people could have heterozygous familial hypercholesterolaemia, and up to one in 300 000 individuals could be homozygous. The phenotypes of heterozygous and homozygous familial hypercholesterolaemia overlap considerably; the response to treatment is also heterogeneous. In this Review, we aim to define a phenotype for severe familial hypercholesterolaemia and identify people at highest risk for cardiovascular disease, based on the concentration of LDL cholesterol in blood and individuals' responsiveness to conventional lipid-lowering treatment. We assess the importance of molecular characterisation and define the role of other cardiovascular risk factors and advanced subclinical coronary atherosclerosis in risk stratification. Individuals with severe familial hypercholesterolaemia might benefit in particular from early and more aggressive cholesterol-lowering treatment (eg, with PCSK9 inhibitors). In addition to better tailored therapy, more precise characterisation of individuals with severe familial hypercholesterolaemia could improve resource use.
UR - http://www.scopus.com/inward/record.url?scp=84969962145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969962145&partnerID=8YFLogxK
U2 - 10.1016/S2213-8587(16)30041-9
DO - 10.1016/S2213-8587(16)30041-9
M3 - Review article
C2 - 27246162
AN - SCOPUS:84969962145
SN - 2213-8587
VL - 4
SP - 850
EP - 861
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 10
ER -