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1. HoFH is a life limiting condition: Clinical characteristics and lifespan of deceased HoFH patients in the HICC registry

Author

Mulder, J., primary, Tromp, T., additional, Reijman, D., additional, Al-Waili, K., additional, Ayesh, M., additional, Bertolini†, S., additional, Blaha, V., additional, Blom, D., additional, Brothers, J., additional, Cuchel, M., additional, Francis, G., additional, Genest, J., additional, Harada-Shiba, M., additional, Hovingh, G.K., additional, Raal, F., additional, Santos, R., additional, Soran, H., additional, Truong, T.H., additional, Verma, I., additional, Wang, L., additional, Wiegman, A., additional, and Van Lennep, J. Roeters, additional

Published
2023
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3. Diagnosis, treatment and cardiovascular outcomes in homozygous familial hypercholesterolaemia: A sex-specific analysis

Author

Mulder, J., primary, Tromp, T., additional, Al-Khnifsawi, M., additional, Bertolini†, S., additional, Blom, D., additional, Chlebus, K., additional, Cuchel, M., additional, Gallo, A., additional, Hovingh, G.K., additional, Kim, N.T., additional, Long, J., additional, Raal, F., additional, Truong, T.H., additional, Boersma, E., additional, and Van Lennep, J. Roeters, additional

Published
2023
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5. 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance

Author

Universitat Rovira i Virgili, Cuchel, M; Raal, FJ; Hegele, RA; Al-Rasadi, K; Arca, M; Averna, M; Bruckert, E; Freiberger, T; Gaudet, D; Harada-Shiba, M; Hudgins, LC; Kayikcioglu, M; Masana, L; Parhofer, KG; van Lennep, JER; Santos, RD; Stroes, ESG; Watts, GF; Wiegman, A; Stock, JK; Tokgözoglu, LS; Catapano, AL; Ray, KK, Universitat Rovira i Virgili, and Cuchel, M; Raal, FJ; Hegele, RA; Al-Rasadi, K; Arca, M; Averna, M; Bruckert, E; Freiberger, T; Gaudet, D; Harada-Shiba, M; Hudgins, LC; Kayikcioglu, M; Masana, L; Parhofer, KG; van Lennep, JER; Santos, RD; Stroes, ESG; Watts, GF; Wiegman, A; Stock, JK; Tokgözoglu, LS; Catapano, AL; Ray, KK

Abstract

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Published
2023

8. Specification of ACMG/AMP guidelines for standardized variant interpretation in familial hypercholesterolemia: On behalf of the clingen FH variant curation expert panel

Author

Iacocca, M.A., primary, Chora, J.R., additional, Freiberger, T., additional, Carrie, A., additional, Sijbrands, E.J., additional, Wand, H., additional, Williams, M., additional, Zimmermann, H., additional, Leon, A., additional, Kurtz, C.L., additional, Tichy, L., additional, Alves, A.C., additional, Wang, J., additional, Cuchel, M., additional, Humphries, S.E., additional, Defesche, J.C., additional, Mata, P., additional, Santos, R.D., additional, Kullo, I.J., additional, Brunham, L.R., additional, Hegele, R.A., additional, Knowles, J.W., additional, and Bourbon, M., additional

Published
2020
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10. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Author

Zanoni, P., Khetarpal, S.A., Larach, D.B., Hancock-Cerutti, W.F., Millar, J.S., Cuchel, M., Derohannessian, S.L., Kontush, A., Surendran, P., Saleheen, D., Trompet, S., Jukema, J.W., de Craen, A.J., Deloukas, P., Sattar, N., Ford, I., Packard, C., Al Shafi Majumder, A., Alam, D.S., di Angelantonio, E., Abecasis, G., Chowdhury, R., Erdmann, J., Nørdestgaard, B.G., Nielsen, S.F., Tybjærg-Hansen, A., Schmidt, R.F., Kuulasmaa, K., Liu, D.J., Perola, M., Blankenberg, S., Salomaa, V., Männistö, S., Amouyel, P., Arveiler, D., Ferrieres, J., Müller-Nurasyid, M., Ferrario, M., Kee, F., Willer, C.J., Samani, N., Schunkert, H., Butterworth, A.S., Howson, J.M.M., Peloso, G.M., Stitziel, N.O., Danesh, J., Kathiresan, S., Rader, D.J., CHD Exome Consortium (), CARDIoGRAM Exome Consortium (), Global Lipids Genetics Consortium (), CHD Exome+ Consortium, CARDIoGRAM Exome Consortium, Global Lipids Genetics Consortium, Watson, S., Schmidt, E.M., Sengupta, S., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M.L., Mora, S., Beckmann, J.S., Bragg-Gresham, J.L., Chang, H.Y., Demirkan, A., Den Hertog, H.M., Do, R., Donnelly, L.A., Ehret, G.B., Esko, T., Feitosa, M.F., Ferreira, T., Fischer, K., Fontanillas, P., Fraser, R.M., Freitag, D.F., Gurdasani, D., Heikkilä, K., Hyppönen, E., Isaacs, A., Jackson, A.U., Johansson, Å., Johnson, T., Kaakinen, M., Kettunen, J., Kleber, M.E., Li, X., Luan, J., Lyytikäinen, L.P., Magnusson, P.K., Mangino, M., Mihailov, E., Montasser, M.E., Nolte, I.M., O'Connell, J.R., Palmer, C.D., Petersen, A.K., Sanna, S., Saxena, R., Service, S.K., Shah, S., Shungin, D., Sidore, C., Song, C., Strawbridge, R.J., Surakka, I., Tanaka, T., Teslovich, T.M., Thorleifsson, G., Van den Herik, E.G., Voight, B.F., Volcik, K.A., Waite, L.L., Wong, A., Wu, Y., Zhang, W., Absher, D., Asiki, G., Barroso, I., Been, L.F., Bolton, J.L., Bonnycastle, L.L., Brambilla, P., Burnett, M.S., Cesana, G., Dimitriou, M., Doney, A.S., Döring, A., Elliott, P., Epstein, S.E., Eyjolfsson, G.I., Gigante, B., Goodarzi, M.O., Grallert, H., Gravito, M.L., Groves, C.J., Hallmans, G., Hartikainen, A.L., Hayward, C., Hernandez, D., Hicks, A.A., Holm, H., Hung, Y.J., Illig, T., Jones, M.R., Kaleebu, P., Kastelein, J.J., Khaw, K.T., Kim, E., Klopp, N., Komulainen, P., Kumari, M., Langenberg, C., Lehtimäki, T., Lin, S.Y., Lindström, J., Loos, R.J., Mach, F., McArdle, W.L., Meisinger, C., Mitchell, B.D., Müller, G., Nagaraja, R., Narisu, N., Nieminen, T.V., Nsubuga, R.N., Olafsson, I., Ong, K.K., Palotie, A., Papamarkou, T., Pomilla, C., Pouta, A., Reilly, M.P., Ridker, P.M., Rivadeneira, F., Rudan, I., Ruokonen, A., Scharnagl, H., Seeley, J., Silander, K., Stancáková, A., Stirrups, K., Swift, A.J., Tiret, L., Uitterlinden, A.G., van Pelt, L.J., Vedantam, S., Wainwright, N., Wijmenga, C., Wild, S.H., Willemsen, G., Wilsgaard, T., Wilson, J.F., Young, E.H., Zhao, J.H., Adair, L.S., Arveiler, D., Assimes, T.L., Bandinelli, S., Bennett, F., Bochud, M., Boehm, B.O., Boomsma, D.I., Borecki, I.B., Bornstein, S.R., Bovet, P., Burnier, M., Campbell, H., Chakravarti, A., Chambers, J.C., Chen, Y.D., Collins, F.S., Cooper, R.S., Dedoussis, G., de Faire, U., Feranil, A.B., Ferrucci, L., Freimer, N.B., Gieger, C., Groop, L.C., Gudnason, V., Gyllensten, U., Hamsten, A., Harris, T.B., Hingorani, A., Hirschhorn, J.N., Hofman, A., Hovingh, G.K., Hsiung, C.A., Humphries, S.E., Hunt, S.C., Hveem, K., Iribarren, C., Järvelin, M.R., Jula, A., Kähönen, M., Kaprio, J., Kesäniemi, A., Kivimaki, M., Kooner, J.S., Koudstaal, P.J., Krauss, R.M., Kuh, D., Kuusisto, J., Kyvik, K.O., Laakso, M., Lakka, T.A., Lind, L., Lindgren, C.M., Martin, N.G., März, W., McCarthy, M.I., McKenzie, C.A., Meneton, P., Metspalu, A., Moilanen, L., Morris, A.D., Munroe, P.B., Njølstad, I., Pedersen, N.L., Power, C., Pramstaller, P.P., Price, J.F., Psaty, B.M., Quertermous, T., Rauramaa, R., Salomaa, V., Sanghera, D.K., Saramies, J., Schwarz, P.E., Sheu, W.H., Shuldiner, A.R., Siegbahn, A., Spector, T.D., Stefansson, K., Strachan, D.P., Tayo, B.O., Tremoli, E., Tuomilehto, J., Uusitupa, M., van Duijn, C.M., Vollenweider, P., Wallentin, L., Wareham, N.J., Whitfield, J.B., Wolffenbuttel, B.H., Ordovas, J.M., Boerwinkle, E., Palmer, C.N., Thorsteinsdottir, U., Chasman, D.I., Rotter, J.I., Franks, P.W., Riatti, S., Cupples, L.A., Sandhu, M.S., Rich, S.S., Boehnke, M., Deloukas, P., Mohlke, K.L., Ingelsson, E., Gu, D., Roberts, R., Watkins, H., Blankenberg, S., Clarke, R., Collins, R., Kim, B.J., McPherson, R., Nieminen, M.S., O'Donnell, C., Schreiber, S., Zalloua, P.A., Zanoni, P, Khetarpal, SA, Larach, DB, Hancock-Cerutti, WF, Rader, DJ, Hypponen, Elina, Biological Psychology, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine

Subjects
Netherlands Twin Register (NTR), 0301 basic medicine, Male, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Scavenger Receptors, DNA Mutational Analysis, Coronary Disease, 030204 cardiovascular system & hematology, scavenger receptor, chemistry.chemical_compound, Mice, 0302 clinical medicine, High-density lipoprotein, Receptor, increased atherosclerosis, levels of plasma, Multidisciplinary, Medicine (all), Homozygote, Scavenger Receptors, Class B, Middle Aged, 3. Good health, Cholesterol, Knockout mouse, Female, lipids (amino acids, peptides, and proteins), Human, Risk, medicine.medical_specialty, Heterozygote, HDL, Proline, Aged, Amino Acid Substitution, Animals, Cholesterol, HDL, Genetic Variation, Humans, Leucine, Protein Processing, Post-Translational, Article, DNA Mutational Analysi, Cholesterol, HDL/blood, Coronary Disease/blood, Coronary Disease/genetics, Leucine/genetics, Proline/genetics, Scavenger Receptors, Class B/genetics, Scavenger Receptors, Class B/metabolism, 03 medical and health sciences, Internal medicine, medicine, Scavenger receptor, Protein Processing, Animal, business.industry, Post-Translational, Heterozygote advantage, SCARB1, 030104 developmental biology, Endocrinology, chemistry, Class B, business, Lipoprotein
Abstract

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant). Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder Aa, Alam DS, Di Angelantonio E, Science (New York, N.Y.), 2016, vol. 351, no. 6278, pp. 1166-1171, 2016 Refereed/Peer-reviewed

Published
2016
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11. Familial hypercholesterolæmia in children and adolescents: Gaining decades of life by optimizing detection and treatment

Author

Wiegman, A., Gidding, S., Watts, G., Chapman, M., Ginsberg, H., Cuchel, M., Ose, L., Averna, M., Boileau, C., Borén, J., Bruckert, E., Catapano, A., Defesche, J., Descamps, O., Hegele, R., Hovingh, G., Humphries, S., Kovanen, P., Kuivenhoven, J., Masana, L., Nordestgaard, B., Pajukanta, P., Parhofer, K., Raal, F., Ray, K., Santos, R., Stalenhoef, A., Steinhagen Thiessen, E., Stroes, E., Taskinen, M., Tybjealigrg Hansen, A., Wiklund, O., Wiegman, A., Gidding, S., Watts, G., Chapman, M., Ginsberg, H., Cuchel, M., Ose, L., Averna, M., Boileau, C., Borén, J., Bruckert, E., Catapano, A., Defesche, J., Descamps, O., Hegele, R., Hovingh, G., Humphries, S., Kovanen, P., Kuivenhoven, J., Masana, L., Nordestgaard, B., Pajukanta, P., Parhofer, K., Raal, F., Ray, K., Santos, R., Stalenhoef, A., Steinhagen- Thiessen, E., Stroes, E., Taskinen, M., Tybjealigrg-Hansen, A., Wiklund, O., and Steinhagen-Thiessen, E.

Subjects
Counseling, European Atherosclerosis Society Consensus Panel, Pediatrics, Cardiac & Cardiovascular Systems, STATIN THERAPY, Settore MED/09 - Medicina Interna, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Familial hypercholesterolemia, Adolescents, Carotid Intima-Media Thickness, INTIMA-MEDIA THICKNESS, Cost of Illness, Pregnancy, Risk Factors, Diagnosis, YOUNG-ADULTS, HIPERCOLESTEROLEMIA (DIAGNÓSTICO, TERAPIA, TENDÊNCIAS), Family history, Young adult, Child, Children, Evidence-Based Medicine, medicine.diagnostic_test, Homozygote, Middle Aged, Familial hypercholesterolæmia, 3. Good health, Economics, Medical, Consensus statement, Ezetimibe, LDL cholesterol, PCSK9 inhibitor, Statin, Treatment, Cardiology and Cardiovascular Medicine, CARDIOVASCULAR-DISEASE, Female, lipids (amino acids, peptides, and proteins), Familial hypercholesterolaemia, Life Sciences & Biomedicine, Diagnosi, medicine.drug, Adult, Heterozygote, medicine.medical_specialty, Adolescent, medicine.drug_class, ENDOTHELIAL FUNCTION, LOW-DENSITY-LIPOPROTEIN, Reviews, COST-EFFECTIVENESS ANALYSIS, 1102 Cardiovascular Medicine And Haematology, Medication Adherence, Hyperlipoproteinemia Type II, Young Adult, Life Expectancy, medicine, Humans, CORONARY-HEART-DISEASE, Genetic Testing, Genetic testing, Science & Technology, Clinical Laboratory Techniques, business.industry, Prevention, Atherosclerosis, medicine.disease, Diet, ASSOCIATION EXPERT PANEL, BLOOD-PRESSURE RESEARCH, Pregnancy Complications, Early Diagnosis, Intima-media thickness, Cardiovascular System & Hematology, Dietary Supplements, Physical therapy, Cardiovascular System & Cardiology, business
Abstract

Contains fulltext : 155263.pdf (Publisher’s version ) (Open Access) Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C >/=5 mmol/L (190 mg/dL), or an LDL-C >/=4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is >/=3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is 10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.

Published
2015

14. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Author

Zanoni, P, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, BRAMBILLA, PAOLO, Zanoni, P, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, and BRAMBILLA, PAOLO

Abstract

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).

Published
2016

16. Homozygous familial hypercholesterolaemia: New insights and guidance for clinicians to improve detection and clinical management. A position paper fromthe Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Author

Universitat Rovira i Virgili, 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, Universitat Rovira i Virgili, and 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

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 ofHoFHand 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 comprehensiveACVDevaluation 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 tes

Published
2015

18. Coronary artery disease-protective A43T variant in APOC3 alters circulating ApoC-III levels in vivo

Author

Khetarpal, S., primary, Varshini, A., additional, Larach, D., additional, Tabita-Martinez, J., additional, McParland, J., additional, McCoy, M., additional, Rodrigues, A., additional, Kiss, D., additional, Zanoni, P., additional, Mucksavage, M., additional, Millar, J., additional, Cuchel, M., additional, Lund-Katz, S., additional, Phillips, M., additional, Kathiresan, S., additional, and Rader, D., additional

Published
2015
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20. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia – A post-hoc analysis of a Phase 3, single-arm, open-label trial

Author

Stefanutti, C., primary, Blom, D.J., additional, Averna, M.R., additional, Meagher, E.A., additional, Theron, H. dT., additional, Marais, A.D., additional, Hegele, R.A., additional, Sirtori, C.R., additional, Shah, P.K., additional, Gaudet, D., additional, Vigna, G.B., additional, Sachais, B.S., additional, Di Giacomo, S., additional, du Plessis, A.M.E., additional, Bloedon, L.T., additional, Balser, J., additional, Rader, D.J., additional, and Cuchel, M., additional

Published
2015
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21. 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

Author

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., Tybjaerg-Hansen, A., Watts, G.F., Averna, M., Boileau, C., Boren, J., Catapano, A.L., Defesche, J.C., Hovingh, G.K., Humphries, S.E., Kovanen, P.T., Masana, L., Pajukanta, P., Parhofer, K.G., Ray, K.K., Stalenhoef, A.F.H., Stroes, E., Taskinen, M.R., Wiegman, A., Wiklund, O., Chapman, M.J., et al., 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., Tybjaerg-Hansen, A., Watts, G.F., Averna, M., Boileau, C., Boren, J., Catapano, A.L., Defesche, J.C., Hovingh, G.K., Humphries, S.E., Kovanen, P.T., Masana, L., Pajukanta, P., Parhofer, K.G., Ray, K.K., Stalenhoef, A.F.H., Stroes, E., Taskinen, M.R., Wiegman, A., Wiklund, O., Chapman, M.J., and et al.

Abstract

Item does not contain fulltext, 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 H

Published
2014

26. Apolipoprotein E polymorphism and serum concentration in Alzheimer's disease in nine European centers: The ApoEurope Study

Author

Siest, G., Bertrand, P.H., Qin, B., Herbeth, B., Serot, J.M., Masana, L., Ribalta, J., Passmore, A.P., Evans, A., Ferrari, M., Tranceschi, M., Shepherd, J., Cuchel, M., Beisiegel, U., Zuchowsky, M., Stavljenić Rukavina, Ana, Sertić, Jadranka, Stojanov, M., Kostić, V., Mitrevski, A., Petrova, V., Sass, C., Merched, A., Salonen, J.K., Tiret, L., and Visvikis, S.

Subjects
apolipoprotein E (apo E), Alzheimer's disease, polymorphism, concentration, risk factor, multicentre study, lipids (amino acids, peptides, and proteins)
Abstract

As part of teh ApoEurope project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the e4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p

Published
2000

43. Cholesterol and all-cause mortality in Honolulu [3] (multiple letters)

Author

Cuchel, M., Rader, D. J., Law, M., Wald, N. J., Tilvis, R. S., Strandberg, T. E., Miettinen, T. A., Terao, T., Weverling-Rijnsburger, A. W. E., Blauw, G. J., Westendorp, R. G. J., Schatz, I. I., Masaki, K., Rodriguez, B., Yano, K., Curb, D., Fernandez-Real, J. -M, Wifredo Ricart, and Ravnskov, U.

44. Homozigot ailevi hiperkolesterolemi: Klinisyenlerin taniyi ve klinik yönetimi geliştirmelerine yönelik yeni anlayişlar ve rehberlik. Avrupa ateroskleroz derneǧi'nin ailevi hiperkolesterolemi üzerine uzlaşi paneli yazili görüşü

Author

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., Kovanen, P. T., Masana, L., Pajukanta, P., Parhofer, K. G., Ray, K. K., Stalenhoef, A. F. H., Stroes, E., Taskinen, M. -R, Albert Wiegman, Chapman, M. J., Wiklund, O., Other departments, Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine, Vascular Medicine, and Paediatric Metabolic Diseases

47. [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]

Author

Cuchel M, Bruckert E, Hn, Ginsberg, Fj, Raal, Rd, Santos, Ra, Hegele, Ja, Kuivenhoven, Bg, Nordestgaard, Os, Descamps, Steinhagen-Thiessen E, Tybjaerg-Hansen A, Gf, Watts, Averna M, catherine boileau, Borén J, Al, Catapano, Jc, Defesche, Gk, Hovingh, Se, Humphries, and Pt, Kovanen

50. Worldwide experience of homozygous familial hypercholesterolaemia:retrospective cohort study

Author

Tycho R Tromp, Merel L Hartgers, G Kees Hovingh, Antonio J Vallejo-Vaz, Kausik K Ray, Handrean Soran, Tomas Freiberger, Stefano Bertolini, Mariko Harada-Shiba, Dirk J Blom, Frederick J Raal, Marina Cuchel, Tycho R. Tromp, Merel L. Hartgers, G. Kees Hovingh, Antonio J. Vallejo-Vaz, Kausik K. Ray, Stefano A. Bertolini, Jing Pang, Gerald F. Watts, Susanne Greber-Platzer, Martin Mäser, Thomas M. Stulnig, Christoph F. Ebenbichler, Khalid Bin Thani, David Cassiman, Olivier S. Descamps, Daisy Rymen, Peter Witters, Raul D. Santos, Liam R. Brunham, Gordon A. Francis, Jacques Genest, Robert A. Hegele, Brooke A. Kennedy, Isabelle Ruel, Mark H. Sherman, Long Jiang, Luya Wang, Željko Reiner, Vladimir Blaha, Richard Ceska, Jana Dvorakova, Lubomir Dlouhy, Pavel Horak, Vladimir Soska, Lukas Tichy, Robin Urbanek, Helena Vaverkova, Michal Vrablik, Stanislav Zemek, Lukas Zlatohlavek, Sameh Emil, Tarek Naguib, Ashraf Reda, Sophie Béliard, Eric Bruckert, Antonio Gallo, Moses S. Elisaf, Genovefa Kolovou, Hofit Cohen, Ronen Durst, Eldad J. Dann, Avishay Elis, Osama Hussein, Eran Leitersdorf, Daniel Schurr, Nitika Setia, Ishwar C. Verma, Mohammed D. Alareedh, Mutaz Al-Khnifsawi, Ali F. Abdalsahib Al-Zamili, Sabah H. Rhadi, Foaad K. Shaghee, Marcello Arca, Maurizio Averna, Andrea Bartuli, Marco Bucci, Paola S. Buonuomo, Paolo Calabrò, Sebastiano Calandra, Manuela Casula, Alberico L. Catapano, Angelo B. Cefalù, Arrigo F.G. Cicero, Sergio D'Addato, Laura D'Erasmo, Alessia Di Costanzo, Tommaso Fasano, Marta Gazzotti, Antonina Giammanco, Gabriella Iannuzzo, Anastasia Ibba, Emanuele A. Negri, Andrea Pasta, Chiara Pavanello, Livia Pisciotta, Claudio Rabacchi, Carlo Ripoli, Tiziana Sampietro, Francesco Sbrana, Fulvio Sileo, Patrizia Suppressa, Patrizia Tarugi, Chiara Trenti, Maria G. Zenti, Mika Hori, Mahmoud H. Ayesh, Sami T. Azar, Fadi F. Bitar, Akl C. Fahed, Elie M. Moubarak, Georges Nemer, Hapizah M. Nawawi, Ramón Madriz, Roopa Mehta, Arjen J. Cupido, Joep C. Defesche, M. Doortje Reijman, Jeanine E. Roeters-van Lennep, Erik S.G. Stroes, Albert Wiegman, Linda Zuurbier, Khalid Al-Waili, Fouzia Sadiq, Krzysztof Chlebus, Mafalda Bourbon, Isabel M. Gaspar, Katarina S. Lalic, Marat V. Ezhov, Andrey V. Susekov, Urh Groselj, Min-Ji Charng, Weerapan Khovidhunkit, Melih Aktan, Bulent B. Altunkeser, Sinan Demircioglu, Melis Kose, Cumali Gokce, Osman Ilhan, Meral Kayikcioglu, Leyla G. Kaynar, Irfan Kuku, Erdal Kurtoglu, Harika Okutan, Osman I. Ozcebe, Zafer Pekkolay, Saim Sag, Osman Z. Salcioglu, Ahmet Temizhan, Mustafa Yenercag, Mehmet Yilmaz, Hamiyet Yilmaz Yasar, Olena Mitchenko, Alexander R.M. Lyons, Christophe A.T. Stevens, Julie A. Brothers, Lisa C. Hudgins, Christina Nguyen, Rano Alieva, Aleksandr Shek, Doan-Loi Do, Ngoc-Thanh Kim, Hong-An Le, Thanh-Tung Le, Mai-Ngoc T. Nguyen, Thanh-Huong Truong, Dirk J. Blom, Frederick J. Raal, VU University medical center, Tromp T.R., Hartgers M.L., Hovingh G.K., Vallejo-Vaz A.J., Ray K.K., Soran H., Freiberger T., Bertolini S., Harada-Shiba M., Blom D.J., Raal F.J., Cuchel M., Bertolini S.A., Pang J., Watts G.F., Greber-Platzer S., Maser M., Stulnig T.M., Ebenbichler C.F., Bin Thani K., Cassiman D., Descamps O.S., Rymen D., Witters P., Santos R.D., Brunham L.R., Francis G.A., Genest J., Hegele R.A., Kennedy B.A., Ruel I., Sherman M.H., Jiang L., Wang L., Reiner Z., Blaha V., Ceska R., Dvorakova J., Dlouhy L., Horak P., Soska V., Tichy L., Urbanek R., Vaverkova H., Vrablik M., Zemek S., Zlatohlavek L., Emil S., Naguib T., Reda A., Beliard S., Bruckert E., Gallo A., Elisaf M.S., Kolovou G., Cohen H., Durst R., Dann E.J., Elis A., Hussein O., Leitersdorf E., Schurr D., Setia N., Verma I.C., Alareedh M.D., Al-Khnifsawi M., Abdalsahib Al-Zamili A.F., Rhadi S.H., Shaghee F.K., Arca M., Averna M., Bartuli A., Bucci M., Buonuomo P.S., Calabro P., Calandra S., Casula M., Catapano A.L., Cefalu A.B., Cicero A.F.G., D'Addato S., D'Erasmo L., Di Costanzo A., Fasano T., Gazzotti M., Giammanco A., Iannuzzo G., Ibba A., Negri E.A., Pasta A., Pavanello C., Pisciotta L., Rabacchi C., Ripoli C., Sampietro T., Sbrana F., Sileo F., Suppressa P., Tarugi P., Trenti C., Zenti M.G., Hori M., Ayesh M.H., Azar S.T., Bitar F.F., Fahed A.C., Moubarak E.M., Nemer G., Nawawi H.M., Madriz R., Mehta R., Cupido A.J., Defesche J.C., Reijman M.D., Roeters-van Lennep J.E., Stroes E.S.G., Wiegman A., Zuurbier L., Al-Waili K., Sadiq F., Chlebus K., Bourbon M., Gaspar I.M., Lalic K.S., Ezhov M.V., Susekov A.V., Groselj U., Charng M.-J., Khovidhunkit W., Aktan M., Altunkeser B.B., Demircioglu S., Kose M., Gokce C., Ilhan O., Kayikcioglu M., Kaynar L.G., Kuku I., Kurtoglu E., Okutan H., Ozcebe O.I., Pekkolay Z., Sag S., Salcioglu O.Z., Temizhan A., Yenercag M., Yilmaz M., Yilmaz Yasar H., Mitchenko O., Lyons A.R.M., Stevens C.A.T., Brothers J.A., Hudgins L.C., Nguyen C., Alieva R., Shek A., Do D.-L., Kim N.-T., Le H.-A., Le T.-T., Nguyen M.-N.T., Truong T.-H., University of Amsterdam, University of Pennsylvania, European Atherosclerosis Society, Experimental Vascular Medicine, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Human Genetics, Paediatric Metabolic Diseases, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, R Tromp, Tycho, L Hartgers, Merel, Kees Hovingh, G, J Vallejo-Vaz, Antonio, K Ray, Kausik, Soran, Handrean, Freiberger, Toma, A Bertolini, Stefano, Harada-Shiba, Mariko, Pang, Jing, F Watts, Gerald, Greber-Platzer, Susanne, Mäser, Martin, M Stulnig, Thoma, F Ebenbichler, Christoph, Bin Thani, Khalid, Cassiman, David, S Descamps, Olivier, Rymen, Daisy, Witters, Peter, D Santos, Raul, R Brunham, Liam, A Francis, Gordon, Genest, Jacque, A Hegele, Robert, A Kennedy, Brooke, Ruel, Isabelle, H Sherman, Mark, Jiang, Long, Wang, Luya, Reiner, Željko, Blaha, Vladimir, Ceska, Richard, Dvorakova, Jana, Dlouhy, Lubomir, Horak, Pavel, Soska, Vladimir, Tichy, Luka, Urbanek, Robin, Vaverkova, Helena, Vrablik, Michal, Zemek, Stanislav, Zlatohlavek, Luka, Emil, Sameh, Naguib, Tarek, Reda, Ashraf, Béliard, Sophie, Bruckert, Eric, Gallo, Antonio, S Elisaf, Mose, Kolovou, Genovefa, Cohen, Hofit, Durst, Ronen, J Dann, Eldad, Elis, Avishay, Hussein, Osama, Leitersdorf, Eran, Schurr, Daniel, Setia, Nitika, C Verma, Ishwar, D Alareedh, Mohammed, Al-Khnifsawi, Mutaz, F Abdalsahib Al-Zamili, Ali, H Rhadi, Sabah, K Shaghee, Foaad, Arca, Marcello, Averna, Maurizio, Bartuli, Andrea, Bucci, Marco, S Buonuomo, Paola, Calabrò, Paolo, Calandra, Sebastiano, Casula, Manuela, L Catapano, Alberico, B Cefalù, Angelo, G Cicero, Arrigo F, D'Addato, Sergio, D'Erasmo, Laura, Di Costanzo, Alessia, Fasano, Tommaso, Gazzotti, Marta, Giammanco, Antonina, Iannuzzo, Gabriella, Ibba, Anastasia, A Negri, Emanuele, Pasta, Andrea, Pavanello, Chiara, Pisciotta, Livia, Rabacchi, Claudio, Ripoli, Carlo, Sampietro, Tiziana, Sbrana, Francesco, Sileo, Fulvio, Suppressa, Patrizia, Tarugi, Patrizia, Trenti, Chiara, G Zenti, Maria, Hori, Mika, H Ayesh, Mahmoud, T Azar, Sami, F Bitar, Fadi, C Fahed, Akl, M Moubarak, Elie, Nemer, George, M Nawawi, Hapizah, Madriz, Ramón, Mehta, Roopa, J Cupido, Arjen, C Defesche, Joep, Doortje Reijman, M, E Roeters-van Lennep, Jeanine, G Stroes, Erik S, Wiegman, Albert, Zuurbier, Linda, Al-Waili, Khalid, Sadiq, Fouzia, Chlebus, Krzysztof, Bourbon, Mafalda, M Gaspar, Isabel, S Lalic, Katarina, V Ezhov, Marat, V Susekov, Andrey, Groselj, Urh, Charng, Min-Ji, Khovidhunkit, Weerapan, Aktan, Melih, B Altunkeser, Bulent, Demircioglu, Sinan, Kose, Meli, Gokce, Cumali, Ilhan, Osman, Kayikcioglu, Meral, G Kaynar, Leyla, Kuku, Irfan, Kurtoglu, Erdal, Okutan, Harika, I Ozcebe, Osman, Pekkolay, Zafer, Sag, Saim, Z Salcioglu, Osman, Temizhan, Ahmet, Yenercag, Mustafa, Yilmaz, Mehmet, Yilmaz Yasar, Hamiyet, Mitchenko, Olena, M Lyons, Alexander R, T Stevens, Christophe A, A Brothers, Julie, C Hudgins, Lisa, Nguyen, Christina, Alieva, Rano, Shek, Aleksandr, Do, Doan-Loi, Kim, Ngoc-Thanh, Le, Hong-An, Le, Thanh-Tung, T Nguyen, Mai-Ngoc, Truong, Thanh-Huong, J Blom, Dirk, J Raal, Frederick, and Cuchel, Marina

Subjects
Adult, Male, Homozygous Familial Hypercholesterolemia, Adolescent, retrospective study, CHILDREN, Doenças Cardio e Cérebro-vasculares, Cohort Studies, Young Adult, Medicine, General & Internal, General & Internal Medicine, Cardiovascular Disease, Humans, Registries, LIPOPROTEIN-APHERESIS, Child, 11 Medical and Health Sciences, Retrospective Studies, Homozygous Familial Hypercholesterolaemia International Clinical Collaborators, Science & Technology, GUIDANCE, clinical characteristic, EVOLOCUMAB, Homozygous familial hypercholesterolemia, Worldwide, Therapies, Cardiovascular disease, General Medicine, CARE, OPEN-LABEL, EFFICACY, INSIGHTS, Child, Preschool, outcome, Female, genetic, Familial Hypercholesterolaemia, Life Sciences & Biomedicine
Abstract

[Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally., [Methods]: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005., [Findings]: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12∙0 years (IQR 5∙5–27∙0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14∙7 mmol/L (IQR 11∙6–18∙4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3∙93 mmol/L, IQR 2∙6–5∙8) versus non-highincome countries (9∙3 mmol/L, 6∙7–12∙7), with greater use of three or more lipid-lowering therapies (LLT; highincome 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24∙5 years (IQR 17∙0–34∙5) versus 37∙0 years (29∙0–49∙0) in high-income countries (adjusted hazard ratio 1∙64, 95% CI 1∙13–2∙38)., [Interpretation]: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH., Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society

Published
2022
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