Laura D'Erasmo1, Ilenia Minicocci2, Antonio Nicolucci3, Paolo Pintus4, Janine E Roeters Van Lennep5, Luis Masana6, Pedro Mata7, Rosa Maria Sánchez-Hernández8, Pablo Prieto-Matos9, Josè T Real10, Juan F Ascaso10, Eduardo Esteve Lafuente11, Miguel Pocovi12, Francisco J Fuentes13, Sandro Muntoni14, Stefano Bertolini15, Cesare Sirtori16, Laura Calabresi16, Chiara Pavanello16, Maurizio Averna17, Angelo Baldassare Cefalu17, Davide Noto17, Adolfo Arturo Pacifico18, Giovanni Mario Pes19, Mariko Harada-Shiba20, Enzo Manzato21, Sabina Zambon21, Alberto Zambon21, Anja Vogt22, Marco Scardapane3, Barbara Sjouke23, Renato Fellin24, Marcello Arca25. 1. Department of Internal Medicine and Clinical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: derasmolaura@gmail.com. 2. Department of Internal Medicine and Clinical Specialties, Sapienza University of Rome, Rome, Italy. 3. Center for Outcomes Research and Clinical Epidemiology, Coreresearch, Inc., Pescara, Italy. 4. Dipartimento Internistico, Centro per le Malattie Dismetaboliche e l'Arteriosclerosi, Cagliari, Italy. 5. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. 6. Research Unit on Lipids and Atherosclerosis, Vascular Medicine and Metabolism Unit, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain, and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. 7. Fundación Hipercoesterolaemia Familiar, Madrid, Spain. 8. Sección de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno Infantil de Gran Canaria, Instituto Universitario de Investigación Biomédica y Sanitaria (IUIBS) de la Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 9. Unidad de Endocrinología Pediátrica Hospital Universitario de Salamanca Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain. 10. Servicio de Endocrinología y Nutrición, Hospital Clínico Valencia, Valencia, Spain, and Department of Medicine, University of Valencia, INCLIVA, CIBERDEM, Madrid, Spain. 11. Servicio Endocrinología y Nutrición, Hospital Universitario Josep Trueta, Girona, Spain. 12. Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza & IIS Aragón, CIBERCV, Zaragoza, Spain. 13. Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain, and Centro de Investigación Biomédica en Red de Fisiopatolgía de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. 14. Department of Biomedical Sciences, University of Cagliari and Centre for Metabolic Diseases and Atherosclerosis, The ME.DI.CO Association, Cagliari, Italy. 15. Department of Internal Medicine, University of Genova, Genova, Italy. 16. Center E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita' degli Studi di Milano, and Dyslipidemia Center, Niguarda Hospital, Milan, Italy. 17. Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy. 18. Unità Operativa Diabetologia e Malattie Metaboliche, Azienda Ospedaliero Universitaria, Sassari, Italy. 19. Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. 20. Department of Molecular Innovation in Lipidology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan. 21. University of Padova, Padova, Italy. 22. Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität (LMU) Klinikum der Universität München, Munich, Germany. 23. Department of Internal and Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 24. Department of Medical Sciences, University of Ferrara, Ferrara, Italy. 25. Department of Internal Medicine and Clinical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: marcello.arca@uniroma1.it.
Abstract
BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. OBJECTIVES: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. METHODS: Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. RESULTS: We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years of age; baseline LDL-C: 571.9 ± 171.7 mg/dl). During a mean follow-up of 14.1 ± 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 ± 85.1 mg/dl (-69.6% from baseline), with a better response in patients taking lomitapide (-88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl. During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%, respectively). No incident stroke was observed. Age (≥30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD. CONCLUSIONS: Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking.
BACKGROUND:Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. OBJECTIVES: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. METHODS: Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. RESULTS: We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years of age; baseline LDL-C: 571.9 ± 171.7 mg/dl). During a mean follow-up of 14.1 ± 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 ± 85.1 mg/dl (-69.6% from baseline), with a better response in patients taking lomitapide (-88.3%). Overall, 23.1% of ARHpatients reached LDL-C of <100 mg/dl. During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%, respectively). No incident stroke was observed. Age (≥30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD. CONCLUSIONS: Despite intensive treatment, LDL-C in ARHpatients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking.