Rodrigo Alonso1, Jose Luis Díaz-Díaz2, Francisco Arrieta3, Francisco Fuentes-Jiménez4, Raimundo de Andrés5, Pedro Saenz6, Gema Ariceta7, José I Vidal-Pardo8, Fatima Almagro9, Rosa Argueso8, Pablo Prieto-Matos10, José P Miramontes11, Xavier Pintó12, Johana Rodriguez-Urrego13, Leopoldo Perez de Isla14, Pedro Mata15. 1. Fundación Hipercolesterolemia Familiar, Madrid, Spain; Department of Nutrition, Clínica Las Condes, Santiago de Chile, Chile. Electronic address: rodrigoalonsok@gmail.com. 2. Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain. 3. Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain. 4. Department of Internal Medicine, IMIBIC, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain. 5. Department of Internal Medicine, Fundación Jiménez Díaz, Madrid, Spain. 6. Department of Internal Medicine, Hospital de Mérida, Mérida, Spain. 7. Department of Pediatric Nephrology, Hospital Vall d'Hebrón, Barcelona, Spain. 8. Department of Endocrinology, Hospital Universitario de Lugo, Lugo, Spain. 9. Department of Internal Medicine, Hospital Donostia, San Sebastian, Spain. 10. Department of Pediatrics, Hospital Universitario, Salamanca, Spain. 11. Department of Internal Medicine, Hospital Universitario, Salamanca, Spain. 12. Department of Internal Medicine, Hospital de Bellvitge, Barcelona, Spain. 13. Fundación Hipercolesterolemia Familiar, Madrid, Spain. 14. Fundación Hipercolesterolemia Familiar, Madrid, Spain; Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain. 15. Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address: pmata@colesterolfamiliar.org.
Abstract
BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.
BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. OBJECTIVE: To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. METHODS: SAFEHEART is a registry of molecularly defined familial hypercholesterolemiapatients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. RESULTS: Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. CONCLUSIONS: HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.
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