Marjet J A M Braamskamp1, Gisle Langslet1, Brian W McCrindle1, David Cassiman1, Gordon A Francis1, Claude Gagne1, Daniel Gaudet1, Katherine M Morrison1, Albert Wiegman1, Traci Turner1, Elinor Miller1, D Meeike Kusters1, Joel S Raichlen1, Paul D Martin1, Evan A Stein1, John J P Kastelein1, Barbara A Hutten2. 1. From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic Center, University Hospitals Leuven, Belgium (D.C.); Healthy Heart Program Prevention Clinic, St. Paul's Hospital, Vancouver, British Columbia, Canada (G.A.F.); Department of Medicine, University of British Columbia, Vancouver, Canada (G.A.F.); Clinique des Maladies Lipidiques de Québec Inc, Québec, QC, Canada (C.G.); Department of Medicine, Université de Montréal, Montréal, Québec, Canada (D.G.); Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada (K.M.M.); Metabolic & Atherosclerosis Research Center, Cincinnati, OH (T.T., E.A.S.); AstraZeneca Pharmaceuticals LP, Wilmington, DE (E.M., J.S.R.); and AstraZeneca, Macclesfield, Cheshire, United Kingdom (P.D.M.). 2. From Department of Vascular Medicine (M.J.A.M.B., D.M.K., J.J.P.K.), Department of Pediatrics (M.J.A.M.B., A.W.), and Department of Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Center, Amsterdam, the Netherlands; Lipid Clinic, Medical Department, Oslo University Hospital, Norway (G.L.); Department of Pediatrics, University of Toronto, Labatt Family Health Center, The Hospital for Sick Children, Ontario, Canada (B.W.M.); Department of Hepatology and Metabolic Center, University Hospitals Leuven, Belgium (D.C.); Healthy Heart Program Prevention Clinic, St. Paul's Hospital, Vancouver, British Columbia, Canada (G.A.F.); Department of Medicine, University of British Columbia, Vancouver, Canada (G.A.F.); Clinique des Maladies Lipidiques de Québec Inc, Québec, QC, Canada (C.G.); Department of Medicine, Université de Montréal, Montréal, Québec, Canada (D.G.); Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada (K.M.M.); Metabolic & Atherosclerosis Research Center, Cincinnati, OH (T.T., E.A.S.); AstraZeneca Pharmaceuticals LP, Wilmington, DE (E.M., J.S.R.); and AstraZeneca, Macclesfield, Cheshire, United Kingdom (P.D.M.). b.a.hutten@amc.uva.nl.
Abstract
BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH. METHODS: Children with HeFH (age, 6-<18 years) and low-density lipoprotein cholesterol >4.9 mmol/L or >4.1 mmol/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6-<10 years) or 20 mg (age, 10-<18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings. P values were adjusted for age, sex, carotid artery site, and family relations. RESULTS: At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively; P=0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030-0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095-0.0192) in unaffected siblings (P=0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408±0.043 and 0.402±0.042 mm, respectively; P=0.2). CONCLUSIONS: In children with HeFH who were ≥6 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01078675.
BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH. METHODS:Children with HeFH (age, 6-<18 years) and low-density lipoprotein cholesterol >4.9 mmol/L or >4.1 mmol/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6-<10 years) or 20 mg (age, 10-<18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings. P values were adjusted for age, sex, carotid artery site, and family relations. RESULTS: At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively; P=0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030-0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095-0.0192) in unaffected siblings (P=0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408±0.043 and 0.402±0.042 mm, respectively; P=0.2). CONCLUSIONS: In children with HeFH who were ≥6 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01078675.
Authors: Gerald F Watts; Samuel S Gidding; Pedro Mata; Jing Pang; David R Sullivan; Shizuya Yamashita; Frederick J Raal; Raul D Santos; Kausik K Ray Journal: Nat Rev Cardiol Date: 2020-01-23 Impact factor: 32.419
Authors: Michał Podgórski; Katarzyna Szatko; Małgorzata Stańczyk; Monika Pawlak-Bratkowska; Agnieszka Konopka; Ewa Starostecka; Marcin Tkaczyk; Sebastian Góreczny; Lena Rutkowska; Agnieszka Gach; Maciej Łukaszewski; Piotr Grzelak; Maciej Banach Journal: Lipids Health Dis Date: 2020-07-14 Impact factor: 3.876