Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-23T03:53:15.289Z Has data issue: false hasContentIssue false
  • English
  • Français

Experience on statin therapy in paediatric age: retrospective study in a Portuguese referral centre

Published online by Cambridge University Press:  15 May 2020

Hugo A. Gomes Open the ORCID record for Hugo A. Gomes [Opens in a new window] ,
Paula Garcia ,
Luísa Diogo ,
António Pires  and
Paula Martins Open the ORCID record for Paula Martins [Opens in a new window]
Hugo A. Gomes
Affiliation:
Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Paula Garcia
Affiliation:
Department of Inherited Metabolic Diseases, Paediatric Hospital – Coimbra Hospital and University Centre (CHUC), Coimbra, Portugal
Luísa Diogo
Affiliation:
Faculty of Medicine, University of Coimbra, Coimbra, Portugal Department of Inherited Metabolic Diseases, Paediatric Hospital – Coimbra Hospital and University Centre (CHUC), Coimbra, Portugal
António Pires
Affiliation:
Faculty of Medicine, University of Coimbra, Coimbra, Portugal Department of Paediatric Cardiology, Paediatric Hospital – Coimbra Hospital and University Centre (CHUC), Coimbra, Portugal
Paula Martins*
Affiliation:
Faculty of Medicine, University of Coimbra, Coimbra, Portugal Department of Paediatric Cardiology, Paediatric Hospital – Coimbra Hospital and University Centre (CHUC), Coimbra, Portugal
*
Author for correspondence: Paula Martins, MD, Department of Paediatric Cardiology, Paediatric Hospital – Coimbra Hospital and University Centre (CHUC), Avenida Afonso Romão, 3000-602Coimbra, Portugal. Tel: +351 239 480 364; Fax: +351 239 717 216. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

The use of statins in children, although not frequent, is recommended in specific clinical contexts, namely, familial hypercholesterolaemia, conditions carrying a moderate-high cardiovascular risk and sub-optimal cholesterol levels after implementation of lifestyle modifications. The aim of this study is to characterise children with dyslipidaemia managed with statins, followed at a tertiary referral centre in central Portugal.

Methods and results:

The authors carried out a retrospective and descriptive study made up of 66 patients (50% males, mean age of therapy onset 11.9 years) followed up at the Cardiovascular Clinic of a tertiary referral centre between January, 2012, and May, 2018. Clinical, analytical, and echocardiographic parameters were analysed. About 60.6% had clinical and/or molecular diagnosis of familial hypercholesterolaemia. On average, each patient had three cardiovascular risk factors, obesity (31%) being most prevalent, followed by arterial hypertension (14%). Statin therapy showed a statistically significant reduction in the lipid profile, particularly in the total cholesterol (23%) and low-density lipoprotein cholesterol (30%) levels, as well as in the carotid intima-media thickness (p = 0.015). Hepatic and muscle integrity markers were within normal range.

Conclusions:

Statins are safe and efficient in the management of children with hypercholesterolaemia. Our study showed that apart from its lipid-lowering properties, it also reduced significantly the carotid intima-media thickness and, implicitly, the cardiovascular risk of these patients.

Keywords

Hydroxymethylglutaryl-CoA reductase inhibitorsdyslipidaemiapaediatricsrisk factorsatherosclerosis
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 6 , June 2020 , pp. 840 - 851
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Timmis, A, Townsend, N, Gale, C, et al.European Society of Cardiology: cardiovascular disease statistics 2017. Eur Heart J 2018; 39: 508–577. doi: 10.1093/eurheartj/ehx628CrossRefGoogle Scholar
de Saúde, Direção-Geral. Direcção de Serviços de Informação e Análise. A Saúde dos Portugueses 2016; 2017. http://hdl.handle.net/10400.26/18278Google Scholar
Catapano, AL, Graham, I, De Backer, G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016; 37: 2999–3058. doi: 10.1093/eurheartj/ehw272CrossRefGoogle ScholarPubMed
Piepoli, MF, Hoes, AW, Agewall, S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2016; 37: 2315–2381. doi: 10.1093/eurheartj/ehw106CrossRefGoogle ScholarPubMed
Cibelle, M, Antunes, M, Rato, Q, Bourbon, M._e_LIPID: Caracterização do Perfil Lipídico da População Portuguesa. Bol Epidemiológico Obs 2015; 4 : 7–10. http://repositorio.insa.pt/bitstream/10400.18/3223/1/Boletim_Epidemiologico_Observacoes_N14_2015_artigo2.pdfGoogle Scholar
Nguyen, D, Kit, B, Carroll, M.Abnormal Cholesterol among Children and Adolescents in the United States, 2011–2014, Vol. 228 (National Center for Health Statistics, ed.); 2015. doi: 10.1021/cb700178sGoogle Scholar
Daniels, SR, Greer, FR.Lipid screening and cardiovascular health in childhood. Pediatrics 2008; 122: 198–208. doi: 10.1542/peds.2008-1349CrossRefGoogle ScholarPubMed
Dalla Pozza, R, Ehringer-Schetitska, D, Fritsch, P, Jokinen, E, Petropoulos, A, Oberhoffer, R.Intima media thickness measurement in children: a statement from the Association for European Paediatric Cardiology (AEPC) Working Group on Cardiovascular Prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis 2015; 238: 380–387. doi: 10.1016/j.atherosclerosis.2014.12.029CrossRefGoogle Scholar
Gidding, SS, Rana, JS, Prendergast, C, et al.Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score in young adults predicts coronary artery and abdominal aorta calcium in middle age. Circulation 2016; 133: 139–146. doi: 10.1161/CIRCULATIONAHA.115.018042CrossRefGoogle ScholarPubMed
National Heart, Lung, and Blood Institute. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Full Report. Vol 12–7486; 2012. http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htmGoogle Scholar
Braamskamp, M, Langslet, G, McCrindle, BW, et al.Effect of rosuvastatin on CIMT in HeFH children: the CHARON study. Atherosclerosis 2014; 235: e18–e19. doi: 10.1016/j.atherosclerosis.2014.05.022CrossRefGoogle Scholar
Koskinen, J, Juonala, M, Dwyer, T, et al.Impact of lipid measurements in youth in addition to conventional clinic-based risk factors on predicting preclinical atherosclerosis in adulthood: the international childhood cardiovascular cohort (i3C) consortium. Circulation 2017; 137: 1246–1255. http://circ.ahajournals.org/content/early/2017/11/22/CIRCULATIONAHA.117.029726CrossRefGoogle Scholar
Juonala, M, Viikari, JSA, Ro, T, et al.Associations of dyslipidemias from childhood to adulthood with carotid intima-media thickness, elasticity, and brachial flow-mediated dilatation in adulthood: the cardiovascular risk in Young Finns study. Arter Thromb Vasc Biol 2008; 28: 1012–1017. doi: 10.1161/ATVBAHA.108.163329CrossRefGoogle ScholarPubMed
Davis, PH, Dawson, JD, Riley, WA, Lauer, RM.Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age. The Muscatine study. Circulation 2001; 104: 2815–2819.CrossRefGoogle ScholarPubMed
Vuorio, A, Kuoppala, J, Kovanen, PT, et al.Statins for children with familial hypercholesterolemia. Review. Cochrane Database Syst Rev 2017; 7. doi: 10.1002/14651858.CD006401.pub4; www.cochranelibrary.comCrossRefGoogle Scholar
Berenson, GS, Srinivasan, SR, Bao, W, Newman, W, Tracy, R.Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. N Engl J Med 1998; 338: 1650–1656.CrossRefGoogle ScholarPubMed
Raitakari, OT, Juonala, M, Kahonen, M, et al.Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the cardiovascular risk in Young Finns study. JAMA 2003; 290: 2277–2283.CrossRefGoogle ScholarPubMed
McCrindle, BW, Urbina, EM, Dennison, BA, et al.Drug Therapy of High-Risk Lipid Abnormalities in Children and Adolescents. A Scientific Statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation 2007; 115: 1948–1967. doi: 10.1161/CIRCULATIONAHA.107.181946CrossRefGoogle Scholar
Mendelson, MM, Regh, T, Chan, J, et al.Correlates of achieving statin therapy goals in children and adolescents with dyslipidemia. J Pediatr 2016; 178: 149–155. doi: 10.1016/j.jpeds.2016.08.003CrossRefGoogle ScholarPubMed
Versmissen, J, Oosterveer, DM, Yazdanpanah, M, et al.Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008; 337: a2423. doi: 10.1136/bmj.a2423CrossRefGoogle ScholarPubMed
Rocha, VZ, Santos, RD.Safety of statin treatment in children with familial hypercholesterolemia: filling the gaps. J Clin Lipidol 2018; 12: 12–15. doi: 10.1016/j.jacl.2017.11.007CrossRefGoogle Scholar
Rodenburg, J, Vissers, MN, Wiegman, A, Van Trotsenburg, ASP, Van Der Graaf, A, De Groot, E. Statin treatment in children with familial: the younger, the better. Circulation 2007; 116: 664–668. doi: 10.1161/CIRCULATIONAHA.106.671016CrossRefGoogle Scholar
Kavey, RW, Allada, V, Daniels, SR, et al.Cardiovascular risk reduction in high-risk pediatric patients. Circulation 2006; 114: 2710–2738. doi: 10.1161/CIRCULATIONAHA.106.179568CrossRefGoogle ScholarPubMed
Medeiros, AM, Alves, AC, Aguiar, P, Bourbon, M.Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia. J Lipid Res 2014; 55: 947–955. doi: 10.1194/jlr.P043182CrossRefGoogle ScholarPubMed
Medeiros, AM, Alves, AC, Francisco, V, Bourbon, M.Update of the Portuguese familial hypercholesterolaemia study. Atherosclerosis 2010; 212: 553–558. doi: 10.1016/j.atherosclerosis.2010.07.012CrossRefGoogle ScholarPubMed
Bourbon, M, Rato, Q.Portuguese familial hypercholesterolemia study: presentation of the study and preliminary results. Rev Port Cardiol 2006; 25: 999–1013. http://www.spc.pt/DL/RPC/artigos/771.pdfGoogle Scholar
De Onis, M, Onyango, A, Borghi, E, Siyam, A, Pinol, A.WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age: Methods and Development. World Health Organization: Department of Nutrition for Health and Development, Geneva, 2006.Google Scholar
World Health Organization. Training Course on Child Growth Assessment. WHO, Geneva, 2008.Google Scholar
Flynn, JT, Kaelber, DC, Baker-Smith, CM, et al.Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017; 140: e20171904. doi: 10.1542/peds.2017-1904CrossRefGoogle ScholarPubMed
Mayer-Davis, EJ, Kahkoska, AR, Jefferies, C, et al.ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2018; 19 (Suppl. 27): 7–19. doi: 10.1111/pedi.12773CrossRefGoogle ScholarPubMed
Cuartero, BG, Lacalle, CG, Lobo, CJ, Vergaz, AG.Índice HOMA y QUICKI, insulina y péptido C en niños sanos. Puntos de corte de riesgo cardiovascular. An Pediatr 2007; 66: 481–490. doi: 10.1157/13102513CrossRefGoogle Scholar
Simova, I.Intima-media thickness: appropriate evaluation and proper measurement, described. e-journal ESC Counc Cardiol Pract 2015; 13: 1–14. https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-13/Intima-media-thickness-Appropriate-evaluation-and-proper-measurement-describedGoogle Scholar
Doyon, A, Kracht, D, Bayazit, AK, et al.Carotid artery intima-media thickness and distensibility in children and adolescents: reference values and role of body dimensions. Hypertension 2013; 62: 550–556. doi: 10.1161/HYPERTENSIONAHA.113.01297CrossRefGoogle ScholarPubMed
Muñoz, A.D.A, Cajal, MMD, Aizpún, JIL, et al.Índice íntima-media carotídeo; valores de normalidad desde los 4 años. Nutr Hosp 2013; 28: 1171–1176. doi: 10.3305/nh.2013.28.4.6611Google Scholar
Rito, A, Sousa, RCD, Mendes, S, Graça, P.Childhood Obesity Surveillance Initiative: COSI Portugal 2016. Ministério da Saúde. Instituto Nacional de Saúde Doutor Ricardo Jorge, IP e outros, Lisboa, 2017.Google Scholar
Sousa Uva, M, Victorino, P, Roquette, R, Machado, A, Matias Dias, C.Prevalência e incidência de hipertensão arterial na população portuguesa. 2014.Google Scholar
Avis, HJ, Vissers, MN, Stein, EA, et al.A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2007; 27: 1803–1810. doi: 10.1161/ATVBAHA.107.145151CrossRefGoogle ScholarPubMed
Wiegman, A, Gidding, SS, Watts, GF, et al.Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015; 36: 2425–2437. doi: 10.1093/eurheartj/ehv157CrossRefGoogle Scholar
Peplies, J, Savva, SC, Buck, C, et al.Percentiles of fasting serum insulin, glucose, HbA1c and HOMA-IR in pre-pubertal normal weight European children from the IDEFICS cohort. Int J Obes 2014; 38: 39–47. doi: 10.1038/ijo.2014.134CrossRefGoogle ScholarPubMed
Jacobson, TA.NLA task force on statin safety – 2014 update. J Clin Lipidol 2014; 8 (3 Suppl): S1–S4. doi: 10.1016/j.jacl.2014.03.003CrossRefGoogle ScholarPubMed
Halcox, JP, Banegas, JR, Roy, C, et al.Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study. BMC Cardiovasc Disord 2017; 17: 1–11. doi: 10.1186/s12872-017-0591-5CrossRefGoogle ScholarPubMed
Grundy, SM, Stone, NJ, Bailey, AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2018. doi: 10.1161/CIR.0000000000000625Google Scholar