Skip to main content

Advertisement

SpringerLink
Log in

One-Month Therapy with Simvastatin Restores Endothelial Function in Hypercholesterolemic Children and Adolescents

  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Simvastatin has been shown to restore endothelial function in children with familial hypercolesterolemia after 28 weeks of treatment. The aim of this study was to evaluate 1-month simvastatin treatment effect on endothelial function in hypercholesterolemic children and adolescents. Eighteen hypercholesterolemic patients (HC group) and 18 healthy controls, aged 6–18 years, were studied with medical history, physical examination, full lipid profile, serum apolipoprotein B (apo B), fibrinogen, hepatic transaminases, and creatine kinase concentrations. Flow-mediated dilatation (FMD) was performed by high-resolution ultrasound of the brachial artery. The HC group received simvastatin 10 mg/day for 1 month. Arterial diameter was measured by two experienced sonographers who were unaware of subjects’ conditions. At baseline, FMD was impaired in the HC group (mean, 5.27 ± 4.67%) compared to controls (mean, 15.05 ± 5.97%) (p < 0.001). After treatment, we observed a significant reduction in total cholesterol (TC) (29%), low-density lipoprotein cholesterol (LDL-C); (37%), apo B concentrations (36%) and FMD restoration (mean, 12.94 ± 7.66%), with an absolute increase of 7.66 ± 8.58 (p = 0.001). These results show that children and adolescents with hypercholesterolemia present endothelial dysfunction, and simvastatin, in addition to significantly reducing TC, LDL-C, and apo B concentrations, restores endothelial function with 1-month treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Aggoun Y, Bonnet D, Sidi D, et al. (2000) Arterial mechanical changes in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 20:2070–2075

    PubMed  CAS  Google Scholar 

  2. Alonso R, Mata P, De Andres R, et al. (2001) Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin. Atherosclerosis 157:423–429

    Article  PubMed  CAS  Google Scholar 

  3. Berenson GS, Srinivasan SR, Bao W, et al. (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338:1650–1656

    Article  PubMed  CAS  Google Scholar 

  4. Celermajer DS, Sorensen KE, Gooch VM, et al. (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340:1111–1115

    Article  PubMed  CAS  Google Scholar 

  5. De Caterina R, Lenzi S (1998) The role of LDL in the origin and progression of atherosclerosis: pathobiological concepts on the origin and development of atherosclerotic lesions and the role of the endothelium. G Ital Cardiol 28:158–167

    PubMed  Google Scholar 

  6. de Jongh S, Lilien MR, Bakker HD, et al. (2002) Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis 163:193–197

    Article  PubMed  Google Scholar 

  7. de Jongh S, Lilien MR, op’t Roodt J, et al. (2002) Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol 40:2117–2121

    Article  PubMed  Google Scholar 

  8. de Jongh S, Ose L, Szamosi T, et al. (2002) Simvastatin in Children Study Group. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. Circulation 106:2231–2237

    Article  PubMed  Google Scholar 

  9. Gerber ZRS, Zielinsky P (1997) Risk factors of atherosclerosis in children. An epidemiologic study. Arq Bras Cardiol 69:231–236

    Article  PubMed  CAS  Google Scholar 

  10. Gordon T, Kannel WB, Castelli WP, Dawber TR (1981) Lipoproteins, cardiovascular disease, and death. The Framingham study. Arch Intern Med 141:1128–1131

    Article  PubMed  CAS  Google Scholar 

  11. Holman RL, McGill HC Jr, Strong JP, Geer JC (1958) The natural history of atherosclerosis: the early aortic lesions as seen in New Orleans in the middle of the 20th century. Am J Pathol 34:209–235

    PubMed  CAS  Google Scholar 

  12. Jarvisalo MJ, Lehtimaki T, Raitakari OT (2004) Determinants of arterial nitrate-mediated dilatation in children: role of oxidized low-density lipoprotein, endothelial function, and carotid intima-media thickness. Circulation 109:2885–2889

    Article  PubMed  CAS  Google Scholar 

  13. Joannides R, Haefeli WE, Linder L, et al. (1995) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319

    PubMed  CAS  Google Scholar 

  14. Kadikoylu G, Yukselen V, Yavasoglu I, Bolaman Z (2003) Hemostatic effects of atorvastatin versus simvastatin. Ann Pharmacother 37:478–484

    Article  PubMed  CAS  Google Scholar 

  15. Laufs U, La Fata V, Plutzky J, Liao JK (1998) Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97:1129–1135

    PubMed  CAS  Google Scholar 

  16. Leeson CP, Whincup PH, Cook DG, et al. (2000) Cholesterol and arterial distensibility in the first decade of life: a population-based study. Circulation 101:1533–1538

    PubMed  CAS  Google Scholar 

  17. Makris TK, Hatzizacharias AN, Krespi PG, et al. (2003) Markers of risk in young offspring with paternal history of myocardial infarction. Int J Cardiol 89:287–293

    PubMed  Google Scholar 

  18. Martinez-Gonzalez J, Llorente-Cortes V, Badimon L (2001) Cellular and molecular biology of atherosclerotic lesions. Rev Esp Cardiol 54:218–231

    PubMed  CAS  Google Scholar 

  19. McCrindle BW, Ose L, Marais AD (2003) Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr 143: 74–80

    Article  PubMed  CAS  Google Scholar 

  20. McGill HC Jr, McMahan CA, Herderick EE, et al. (2000) Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr 72(5 Suppl):1307S–1315S

    PubMed  CAS  Google Scholar 

  21. Newman WP 3rd, Freedman DS, Voors AW, et al. (1986) Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study. N Engl J Med 314:138–144

    Article  PubMed  Google Scholar 

  22. O’Driscoll G, Green D, Taylor RR (1997) Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation 95:1126–1131

    PubMed  CAS  Google Scholar 

  23. Reddy KG, Nair RN, Sheehan HM, Hodgson JM (1994) Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 23:833–843

    Article  PubMed  CAS  Google Scholar 

  24. Reinhart WH (2003) Fibrinogen—marker or mediator of vascular disease? Vasc Med 8:211–216

    Article  PubMed  Google Scholar 

  25. Scandinavian Simvastatin Survival Group (2000) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389

    Google Scholar 

  26. Singh TP, Groehn H, Kazmers A (2003) Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol 41:661–665

    Article  PubMed  Google Scholar 

  27. Wiegman A, de Groot E, Hutten BA, et al. (2004) Arterial intima-media thickness in children heterozygous for familial hypercholesterolaemia. Lancet 363:369–370

    Article  PubMed  Google Scholar 

  28. Wiegman A, Hutten BA, de Groot E, et al. (2004) Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. J Am Med Assoc 292:331–337

    Article  CAS  Google Scholar 

  29. World Health Organization (1999) Report of a Second WHO Consultation. Geneva 1-23. WHO/HGN/FH/CONS/99.2

  30. Zeiher AM, Drexler H, Wollschlager H, Just H (1991) Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 83:391–401

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the children who participated in this study as well as their parents who trusted our team.

Author information

Authors and Affiliations

  1. Instituto Dante Pazzanese de Cardiologia, Av. Dr. Dante Pazzanese, 500, Bairro Ibirapuera, 04012-180, São Paulo, Brazil

    Waldinai Pereira Ferreira, Marcelo Chiara Bertolami, Simone Nascimento Santos, Marcos Roberto A.C. Barros, Rodrigo Bellio de Matos Barretto & Sèrgio Cunha Pontes Jr

  2. Cardiology Discipline of Universidade Federal de São Paulo, Rua Napoleão de Barros, 715 - Vila Clementino, 04024-002, São Paulo, Brazil

    Waldinai Pereira Ferreira, Francisco Hermann Fonseca & Antonio Carlos Carvalho

  3. Rua Comendador Gabriel Calfat, 175, Bairro Morumbi, CEP 05621-000, São Paulo, SP, Brazil

    Waldinai Pereira Ferreira

Authors
  1. Waldinai Pereira Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcelo Chiara Bertolami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simone Nascimento Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcos Roberto A.C. Barros
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rodrigo Bellio de Matos Barretto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sèrgio Cunha Pontes Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francisco Hermann Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonio Carlos Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Waldinai Pereira Ferreira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferreira, W.P., Bertolami, M.C., Santos, S.N. et al. One-Month Therapy with Simvastatin Restores Endothelial Function in Hypercholesterolemic Children and Adolescents. Pediatr Cardiol 28, 8–13 (2007). https://doi.org/10.1007/s00246-005-1304-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-005-1304-x

Keywords

Search

Navigation