Hypercholesterolemia in Youth: Opportunities and Obstacles to Prevent Premature Atherosclerotic Cardiovascular Disease

Abstract

Treatment of hypercholesterolemia in youth is predicated on the knowledge that we can identify those youth with this atherosclerotic risk factor most likely to develop premature cardiovascular disease. Unfortunately, this is not the case. Before we can adequately address appropriate lipid-lowering therapies in this special population, we must address and resolve current barriers related to screening and diagnosis. In this article, we describe some of the opportunities and obstacles that clinicians and policy makers confront when applying the current pediatric guidelines focused on screening and treating hypercholesterolemia in the pediatric population.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Personen E, Liuba P: Footprints of atherosclerotic coronary heart disease in children. Rev Port Cardiol 2004, 23:127–131.

    PubMed  Google Scholar 

  2. 2.

    Roger VL: Lifestyle and cardiovascular health: individual and societal choices. JAMA 2009, 302:437–439.

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Canto JG, Iskandrian AE: Major risk factors for cardiovascular disease: debunking the "only 50%" myth. JAMA 2003, 290:947–949.

    Article  PubMed  Google Scholar 

  4. 4.

    McGill HC Jr, McMahan CA, Gidding SS: Preventing heart disease in the 21st century: implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Circulation 2008, 117:1216–1227.

    Article  PubMed  Google Scholar 

  5. 5.

    American Academy of Pediatrics: National Cholesterol Education Program: report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics 1992, 89:S525–S584.

    Google Scholar 

  6. 6.

    •• 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. This article describes the pathophysiologic changes in youth, some of the problems with the existing pediatric guidelines, and medications for treating hyperlipidemia in youth.

    Article  PubMed  Google Scholar 

  7. 7.

    •• Daniels SR, Greer FR; Committee on Nutrition: Lipid screening and cardiovascular health in childhood. Pediatrics 2008, 122:198–208. This report replaces the 1998 pediatric NCEP guidelines. It explains the rationale for the cut points that were chosen to risk stratify children as well as dietary and pharmacologic approaches for treating hypercholesterolemia in youth.

    Article  PubMed  Google Scholar 

  8. 8.

    • Haney EM, Huffman LH, Bougatsos C, et al.: Screening and treatment for lipid disorders in children and adolescents: systematic evidence review for the US Preventive Services Task Force. Pediatrics 2007, 120:e189–e214. This article summarizes the current evidence and lack of evidence for screening and treatment of hypercholesterolemia in the pediatric population.

    Article  PubMed  Google Scholar 

  9. 9.

    Levenson JW, Skerrett PJ, Gaziano JM: Reducing the global burden of cardiovascular disease: the role of risk factors. Prev Cardiol 2002, 5:188–199.

    Article  PubMed  Google Scholar 

  10. 10.

    Kavey RE, Allada V, Daniels SR, et al.: Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research. Circulation 2006, 114:2710–2738.

    Article  PubMed  Google Scholar 

  11. 11.

    Norman M: Low birth weight and the developing vascular tree: a systematic review: Acta Paediatr 2008, 97:1165–1172.

    Article  PubMed  Google Scholar 

  12. 12.

    Barker DJ, Gluckman PD, Godfrey KM, et al.: Fetal nutrition and cardiovascular disease in adult life. Lancet 1993, 341:938–941.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Barker DJ: The developmental origins of insulin resistance: Horm Res 2005, 64: (Suppl 3):2–7.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Leunissen RW, Kerkhof GF, Stijnen T, Hokken-Koelega A: Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood. JAMA 2009, 301:2234–2242.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    • Jenssen BP, Jacobson MS: Screening adolescents for lipid disorders: what is the best approach? Adolesc Med State Art Rev 2008, 19:507–520. This is an excellent summary of some of the challenges of diagnosis and treatment of hypercholesterolemia in the pediatric population.

    PubMed  Google Scholar 

  16. 16.

    Eissa MA, Wen E, Mihalopoulos NL, et al.: Evaluation of AAP guidelines for cholesterol screening in youth: Project HeartBeat! Am J Prev Med 2009, 37(Suppl 1):S71–S77.

    Article  PubMed  Google Scholar 

  17. 17.

    US Census Bureau: American FactFinder. Available at http://factfinder.census.gov. Accessed August 30, 2009.

  18. 18.

    Stephens MB, Reamy BV; Primary Care Education and Research Learning Network: A novel approach using an electronic medical record to identify children and adolescents at risk for dyslipidemia: a study from the Primary Care Education and Research Learning (PEARL) network. J Am Board Fam Med 2008, 21:356–357.

    Article  PubMed  Google Scholar 

  19. 19.

    Rich EC, Burke W, Heaton CJ, et al.: Reconsidering the family history in primary care. J Gen Intern Med 2004, 19:273–280.

    Article  PubMed  Google Scholar 

  20. 20.

    Soni A: Cholesterol Screening among the U.S. Noninstitutionalized Adult Population Age 20 and Older, 2005. AHRQ statistical brief #187. Available at http://www.meps.ahrq.gov/mepsweb/data_files/pulbications/st187/stat187.pdf. Accessed September 14, 2009.

  21. 21.

    Ford ES, Li C, Pearson WS, et al.: Trends in hypercholesterolemia, treatment and control among United States adults. Int J Cardiol 2008 Dec 9 (Epub ahead of print).

  22. 22.

    Magnussen CG, Raitakari OT, Thomson R, et al.: Utility of currently recommended pediatric dyslipidemia classifications in predicting dyslipidemia in adulthood: evidence from the Childhood Determinants of Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study. Circulation 2008, 117:32–42.

    Article  PubMed  Google Scholar 

  23. 23.

    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of the Third Report of the National Cholesterol Education. Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001, 285:2486–2497.

    Google Scholar 

  24. 24.

    Chobanian AV, Bakris GL, Black HR, et al.: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003, 42:1206–1252.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Vasan RS, Kannel WB.: Strategies for cardiovascular risk assessment and prevention over the life course: progress amid imperfections. Circulation 2009, 120:360–363.

    Article  PubMed  Google Scholar 

  26. 26.

    The Kaiser Family Foundation: US Census Bureau, March 2007 and March 2008 Current Population Survey. Available at http://www.statehealthfacts.kff.org. Accessed September 16, 2009.

  27. 27.

    Watts GF, Lewis B, Sullivan DR: Familial hypercholesterolemia: a missed opportunity in preventive medicine. Nat Clin Pract Cardiovasc Med 2007, 4:404–405.

    Article  PubMed  Google Scholar 

  28. 28.

    Marks D, Wonderling D, Thorogood M, et al.: Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia. BMJ 2002, 324:1303.

    Article  PubMed  Google Scholar 

  29. 29.

    Tierney WM, Overhage JM, McDonald CJ: Toward electronic medical records that improve care. Ann Intern Med 1995, 122:725–726.

    CAS  PubMed  Google Scholar 

  30. 30.

    Williams RR, Hunt SC, Schumacher MC, et al.: Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol 1993, 72:171–176.

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Go AS, Magid DJ, Wells B, et al.: The Cardiovascular Research Network (CVRN): a new paradigm for cardiovascular quality and outcomes research. Circ Cardiovasc Quality Outcomes 2008, 1:138–147.

    Article  Google Scholar 

  32. 32.

    McNeal CJ, Wilson DP, Christou D, et al.: The use of surrogate vascular markers in youth at risk for premature cardiovascular disease. J Pediatr Endocrinol Metab 2009, 22:195–211.

    CAS  PubMed  Google Scholar 

  33. 33.

    Rodenburg J, Vissers MN, Wiegman A, et al.: Statin treatment in children with familial hypercholesterolemia: the younger, the better. Circulation 2007, 116:664–668.

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Jarvisalo MJ, Harmoinen A, Hakanen M, et al.: Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 2002, 22:1323–1328.

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Ford ES; National Health and Nutrition Examination Survey: C-reactive protein concentration and cardiovascular disease risk factors in children: findings from the National Health and Nutrition Examination Survey 1999-2000. Circulation 2003, 108:1053–1058.

    Google Scholar 

  36. 36.

    Ridker PM: C-reactive protein: eighty years from discovery to emergence as a major risk marker for cardiovascular disease. Clin Chem 2009, 55:209–215.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Soferman R, Glatstein M, Sivan Y, Weisman Y: HsCRP levels: measurement of airway inflammation in asthmatic children. Pediatr Int 2008, 50:12–16.

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Fuligni AJ, Telzer EH, Bower J, et al.: A preliminary study of daily interpersonal stress and C-reactive protein levels among adolescents from Latin American and European backgrounds. Psychosom Med 2009, 71:329–333.

    Article  PubMed  Google Scholar 

  39. 39.

    McMahan CA, Gidding SS, Fayad ZA, et al.: Risk scores predict atherosclerotic lesions in young people. Arch Intern Med 2005, 165:883–890.

    Article  PubMed  Google Scholar 

  40. 40.

    • McMahan CA, Gidding SS, Viikari JS, et al.: Association of Pathobiologic Determinants of Atherosclerosis in Youth risk score and 15-year change in risk score with carotid artery intima-media thickness in young adults (from the Cardiovascular Risk in Young Finns Study). Am J Cardiol 2007, 100:1124–1129. This article describes the development of the PDAY risk score. This article is also important because it demonstrates that the relative importance of risk factors in youth is different from that in adults.

    Article  PubMed  Google Scholar 

  41. 41.

    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.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Berenson GS, Srinivasan SR, Bao W, et al.: Association between multiple cardiovascular risk factors and the early development of atherosclerosis. Bogalusa Heart Study. N Engl J Med 1998, 338:1650–1656.

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Kwiterovich PO: Primary and secondary disorders of lipid metabolism in pediatrics. Pediatr Endocrinol Rev 2008, 5:727–738.

    PubMed  Google Scholar 

  44. 44.

    Kwiterovich PO Jr: Recognition and management of dyslipidemia in children and adolescents. J Clin Endocrinol Metab 2008, 93:4200–4209.

    Article  CAS  PubMed  Google Scholar 

  45. 45.

    Zappalla FR, Gidding SS: Lipid management in children. Endocrinol Metab Clin North Am 2009, 38:171–183.

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Managing Lipid Disorders in Children—A Special Pediatric Section. J Clin Lipidol 2008, 2:118–189.

  47. 47.

    Belay B, Racine AD, Belamarich PF: Underrepresentation of non-white children in trials of statins in children with heterozygous familial hypercholesterolemia. Ethn Dis 2009, 19:166–171.

    PubMed  Google Scholar 

  48. 48.

    Browne B, Vasquez S: Pediatric dyslipidemias: prescription medication efficacy and safety. J Clin Lipidol 2008, 2:189–201.

    Article  Google Scholar 

  49. 49.

    Shaddy RE, Boucek MM, Hsu DT, et al.: Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA 2007, 298:1171–1179.

    Article  PubMed  Google Scholar 

  50. 50.

    Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH: Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006, 354:1264–1272.

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Gillman MW: Childhood prevention of hypertensive cardiovascular disease. J Pediatr 2009, 155:159–161.

    Article  PubMed  Google Scholar 

  52. 52.

    Labarthe DR: Prevention of cardiovascular risk factors in the first place. Prev Med 1999, 29:S72–S78.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

We appreciate the contributions of Dr. Rachel Novotny (University of Hawaii) and Drs. Angie Hochhalter and E. E. Terry at Scott & White to the preparation of this manuscript.

Disclosure

Drs. McNeal and Cassidy-Bushrow are investigators within the Cardiovascular Research Network supported by the National Heart, Lung, and Blood Institute (NHLBI) grant U19-HL91179. Dr. McNeal was supported by a grant from the American Heart Association No other potential conflicts of interest relevant to this article were reported.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Catherine J. McNeal.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

McNeal, C.J., Dajani, T., Wilson, D. et al. Hypercholesterolemia in Youth: Opportunities and Obstacles to Prevent Premature Atherosclerotic Cardiovascular Disease. Curr Atheroscler Rep 12, 20–28 (2010). https://doi.org/10.1007/s11883-009-0072-0

Download citation

Keywords

  • Hypercholesterolemia
  • Youth
  • Atherosclerotic cardiovascular disease