Skip to main content

Advertisement

SpringerLink
Log in

Screening for Hypercholesterolemia in Children: What Strategies Can Be Employed

  • Pediatrics (S. Gidding, Section Editor)
  • Published:
Current Cardiovascular Risk Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Familial hypercholesterolemia (FH) is an important, treatable cause of elevated LDL cholesterol that can be remediated to lower risk of premature coronary artery disease.

Recent Findings

Strategies for identification include universal screening, cascade screening of relatives of persons found with either early cardiovascular disease (CVD) or LDL-C consistent with FH, and big data approaches to identify persons with high cholesterol and premature CVD.

Summary

Universal screening of children is advocated to find FH at an early age with still asymptomatic parents and negative family history.

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

Similar content being viewed by others

References

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

  1. Gidding SS et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015;132(22):2167–92.

    Article  PubMed  Google Scholar 

  2. • Elis A, Zhou R, Stein EA. Effect of lipid-lowering treatment on natural history of heterozygous familial hypercholesterolemia in past three decades. Am J Cardiol. 2011;108(2):223–6. One thousand adult patients with FH were treated from 1974 to 2008, and charts of a random sample of 327 were reviewed. Fifty-five percent reduction in LDL (from 256 to 116 mg/dl) was achieved in the group with statin, combined with other agents in 45%. Subjects usually presented with a coronary event and mean age to second event increased from 5.3 to 7.4 years.

    Article  PubMed  Google Scholar 

  3. Sjouke B et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J. 2015;36(9):560–5.

    Article  PubMed  Google Scholar 

  4. Williams R et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993;72:171–6.

    Article  CAS  PubMed  Google Scholar 

  5. •• Simon Broom Registry Group, S.B.R. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ. 1991;303(6807):893–6. This seminal report from the Simon Broome Registry Group showed excessive mortality in young persons with familial hypercholesterolemia. This study from England and Wales showed a standardized mortality ratio of nearly 10,000:1 in FH subjects age 20 to 39 years old compared to the general population.

    Article  Google Scholar 

  6. Benn M et al. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen general population study estimated a prevalence of 1 in 217. Eur Heart J. 2016;37(17):1384–94.

    Article  PubMed  Google Scholar 

  7. Benn M et al. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012;97(11):3956–64.

    Article  CAS  PubMed  Google Scholar 

  8. Jannes CE et al. Familial hypercholesterolemia in Brazil: cascade screening program, clinical and genetic aspects. Atherosclerosis. 2015;238(1):101–7.

    Article  CAS  PubMed  Google Scholar 

  9. Mickiewicz A et al. Efficacy of clinical diagnostic criteria for familial hypercholesterolemia genetic testing in Poland. Atherosclerosis. 2016;249:52–8.

    Article  CAS  PubMed  Google Scholar 

  10. Maurer F et al. Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia—a proof-of-concept study. Swiss Med Wkly. 2016;146:w14326.

    PubMed  Google Scholar 

  11. Khera AV et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–89.

    Article  CAS  PubMed  Google Scholar 

  12. Stempel H, et al. Referral patterns and cascade screening for familial hypercholesterolemia in a pediatric lipid clinic. J Pediatr. 2016;178:285–7.

  13. Wald DS et al. Child–parent familial hypercholesterolemia screening in primary care. N Engl J Med. 2016;375(17):1628–37.

    Article  CAS  PubMed  Google Scholar 

  14. • Klancar G et al. Universal screening for familial hypercholesterolemia in children. J Am Coll Cardiol. 2015;66(11):1250–7. This study from the European Atherosclerosis Society showed an incidence of FH approaching 1/200 and suggested criteria for targeted cascade screening. The authors note that <1% of FH subjects are identified in most countries.

    Article  PubMed  Google Scholar 

  15. Williams R et al. Documented need for more effective diagnosis and treatment of familial hypercholesterolemia according to data from 502 heterozygotes in Utah. Am J Cardiol. 1993;72:18D–24.

    Article  CAS  PubMed  Google Scholar 

  16. Nordestgaard BG et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Qureshi N et al. Feasibility of improving identification of familial hypercholesterolaemia in general practice: intervention development study. BMJ Open. 2016;6(5), e011734.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Schofield J, et al. Knowledge gaps in the management of familial hypercholesterolaemia. A UK based survey. Atherosclerosis. 2016.

  19. Marks D et al. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003;168(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  20. Enos W, Holmes R, Beyer J. Coronary disease among United States soldiers killed in action in Korea. JAMA. 1953;152(12):1090–3.

    Article  CAS  Google Scholar 

  21. McNamara J et al. Coronary artery disease in combat casualties in Vietnam. JAMA. 1971;216(7):1185–7.

    Article  CAS  PubMed  Google Scholar 

  22. Tracy RE et al. Risk factors and atherosclerosis in youth autopsy findings of the Bogalusa Heart Study. Am J Med Sci. 1995;310:S37–41.

    Article  PubMed  Google Scholar 

  23. McGill Jr HC et al. Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol. 1997;17(1):95–106.

    Article  PubMed  Google Scholar 

  24. Kusters DM et al. Carotid intima-media thickness in children with familial hypercholesterolemia. Circ Res. 2014;114(2):307–10.

    Article  CAS  PubMed  Google Scholar 

  25. Kusters DM et al. Design and baseline data of a pediatric study with rosuvastatin in familial hypercholesterolemia. J Clin Lipidol. 2013;7(5):408–13.

    Article  PubMed  Google Scholar 

  26. Ritchie SK et al. Universal versus targeted blood cholesterol screening among youth: the CARDIAC project. Pediatrics. 2010;126(2):260–5.

    Article  PubMed  Google Scholar 

  27. WV Dept. of Health and Human Resources, The burden of cardiovascular disease in West Virginia. 2011.

  28. Lilly CL et al. Trends in serum lipids among 5th grade CARDIAC participants, 2002–2012. J Epidemiol Community Health. 2014;68(3):218–23.

    Article  PubMed  Google Scholar 

  29. Expert Panel on Integrated Guidelines for Cardiovascular, H et al. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128 Suppl 5:S213–56.

    Google Scholar 

  30. Force, U.S.P.S.T. et al. Screening for lipid disorders in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA. 2016;316(6):625–33.

    Article  Google Scholar 

  31. Vinci S, et al. Cholesterol testing among children and adolescents during health visits. JAMA. 2014;311(17):1804–6.

  32. Braamskamp MJ et al. Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood. Atherosclerosis. 2015;241(2):427–32.

    Article  CAS  PubMed  Google Scholar 

  33. Braamskamp MJ et al. Long-term statin treatment in children with familial hypercholesterolemia: more insight into tolerability and adherence. Paediatr Drugs. 2015;17(2):159–66.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Besseling J et al. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA. 2015;313(10):1029–36.

    Article  CAS  PubMed  Google Scholar 

  35. Yu Q, Su X, Liu E. Could familial hypercholesterolemia oppose the diabetogenic effect of statin? Comments on a new SAFEHEART study. Int J Cardiol. 2016;202:954–5.

    Article  PubMed  Google Scholar 

  36. Umans-Eckenhausen MAW et al. Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands. Lancet. 2001;357(9251):165–8.

    Article  CAS  PubMed  Google Scholar 

  37. Andersen R, Andersen L. Examining barriers to cascade screening for familial hypercholesterolemia in the United States. J Clin Lipidol. 2016;10(2):225–7.

    Article  PubMed  Google Scholar 

  38. Galema-Boers JM et al. Cascade screening of familial hypercholesterolemia must go on. Atherosclerosis. 2015;242(2):415–7.

    Article  CAS  PubMed  Google Scholar 

  39. Lee W et al. Identification of a common low density lipoprotein receptor mutation in the west of Scotland. J Med Genet. 1998;35:573–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kusters DM et al. Founder mutations in the Netherlands: geographical distribution of the most prevalent mutations in the low-density lipoprotein receptor and apolipoprotein B genes. Neth Heart J. 2011;19(4):175–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hobbs H et al. Deletion in the gene for the low-density-lipoprotein receptor in a majority of French Canadians with familial hypercholesterolemia. N Eng J Med. 1987;317:734–7.

    Article  CAS  Google Scholar 

  42. Kolvisto U et al. The familial hypercholesterolemia (FH)-North Karelia mutation of the low density lipoprotein receptor gene deletes seven nucleotides of exon 6 and is a common cause of FH in Finland. J Clin Invest. 1992;90:219–28.

    Article  Google Scholar 

  43. Defesche J et al. South African founder mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia in the Dutch population. Hum Genet. 1993;92:567–70.

    Article  CAS  PubMed  Google Scholar 

  44. Durst R et al. Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews. Am J Hum Genet. 2001;68(5):1172–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pyles L, et al. Correlation of sibling lipid levels from a statewide child cardiac risk factor registry. Circulation. 2016;133(S1):AP031.

  46. Deskins S et al. Preventive care in Appalachia—use of the theory of planned behavior to identify barriers to participation in cholesterol screenings among West Virginians. J Rural Health. 2006;22(4):367–74.

    Article  PubMed  Google Scholar 

  47. Peissig PL et al. Relational machine learning for electronic health record-driven phenotyping. J Biomed Inform. 2014;52:260–70.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Liao KP et al. Methods to develop an electronic medical record phenotype algorithm to compare the risk of coronary artery disease across 3 chronic disease cohorts. PLoS One. 2015;10(8), e0136651.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Troeung L et al. A new electronic screening tool for identifying risk of familial hypercholesterolaemia in general practice. Heart. 2016;102(11):855–61.

    Article  PubMed  Google Scholar 

  50. Hicks KA et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards). J Am Coll Cardiol. 2015;66(4):403–69.

    Article  PubMed  Google Scholar 

  51. Zhou M, Zhao D. Familial hypercholesterolemia in Asian populations. J Atheroscler Thromb. 2016;23:539–49.

  52. Pang J et al. Prevalence of familial hypercholesterolemia in adolescents: potential value of universal screening? J Pediatr. 2016;170:315–6.

    Article  PubMed  Google Scholar 

  53. Talmud PJ et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case–control study. Lancet. 2013;381(9874):1293–301.

    Article  CAS  PubMed  Google Scholar 

  54. Versmissen J et al. Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach. Eur J Hum Genet. 2015;23(3):381–7.

    Article  CAS  PubMed  Google Scholar 

  55. Nelson CP et al. Genetically determined height and coronary artery disease. N Engl J Med. 2015;372(17):1608–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Marks D et al. Screening for hypercholesterolemia versus case finding for familial hypercholesterolemia: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2000;4(29):1–119.

    CAS  PubMed  Google Scholar 

  57. Nherera L et al. Cost-effectiveness analysis of the use of a high-intensity statin compared to a low-intensity statin in the management of patients with familial hypercholesterolaemia. Curr Med Res Opin. 2010;26(3):529–36.

    Article  CAS  PubMed  Google Scholar 

  58. Shah P et al. Pharmacoeconomics of PCSK9 inhibitors in 103 hypercholesterolemic patients referred for diagnosis and treatment to a cholesterol treatment center. Lipids Health Dis. 2016;15(1):132.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Gidding SS. Why cholesterol testing in children and adolescents matters. JAMA Cardiol. 2016;1(8):859–61.

  60. Wiegman A et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia. JAMA. 2004;292(3):331–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Paula Nicholson and Emily Polak for the CARDIAC data management, and the CARDIAC area coordinators (Kathryn Greenlief, Janetta Massie, Dalena Riggs, Robin VanFleet, Tammy Vicars, Tina Whitt) for the data collection. Special thanks also to Derek Belcher, Leslie Cottrell, Christa Lilly, Valerie Minor, Emily Murphy, and Susie Ritchie for their work with the CARDIAC project.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Section of Pediatric Cardiology, CARDIAC Project, West Virginia University School of Medicine, WVU Children’s Hospital, 1 Medical Center Drive, Box 9214, Morgantown, WV, 26506-9214, USA

    Lee A. Pyles & William A. Neal

  2. College of Physical Activity and Sport Sciences, PAS 269, 375 Birch St., P.O. Box 6116, Morgantown, WV, 26505, USA

    Eloise Elliott

Authors
  1. Lee A. Pyles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eloise Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William A. Neal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lee A. Pyles.

Ethics declarations

Conflict of Interest

Drs. Pyles, Elliott, and Neal have no conflicts of interests to declare.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Pediatrics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pyles, L.A., Elliott, E. & Neal, W.A. Screening for Hypercholesterolemia in Children: What Strategies Can Be Employed. Curr Cardiovasc Risk Rep 11, 5 (2017). https://doi.org/10.1007/s12170-017-0531-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12170-017-0531-z

Keywords

Search

Navigation