Skip to main content
Log in

Combined Dyslipidemia in Children and Adolescents: a Proposed New Management Approach

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Combined dyslipidemia (CD), the predominant abnormal lipid pattern in children and adolescents, is characterized by moderate/severe triglyceride elevation with reduced high-density lipoprotein cholesterol. CD is prevalent, present in 30–50% of obese adolescents. Epidemiologic and lipid sub-population findings demonstrate CD to be highly atherogenic. In the short term, CD responds well to lifestyle change; long-term results are lacking.

Recent Findings

Major longitudinal studies now confirm that CD in childhood predicts early cardiovascular disease events in adults. Targeted nutritional interventions can be safely and effectively introduced in young children. These findings support introduction of a new approach to CD management.

Summary

New evidence supporting the atherosclerotic risk associated with CD and the effectiveness of lifelong diet interventions is reviewed and a new family-based primordial approach to CD beginning in infancy is proposed. Aligned with existing pediatric care recommendations, this has the potential to significantly decrease the development of CD.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

  1. Shiels MS, Haque AT, Berrington de González A, et al. Leading causes of death in the US during the COVID-19 pandemic, March 2020 to October 2021. JAMA Intern Med. 2022;182(8):883–6. https://doi.org/10.1001/jamainternmed.2022.2476.

    Article  PubMed  Google Scholar 

  2. • Jacobs DR, Woo JG, Sinaiko AR, et al. Childhood cardiovascular risk factors and adult cardiovascular events. N Engl J Med. 2022;386(20):1877–88. https://doi.org/10.1056/NEJMoa2109191. The International Childhood Cardiovascular Cohort Consortium (i3C) is a collaboration of seven large, longitudinal studies which measured CV RFs in children who were then followed into adulthood. Analyses from this collaboration now provide strong evidence associating childhood dyslipidemia and obesity with CVD events in adult life.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Morrison JA, Glueck CJ, Horn PS, et al. Pediatric triglycerides predict cardiovascular disease events in the fourth to fifth decade of life. Metabolism. 2009;58(9):1277–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. National Heart, Lung and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report. Pediatrics. 2011;128(Suppl 5):S213–56. www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm.

  5. Kit BK, Kuklina E, Carroll MD, et al. Prevalence of and trends in dyslipidemia and blood pressure among US children and adolescents, 1999-2012. JAMA Pediatr. 2015;169:272.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Perak AM, Ning H, Kit BK, et al. Trends in levels of lipids and apolipoprotein B in US youths aged 6 to 19 years, 1999-2016. JAMA. 2019;321(19):1895–905. https://doi.org/10.1001/jama.2019.4984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Centers for Disease Control and Prevention (CDC). Prevalence of abnormal lipid levels among youths —United States, 1999–2006. Morb Mortal Wkly Rep. 2010;59(2) http://www.cdc.gov/nchs/nhanes.htm

  8. Hu K, Staino AE. Trends in obesity prevalence among children and adolescents aged 2 to 19 years in the US from 2011 to 2020. JAMA Pediatr. 2022;176(10):1037–9.

    Article  PubMed  Google Scholar 

  9. Gill PK, Hegele RA. Familial combined hyperlipidemia is a polygenic trait. Curr Opin Lipidol. 2022;33(2):126–32. https://doi.org/10.1097/MOL.0000000000000796.

    Article  CAS  PubMed  Google Scholar 

  10. Burns SF, Lee SJ, Arslanian SA. Surrogate lipid markers for small dense low-density lipoprotein particles in overweight youth. J Pediatr. 2012;161(6):991–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cromwell WC, Otvos JD, Keyes MJ, et al. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study – implications for LDL management. J Clin Lipidol. 2007;1(6):583–92.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Turer CB, Brady TM, de Ferranti SD. Obesity, hypertension, and dyslipidemia in childhood are key modifiable antecedents of adult cardiovascular disease. Circulation. 2018;137:1256–9. https://doi.org/10.1161/CIRCULATIONAHA.118.032531.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bao W, Srinivasan SR, Berenson GS. Persistent elevation of plasma insulin levels is associated with increased cardiovascular risk in children and young adults. The Bogalusa Heart Study. Circulation. 1996;93(1):54–9. PMID: 8616941. https://doi.org/10.1161/01.cir.93.1.54.

    Article  CAS  PubMed  Google Scholar 

  14. Hannon TS, Bacha F, Lee SJ, et al. Use of markers of dyslipidemia to identify overweight youth with insulin resistance. Pediatr Diabetes. 2006;7:260–6.

    Article  PubMed  Google Scholar 

  15. De Ferranti SD, Gauvreau K, Ludwig DS, et al. Prevalence of the metabolic syndrome in American adolescents: findings from the third national health and nutrition survey. Circulation. 2004;110:2494–7.

    Article  PubMed  Google Scholar 

  16. Morrison JA, Friedman LA, Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics. 2007;120:340–5.

    Article  PubMed  Google Scholar 

  17. Ferranti SD, Newburger JW. Dyslipidemia in children: management. Waltham, MA, USA: UpToDate; 2020.

    Google Scholar 

  18. • Kavey RE. Combined dyslipidemia in children and adolescents. In: Endotext [Internet]. South Dartmouth(MA): MD Text.com, Inc.; 2000–2020. www.endotext.org. This review describes the contemporary approach to a diagnosis of combined dyslipidemia in childhood.

    Google Scholar 

  19. Valaiyapathi B, Sunil B, Ashraf AP. Approach to hypertriglyceridemia in the pediatric population. Pediatr Rev. 2017;38(9):424–34. https://doi.org/10.1542/pir.2016-0138.

    Article  PubMed  Google Scholar 

  20. Pratt RE, Kavey RE, Quinzi D. Combined dyslipidemia in obese children: response to a focused lifestyle approach. J Clin Lipidol. 2014;8:181–6. https://doi.org/10.1016/j.jacl.2014.01.003.

    Article  PubMed  Google Scholar 

  21. Jacobson TA, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9:S1–S122. https://doi.org/10.1016/j.jacl.2015.09.002.

    Article  PubMed  Google Scholar 

  22. Dwyer T, Sun C, Magnussen CG, et al. Cohort Profile: the International Childhood Cardiovascular Cohort (i3C) consortium. Int J Epidemiol. 2013;42(1):86–96. https://doi.org/10.1093/ije/dys004. Epub 2012 Mar 20. PMID: 22434861 PMCID: PMC3600617

    Article  PubMed  Google Scholar 

  23. Sinaiko AR, Jacobs DR, Wee JG, et al. The International Childhood Cardiovascular Cohort (i3C) consortium outcomes study of childhood cardiovascular risk factors and adult cardiovascular morbidity and mortality: Design and recruitment. Contemp Clin Trials. 2018;69:55–64. https://doi.org/10.1016/j.cct.2018.04.009. Epub 2018 Apr 22

    Article  PubMed  PubMed Central  Google Scholar 

  24. Woo JG, Zhang N, Fenchel M, et al. Prediction of adult class II/III obesity from childhood BMI: the i3C consortium. Int J Obes (Lond). 2019;44 https://doi.org/10.1038/s41366-019-0461-6.

  25. Yan Y, Bazzano LA, Juonala M, et al. Long-term burden of increased body mass index from childhood on adult dyslipidemia: the i3C consortium study. J Clin Med. 2019;8(10) pii: E1725 https://doi.org/10.3390/jcm8101725.

  26. Hu T, Jacobs DR Jr, Sinaiko AR, et al. Childhood BMI and fasting glucose and insulin predict adult type 2 diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium. Diabetes Care. 2020;43(11):2821–9. https://doi.org/10.2337/dc20-0822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. • Lapinleimu H, Viikari J, Jokinen E, et al. Prospective randomized trial in 1062 infants of diet low in saturated fat and cholesterol. Lancet. 1995;345:471–6. https://doi.org/10.2337/dc18-0869. The Special Turku Coronary Risk Factor Intervention Project (STRIP) was a prospective, randomized trial which began in 1990 when subjects were 7 months of age and continued for 20 years. Intervention children received individualized diet counseling, aimed at achieving a low fat, low saturated fat, and low cholesterol diet. Throughout the study and at 6-year post evaluation, intervention subjects had lower fat and saturated fat intake. Longitudinal analyses showed consistently lower levels of TC and LDL-C in intervention participants. At the post evaluation, serum glucose and IR were also significantly lower in intervention subjects. The STRIP trial showed convincingly that nutritional interventions can be safely introduced in youth and sustained throughout childhood with long-term beneficial results.

    Article  CAS  PubMed  Google Scholar 

  28. Niinikoski H, Pahkala K, Ala-Korpela M, et al. Effect of repeated dietary counseling on serum lipoproteins from infancy to adulthood. Pediatrics. 2012;129:e704–13. https://doi.org/10.1542/peds.2011-1503.

    Article  PubMed  Google Scholar 

  29. Kahanen M, Lagstrom H, Pahkala K, et al. Dietary and lifestyle counselling reduces the clustering of overweight-related cardiometabolic risk factors in adolescents. Acta Paediatr. 2010;99(6):888–95. PMID: 20002624. https://doi.org/10.1111/j.1651-2227.2009.01636.

    Article  Google Scholar 

  30. Oranta O, Pahkala K, Ruottinen S, et al. Infancy-onset dietary counseling of low-saturated-fat diet improves insulin sensitivity in healthy adolescents 15-20 years of age: the Special Turku Coronary Risk Factor Intervention Project (STRIP) study. Diabetes Care. 2013;36:2952–9. https://doi.org/10.2337/dc13-0361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Niinikoski H, Jula A, Viikari J, et al. Blood pressure is lower in children and adolescents with a low-saturated-fat diet since infancy: the special Turku coronary risk factor intervention project. Hypertension. 2009;53:918–24. https://doi.org/10.1161/HYPERTENSIONAHA.109.130146.

    Article  CAS  PubMed  Google Scholar 

  32. Pahkala K, Hietalampi H, Laitinen TT, et al. Ideal cardiovascular health in adolescence: effect of lifestyle intervention and association with vascular intima-media thickness and elasticity (the Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] study). Circulation. 2013;127:2088–96. https://doi.org/10.1161/CIRCULATIONAHA.112.000761.

    Article  PubMed  Google Scholar 

  33. Lehtovirta M, Matthews LA, Laitinen TT, et al. Achievement of the targets of the 20-year infancy-onset dietary intervention-association with metabolic profile from childhood to adulthood. Nutrients. 2021;13(2):533. PMID: 33562015 PMCID: PMC7915301. https://doi.org/10.3390/nu13020533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pahkala K, Laitinen TT, Niinikoski H, et al. Effects of 20-year infancy-onset dietary counselling on cardiometabolic risk factors in the Special Turku Coronary Risk Factor Intervention Project (STRIP): 6-year post-intervention follow-up. Lancet Child Adolesc Health. 2020;4(5):359–69. https://doi.org/10.1016/S2352-4642(20)30059-6.

    Article  CAS  PubMed  Google Scholar 

  35. Nupponen M, Pahkala K, Juonala M, et al. Metabolic syndrome from adolescence to early adulthood: effect of infancy-onset dietary counseling of low saturated fat: the Special Turku Coronary Risk Factor Intervention Project (STRIP). Circulation. 2015;131(7):605–13. https://doi.org/10.1161/CIRCULATIONAHA.114.010532. Epub 2015 Jan 20

    Article  CAS  PubMed  Google Scholar 

  36. Laitinen TT, Nuotio J, Juonola H, et al. Success in achieving the targets of the 20-year infancy-onset dietary intervention: association with insulin sensitivity and serum lipids. Diabetes Care. 2018;41(10):2236–44. https://doi.org/10.2337/dc18-0869.

    Article  CAS  PubMed  Google Scholar 

  37. Patrick H, Nicklas TA. A review of family and social determinants of children’s eating patterns and diet quality. J Amer Coll Nutrition. 2005;24(2):83–92. https://doi.org/10.1080/07315724.2005.10719448.

    Article  Google Scholar 

  38. Pachuki MC, Lovenheim M, Harding M. Within-family obesity associations: evaluation of parent, child, and sibling relationships. Amer J Prev Med. 2014;47(4):382–91. https://doi.org/10.1016/j.amepre.2014.05.018.

    Article  Google Scholar 

  39. Marateb HR, MohebbianR KR, et al. Prediction of dyslipidemia using gene mutations, family history of diseases and anthropometric indicators in children and adolescents: the CASPIAN-III study. Comput Struct Biotechnol J. 2016;(Suppl. 5) https://doi.org/10.1016/j.csbj.2018.02.009.

  40. Meigs JB, Cupples LA, Wilson PW. Parental transmission of type 2 diabetes: the Framingham offspring study. Diabetes. 2000;49:2201–7. https://doi.org/10.2337/diabetes.49.12.2201.

    Article  CAS  PubMed  Google Scholar 

  41. Lloyd-Jones DM, Nam BH, D'Agostino RB Sr, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA. 2004;291(18):2204–11.

    Article  CAS  PubMed  Google Scholar 

  42. Gaeta G, De Michele M, Cuomo S, et al. Arterial abnormalities in the offspring of patients with premature myocardial infarction. N Engl J Med. 2000;343(12):840–6.

    Article  CAS  PubMed  Google Scholar 

  43. Adult Obesity Facts. Centers for Disease Control and Prevention. 2021; https://www.cdc.gov/obesity/data/adult.html

    Google Scholar 

  44. Obesity and Dyslipidemia. Edited by Feingold KR, Anawalt B, Boyce A, et al. South Dartmouth (MA): MDText.com, Inc.; 2020. www.endotext.org.

  45. National Diabetes Statistics Report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2020.

  46. Bright Futures. Guidelines for Health Supervision of Infants, Children and Adolescents. Fourth edition. American Academy of Pediatrics. Edited by Hagen JF, Shaw JS, Duncan PM. Publication Date: February 21, 2018. https://www.aap.org/en/practice-management/bright-futures/bright-futures-materials-and-tools/bright-futures-guidelines-and-pocket-guide/.

  47. Taveras EM, Rifas-Shiman SL, Belfort MB, et al. Weight status in the first 6 months of life and obesity at 3 years of age. Pediatrics. 2009;123(4):1177–83. https://doi.org/10.1542/peds.2008-1149. PMID: 19336378; PMCID: PMC2761645

    Article  PubMed  Google Scholar 

  48. Birch LL, Anzman-Frascaa PIM. Starting early: obesity prevention during infancy. In: Drewnowski A, Rolls BJ, editors. Obesity treatment and prevention: new directions. Nestlé Nutr Inst Workshop Ser, vol. 73; 2012. p. 81–94. Nestec Ltd., Vevey/S. Karger AG. Basel, ©.

    Chapter  Google Scholar 

  49. Guo SS, Wu W, Chumlea WC, Roche AF. Predicting overweight and obesity in adulthood from body mass index values in childhood and adolescence. Am J Clin Nutr. 2002;76(3):653–8. https://doi.org/10.1093/ajcn/76.3.653.

    Article  CAS  PubMed  Google Scholar 

  50. Keller A, Bucher Della Torre S. Sugar-sweetened beverages and obesity among children and adolescents: a review of systematic literature reviews. Child Obes. 2015;11(4):338–46. https://doi.org/10.1089/chi.2014.0117. PMID: 26258560; PMCID: PMC4529053

    Article  PubMed  PubMed Central  Google Scholar 

  51. Field AE, Sonneville KR, Falbe J, et al. Association of sports drinks with weight gain among adolescents and young adults. Obesity (Silver Spring). 2014;22(10):2238–43. https://doi.org/10.1002/oby.20845. PMID: 25044989; PMCID: PMC4180814

    Article  PubMed  Google Scholar 

  52. Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev. 2016;17(2):95–107. https://doi.org/10.1111/obr.12334. Epub 2015 Dec 23

    Article  CAS  PubMed  Google Scholar 

  53. Guidelines for Physical Activity in Americans. U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. Division of Nutrition, Physical Activity, and Obesity. Office of Disease Prevention and Health Promotion; 2020. HealthyPeople.gov website. https://www.healthypeople.gov/2020/topics

    Google Scholar 

  54. Janssen I, LeBlanc AG. Systematic review of the health benefits of physical activity and fitness in school-aged children and youth. Int J Beh Nutr Phys Activity. 2010;7:40–56.

    Article  Google Scholar 

  55. Davis CL, Pollock NK, Waller JL, et al. Exercise dose and diabetes risk in overweight and obese children A randomized controlled trial. JAMA. 2012;308(11):1103–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bustamante EE, Ramer JD, Santiago-Rodríguez ME, et al. The S.P.A.C.E hypothesis: physical activity as medium — not medicine — for public health impact. Exerc Sport Sci Rev. 2021;49(2):133–45. https://doi.org/10.1249/JES.0000000000000248.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Pate RR, Dowda M. Raising an active and healthy generation: a comprehensive public health initiative. Exerc Sport Sci Rev. 2019;47(1):3–14. https://doi.org/10.1249/jes.0000000000000171. PMID: 30334849

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rae-Ellen W. Kavey.

Ethics declarations

Conflict of Interest

Rae-Ellen W. Kavey has no conflicts of interest.

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

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kavey, RE.W. Combined Dyslipidemia in Children and Adolescents: a Proposed New Management Approach. Curr Atheroscler Rep 25, 237–245 (2023). https://doi.org/10.1007/s11883-023-01099-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-023-01099-x

Keywords

Navigation