Issue #31 – Cardiometabolic Risk in Down Syndrome

Posted on adminDSPosted in All Articles, Down Syndrome and Congenital Heart Defects

With improvements in medical care, we now celebrate a life expectancy of nearly 60 years for individuals with Down syndrome.  With improved survival, healthcare providers need to learn how to address common chronic health concerns in adults with Down syndrome, such as obesity, diabetes, and cardiovascular disease. Individuals with Down syndrome are at increased risk for obesity, and in the general population, obesity is a risk factor for type 2 diabetes and heart problems.  It is not clear if the same is true in adults with Down syndrome.

Scientific evidence clarifying the risk of cardiovascular disease in individuals with Down syndrome is lacking, and the available information is conflicting. Atherosclerosis is the buildup of fatty plaques on the walls of arteries, and is a risk factor for heart failure, heart attacks, and stroke.  In a research study in 1977, the investigators concluded that adults with Down syndrome were protected from atherosclerotic disease because they did not find any fatty plaques in the coronary arteries of five adults with Down syndrome, compared to adults without Down syndrome1. However, a 2003 study reported deaths due to cardiovascular disease to be 6 times greater in Down syndrome, and 3 large studies reported increased death due to CVD in Down syndrome2,3,4,5. In 2020, the Global Down Syndrome Foundation published medical care guidelines for adults with DS6.  The GLOBAL Workgroup felt that atherosclerotic cardiovascular disease is less common in adults with Down syndrome based on clinical experience.  However, given the limitation of existing research, the workgroup recommended screening cholesterol levels every 5 years starting at age 40, using the same measures used for adults without DS. Thus, more research is needed in this area.

There is also evidence that diabetes-related deaths are higher in individuals with Down syndrome, but the type of diabetes was not noted3. Individuals with Down syndrome are known to be at increased risk for developing type 1 diabetes, but it is not clear whether they are at increased risk for type 2 diabetes, which is the type of diabetes typically associated with obesity.  Based on a large study in the United Kingdom that showed significantly higher prevalence of diabetes in adults with Down syndrome compared to adults without, the GLOBAL Workgroup recommended screening adults with Down syndrome for diabetes every 3 years starting at age 21 for those who are obese, and starting at age 30 for all individuals with Down syndrome6.

There has been even less research on risk of diabetes and heart disease in children with Down syndrome. In 2015, the Centers for Disease Control published growth curves for children with Down syndrome7.  Growth curves are used to track the growth patterns of children over time. These growth curves were specifically based on other children with Down syndrome, which is important given that individuals with Down syndrome are shorter than their peers and have different body proportions.  However, the authors suggested that health providers do not use the new growth charts for body mass index (BMI), as many children in the study were obese, and the new growth curves may “normalize” obesity. The authors recommend using the BMI growth chart for typically-developing children for children with Down syndrome as well.

In examining the risk for cardiovascular disease and diabetes in children with Down syndrome, a recent study by Magge et al. found that children ages 10-20 years old with Down syndrome had more abnormal lipid levels compared to youth of similar age, race, ethnicity and BMI, without Down syndrome.  Additionally, the authors found that youth with Down syndrome and overweight/obesity had increased odds of prediabetes, even after accounting for differences in BMI8. This could imply that they will have higher risk for CVD and type 2 diabetes as adults, but more research is needed.

Given the conflicting and limited evidence that has been published to date, it is important for further long-term studies to be conducted to understand cardiovascular and diabetes risk in individuals with Down syndrome so that healthcare providers know how to best care for children and adults with Down syndrome.

References

  1. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down’s syndrome: an atheroma-free model? Br Med J. 1977;2(6081):226-8. Epub 1977/07/23. PubMed PMID: 141966; PMCID: PMC1631400.
  2. Hill DA, Gridley G, Cnattingius S, Mellemkjaer L, Linet M, Adami HO, Olsen JH, Nyren O, Fraumeni JF, Jr. Mortality and cancer incidence among individuals with Down syndrome. Arch Intern Med. 2003;163(6):705-11.Epub 2003/03/18. PubMed PMID: 12639204.
  3. Sobey CG, Judkins CP, Sundararajan V, Phan TG, Drummond GR, Srikanth VK. Risk of Major Cardiovascular Events in People with Down Syndrome. PLoS One. 2015;10(9):e0137093. Epub 2015/10/01. doi: 10.1371/journal.pone.0137093. PubMed PMID: 26421620; PMCID: PMC4589343.
  4. Hermon C, Alberman E, Beral V, Swerdlow AJ. Mortality and cancer incidence in persons with Down’s syndrome, their parents and siblings. Ann Hum Genet. 2001;65(Pt 2):167-76. doi: doi:10.1017/S0003480001008508. PubMed PMID: 11427176.
  5. Day SM, Strauss DJ, Shavelle RM, Reynolds RJ. Mortality and causes of death in persons with Down syndrome in California. Dev Med Child Neurol. 2005;47(3):171-6. PubMed PMID: 15739721.
  6. Tsou AY, Bulova P, Capone G, et al. Medical Care of Adults With Down Syndrome: A Clinical Guideline. 2020;324(15):1543–1556. doi:10.1001/jama.2020.17024
  7. Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, Freedman DS, Thorpe P. Growth Charts for Children With Down Syndrome in the United States. Pediatrics. 2015;136(5):e1204-11. doi: 10.1542/peds.2015-1652. PubMed PMID: 26504127; PMCID: 5451269.
  8. Magge SN, Zemel BS, Pipan ME, Gidding SS, Kelly A. Cardiometabolic Risk and Body Composition in Youth With Down Syndrome. Pediatrics. 2019 Aug;144(2):e20190137. doi: 10.1542/peds.2019-0137. Epub 2019 Jul 17. PMID: 31315916; PMCID: PMC6855833.

 

Authors:

Jacquelyn Manfredo, Medical Degree (MD), Pediatric Endocrine Fellow at Johns Hopkins Hospital

 Sheela Magge, MD, Master of Science in Clinical Epidemiology (MSCE), Director of Division of Pediatric Endocrinology and Associate Professor at Johns Hopkins Hospital