Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome

  • Andrea Kelly
  • Samuel S. Gidding
  • Rachel Walega
  • Claire Cochrane
  • Sarah Clauss
  • Ray R. Townsend
  • Melissa Xanthopoulos
  • Mary E. Pipan
  • Babette S. Zemel
  • Sheela N. Magge
  • Meryl S. Cohen
Original Article


Median survival in Down syndrome (DS) is 60 years, but cardiovascular disease risk and its markers such as left ventricular mass (LVM) have received limited attention. In youth, LVM is typically scaled to height2.7 as a surrogate for lean body mass (LBM), the strongest predictor of LVM, but whether this algorithm applies to DS, a condition which features short stature, is unknown. To examine the relationships of LVM and function with height, LBM, and moderate-to-vigorous physical activity(MVPA) in DS, DS youth aged 10–20 years, and age-, sex-, BMI-, race-matched nonDS controls underwent echocardiography for LVM, ejection fraction (EF), and left ventricular diastolic function (measured as E/E′); dual-energy X-ray absorptiometry (DXA)-measured LBM; accelerometry for MVPA. (DS vs. nonDS median [min–max]): DS had lower height (cm) (144.5 [116.7–170.3] vs. 163.3 [134.8–186.7]; p < 0.0001); LBM (kg) (33.48 [14.5–62.3] vs 41.8 [18.07–72.46], p < 0.0001); and LVM (g) (68.3 [32.1–135] vs 94.0 [43.9–164.6], p < 0.0001); similar EF (%) (65 [54–77] vs 64 [53–77], p = 0.59); and higher E/E′ (8.41 [5.54–21.4] vs 5.81 [3.44–9.56], p < 0.0001). In height2.7-adjusted models, LVM was lower in DS (β = − 7.7, p = 0.02). With adjustment for LBM, LVM was even lower in DS (β = − 15.1, p < 0.0001), a finding not explained by MVPA. E/E′ remained higher in DS after adjustment for age, height, HR, SBP, and BMI (β = 2.6, p < 0.0001). DS was associated with stiffer left ventricles and lower LVM, the latter magnified with LBM adjustment. Scaling to height2.7, the traditional approach for assessing LVM in youth, may underestimate LVM differences in DS. Whether lower LVM and diastolic function are intrinsic to DS, pathologic, or protective remains unknown.

Clinical Trial Registration: NCT01821300.


Down syndrome Left ventricular mass Left ventricular diastolic function Body composition Echocardiogram 



We thank the study participants and their families, as well as research coordinators Amber Lauff and Priscilla Andalia and students Sarah Appeadu, Elizabeth Stulpin, Claire Trindle, Natalie Rosetti, Jeffrey Signora, Cassandra Zhi, Cedar Slovacek, Suzanne M. Arnott, Monica N. Salama, and Emily Eicheldinger for their diligent efforts. In addition, we thank the CHOP Clinical and Translational Research Center, the CNHS Clinical Research Unit, the CHOP Pediatric Research Consortium, and the CHOP Recruitment Enhancement Core, without whom this study would not have been possible, for their contributions.


This study was supported by NIH R01HD071981 (Kelly/Magge), NIH National Center for Research Resources and the National Center for Advancing Translational Sciences through Grant UL1TR000003, Bethesda, MD, USA and Research Electronic Data Capture (REDCap). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Compliance with Ethical Standards

Conflict of interest

The authors have no financial relationships relevant to this article to disclose. The authors have no conflicts of interest to disclose.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Supplementary material

246_2018_2014_MOESM1_ESM.pptx (58 kb)
Supplemental Figure 1. Relationship of Left Ventricular Mass Adjusted for Age, HR, SBP, LBM, Black-, MVR-, &#x0026; CHD-status with Moderate-to-Vigorous Physical Activity. Shown are adjusted-LVM in DS [(x no CHD), (+ h/o CHD not requiring surgical repair), (Δ h/o CHD repaired surgically)] and matched controls (●) vs MVPA (min). Fitted lines for LVM vs MVPA for DS (●●●) and Controls (- - -) are also shown. LVM remained lower in DS (-13.9 g [95% CI: -20.6 to -7.3], p&#x003C;0.0001) even after adjustment for MVPA. A DS*MVPA interaction was present (p = 0.029; likelihood ratio test=0.021), such that in DS increasing MVPA was associated with lower LVM. (PPTX 58 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andrea Kelly
    • 1
    • 2
    • 11
  • Samuel S. Gidding
    • 3
  • Rachel Walega
    • 4
  • Claire Cochrane
    • 1
  • Sarah Clauss
    • 5
  • Ray R. Townsend
    • 6
  • Melissa Xanthopoulos
    • 7
  • Mary E. Pipan
    • 2
    • 8
  • Babette S. Zemel
    • 2
    • 9
  • Sheela N. Magge
    • 4
  • Meryl S. Cohen
    • 2
    • 10
  1. 1.Division of Endocrinology & DiabetesThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Department of PediatricsPerelman School of Medicine of University of PennsylvaniaPhiladelphiaUSA
  3. 3.Familial Hypercholesterolemia FoundationPasadenaUSA
  4. 4.Division of Endocrinology and Diabetes, Center for Translational ScienceChildren’s National Health SystemWashingtonUSA
  5. 5.Division of CardiologyChildren’s National Health SystemWashingtonUSA
  6. 6.Department of MedicinePerelman School of Medicine of University of PennsylvaniaPhiladelphiaUSA
  7. 7.Department of Child and Adolescent Psychiatry and Behavioral SciencesThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  8. 8.Division of Behavioral PediatricsChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  9. 9.Division of Gastroenterology, Hepatology, & NutritionThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  10. 10.Division of CardiologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  11. 11.Division of Endocrinology & DiabetesRoberts Center for Pediatric ResearchPhiladelphiaUSA

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