Skip to main content
SpringerLink
Log in

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study

  • Computed Tomography
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results.

Methods

In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors).

Results

Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33).

Conclusion

CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates.

Key Points

• Aortic root dimensions are determined by genetic and environmental effects.

• Transthoracic echocardiography (TTE) demonstrated moderate to no genetic effects on aortic root dimensions.

• Computed tomography angiography might provide more accurate heritability estimates compared to TTE.

• Three-dimensional imaging techniques are needed to reliably quantify aortic root dimensions.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ACDE:

additive genetic, common environment, dominant genetic, unique environment

BMI:

body mass index

CTA:

computed tomography angiography

DZ:

dizygotic twins

ECG:

electrocardiography

ICC:

intraclass correlation

LVOT:

left ventricular outflow tract

MZ:

monozygotic twins

TTE:

transthoracic echocardiography

References

  1. Ho SY (2009) Structure and anatomy of the aortic root. Eur J Echocardiogr 10:i3–i10

    Article  PubMed  Google Scholar 

  2. Isselbacher EM (2005) Thoracic and abdominal aortic aneurysms. Circulation 111:816–828

    Article  PubMed  Google Scholar 

  3. Lebowitz NE, Bella JN, Roman MJ et al (2000) Prevalence and correlates of aortic regurgitation in American Indians: the Strong Heart Study. J Am Coll Cardiol 36:461–467

    Article  CAS  PubMed  Google Scholar 

  4. Roman MJ, Devereux RB, Niles NW et al (1987) Aortic root dilatation as a cause of isolated, severe aortic regurgitation. Prevalence, clinical and echocardiographic patterns, and relation to left ventricular hypertrophy and function. Ann Intern Med 106:800–807

    Article  CAS  PubMed  Google Scholar 

  5. Eisenberg MJ, Rice SA, Paraschos A, Caputo GR, Schiller NB (1993) The clinical spectrum of patients with aneurysms of the ascending aorta. Am Heart J 125:1380–1385

    Article  CAS  PubMed  Google Scholar 

  6. Nicod P, Bloor C, Godfrey M et al (1989) Familial aortic dissecting aneurysm. J Am Coll Cardiol 13:811–819

    Article  CAS  PubMed  Google Scholar 

  7. Bella JN, MacCluer JW, Roman MJ et al (2002) Genetic influences on aortic root size in American Indians: the strong heart study. Arterioscler Thromb Vasc Biol 22:1008–1011

    Article  CAS  PubMed  Google Scholar 

  8. Roman MJ, Devereux RB, Kramer-Fox R, O'Loughlin J (1989) Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 64:507–512

    Article  CAS  PubMed  Google Scholar 

  9. Vasan RS, Larson MG, Levy D (1995) Determinants of echocardiographic aortic root size. The Framingham heart study. Circulation 91:734–740

    Article  CAS  PubMed  Google Scholar 

  10. Lam CS, Xanthakis V, Sullivan LM et al (2010) Aortic root remodeling over the adult life course: longitudinal data from the Framingham heart study. Circulation 122:884–890

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kim M, Roman MJ, Cavallini MC, Schwartz JE, Pickering TG, Devereux RB (1996) Effect of hypertension on aortic root size and prevalence of aortic regurgitation. Hypertension 28:47–52

    Article  CAS  PubMed  Google Scholar 

  12. Covella M, Milan A, Totaro S et al (2014) Echocardiographic aortic root dilatation in hypertensive patients: a systematic review and meta-analysis. J Hypertens 32:1928–1935, discussion 1935

  13. Jin Y, Kuznetsova T, Bochud M et al (2011) Heritability of left ventricular structure and function in Caucasian families. Eur J Echocardiogr 12:326–332

    PubMed  PubMed Central  Google Scholar 

  14. Tzikas A, Schultz CJ, Piazza N et al (2011) Assessment of the aortic annulus by multislice computed tomography, contrast aortography, and trans-thoracic echocardiography in patients referred for transcatheter aortic valve implantation. Catheter Cardiovasc Interv 77:868–875

    Article  PubMed  Google Scholar 

  15. Schuhbaeck A, Achenbach S, Pflederer T et al (2014) Reproducibility of aortic annulus measurements by computed tomography. Eur Radiol 24:1878–1888

    Article  PubMed  Google Scholar 

  16. Lu TL, Huber CH, Rizzo E, Dehmeshki J, von Segesser LK, Qanadli SD (2009) Ascending aorta measurements as assessed by ECG-gated multi-detector computed tomography: a pilot study to establish normative values for transcatheter therapies. Eur Radiol 19:664–669

    Article  PubMed  Google Scholar 

  17. Rixe J, Schuhbaeck A, Liebetrau C et al (2012) Multi-detector computed tomography is equivalent to trans-oesophageal echocardiography for the assessment of the aortic annulus before transcatheter aortic valve implantation. Eur Radiol 22:2662–2669

    Article  PubMed  Google Scholar 

  18. Ocak I, Lacomis JM, Deible CR, Pealer K, Parag Y, Knollmann F (2009) The aortic root: comparison of measurements from ECG-gated CT angiography with transthoracic echocardiography. J Thorac Imaging 24:223–226

    Article  PubMed  Google Scholar 

  19. Maurovich-Horvat P, Tarnoki DL, Tarnoki AD et al (2015) Rationale, design, and methodological aspects of the BUDAPEST-GLOBAL study (burden of atherosclerotic plaques study in twins-genetic loci and the burden of atherosclerotic lesions). Clin Cardiol 38:699–707

    Article  PubMed  Google Scholar 

  20. Littvay L, Metneki J, Tarnoki AD, Tarnoki DL (2013) The Hungarian twin registry. Twin Res Hum Genet 16:185–189

    Article  PubMed  Google Scholar 

  21. Litmanovich D, Zamboni GA, Hauser TH, Lin PJ, Clouse ME, Raptopoulos V (2008) ECG-gated chest CT angiography with 64-MDCT and tri-phasic IV contrast administration regimen in patients with acute non-specific chest pain. Eur Radiol 18:308–317

    Article  PubMed  Google Scholar 

  22. Achenbach S, Delgado V, Hausleiter J, Schoenhagen P, Min JK, Leipsic JA (2012) SCCT expert consensus document on computed tomography imaging before transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR). J Cardiovasc Comput Tomogr 6:366–380

    Article  PubMed  Google Scholar 

  23. Lang RM, Bierig M, Devereux RB et al (2005) Recommendations for chamber quantification: a report from the American Society of echocardiography's guidelines and standards committee and the chamber quantification writing group, developed in conjunction with the European association of echocardiography, a branch of the European society of cardiology. J Am Soc Echocardiogr 18:1440–1463

    Article  PubMed  Google Scholar 

  24. Neale M (1992) Methodology for genetic studies of twins and families. Springer Netherlands, Dordrecht

    Book  Google Scholar 

  25. R Core Team (2015) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  26. Kottner J, Audige L, Brorson S et al (2011) Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were proposed. J Clin Epidemiol 64:96–106

    Article  PubMed  Google Scholar 

  27. Neale MC, Hunter MD, Pritikin JN et al (2015) OpenMx 2.0: extended structural equation and statistical modeling. Psychometrika. doi:10.1007/s11336-014-9435-8

    PubMed  Google Scholar 

  28. Thomas Lumley using Fortran code by Alan Miller (2009) Leaps: regression subset selection. R package version 2.9

  29. Messika-Zeitoun D, Serfaty JM, Brochet E et al (2010) Multimodal assessment of the aortic annulus diameter: implications for transcatheter aortic valve implantation. J Am Coll Cardiol 55:186–194

    Article  PubMed  Google Scholar 

  30. Tops LF, Wood DA, Delgado V et al (2008) Noninvasive evaluation of the aortic root with multislice computed tomography implications for transcatheter aortic valve replacement. JACC Cardiovasc Imaging 1:321–330

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Levente Littvay, PhD, from the Central European University (Budapest, Hungary) for his instrumental help in the statistical analysis. The scientific guarantor of this publication is Pál Maurovich-Horvat MD, PhD, MPH. The authors of this manuscript declare relationships with the following companies: Szilard Voros, MD, is a shareholder in Global Genomics Group, LLC, and receives salary from Global Genomics Group, LLC. This study has received funding by a grant from the EFSD (European Foundation for the Study of Diabetes) New Horizons Program to György Jermendy, MD. Global Genomics Group contributed funding for CT imaging and blood-based biomarker measurements. One of the authors has significant statistical expertise. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, classical twin study, performed at one institution.

Author information

Author notes

    Authors and Affiliations

    1. MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Városmajor St. 68, H-1122, Budapest, Hungary

      Csilla Celeng, Márton Kolossváry, Attila Kovács, Andrea Ágnes Molnár, Bálint Szilveszter, Mihály Károlyi, Ádám L. Jermendy, Júlia Karády, Béla Merkely & Pál Maurovich-Horvat

    2. Department of Hydrodynamic Systems, Budapest University of Technology and Economics, Budapest, Hungary

      Tamás Horváth

    3. Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary

      Ádám D. Tárnoki & Dávid L. Tárnoki

    4. Global Genomics Group, Atlanta, GA, USA

      Szilard Voros

    5. Medical Department, Bajcsy-Zsilinszky Hospital, Budapest, Hungary

      György Jermendy

    Authors
    1. Csilla Celeng
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Márton Kolossváry
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Attila Kovács
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Andrea Ágnes Molnár
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Bálint Szilveszter
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Tamás Horváth
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Mihály Károlyi
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Ádám L. Jermendy
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Ádám D. Tárnoki
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Dávid L. Tárnoki
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Júlia Karády
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Szilard Voros
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. György Jermendy
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Béla Merkely
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. Pál Maurovich-Horvat
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Pál Maurovich-Horvat.

    Additional information

    Béla Merkely and Pál Maurovich-Horvat contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary Table 1

    (DOCX 48 kb)

    Supplementary Table 2

    (DOCX 48 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Celeng, C., Kolossváry, M., Kovács, A. et al. Aortic root dimensions are predominantly determined by genetic factors: a classical twin study. Eur Radiol 27, 2419–2425 (2017). https://doi.org/10.1007/s00330-016-4590-1

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00330-016-4590-1

    Keywords

    Search

    Navigation