Skip to main content
SpringerLink
Log in

Coronary plaque burden in Turner syndrome a coronary computed tomography angiography study

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Turner syndrome (TS) is associated with coronary artery disease (CAD), an important cause of premature death in TS. However, the determinants of CAD in women with TS remain unknown. In a cross-sectional study design, 168 women without clinical evidence of CAD (115 with TS and 53 without TS) were assessed for the presence and volume of subclinical CAD using coronary CT angiography. Karyotype, the presence of congenital heart defects and conventional cardiovascular risk factors were also registered. Comparative analyses were performed (1) between women with and without TS and (2) in the TS group, between women with and without subclinical CAD. The prevalence of CAD, in crude and adjusted analyses, was not increased for women with TS (crude prevalence: 40 [35%] in TS vs. 25 [47%] in controls, p = 0.12). The volume of atherosclerosis was not higher in women with TS compared with controls (median and interquartile range 0 [0–92] in TS vs. 0 [0–81]mm3 in controls, p = 0.29). Among women with TS, women with subclinical CAD were older (46 ± 13 vs. 37 ± 11 years, p < 0.001), had higher blood pressure (systolic blood pressure 129 ± 16 vs. 121 ± 16 mmHg, p < 0.05) and were more frequently diagnosed with type 2 diabetes (5 [13%] vs. 2 [3%], p < 0.05). Karyotype or congenital heart defects were not associated with subclinical CAD. Some women with TS show early signs of CAD, however overall, not more than women without TS. Conventional cardiovascular risk factors were the principal determinants of CAD also in TS, and CAD prevention strategies should be observed.

ClinicalTrial.gov Identifier: NCT01678261 (https://clinicaltrials.gov/ct2/show/NCT01678261)

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
Fig. 4

Similar content being viewed by others

Abbreviations

CAD:

Coronary artery disease

CP:

Calcified plaque

HbA1c:

Hemoglobin A1c

LDL:

Low-density lipoprotein

LDNCP:

Low-density non-calcified plaque

NCP:

Non-calcified plaque

TGF:

Transforming growth factor

TP:

Total plaque

TS:

Turner syndrome

References

  1. Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA, United Kingdom Clinical Cytogenetics (2008) Mortality in women with turner syndrome in Great Britain: a national cohort study. J Clin Endocrinol Metab 93:4735–4742

    Article  CAS  Google Scholar 

  2. Schoepp M, Hannah-Shmouni F, Matta J, Ghanem AM, Hanover JA, Abd-Elmoniem KZ, Gharib AM (2018) Coronary calcification in adults with Turner syndrome. Genet Med 20:664–668

    Article  Google Scholar 

  3. Conroy RM, Pyorala K, Fitzgerald AE, Sans S, Menotti A, De Backer G, De Bacquer D, Ducimetiere P, Jousilahti P, Keil U, Njolstad I, Oganov, Thomsen, Tunstall-Pedoe, Tverdal, Wedel, Whincup, Wilhelmsen, Graham, and group (2003) Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 24:987–1003

    Article  CAS  Google Scholar 

  4. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD et al (2010) Emerging risk factors diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222

    Article  CAS  Google Scholar 

  5. Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, International Turner Syndrome Consensus (2017) Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 177:G1–G70

    Article  CAS  Google Scholar 

  6. Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt C (2006) Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 91:3897–3902

    Article  CAS  Google Scholar 

  7. El-Mansoury M, Barrenas ML, Bryman I, Hanson C, Larsson C, Wilhelmsen L, Landin-Wilhelmsen K (2007) Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome. Clin Endocrinol (Oxf) 66:744–751

    Article  CAS  Google Scholar 

  8. Viuff MH, Trolle C, Wen J, Jensen JM, Norgaard BL, Gutmark EJ, Gutmark-Little I, Mortensen KH, Gravholt CH, Andersen NH (2016) Coronary artery anomalies in Turner Syndrome. J Cardiovasc Comput Tomogr 10:480–484

    Article  Google Scholar 

  9. Thunstrom S, Krantz E, Thunstrom E, Hanson C, Bryman I, Landin-Wilhelmsen K (2019) Incidence of aortic dissection in Turner syndrome. Circulation 139:2802–2804

    Article  Google Scholar 

  10. Koenraadt WM, Siebelink HM, Bartelings MM, Schalij MJ, van der Vlugt MJ, van den Bosch AE, Budde RP, Roos-Hesselink JW, Duijnhouwer AL, van den Hoven AT, DeRuiter MC (2019) Coronary anatomy in Turner syndrome versus patients with isolated bicuspid aortic valves. Heart 105:701–707

    Article  Google Scholar 

  11. Pasquino AM, Passeri F, Pucarelli I, Segni M, Municchi G, Italian Study Group for Turner's Syndrome (1997) Spontaneous pubertal development in Turner's syndrome. J Clin Endocrinol Metab 82:1810–1813

    CAS  PubMed  Google Scholar 

  12. Lobo RA, Pickar JH, Stevenson JC, Mack WJ, Hodis HN (2016) Back to the future: Hormone replacement therapy as part of a prevention strategy for women at the onset of menopause. Atherosclerosis 254:282–290

    Article  CAS  Google Scholar 

  13. Davis SM, Geffner ME (2019) Cardiometabolic health in Turner syndrome. Am J Med Genet C Semin Med Genet 181:52–58

    Article  Google Scholar 

  14. Hjerrild BE, Mortensen KH, Sorensen KE, Pedersen EM, Andersen NH, Lundorf E, Hansen KW, Horlyck A, Hager A, Christiansen JS, Gravholt CH (2010) Thoracic aortopathy in Turner syndrome and the influence of bicuspid aortic valves and blood pressure: a CMR study. J Cardiovasc Magn Reson 12:12

    Article  Google Scholar 

  15. Mortensen KH, Hjerrild BE, Stochholm K, Andersen NH, Sorensen KE, Lundorf E, Horlyck A, Pedersen EM, Christiansen JS, Gravholt CH (2011) Dilation of the ascending aorta in Turner syndrome—a prospective cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 13:24

    Article  Google Scholar 

  16. Funck KL, Laugesen E, Ovrehus K, Jensen JM, Norgaard BL, Dey D, Hansen TK, Poulsen PL (2017) Increased high-risk coronary plaque burden is associated with arterial stiffness in patients with type 2 diabetes without clinical signs of coronary artery disease: a computed tomography angiography study. J Hypertens 35:1235–1243

    Article  CAS  Google Scholar 

  17. Raff GL, Abidov A, Achenbach S, Berman DS, Boxt LM, Budoff MJ, Cheng V, DeFrance T, Hellinger JC, Karlsberg RP (2009) SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 3:122–136

    Article  Google Scholar 

  18. Dey D, Cheng VY, Slomka PJ, Nakazato R, Ramesh A, Gurudevan S, Germano G, Berman DS (2009) Automated 3-dimensional quantification of noncalcified and calcified coronary plaque from coronary CT angiography. J Cardiovasc Comput Tomogr 3:372–382

    Article  Google Scholar 

  19. Perez-Pomares JM, de la Pompa JL, Franco D, Henderson D, Ho SY, Houyel L, Kelly RG, Sedmera D, Sheppard M, Sperling S, Thiene G et al (2016) Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology–a position statement of the development, anatomy, and pathology ESC Working Group. Cardiovasc Res 109:204–216

    Article  CAS  Google Scholar 

  20. Belotti F (2015) twopm: Two-part models. Stata J 15:3–20

    Article  Google Scholar 

  21. Jansen H, Samani NJ, Schunkert H (2014) Mendelian randomization studies in coronary artery disease. Eur Heart J 35:1917–1924

    Article  CAS  Google Scholar 

  22. Freriks K, Timmers HJ, Netea-Maier RT, Beerendonk CC, Otten BJ, Traas MA, Mieloo H, van de Zande GW, Hoefsloot LH, Hermus AR, Smeets DF (2013) Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome. Eur J Med Genet 56:497–501

    Article  Google Scholar 

  23. Mortensen KH, Andersen NH, Gravholt CH (2012) Cardiovascular phenotype in Turner syndrome–integrating cardiology, genetics, and endocrinology. Endocr Rev 33:677–714

    Article  CAS  Google Scholar 

  24. Boudoulas KD, Wolfe B, Ravi Y, Lilly S, Nagaraja HN, Sai-Sudhakar CB (2015) The aortic stenosis complex: aortic valve, atherosclerosis, aortopathy. J Cardiol 65:377–382

    Article  Google Scholar 

  25. Viuff MH, Berglund A, Juul S, Andersen NH, Stochholm K, Gravholt CH (2020) Sex hormone replacement therapy in Turner syndrome: impact on morbidity and mortality. J Clin Endocrinol Metab 105:468–478

    Article  Google Scholar 

  26. Cho I, Al'Aref SJ, Berger A, Ó Hartaigh B, Gransar H, Valenti V, Lin FY, Achenbach S, Berman DS, Budoff MJ, Callister TQ et al (2018) Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study. Eur Heart J 39:934–941

    Article  Google Scholar 

  27. Deseive S, Straub R, Kupke M, Broersen A, Kitslaar PH, Stocker TJ, Massberg S, Hadamitzky M, Hausleiter J (2019) Impact of diabetes on coronary artery plaque volume by coronary CT angiography and subsequent adverse cardiac events. J Cardiovasc Comput Tomogr 13:31–37

    Article  Google Scholar 

  28. Muhlestein JB, Lappe DL, Lima JA, Rosen BD, May HT, Knight S, Bluemke BA, Towner SR, Le V, Bair TL, Vavere AL (2014) Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA 312:2234–2243

    Article  CAS  Google Scholar 

  29. Johnson B, Buelow M, Earing M, Cohen S, Bartz P, Ginde S (2019) Coronary artery disease screening in adults with congenital heart disease prior to cardiac surgery. Congenit Heart Dis 14:895–900

    Article  Google Scholar 

Download references

Acknowledgements

Claus H. Gravholt is a member of the European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Project ID number 739543.

Funding

Anthonie Duijnhouwer, Lidia Bons and Jolien Roos-Hesselink received a grant from the Netherlands Heart Foundation (Grant number NHS 2013T093). Claus H. Gravholt received grants from the Novo Nordisk Foundation (Grant agreement NNF13OC0003234 and NNF15OC0016474).

Author information

Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 99, 8200, Aarhus N, Denmark

    Kristian L. Funck, Mette H. Viuff, Jan Wen & Claus H. Gravholt

  2. Diagnostic Center, Regional Hospital Central Jutland, Silkeborg, Denmark

    Kristian L. Funck

  3. Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands

    Ricardo P. J. Budde

  4. Department of Cardiology, Aarhus University Hospital, Århus, Denmark

    Jesper M. Jensen & Bjarne L. Nørgaard

  5. Department of Cardiology, Erasmus MC, Erasmus University, Rotterdam, The Netherlands

    Lidia R. Bons & Jolien W. Roos-Hesselink

  6. Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands

    Anthonie L. Duijnhouwer

  7. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA, USA

    Damini Dey

  8. Centre for Cardiovascular Imaging Department, Cardiorespiratory Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK

    Kristian H. Mortensen

  9. Department of Cardiology, Odense University Hospital, Odense, Denmark

    Niels H. Andersen

  10. Department of Molecular Medicine, Aarhus University Hospital, Århus, Denmark

    Claus H. Gravholt

Authors
  1. Kristian L. Funck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ricardo P. J. Budde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mette H. Viuff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesper M. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bjarne L. Nørgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lidia R. Bons
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anthonie L. Duijnhouwer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Damini Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kristian H. Mortensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Niels H. Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jolien W. Roos-Hesselink
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Claus H. Gravholt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KLF: formal analysis, methodology, software, visualization, roles/writing—original draft; RPJB: project administration; resources, supervision, writing—review and editing; MHV: investigation, project administration, writing—review and editing; JW: investigation, project administration, writing—review and editing; JMJ: methodology, writing—review and editing; BLN: methodology, writing—review and editing; LRB: investigation, funding acquisition, project administration, writing—review and editing; ALD: project administration; resources, supervision, writing—review and editing; DD: methodology, software, writing—review and editing; KHM: methodology, writing—review and editing; NHA: methodology, writing—review and editing; JWRH: project administration; resources, supervision, writing—review and editing; CHG: project administration; resources, supervision, writing—original draft.

Corresponding author

Correspondence to Kristian L. Funck.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Funck, K.L., Budde, R.P.J., Viuff, M.H. et al. Coronary plaque burden in Turner syndrome a coronary computed tomography angiography study. Heart Vessels 36, 14–23 (2021). https://doi.org/10.1007/s00380-020-01660-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-020-01660-7

Keywords

Search

Navigation