Top

Published in:

Open Access 01-12-2020 | Ehlers-Danlos Syndrome | Research article

Increased augmentation index in patients with Ehlers-Danlos syndrome

Authors: Maurice Roeder, Sira Thiel, Frederic Baumann, Noriane A. Sievi, Marianne Rohrbach, Malcolm Kohler, Thomas Gaisl

Published in: BMC Cardiovascular Disorders | Issue 1/2020

Abstract

Background

Ehlers-Danlos Syndrome (EDS) comprises a heterogeneous group of diseases characterized by joint hypermobility, connective tissue friability, and vascular fragility. Reliable prognostic factors predicting vascular disease progression (e.g. arterial aneurysms, dissections, and ruptures) in EDS patients are still missing. Recently, applanation tonometry derived augmentation index (AIx), an indirect marker of arterial stiffness, has shown to be positively associated with progression of aortic disease in Marfan syndrome. In this study, we assessed aortic AIx in patients with EDS and matched healthy controls.

Methods

We performed noninvasive applanation tonometry in 61 adults with EDS (43 women and 18 men aged 39.3 ± 14.6 years) and 61 age-, gender-, height-, and weight-matched healthy controls. Radial artery pulse waveforms were recorded and analyzed using the SphygmoCor System (AtCor Medical, Sydney, NSW, Australia). Calculated AIx was adjusted to a heart rate of 75/min. Groups were compared and association between AIx and EDS was determined by univariate and multivariate regression analysis.

Results

EDS patients were categorized in classical type EDS (34%), hypermobile type EDS (43%), vascular type EDS (5%), or remained unassignable (18%) due to overlapping features. EDS patients showed a significantly increased aortic AIx compared to healthy controls (22.8% ± 10.1 vs 14.8% ± 14.0, p < 0.001). EDS showed a positive association with AIx; independent of age, sex, height, blood pressure, medication, and pack years of smoking.

Conclusions

Patients with EDS showed elevated AIx, indicating increased arterial stiffness when compared to healthy controls. Further investigations are needed in order to assess the prognostic value of increased AIx for cardiovascular outcomes in patients with EDS.

Genetic Home Reference, https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome#statistics, accessed on 04 August 2020.

Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C: Semin Med Genet. 2017;175(1):8–26.

Malfait F. Vascular aspects of the Ehlers-Danlos Syndromes. Matrix Biol. 2018;71–72:380–95.PubMed

Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Gene Med. 2014;16(12):881–8.

Brooke BS, Arnaoutakis G, McDonnell NB, Black JH 3rd. Contemporary management of vascular complications associated with Ehlers-Danlos syndrome. J Vasc Surg. 2010;51(1):131–8 discussion 8-9.PubMed

Geisbusch P, Kotelis D, von Tengg-Kobligk H, Hyhlik-Durr A, Allenberg JR, Bockler D. Thoracic aortic endografting in patients with connective tissue diseases. J Endovasc Ther. 2008;15(2):144–9.PubMed

Mortani Barbosa EJ, Jr., Pyeritz RE, Litt H, Desjardins B. Vascular Ehlers-Danlos syndrome presenting as rapidly progressive multiple arterial aneurysms and dissections. Am J Med Gene A. 2011;155a(12):3090–4.

Shalhub S, Black JH 3rd, Cecchi AC, Xu Z, Griswold BF, Safi HJ, et al. Molecular diagnosis in vascular Ehlers-Danlos syndrome predicts pattern of arterial involvement and outcomes. J Vasc Surg. 2014;60(1):160–9.PubMedPubMedCentral

Lum YW, Brooke BS, Black JH 3rd. Contemporary management of vascular Ehlers-Danlos syndrome. Curr Opin Cardiol. 2011;26(6):494–501.PubMed

10.

Nürnberger J, Keflioglu-Scheiber A, Opazo Saez AM, Wenzel RR, Philipp T, Schäfers RF. Augmentation index is associated with cardiovascular risk. J Hypertens. 2002;20(12):2407–14.PubMed

11.

Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588–605.PubMed

12.

Mortensen K, Aydin MA, Rybczynski M, Baulmann J, Schahidi NA, Kean G, et al. Augmentation index relates to progression of aortic disease in adults with Marfan syndrome. Am J Hypertens. 2009;22(9):971–9.PubMed

13.

Payne RA, Hilling-Smith RC, Webb DJ, Maxwell SR, Denvir MA. Augmentation index assessed by applanation tonometry is elevated in Marfan Syndrome. J Cardiothorac Surg. 2007;2:43.PubMedPubMedCentral

14.

Gaisl T, Giunta C, Bratton DJ, Sutherland K, Schlatzer C, Sievi N, et al. Obstructive sleep apnoea and quality of life in Ehlers-Danlos syndrome: a parallel cohort study. Thorax. 2017;72(8):729–35.PubMed

15.

Steinmann B, Royce PM, Superti-Furga A. The Ehlers-Danlos Syndrome. In: Steinmann B, Royce PM. Connective Tissue and its Heritable Disorders, 2002, p. 431–523.

16.

Grahame R, Bird HA, Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J Rheumatol. 2000;27(7):1777–9.PubMed

17.

Giunta C, Randolph A, Al-Gazali LI, Brunner HG, Kraenzlin ME, Steinmann B. Nevo syndrome is allelic to the kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VIA). Am J Med Gene A. 2005;133a(2):158–64.

18.

Pasquali M, Dembure PP, Still MJ, Elsas LJ. Urinary pyridinium cross-links: a noninvasive diagnostic test for Ehlers-Danlos syndrome type VI. N Engl J Med. 1994;331(2):132–3.PubMed

19.

Steinmann B, Eyre DR, Shao P. Urinary pyridinoline cross-links in Ehlers-Danlos syndrome type VI. Am J Hum Genet. 1995;57(6):1505–8.PubMedPubMedCentral

20.

Pauca Alfredo L, O’Rourke Michael F, Kon ND. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001;38(4):932–7.

21.

Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ. The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol. 2000;525(Pt 1):263–70.PubMedPubMedCentral

22.

Wilkinson IB, Mohammad NH, Tyrrell S, Hall IR, Webb DJ, Paul VE, et al. Heart rate dependency of pulse pressure amplification and arterial stiffness. Am J Hypertens. 2002;15(1 Pt 1):24–30.PubMed

23.

Cohen J. Applied multiple regression correlation analysis for the behavioral sciences. 3rd ed. Mahwah: Erlbaum; 2003. p. 703.

24.

Cohen JW. Statistical power analysis for the behavioral sciences. Second Edition, reprinted 2009 ed. New York: Psychology Press; 1988. XXI, 567 Seiten p.

25.

O'Rourke MF, Mancia G. Arterial stiffness. J Hypertens. 1999;17(1):1–4.PubMed

26.

O'Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE. Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens. 2002;15(5):426–44.PubMed

27.

Janner JH, Godtfredsen NS, Ladelund S, Vestbo J, Prescott E. Aortic augmentation index: reference values in a large unselected population by means of the SphygmoCor device. Am J Hypertens. 2010;23(2):180–5.PubMed

28.

Matsui Y, Kario K, Ishikawa J, Eguchi K, Hoshide S, Shimada K. Reproducibility of arterial stiffness indices (pulse wave velocity and augmentation index) simultaneously assessed by automated pulse wave analysis and their associated risk factors in essential hypertensive patients. Hypertens Res. 2004;27(11):851–7.PubMed

29.

O'Rourke MF, Adji A. An updated clinical primer on large artery mechanics: implications of pulse waveform analysis and arterial tonometry. Curr Opin Cardiol. 2005;20(4):275–81.PubMed

30.

Rehill N, Beck CR, Yeo KR, Yeo WW. The effect of chronic tobacco smoking on arterial stiffness. Br J Clin Pharmacol. 2006;61(6):767–73.PubMedPubMedCentral

31.

Cheng JL, Au JS, Guzman JC, Morillo CA, MacDonald MJ. Cardiovascular profile in postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome type III. Clin Auton Res. 2017;27(2):113–6.PubMed

32.

Merlocco A, Lacro RV, Gauvreau K, Rabideau N, Singh MN, Prakash A. Longitudinal changes in segmental aortic stiffness determined by cardiac magnetic resonance in children and young adults with connective tissue disorders (the Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes, and nonspecific connective tissue disorders). Am J Cardiol. 2017;120(7):1214–9.PubMed

33.

Mirault T, Pernot M, Frank M, Couade M, Niarra R, Azizi M, et al. Carotid stiffness change over the cardiac cycle by ultrafast ultrasound imaging in healthy volunteers and vascular Ehlers-Danlos syndrome. J Hypertens. 2015;33(9):1890–6 discussion 6.PubMed

34.

Sonesson B, Hansen F, Länne T. The mechanical properties of elastic arteries in Ehlers-Danlos syndrome. Eur J Vasc Endovasc Surg. 1997;14(4):258–64.PubMed

35.

Miller AJ, Schubart JR, Sheehan T, Bascom R, Francomano CA. Arterial elasticity in Ehlers-Danlos syndromes. Genes. 2020;11(1):55.PubMedCentral

36.

Callewaert B, Malfait F, Loeys B, De Paepe A. Ehlers-Danlos syndromes and Marfan syndrome. Best Pract Res Clin Rheumatol. 2008;22(1):165–89.PubMed

37.

Bascom R, Schubart JR, Mills S, Smith T, Zukley LM, Francomano CA, et al. Heritable disorders of connective tissue: description of a data repository and initial cohort characterization. Am J Med Genet A. 2019;179(4):552–60.PubMedPubMedCentral

38.

Nichols WW ORM. McDonald’s blood flow in arteries. 1990.

39.

Bank AJ, Kaiser DR, Rajala S, Cheng A. In vivo human brachial artery elastic mechanics: effects of smooth muscle relaxation. Circulation. 1999;100(1):41–7.PubMed

40.

Bank Alan J, Wang H, Holte James E, Mullen K, Shammas R, Kubo SH. Contribution of collagen, elastin, and smooth muscle to in vivo human brachial Artery Wall stress and elastic modulus. Circulation. 1996;94(12):3263–70.

41.

Boutouyrie P, Lacolley P, Briet M, Regnault V, Stanton A, Laurent S, et al. Pharmacological modulation of arterial stiffness. Drugs. 2011;71(13):1689–701.PubMed

42.

Stewart AD, Millasseau SC, Kearney MT, Ritter JM, Chowienczyk PJ. Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans. Hypertension. 2003;42(5):915–8.PubMed

43.

Milewicz DM, Reid AJ, Cecchi AC. Vascular Ehlers-Danlos syndrome: exploring the role of inflammation in arterial disease. Circ Cardiovasc Genet. 2014;7(1):5–7.PubMedPubMedCentral

44.

De Wandele I, Rombaut L, Leybaert L, Van de Borne P, De Backer T, Malfait F, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Semin Arthritis Rheum. 2014;44(1):93–100.PubMed

45.

Benetos A, Laurent S, Hoeks AP, Boutouyrie PH, Safar ME. Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries. Arterioscler Thromb. 1993;13(1):90–7.PubMed

46.

Resnick LM, Militianu D, Cunnings AJ, Pipe JG, Evelhoch JL, Soulen RL. Direct magnetic resonance determination of aortic distensibility in essential hypertension: relation to age, abdominal visceral fat, and in situ intracellular free magnesium. Hypertension. 1997;30(3 Pt 2):654–9.PubMed

47.

Boutouyrie P, Germain DP, Fiessinger JN, Laloux B, Perdu J, Laurent S. Increased carotid wall stress in vascular Ehlers-Danlos syndrome. Circulation. 2004;109(12):1530–5.PubMed

48.

Shingu Y, Shiiya N, Ooka T, Tachibana T, Kubota S, Morita S, et al. Augmentation index is elevated in aortic aneurysm and dissection. Ann Thorac Surg. 2009;87(5):1373–7.PubMed

49.

Rombaut L, Malfait F, Cools A, De Paepe A, Calders P. Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers-Danlos syndrome hypermobility type. Disabil Rehabil. 2010;32(16):1339–45.PubMed

50.

Park W, Park H-Y, Lim K, Park J. The role of habitual physical activity on arterial stiffness in elderly individuals: a systematic review and meta-analysis. J Exerc Nutrition Biochem. 2017;21(4):16–21.PubMedPubMedCentral

51.

Sievi NA, Franzen D, Kohler M, Clarenbach CF. Physical inactivity and arterial stiffness in COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:1891–7.PubMedPubMedCentral

52.

Ong K-T, Perdu J, De Backer J, Bozec E, Collignon P, Emmerich J, et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet. 2010;376(9751):1476–84.PubMed

53.

Morissette R, Schoenhoff F, Xu Z, Shilane DA, Griswold BF, Chen W, et al. Transforming growth factor-beta and inflammation in vascular (type IV) Ehlers-Danlos syndrome. Circ Cardiovasc Genet. 2014;7(1):80–8.PubMed

54.

Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352(6333):337–9.PubMed

55.

Murdoch JL, Walker BA, Halpern BL, Kuzma JW, McKusick VA. Life expectancy and causes of death in the Marfan syndrome. N Engl J Med. 1972;286(15):804–8.PubMed

Title: Increased augmentation index in patients with Ehlers-Danlos syndrome
Authors: Maurice Roeder
Sira Thiel
Frederic Baumann
Noriane A. Sievi
Marianne Rohrbach
Malcolm Kohler
Thomas Gaisl
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Ehlers-Danlos Syndrome
Marfan Syndrome
Measurement of Intraocular Pressure
Published in: BMC Cardiovascular Disorders / Issue 1/2020
Electronic ISSN: 1471-2261
DOI: https://doi.org/10.1186/s12872-020-01684-x

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Increased augmentation index in patients with Ehlers-Danlos syndrome

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Procedural sedation for direct current cardioversion: a feasibility study between two management strategies in the emergency department

The COngenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry: a descriptive study from single-center hospital registry of adult congenital heart disease and pulmonary hypertension in Indonesia

Quantification of myocardial strain in patients with isolated left ventricular non-compaction and healthy subjects using deformable registration algorithm: comparison with feature tracking

Efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in treating ST-segment elevation myocardial infarction patients: a randomized, controlled study

Postoperative supraventricular tachycardia and polymorphic ventricular tachycardia due to a novel SCN5A variant: a case report of a rare comorbidity that is difficult to diagnose

Higher fatty liver index is associated with increased risk of new onset heart failure in healthy adults: a nationwide population-based study in Korea

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page