Skip to main content

Advertisement

Log in

Increased epicardial adipose tissue thickness correlates with endothelial dysfunction in spondyloarthritis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Introduction

We aimed to investigate the relationship between epicardial adipose tissue (EAT) thickness, flow-mediated dilation (FMD), and carotid intima-media thickness (cIMT) in spondyloarthritis (SpA) patients compared to healthy controls.

Methods

We performed a cross-sectional study including SpA patients aged ≤ 50 years without traditional cardiovascular risk factors and healthy controls matched for age and gender. Baseline characteristics, laboratory data, and SpA-related parameters were recorded. All participants underwent ultrasound examination with measurement of EAT thickness, FMD, and cIMT by both an experienced cardiologist and radiologist blinded to clinical data. The relationships between the ultrasound measurements were analyzed using Spearman’s correlation coefficient and Person correlation.

Results

The study included 94 subjects (47 SpA and 47 healthy controls). The sex-ratio was 2.35; the median age of patients was 36 years (IQR: 28–46), and the median disease duration was 11 years (IQR: 5–16). Compared to the control group, SpA patients had significantly higher values of EAT thickness (p = 0.001) and cIMT (p < 0.0001). FMD values were significantly lower in SpA patients compared to controls (p = 0.008). The univariate analysis detected a significant negative association between EAT thickness and FMD (p = 0.026; r =  − 0.325), and between left cIMT and FMD (p = 0.027; r =  − 0.322). No association was found between EAT thickness and cIMT.

Conclusion

EAT thickness, FMD, and cIMT were significantly impaired in SpA patients compared with healthy controls supporting evidence of accelerated atherosclerosis in SpA. EAT thickness was correlated to endothelial dysfunction suggesting the role of EAT in predicting the early reversible stages of atherosclerosis.

Key Points

Spondyloarthritis is associated with impaired subclinical atherosclerosis markers accurately increased epicardial fat and carotid intima-media thickness and endothelial dysfunction.

Increased epicardial fat thickness is correlated with impaired endothelial function in spondyloarthritis patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Peters MJ, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT (2004) Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum 34:585–592. https://doi.org/10.1016/j.semarthrit.2004.07.010

    Article  PubMed  Google Scholar 

  2. Łosińska K, Korkosz M, Kwaśny-Krochin B (2019) Endothelial dysfunction in patients with ankylosing spondylitis. Reumatologia/Rheumatology 57:100–105. https://doi.org/10.5114/reum.2019.84815

    Article  PubMed  Google Scholar 

  3. Kerekes G, Soltész P, Nurmohamed MT, Gonzalez-Gay MA, Turiel M, Végh E, Shoenfeld Y, McInnes I, Szekanecz Z (2012) Validated methods for assessment of subclinical atherosclerosis in rheumatology. Nat Rev Rheumatol 8:224–234. https://doi.org/10.1038/nrrheum.2012.16

    Article  CAS  PubMed  Google Scholar 

  4. Moroni L, Selmi C, Angelini C, Meroni PL (2017) Evaluation of endothelial function by flow-mediated dilation: a comprehensive review in rheumatic disease. Arch Immunol Ther Exp (Warsz) 65:463–475. https://doi.org/10.1007/s00005-017-0465-7

    Article  Google Scholar 

  5. Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M (2013) Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 33:1077–1084. https://doi.org/10.1161/ATVBAHA.112.300829

    Article  CAS  PubMed  Google Scholar 

  6. Marchington JM, Mattacks CA, Pond CM (1989) Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties. Comp Biochem Physiol B 94:225–232. https://doi.org/10.1016/0305-0491(89)90337-4

    Article  CAS  PubMed  Google Scholar 

  7. Ansari MA, Mohebati M, Poursadegh F, Foroughian M, Shamloo AS (2018) Is echocardiographic epicardial fat thickness increased in patients with coronary artery disease? A systematic review and meta-analysis. Electron Physician 10:7249–7258. https://doi.org/10.19082/7249

    Article  PubMed  PubMed Central  Google Scholar 

  8. Resorlu H, Akbal A, Resorlu M, Gokmen F, Ates C, Uysal F, Adam G, Aylanc N, Arslan M, İnceer BS (2015) Epicardial adipose tissue thickness in patients with ankylosing spondylitis. Clin Rheumatol 34:295–299. https://doi.org/10.1007/s10067-014-2568-4

    Article  PubMed  Google Scholar 

  9. Surucu GD, Yildirim A, Yetisgin A, Akturk E (2019) Epicardial adipose tissue thickness as a new risk factor for atherosclerosis in patients with ankylosing spondylitis. J Back Musculoskelet Rehabil 32:237–243. https://doi.org/10.3233/BMR-160650

    Article  PubMed  Google Scholar 

  10. Iacobellis G, Willens HJ (2009) Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr 22:1311–1319; quiz 1417–8. https://doi.org/10.1016/j.echo.2009.10.013

    Article  PubMed  Google Scholar 

  11. Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, Green DJ, Ghiadoni L (2019) Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J 40:2534–2547. https://doi.org/10.1093/eurheartj/ehz350

    Article  PubMed  Google Scholar 

  12. Choi H, Uceda DE, Dey AK, Mehta NN (2019) Application of Non-invasive Imaging in Inflammatory Disease Conditions to Evaluate Subclinical Coronary Artery Disease. Curr Rheumatol Rep 22:1. https://doi.org/10.1007/s11926-019-0875-0

    Article  CAS  PubMed  Google Scholar 

  13. Demir K, Avcı A, Ergulu Esmen S, Tuncez A, Yalcın MU, Yılmaz A, Altunkeser BB (2021) Assessment of arterial stiffness and epicardial adipose tissue thickness in predicting the subclinical atherosclerosis in patients with ankylosing spondylitis. Clin Exp Hypertens 43:169–174. https://doi.org/10.1080/10641963.2020.1833025

    Article  PubMed  Google Scholar 

  14. Çağlar SO, Boyraz İ, Erdem F, Yazici S, Çağlar H, Koç B, Çağlar E, Yazici M (2016) Evaluation of Atrial Conduction Times, Epicardial Fat Thickness and Carotid Intima-Media Thickness in Patients With Ankylosing Spondylitis. Arch Rheumatol 31:353–358. https://doi.org/10.5606/ArchRheumatol.2016.5867

    Article  PubMed  PubMed Central  Google Scholar 

  15. Büyükterzi Z, Alpaydin MS, Akkurt HE, Yilmaz H (2019) Epicardial adipose tissue thickness is associated with disease severity in patients with newly- diagnosed ankylosing spondylitis. Kocaeli Med J 8:97–103. https://doi.org/10.5505/ktd.2019.80037

    Article  Google Scholar 

  16. Üstün N, Kurt M, Atci N, Yağiz E, Güler H, Turhanoğlu A (2014) Increased epicardial fat tissue is a marker of subclinic atherosclerosis in ankylosing spondylitis. Arch Rheumatol 29:267–272. https://doi.org/10.5606/ArchRheumatol.2014.4606

    Article  Google Scholar 

  17. Boyraz I, Caglar S, Erdem F, Yazici M, Yazici S, Koc B, Gunduz R, Karakoyun A (2016) Assessment of relation between neutrophil lympocyte, platelet lympocyte ratios and epicardial fat thickness in patients with ankylosing spondylitis. Med Glas (Zenica) 13:14–17. https://doi.org/10.17392/832-16

    Article  Google Scholar 

  18. Öz A, Coşkun H, Çınar T, Efe SÇ, Öz N, Ayça B, Karabağ T, Aytekin E (2020) Evaluation of atrial conduction times and epicardial adipose Ttssue thickness in patients with ankylosing spondylitis. Istanb Med J 21:430–435. https://doi.org/10.4274/imj.galenos.2020.35002

    Article  Google Scholar 

  19. Bai R, Zhang Y, Liu W, Ma C, Chen X, Yang J, Sun D (2019) The relationship of ankylosing spondylitis and subclinical atherosclerosis: a systemic review and meta-analysis. Angiology 70:492–500. https://doi.org/10.1177/0003319718814309

    Article  PubMed  Google Scholar 

  20. Cure E, Icli A, Uslu AU, Sakiz D, Cure MC, Baykara RA, Yavuz F, Arslan S, Kucuk A (2018) Atherogenic index of plasma: a useful marker for subclinical atherosclerosis in ankylosing spondylitis: AIP associate with cIMT in AS. Clin Rheumatol 37:1273–1280. https://doi.org/10.1007/s10067-018-4027-0

    Article  PubMed  Google Scholar 

  21. Serdaroğlu Beyazal M, Erdoğan T, Türkyılmaz AK, Devrimsel G, Cüre MC, Beyazal M, Sahin I (2016) Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis. Clin Rheumatol 35:2235–2241. https://doi.org/10.1007/s10067-016-3198-9

    Article  PubMed  Google Scholar 

  22. Hamdi W, Chelli BM, Zouch I, Ghannouchi MM, Haouel M, Ladeb MF, Kchir MM (2012) Assessment of preclinical atherosclerosis in patients with ankylosing spondylitis. J Rheumatol 39:322–326. https://doi.org/10.3899/jrheum.110792

    Article  CAS  PubMed  Google Scholar 

  23. Bodnár N, Kerekes G, Seres I, Paragh G, Kappelmayer J, Némethné ZG, Szegedi G, Shoenfeld Y, Sipka S, Soltész P, Szekanecz Z, Szántó S (2011) Assessment of subclinical vascular disease associated with ankylosing spondylitis. J Rheumatol 38:723–729. https://doi.org/10.3899/jrheum.100668

    Article  PubMed  Google Scholar 

  24. Verma I, Syngle A, Krishan P, Garg N (2017) Endothelial progenitor cells as a marker of endothelial dysfunction and atherosclerosis in ankylosing spondylitis: a cross-sectional study. Int J Angiol 26:36–42. https://doi.org/10.1055/s-0036-1593445

    Article  PubMed  Google Scholar 

  25. Sari I, Okan T, Akar S, Cece H, Altay C, Secil M, Birlik M, Onen F, Akkoc N (2006) Impaired endothelial function in patients with ankylosing spondylitis. Rheumatology 45:283–286. https://doi.org/10.1093/rheumatology/kei145

    Article  CAS  PubMed  Google Scholar 

  26. Aydın H, Toprak A, Deyneli O, Yazıcı D, Tarçın Ö, Sancak S, Yavuz D, Akalin S (2010) Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome. Metab Syndr Relat Disord 8:229–234. https://doi.org/10.1089/met.2009.0080

    Article  PubMed  Google Scholar 

  27. Aslan AN, Keleş T, Ayhan H, Kasapkara HA, Akçay M, Durmaz T, Sarı C, Baştuğ S, Çakır B, Bozkurt E (2015) The relationship between epicardial fat thickness and endothelial dysfunction in type I diabetes mellitus. Echocardiography 32:1745–1753. https://doi.org/10.1111/echo.12960

    Article  PubMed  Google Scholar 

  28. Temiz A, Gökmen F, Gazi E, Akbal A, Barutçu A, Bekler A, Altun B, Tan YZ, Güneş F, Şen H (2015) Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and carotid intima-media thickness: associations in rheumatoid arthritis patients. Herz 40:217–224. https://doi.org/10.1007/s00059-014-4140-z

    Article  PubMed  Google Scholar 

  29. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Blat LS, Brien SO, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y (2003) Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 108:2460–2466. https://doi.org/10.1161/01.CIR.0000099542.57313.C5

    Article  PubMed  Google Scholar 

  30. Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY, Yoon MH, Hwang GS, Tahk SJ, Shin JH (2008) Relationship of epicardial adipose tissue by echocardiography to coronary artery disease. Heart 94:e7. https://doi.org/10.1136/hrt.2007.118471

    Article  PubMed  Google Scholar 

  31. Tachibana M, Miyoshi T, Osawa K, Toh N, Oe H, Nakamura K, Naito T, Sato S, Kanazawa S, Ito H (2016) Measurement of epicardial fat thickness by transthoracic echocardiography for predicting high-risk coronary artery plaques. Heart Vessels 31:1758–1766. https://doi.org/10.1007/s00380-016-0802-5

    Article  PubMed  Google Scholar 

  32. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE (1994) Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 24:1468–1474. https://doi.org/10.1016/0735-1097(94)90141-4

    Article  CAS  PubMed  Google Scholar 

  33. Lakshmanan S, Shekar C, Kinninger A, Birudaraju D, Dahal S, Onuegbu A, Cherukuri L, Hamal S, Flores F, Dailing C, Roy SK, Budoff M (2020) Association of flow mediated vasodilation and burden of subclinical atherosclerosis by coronary CTA. Atherosclerosis 302:15–19. https://doi.org/10.1016/j.atherosclerosis.2020.04.009

    Article  CAS  PubMed  Google Scholar 

  34. Tan KCB, Xu A, Chow WS, Lam MCW, Ai VHG, Tam SCF, Lam KSL (2004) Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 89:765–769. https://doi.org/10.1210/jc.2003-031012

    Article  CAS  PubMed  Google Scholar 

  35. Dick GM, Katz PS, Farias M, Morris M, James J, Knudson JD, Tune JD (2006) Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation. Am J Physiol Heart Circ Physiol 291:H2997-3002. https://doi.org/10.1152/ajpheart.01035.2005

    Article  CAS  PubMed  Google Scholar 

  36. Karastergiou K, Evans I, Ogston N, Miheisi N, Nair D, Kaski JC, Jahangiri M, Vidya MA (2010) Epicardial adipokines in obesity and coronary artery disease induce atherogenic changes in monocytes and endothelial cells. Arterioscler Thromb Vasc Biol 30:1340–1346. https://doi.org/10.1161/ATVBAHA.110.204719

    Article  CAS  PubMed  Google Scholar 

  37. Zhang C (2008) The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol 103:398–406. https://doi.org/10.1007/s00395-008-0733-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Picchi A, Gao X, Belmadani S, Potter BJ, Focardi M, Chilian WM, Zhang C (2006) Tumor necrosis factor-α induces endothelial dysfunction in the prediabetic metabolic syndrome. Circ Res 99:69–77. https://doi.org/10.1161/01.RES.0000229685.37402.80

    Article  CAS  PubMed  Google Scholar 

  39. Wassmann S, Stumpf M, Strehlow K, Schmid A, Schieffer B, Böhm M, Nickenig G (2004) Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor. Circ Res 94:534–541. https://doi.org/10.1161/01.RES.0000115557.25127.8D

    Article  CAS  PubMed  Google Scholar 

  40. Sengul C, Cevik C, Ozveren O, Oduncu V, Sunbul A, Akgun T, Can MM, Semiz E, Dindar I (2011) Echocardiographic epicardial fat thickness is associated with carotid intima-media thickness in patients with metabolic syndrome. Echocardiography 28:853–858. https://doi.org/10.1111/j.1540-8175.2011.01471.x

    Article  PubMed  Google Scholar 

  41. Erdoğan T, Durakoğlugil ME, Çetin M, Altan Kocaman S, Duman H, Çiçek Y, Şatıroğlu Ö (2019) Epicardial adipose tissue predicts carotid intima-media thickness independently of body mass index and waist circumference. Acta Cardiol Sin 35:32–41. https://doi.org/10.6515/ACS.201901_35(1).20180628A

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nelson MR, Mookadam F, Thota V, Emani U, Al Harthi M, Lester SJ, Cha S, Stepanek J, Hurst RT (2011) Epicardial fat: an additional measurement for subclinical atherosclerosis and cardiovascular risk stratification? J Am Soc Echocardiogr 24:339–345. https://doi.org/10.1016/j.echo.2010.11.008

    Article  PubMed  Google Scholar 

  43. Iacobellis G (2015) Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol 11:363–371. https://doi.org/10.1038/nrendo.2015.58

    Article  CAS  PubMed  Google Scholar 

  44. Reiss AB, Siegart NM, De Leon J (2017) Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clin Lipidol 12:14–23. https://doi.org/10.1080/17584299.2017.1319787

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takwa Mehmli.

Ethics declarations

Statement of ethics and consent

Our locally appointed ethics committee “Charles Nicolle Hospital local committee” has approved the research protocol. Our institution does not provide us an ethics board approval number. Our study was performed in line with the Declaration of Helsinki.

Consent to participate and to publish

Written informed consent was obtained from all patients.

Disclosures

None.

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

Tekaya, A.B., Mehmli, T., Mrad, I.B. et al. Increased epicardial adipose tissue thickness correlates with endothelial dysfunction in spondyloarthritis. Clin Rheumatol 41, 3017–3025 (2022). https://doi.org/10.1007/s10067-022-06261-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-022-06261-5

Keywords

Navigation