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Thromb Haemost
DOI: 10.1055/a-2632-3249
Endothelium and Angiogenesis

Association of Endothelial Glycocalyx Integrity with Left Ventricular Performance and Remodeling after Acute Myocardial Infarction: A 12-month Follow-up Study

John Thymis
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
Konstantinos Katogiannis
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
George Pavlidis
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
Dimitrios Vlastos
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
Damianos Tsilivarakis
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
Gavriella Kostelli
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
John Parissis
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
,
Panagiota Efstathia Nikolaou
2   School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece
,
Ioanna Andreadou   †
2   School of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece
,
Vaia Lambadiari
3   2nd Department of Internal-Medicine, Diabetes Centre, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
,
Ignatios Ikonomidis 
1   2nd Department of Cardiology, School of Medicine University General Hospital “Attikon,” National and Kapodistrian University of Athens, Athens, Greece
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Abstract

Background and Purpose

ST elevation myocardial infarction (STEMI) patients display endothelial dysfunction. We investigated whether endothelial glycocalyx thickness is affected in STEMI patients and may predict left ventricular performance post event.

Methods

We examined 278 STEMI patients and 140 matched controls. We measured: (a) perfused boundary region (PBR) of the sublingual microvessels (range 4 to 25 μm; increased value indicates reduced endothelial glycocalyx integrity) at baseline; (b) left ventricular ejection fraction (LVEF) and global longitudinal strain (LVGLS), at baseline and at 12 months, (c) the percentage change of left ventricular end-systolic volume (ΔLVESV) at 12 months.

Results

Compared with matched controls, STEMI patients had higher PBR4–25 (2.11 ± 0.17 μm vs. 1.98 ± 0.20 μm, p < 0.001). In a model including age, sex, hypertension, diabetes, hyperlipidemia, smoking, family history of coronary artery disease, number of diseased vessels, location of STEMI medication, and high-sensitivity troponin T (hs-troponin), PBR4–25 was independently associated with LVEF and LVGLS at 48 hours post-MI (for LVEF: unstandardized β coefficient: −4.71, 95% CI: −8.53 to −0.71, p = 0.019 and for LVGLS: 2.89, 95%CI: 1.63–4.16, p < 0.001). Using multivariable analysis, PBR4–25 remained a significant predictor of the percentage change in LVEF, LVGLS, and ΔLVESV at 12-month follow-up (LVEF change: unstandardized β coefficient: −1.38, 95% CI: −1.80 to −0.96, p < 0.001; for LV GLS change: −0.66, 95% CI: −1.14 to −0.18, p = 0.007 and for ΔLVESV: 1.42, 95% CI: 0.06–2.93, p = 0.039). A PBR4–25 cut-off value of 2.29 μm could detect LV EF less than 45% at 48 h as well as at 12 months (AUC: 0.82, p < 0.001 and AUC: 0.80; p < 0.001).

Conclusion

Endothelial glycocalyx assessment is associated with myocardial performance after STEMI.

Keywords

glycocalyx - ST elevation myocardial infarction - left ventricular global longitudinal strain - left ventricular ejection fraction

† Deceased.


Ethical Approval Statement

The present study was carried out in accordance with the principles outlined in the Declaration of Helsinki and received approval from the hospital's Ethics Committee (Approval number: 301/27-6-2014). All participants provided written informed consent before joining the study.


Supplementary Material



Publication History

Received: 05 May 2025

Accepted: 10 June 2025

Article published online:
10 July 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation 2007; 115 (10) 1285-1295
    PubMedSearch in Google Scholar
  • 2 Gori T. Endothelial function: a short guide for the interventional cardiologist. Int J Mol Sci 2018; 19 (12) 3838
    PubMedSearch in Google Scholar
  • 3 Brands J, Hubel CA, Althouse A, Reis SE, Pacella JJ. Noninvasive sublingual microvascular imaging reveals sex-specific reduction in glycocalyx barrier properties in patients with coronary artery disease. Physiol Rep 2020; 8 (02) e14351
    PubMedSearch in Google Scholar
  • 4 Wu Y, Pan N, An Y, Xu M, Tan L, Zhang L. Diagnostic and prognostic biomarkers for myocardial infarction. Front Cardiovasc Med 2021; 7: 617277
    CrossrefPubMedSearch in Google Scholar
  • 5 Bavia L, Lidani KCF, Andrade FA, Sobrinho MIAH, Nisihara RM, de Messias-Reason IJ. Complement activation in acute myocardial infarction: an early marker of inflammation and tissue injury?. Immunol Lett 2018; 200: 18-25
    PubMedSearch in Google Scholar
  • 6 Kusche-Vihrog K, Urbanova K, Blanqué A. et al. C-reactive protein makes human endothelium stiff and tight. Hypertension 2011; 57 (02) 231-237
    PubMedSearch in Google Scholar
  • 7 Puymirat E, Simon T, Cayla G. et al; USIK, USIC 2000, and FAST-MI investigators. USIK, USIC 2000, and FAST-MI Investigators. Acute myocardial infarction: changes in patient characteristics, management, and 6-month outcomes over a period of 20years in the FAST-MI program (French Registry of Acute ST Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015. Circulation 2017; 136 (20) 1908-1919
    CrossrefPubMedSearch in Google Scholar
  • 8 Jung C, Ferrari M, Rödiger C. et al. Evaluation of the sublingual microcirculation in cardiogenic shock. Clin Hemorheol Microcirc 2009; 42 (02) 141-148
    PubMedSearch in Google Scholar
  • 9 Alexander Y, Osto E, Schmidt-Trucksäss A. et al. Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. Cardiovasc Res 2021; 117 (01) 29-42
    CrossrefPubMedSearch in Google Scholar
  • 10 Adrie C, Adib-Conquy M, Laurent I. et al. Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome. Circulation 2002; 106 (05) 562-568
    CrossrefPubMedSearch in Google Scholar
  • 11 Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 2007; 454 (03) 345-359
    PubMedSearch in Google Scholar
  • 12 Pries AR, Secomb TW, Gaehtgens P. The endothelial surface layer. Pflugers Arch 2000; 440 (05) 653-666
    PubMedSearch in Google Scholar
  • 13 Ikonomidis I, Thymis J, Simitsis P. et al. Impaired endothelial glycocalyx predicts adverse outcome in subjects without overt cardiovascular disease: a 6-year follow-up study. J Cardiovasc Transl Res 2022; 15 (04) 890-902
    PubMedSearch in Google Scholar
  • 14 Levick JR, Michel CC. Microvascular fluid exchange and the revised Starling principle. Cardiovasc Res 2010; 87 (02) 198-210
    CrossrefPubMedSearch in Google Scholar
  • 15 Constantinescu AA, Vink H, Spaan JA. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler Thromb Vasc Biol 2003; 23 (09) 1541-1547
    PubMedSearch in Google Scholar
  • 16 Gouverneur M, Spaan JA, Pannekoek H, Fontijn RD, Vink H. Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol 2006; 290 (01) H458-H2
    PubMedSearch in Google Scholar
  • 17 Eickhoff MK, Winther SA, Hansen TW. et al. Assessment of the sublingual microcirculation with the GlycoCheck system: reproducibility and examination conditions. PLoS One 2020; 15 (12) e0243737
    PubMedSearch in Google Scholar
  • 18 Gorshkov AY, Klimushina MV, Boytsov SA, Kots AY, Gumanova NG. Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall. Microcirculation 2018; 25 (04) e12454
    PubMedSearch in Google Scholar
  • 19 Vahldieck C, Cianflone E, Fels B. et al. Endothelial glycocalyx and cardiomyocyte damage is prevented by recombinant syndecan-1 in acute myocardial infarction. Am J Pathol 2023; 193 (04) 474-492
    PubMedSearch in Google Scholar
  • 20 Jung C, Fuernau G, Muench P. et al. Impairment of the endothelial glycocalyx in cardiogenic shock and its prognostic relevance. Shock 2015; 43 (05) 450-455
    PubMedSearch in Google Scholar
  • 21 Ibanez B, James S, Agewall S. et al; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39 (02) 119-177
    CrossrefPubMedSearch in Google Scholar
  • 22 Lang RM, Badano LP, Mor-Avi V. et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28 (01) 1-39.e14
    CrossrefPubMedSearch in Google Scholar
  • 23 Ikonomidis I, Pavlidis G, Thymis J. et al. Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and their combination on endothelial glycocalyx, arterial function, and myocardial work index in patients with type 2 diabetes mellitus after 12-month treatment. J Am Heart Assoc 2020; 9 (09) e015716
    PubMedSearch in Google Scholar
  • 24 Sugimoto T, Dulgheru R, Bernard A. et al. Echocardiographic reference ranges for normal left ventricular 2D strain: results from the EACVI NORRE study. Eur Heart J Cardiovasc Imaging 2017; 18 (08) 833-840
    CrossrefPubMedSearch in Google Scholar
  • 25 Pavlidis G, Tsilivarakis D, Katogiannis K. et al. Association of aortic stiffness early post myocardial infarction with left ventricular remodelling. Eur J Clin Invest 2024; 54 (01) e14090
    PubMedSearch in Google Scholar
  • 26 Ikonomidis I, Katsanaki E, Thymis J. et al. The effect of 4-month treatment with glycocalyx dietary supplement on endothelial glycocalyx integrity and vascular function in patients with psoriasis. Nutrients 2024; 16 (15) 2572
    PubMedSearch in Google Scholar
  • 27 Lekakis J, Abraham P, Balbarini A. et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil 2011; 18 (06) 775-789
    PubMedSearch in Google Scholar
  • 28 Lee DH, Dane MJC, van den Berg BM. et al; NEO study group. Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion. PLoS One 2014; 9 (05) e96477
    CrossrefPubMedSearch in Google Scholar
  • 29 Pillinger NL, Kam P. Endothelial glycocalyx: basic science and clinical implications. Anaesth Intensive Care 2017; 45 (03) 295-307
    PubMedSearch in Google Scholar
  • 30 Wernly B, Fuernau G, Masyuk M. et al. Syndecan-1 predicts outcome in patients with ST- segment elevation infarction independent from infarct-related myocardial injury. Sci Rep 2019; 9 (01) 18367
    CrossrefPubMedSearch in Google Scholar
  • 31 Ostrowski SR, Pedersen SH, Jensen JS, Mogelvang R, Johansson PI. Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines. Crit Care 2013; 17 (01) R32
    PubMedSearch in Google Scholar
  • 32 Abassi Z, Armaly Z, Heyman SN. Glycocalyx degradation in ischemia-reperfusion injury. Am J Pathol 2020; 190 (04) 752-767
    PubMedSearch in Google Scholar
  • 33 Jaarsma C, Vink H, van Haare J. et al. Non-invasive assessment of microvascular dysfunction in patients with microvascular angina. Int J Cardiol 2017; 248: 433-439
    PubMedSearch in Google Scholar
  • 34 Mulders TA, Nieuwdorp M, Stroes ES, Vink H, Pinto-Sietsma SJ. Non-invasive assessment of microvascular dysfunction in families with premature coronary artery disease. Int J Cardiol 2013; 168 (05) 5026-5028
    PubMedSearch in Google Scholar
  • 35 Rovas A, Osiaevi I, Buscher K. et al. Microvascular dysfunction in COVID-19: the MYSTIC study. Angiogenesis 2021; 24 (01) 145-157
    PubMedSearch in Google Scholar
  • 36 Vink H, Constantinescu AA, Spaan JA. Oxidized lipoproteins degrade the endothelial surface layer: implications for platelet-endothelial cell adhesion. Circulation 2000; 101 (13) 1500-1502
    PubMedSearch in Google Scholar
  • 37 Ikonomidis I, Marinou M, Vlastos D. et al. Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program. Atherosclerosis 2017; 262: 123-130
    PubMedSearch in Google Scholar
  • 38 Chirinos JA, Phan TS, Syed AA. et al. Late systolic myocardial loading is associated with left atrial dysfunction in hypertension. Circ Cardiovasc Imaging 2017; 10 (06) e006023
    PubMedSearch in Google Scholar
  • 39 Ohyama Y, Ambale-Venkatesh B, Noda C. et al. Association of aortic stiffness with left ventricular remodeling and reduced left ventricular function measured by magnetic resonance imaging: the multi-ethnic study of atherosclerosis. Circ Cardiovasc Imaging 2016;9(07):10.1161/CIRCIMAGING.115.004426 e004426
    PubMed
  • 40 Ikonomidis I, Voumvourakis A, Makavos G. et al. Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives. J Clin Hypertens (Greenwich) 2018; 20 (04) 672-679
    PubMedSearch in Google Scholar
  • 41 Khullar N, Buckley AJ, O'Connor C. et al. Peak troponin T in STEMI: a predictor of all-cause mortality and left ventricular function. Open Heart 2022; 9 (01) e001863
    PubMedSearch in Google Scholar
  • 42 Zhao L, Xin M, Piao X, Zhang S, Li Y, Cheng XW. Prognostic implications of the admission cardiac troponin I levels and door-to-balloon time on clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. Ther Clin Risk Manag 2022; 18: 31-45
    PubMedSearch in Google Scholar
  • 43 Ikonomidis I, Vlastos D, Andreadou I. et al. Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study. Basic Res Cardiol 2021; 116 (01) 9
    PubMedSearch in Google Scholar
  • 44 Nikolaou PE, Konijnenberg LSF, Kostopoulos IV. et al. Empagliflozin in acute myocardial infarction reduces no-reflow and preserves cardiac function by preventing endothelial damage. JACC Basic Transl Sci 2024; 10 (01) 43-61
    PubMedSearch in Google Scholar
  • 45 Ikonomidis I, Katogiannis K, Chania C. et al. Association of hydroxytyrosol enriched olive oil with vascular function in chronic coronary disease. Eur J Clin Invest 2023; 53 (07) e13983
    PubMedSearch in Google Scholar