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Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease: a 6-Year Follow-up Study

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Abstract

We investigated whether disturbance of glycocalyx integrity is related with increased cardiovascular risk. In 600 healthy subjects, we measured perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter ranging 5–25 µm using a dedicated camera (Sideview Darkfield Imaging). Increased PBR indicates reduced glycocalyx thickness. We prospectively monitored the occurrence of cardiovascular events (MACE-death, myocardial infarction, and stroke) during a 6-year follow-up. Fifty-seven MACE were documented. Increased values of PBR5-25 predicted higher risk for MACE in a model including sex, age, hyperlipidemia, diabetes, hypertension, smoking, family history of coronary disease, treatment with ACEi/ARBs, or lipid-lowering agents (hazard ratio (HR), 6.44, p = 0.011; net reclassification improvement (NRI), 28%; C-statistic: 0.761). PBR5-25 was an independent and additive predictor of outcome when added in a model including the European Heart SCORE, diabetes, family history of CAD, and medication (HR, 4.71; NRI: 39.7%, C-statistic from 0.653 to 0.693; p < 0.01).Glycocalyx integrity is an independent and additive predictor to risk factors for MACE at 6-year follow-up in individuals without cardiovascular disease. ClinicalTrials.govIdentifier:NCT04646252.

Graphical abstract

PBR5-25 was an independent and additive predictor of adverse cardiovascular events in a model including the European Heart SCORE, diabetes, family history of coronary disease, and medication (HR: 4.71, NRI: 39.7%, C-statistic from 0.653 to 0.693; p < 0.01, NRI:37.9%).

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to information that could compromise the privacy of research participants but are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Abbreviations

ACEi/ARBs:

Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers

AMI:

Acute myocardial infarction

CAD:

Coronary artery disease

DM:

Diabetes mellitus

GLS:

Global longitudinal strain

HF:

Heart failure

HR:

Hazard ratio

MACE:

Major adverse cardiovascular events

NO:

Nitric oxide

NRI:

Net reclassification improvement

PAD:

Peripheral arterial disease

PBR:

Perfused boundary region

RBC:

Red blood cell

SDF:

Sideview Darkfield

TGs:

Triglycerides

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Authors and Affiliations

  1. Laboratory of Preventive Cardiology, 2nd Department of Cardiology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Ignatios Ikonomidis, John Thymis, Panagiotis Simitsis, Georgia-Angeliki Koliou, Spiridon Katsanos, Charilaos Triantafyllou, George Pavlidis, Eftihia Polyzogopoulou, Konstantinos Katogiannis, Dimitrios Vlastos, Gavriella Kostelli, Helen Triantafyllidi, John Parissis, John Lekakis & Gerasimos Filippatos

  2. EACVI, Laboratory of Preventive Cardiology, 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Athens, 12462, Haidari, Greece

    Ignatios Ikonomidis

  3. 2nd Department of Internal Medicine, Research Unit and Diabetes Centre, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Foteini Kousathana, Aikaterini Kountouri & Vaia Lambadiari

  4. 2nd Department of Dermatology and Venereology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Evangelia Papadavid

Authors
  1. Ignatios Ikonomidis
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  2. John Thymis
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  3. Panagiotis Simitsis
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  4. Georgia-Angeliki Koliou
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  6. Charilaos Triantafyllou
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  7. Foteini Kousathana
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  11. Konstantinos Katogiannis
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  17. John Lekakis
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  18. Gerasimos Filippatos
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  19. Vaia Lambadiari
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Contributions

Authors contributions is as follows: (1) study conception and design (Ignatios Ikonomidis, John Thymis, Vaia Lambadiari); (2) laboratory measurements (Foteini Kousathana, Charilaos Triantafyllou, Gavriella Kostelli, Dimitrios Vlastos, Aikaterini Kountouri, Eftihia Polyzogopoulou); (3) data analysis and interpretation (Georgia-Angeliki Koliou, Panagiotis Simitsis, George Pavlidis, Konstantinos Katogiannis, Helen Triantafyllidi, Spiridon Katsanos); and (4) drafting of the manuscript (John Lekakis, John Parissis, Gerasimos Filippatos, Evangelia Papadavid). All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ignatios Ikonomidis.

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The study was conducted according to the principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee of Attikon University Hospital.

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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. of Cardiovasc. Trans. Res. 15, 890–902 (2022). https://doi.org/10.1007/s12265-021-10180-2

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