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Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV

INTRODUCTION: People living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circul...

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Autores principales: Grønbæk, Sylvester Klöcker, Høgh, Julie, Knudsen, Andreas Dehlbæk, Pham, Michael Huy Cuong, Sigvardsen, Per Ejlstrup, Fuchs, Andreas, Kühl, Jørgen Tobias, Køber, Lars, Gerstoft, Jan, Benfield, Thomas, Ostrowski, Sisse Rye, Kofoed, Klaus Fuglsang, Nielsen, Susanne Dam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933775/
https://www.ncbi.nlm.nih.gov/pubmed/36817421
http://dx.doi.org/10.3389/fimmu.2023.1115894
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author Grønbæk, Sylvester Klöcker
Høgh, Julie
Knudsen, Andreas Dehlbæk
Pham, Michael Huy Cuong
Sigvardsen, Per Ejlstrup
Fuchs, Andreas
Kühl, Jørgen Tobias
Køber, Lars
Gerstoft, Jan
Benfield, Thomas
Ostrowski, Sisse Rye
Kofoed, Klaus Fuglsang
Nielsen, Susanne Dam
author_facet Grønbæk, Sylvester Klöcker
Høgh, Julie
Knudsen, Andreas Dehlbæk
Pham, Michael Huy Cuong
Sigvardsen, Per Ejlstrup
Fuchs, Andreas
Kühl, Jørgen Tobias
Køber, Lars
Gerstoft, Jan
Benfield, Thomas
Ostrowski, Sisse Rye
Kofoed, Klaus Fuglsang
Nielsen, Susanne Dam
author_sort Grønbæk, Sylvester Klöcker
collection PubMed
description INTRODUCTION: People living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH. METHODS: Five hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH. RESULTS: PLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)). CONCLUSIONS: SCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.
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spelling pubmed-99337752023-02-17 Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV Grønbæk, Sylvester Klöcker Høgh, Julie Knudsen, Andreas Dehlbæk Pham, Michael Huy Cuong Sigvardsen, Per Ejlstrup Fuchs, Andreas Kühl, Jørgen Tobias Køber, Lars Gerstoft, Jan Benfield, Thomas Ostrowski, Sisse Rye Kofoed, Klaus Fuglsang Nielsen, Susanne Dam Front Immunol Immunology INTRODUCTION: People living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH. METHODS: Five hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH. RESULTS: PLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)). CONCLUSIONS: SCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH. Frontiers Media S.A. 2023-02-02 /pmc/articles/PMC9933775/ /pubmed/36817421 http://dx.doi.org/10.3389/fimmu.2023.1115894 Text en Copyright © 2023 Grønbæk, Høgh, Knudsen, Pham, Sigvardsen, Fuchs, Kühl, Køber, Gerstoft, Benfield, Ostrowski, Kofoed and Nielsen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Grønbæk, Sylvester Klöcker
Høgh, Julie
Knudsen, Andreas Dehlbæk
Pham, Michael Huy Cuong
Sigvardsen, Per Ejlstrup
Fuchs, Andreas
Kühl, Jørgen Tobias
Køber, Lars
Gerstoft, Jan
Benfield, Thomas
Ostrowski, Sisse Rye
Kofoed, Klaus Fuglsang
Nielsen, Susanne Dam
Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
title Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
title_full Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
title_fullStr Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
title_full_unstemmed Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
title_short Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
title_sort aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with hiv
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933775/
https://www.ncbi.nlm.nih.gov/pubmed/36817421
http://dx.doi.org/10.3389/fimmu.2023.1115894
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