Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients - an exploratory study

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Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients - an exploratory study. / Bjerre, Kamilla Pernille; Clemmensen, Tor Skibsted; Poulsen, Steen Hvitfeldt; Hvas, Anne-Mette; Holm, Niels Ramsing; Grove, Erik Lerkevang; Bouchelouche, Kirsten; Kristensen, Steen Dalby; Eiskjaer, Hans.

I: Clinical Transplantation, Bind 35, Nr. 1, e14133, 01.2021.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{da7ed74e63e94174b2b336f8784f286a,
title = "Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients - an exploratory study",
abstract = "BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients.METHODS: We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O-H2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death.RESULTS: We found consistent differences in two proteins involved in cholesterol homeostasis; significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p<0.05) and significantly decreased paraoxonase 3 (PON3) (p<0.05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p<0.05) and borderline significantly increased in patients experiencing major adverse cardiac events (p=0.10) and patients with macrovascular CAV (p=0.05).CONCLUSIONS: We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.",
keywords = "biomarkers, cardiac allograft vasculopathy, coronary artery disease, heart transplantation, proteomics",
author = "Bjerre, {Kamilla Pernille} and Clemmensen, {Tor Skibsted} and Poulsen, {Steen Hvitfeldt} and Anne-Mette Hvas and Holm, {Niels Ramsing} and Grove, {Erik Lerkevang} and Kirsten Bouchelouche and Kristensen, {Steen Dalby} and Hans Eiskjaer",
note = "This article is protected by copyright. All rights reserved.",
year = "2021",
month = jan,
doi = "10.1111/ctr.14133",
language = "English",
volume = "35",
journal = "Clinical Transplantation",
issn = "0902-0063",
publisher = "Wiley-Blackwell Munksgaard",
number = "1",

}

RIS

TY - JOUR

T1 - Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients - an exploratory study

AU - Bjerre, Kamilla Pernille

AU - Clemmensen, Tor Skibsted

AU - Poulsen, Steen Hvitfeldt

AU - Hvas, Anne-Mette

AU - Holm, Niels Ramsing

AU - Grove, Erik Lerkevang

AU - Bouchelouche, Kirsten

AU - Kristensen, Steen Dalby

AU - Eiskjaer, Hans

N1 - This article is protected by copyright. All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients.METHODS: We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O-H2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death.RESULTS: We found consistent differences in two proteins involved in cholesterol homeostasis; significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p<0.05) and significantly decreased paraoxonase 3 (PON3) (p<0.05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p<0.05) and borderline significantly increased in patients experiencing major adverse cardiac events (p=0.10) and patients with macrovascular CAV (p=0.05).CONCLUSIONS: We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.

AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients.METHODS: We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O-H2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death.RESULTS: We found consistent differences in two proteins involved in cholesterol homeostasis; significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p<0.05) and significantly decreased paraoxonase 3 (PON3) (p<0.05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p<0.05) and borderline significantly increased in patients experiencing major adverse cardiac events (p=0.10) and patients with macrovascular CAV (p=0.05).CONCLUSIONS: We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.

KW - biomarkers

KW - cardiac allograft vasculopathy

KW - coronary artery disease

KW - heart transplantation

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=85096690791&partnerID=8YFLogxK

U2 - 10.1111/ctr.14133

DO - 10.1111/ctr.14133

M3 - Journal article

C2 - 33128247

VL - 35

JO - Clinical Transplantation

JF - Clinical Transplantation

SN - 0902-0063

IS - 1

M1 - e14133

ER -