Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy

Background: In the PROSPECT-II study, near infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) was used to characterize atherosclerotic plaques in the coronary arteries. NIRS-derived lipid core burden index (LCBI) and IVUS-derived plaque burden (PB) were able to identify plaques strongl...

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Main Authors: Tania Sharma, Akiko Maehara, Michael Maeng, Lars Kjøller-Hansen, Thomas Engstrøm, Ori Ben-Yehuda, Mitsuaki Matsumura, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf Inge Larsen, Sasha Koul, Rebecca Rylance, Gary S. Mintz, Ziad A. Ali, Stefan K. James, Gregg W. Stone, David Erlinge
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Language:English
Published: Elsevier 2025-09-01
Series:International Journal of Cardiology. Cardiovascular Risk and Prevention
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772487525000789
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author Tania Sharma
Akiko Maehara
Michael Maeng
Lars Kjøller-Hansen
Thomas Engstrøm
Ori Ben-Yehuda
Mitsuaki Matsumura
Ole Fröbert
Jonas Persson
Rune Wiseth
Alf Inge Larsen
Sasha Koul
Rebecca Rylance
Gary S. Mintz
Ziad A. Ali
Stefan K. James
Gregg W. Stone
David Erlinge
author_facet Tania Sharma
Akiko Maehara
Michael Maeng
Lars Kjøller-Hansen
Thomas Engstrøm
Ori Ben-Yehuda
Mitsuaki Matsumura
Ole Fröbert
Jonas Persson
Rune Wiseth
Alf Inge Larsen
Sasha Koul
Rebecca Rylance
Gary S. Mintz
Ziad A. Ali
Stefan K. James
Gregg W. Stone
David Erlinge
author_sort Tania Sharma
collection DOAJ
description Background: In the PROSPECT-II study, near infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) was used to characterize atherosclerotic plaques in the coronary arteries. NIRS-derived lipid core burden index (LCBI) and IVUS-derived plaque burden (PB) were able to identify plaques strongly associated with adverse cardiovascular events. Aim: Our aim was to identify biomarkers associated with LCBI or PB in the coronary arteries. Methods: 898 patients with recent myocardial infarction underwent percutaneous coronary intervention. Blood samples to analyze plasma levels of 179 proteins associated with cardiovascular disease were procured and a combined NIRS-IVUS catheter was used to analyze the coronary arteries. Adjusted linear regression models were calculated between the biomarkers and the outcomes of interest, adjusted for multiplicity testing. Kaplan-Meier survival curves of biomarkers divided by median were assessed with the log-rank test. Adjusted Cox proportional models were calculated for major adverse cardiovascular events. Results: A total of 24 proteins were associated with PB and 28 proteins with LCBI. Eight of these biomarkers were associated with both increased pan-coronary LCBI and PB; IL-18R1, CSF-1, VEGFA, EN-RAGE, cathepsin D, PCSK9, transferrin receptor protein 1 and OPN. After adjusting for multiplicity, angiopoietin like 3 (ANGPTL3) retained its association with LCBI, and IL-18R1 and CSF-1 retained their association with PB. Conclusion: We were able to identify distinct biomarker patterns associated with PB and LCBI. IL-18R1 and CSF-1 had a strong relationship with PB. ANGPTL3 was associated with lipid rich plaques but not with PB, supporting its role in lipid accumulation and development of vulnerable plaques.
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spelling doaj-art-0911dcbf01bc403491c0162c07c5a1442025-08-24T05:15:16ZengElsevierInternational Journal of Cardiology. Cardiovascular Risk and Prevention2772-48752025-09-012620044010.1016/j.ijcrp.2025.200440Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudyTania Sharma0Akiko Maehara1Michael Maeng2Lars Kjøller-Hansen3Thomas Engstrøm4Ori Ben-Yehuda5Mitsuaki Matsumura6Ole Fröbert7Jonas Persson8Rune Wiseth9Alf Inge Larsen10Sasha Koul11Rebecca Rylance12Gary S. Mintz13Ziad A. Ali14Stefan K. James15Gregg W. Stone16David Erlinge17Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; Corresponding author.New York-Presbyterian Hospital and Columbia University Irving Medical Center, New York, NY, USA; Cardiovascular Research Foundation, New York, NY, USADepartment of Cardiology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkZealand University Hospital, Roskilde, DenmarkRigshospitalet, University of Copenhagen, Copenhagen, DenmarkCardiovascular Research Foundation, New York, NY, USA; University of California San Diego, San Diego, CA, USACardiovascular Research Foundation, New York, NY, USAOrebro University, Faculty of Health, Orebro, Sweden and Department of Biomedicine, Aarhus University, DenmarkDepartment of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, SwedenSt Olavs Hospital, Trondheim, NorwayStavanger University Hospital, Stavanger, NorwayDepartment of Cardiology, Clinical Sciences, Lund University, Lund, SwedenDepartment of Cardiology, Clinical Sciences, Lund University, Lund, SwedenCardiovascular Research Foundation, New York, NY, USACardiovascular Research Foundation, New York, NY, USADepartment of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, SwedenThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USADepartment of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; University of California San Diego, San Diego, CA, USABackground: In the PROSPECT-II study, near infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) was used to characterize atherosclerotic plaques in the coronary arteries. NIRS-derived lipid core burden index (LCBI) and IVUS-derived plaque burden (PB) were able to identify plaques strongly associated with adverse cardiovascular events. Aim: Our aim was to identify biomarkers associated with LCBI or PB in the coronary arteries. Methods: 898 patients with recent myocardial infarction underwent percutaneous coronary intervention. Blood samples to analyze plasma levels of 179 proteins associated with cardiovascular disease were procured and a combined NIRS-IVUS catheter was used to analyze the coronary arteries. Adjusted linear regression models were calculated between the biomarkers and the outcomes of interest, adjusted for multiplicity testing. Kaplan-Meier survival curves of biomarkers divided by median were assessed with the log-rank test. Adjusted Cox proportional models were calculated for major adverse cardiovascular events. Results: A total of 24 proteins were associated with PB and 28 proteins with LCBI. Eight of these biomarkers were associated with both increased pan-coronary LCBI and PB; IL-18R1, CSF-1, VEGFA, EN-RAGE, cathepsin D, PCSK9, transferrin receptor protein 1 and OPN. After adjusting for multiplicity, angiopoietin like 3 (ANGPTL3) retained its association with LCBI, and IL-18R1 and CSF-1 retained their association with PB. Conclusion: We were able to identify distinct biomarker patterns associated with PB and LCBI. IL-18R1 and CSF-1 had a strong relationship with PB. ANGPTL3 was associated with lipid rich plaques but not with PB, supporting its role in lipid accumulation and development of vulnerable plaques.http://www.sciencedirect.com/science/article/pii/S2772487525000789Vulnerable plaqueMyocardial infarctionPlaque burdenLipid rich plaqueAtherosclerosis
spellingShingle Tania Sharma
Akiko Maehara
Michael Maeng
Lars Kjøller-Hansen
Thomas Engstrøm
Ori Ben-Yehuda
Mitsuaki Matsumura
Ole Fröbert
Jonas Persson
Rune Wiseth
Alf Inge Larsen
Sasha Koul
Rebecca Rylance
Gary S. Mintz
Ziad A. Ali
Stefan K. James
Gregg W. Stone
David Erlinge
Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy
International Journal of Cardiology. Cardiovascular Risk and Prevention
Vulnerable plaque
Myocardial infarction
Plaque burden
Lipid rich plaque
Atherosclerosis
title Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy
title_full Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy
title_fullStr Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy
title_full_unstemmed Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy
title_short Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy
title_sort circulating protein biomarkers and their association with vulnerable plaque characteristics a prospect ii substudy
topic Vulnerable plaque
Myocardial infarction
Plaque burden
Lipid rich plaque
Atherosclerosis
url http://www.sciencedirect.com/science/article/pii/S2772487525000789
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