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

Sharma, Tania LU ; Maehara, Akiko ; Maeng, Michael ; Kjøller-Hansen, Lars ; Engstrøm, Thomas LU ; Ben-Yehuda, Ori ; Matsumura, Mitsuaki ; Fröbert, Ole ; Persson, Jonas and Wiseth, Rune , et al. (2025) In International Journal of Cardiology: Cardiovascular Risk and Prevention 26.
Abstract

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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Lipid rich plaque, Myocardial infarction, Plaque burden, Vulnerable plaque
in
International Journal of Cardiology: Cardiovascular Risk and Prevention
volume
26
article number
200440
publisher
Elsevier
external identifiers
  • scopus:105005939739
  • pmid:40503438
ISSN
2772-4875
DOI
10.1016/j.ijcrp.2025.200440
language
English
LU publication?
yes
id
b0912ffa-a707-49d9-9c00-e25862ceadce
date added to LUP
2025-07-16 09:21:18
date last changed
2025-07-17 03:14:20
@article{b0912ffa-a707-49d9-9c00-e25862ceadce,
  abstract     = {{<p>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.</p>}},
  author       = {{Sharma, Tania and Maehara, Akiko and Maeng, Michael and Kjøller-Hansen, Lars and Engstrøm, Thomas and Ben-Yehuda, Ori and Matsumura, Mitsuaki and Fröbert, Ole and Persson, Jonas and Wiseth, Rune and Larsen, Alf Inge and Koul, Sasha and Rylance, Rebecca and Mintz, Gary S. and Ali, Ziad A. and James, Stefan K. and Stone, Gregg W. and Erlinge, David}},
  issn         = {{2772-4875}},
  keywords     = {{Atherosclerosis; Lipid rich plaque; Myocardial infarction; Plaque burden; Vulnerable plaque}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Cardiology: Cardiovascular Risk and Prevention}},
  title        = {{Circulating protein biomarkers and their association with vulnerable plaque characteristics – a PROSPECT II substudy}},
  url          = {{http://dx.doi.org/10.1016/j.ijcrp.2025.200440}},
  doi          = {{10.1016/j.ijcrp.2025.200440}},
  volume       = {{26}},
  year         = {{2025}},
}