Dataset Information

Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI.

ABSTRACT:

Background and aim

The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention.

Methods

A total of 434 patients with STEMI aged ≥18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. Finally, 235 patients who meet the inclusion criteria were enrolled and the cohort was divided into 3 groups according to PCSK9 and PTX3 levels: group A: PCSK9 < median and Pentraxin 3 (N = 72/30.6%); group B: PCSK9 ≥ median or Pentraxin 3≥ median (N = 91/38.7%); group C: PCSK9 ≥ median and Pentraxin 3≥ median (N = 72/30.6%). MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischemic stroke, revascularization and heart failure.

Outcomes

During a median follow-up of 2.01 years, 50 patients has occurred MACE. Two-year MACE was higher in group C (23/31.9%) than in group B (16/17.6%) and group A (11/15.3%) (p = 0.028). There was a correlation between PCSK9 and PTX3 (r = 0.302, p < 0.003). In multivariable analysis adjusted for age, gender, risk factors, and serum indexes, being in group C remained independently associated with an increased risk of MACE (hazard ratio [HR]: 2.90; p = 0.010), and group B tended to have higher MACE (HR: 1.76; p = 0.172) compared with group A. Among patients with plaque erosion by OCT, group C was independently associated with an increased risk of MACE (HR: 9.04; p = 0.048) after fully adjustment. However, the significant association was absence among patients with plaque rupture.

Conclusion and relevance

This study demonstrated the usefulness of combined measures of PCSK9 and PTX3 to enhance risk stratification in patients with STEMI especially among patients with plaque erosion. Patients with elevation of both PCSK9 and PTX3 had a markedly increased risk of MACE.

SUBMITTER: Zhao X

PROVIDER: S-EPMC8524062 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI.

Zhao Xiaoxiao X Song Li L Wang Ying Y Li Jiannan J Zhou Jinying J Chen Runzhen R Liu Chen C Zhou Peng P Sheng Zhaoxue Z Chen Yi Y Zhao Hanjun H Yan Hongbing H

Journal of inflammation research 20211014

<h4>Background and aim</h4>The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention.<h4>Methods</h4>A total of 434 patients with STEMI aged ≥18 years who under ...[more]

PMID: 34703271

Similar Datasets

Project description:Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD. We applied an integrative approach, combining genetic, transcriptomic and proteomic data from three vascular biobanks comprising carotid atherosclerosis, thoracic and abdominal aneurysms, with patient clinical parameters and immunohistochemistry of vascular biopsies. Apart from PCSK4, all PCSK family members lie in genetic regions containing variants associated with human cardiovascular traits. Transcriptomic analyses revealed that FURIN, PCSK5, MBTPS1 were downregulated, while PCSK6/7 were upregulated in plaques vs. control arteries. In abdominal aneurysms, FURIN, PCSK5, PCSK7, MBTPS1 were downregulated, while PCSK6 was enriched in diseased media. In thoracic aneurysms, only FURIN was significantly upregulated. Network analyses of the upstream and downstream pathways related to PCSKs were performed on the omics data from vascular biopsies, revealing mechanistic relationships between this protein family and disease. Cell type correlation analyses and immunohistochemistry showed that PCSK transcripts and protein levels parallel each other, except for PCSK9 where transcript was not detected, while protein was abundant in vascular biopsies. Correlations to clinical parameters revealed a positive association between FURIN plaque levels and serum LDL, while PCSK6 was negatively associated with Hb. PCSK5/6/7 were all positively associated with adverse cardiovascular events. Our results show that PCSK6 is abundant in plaques and abdominal aneurysms, while FURIN upregulation is characteristic for thoracic aneurysms. PCSK9 protein, but not the transcript, was present in vascular lesions, suggesting its accumulation from circulation. Integrating our results lead to the development of a novel 'molecular' 5D framework. Here, we conducted the first integrative study of the proprotein convertase family in this context. Our results using this translational pipeline, revealed primarily PCSK6, followed by PCSK5, PCSK7 and FURIN, as proprotein convertases with the highest novel therapeutic potential.

Dataset Information

Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI.

Background and aim

Methods

Outcomes

Conclusion and relevance

Publications

Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI.

Similar Datasets

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