Skip to main content
Journal cover image

High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction.

Publication ,  Journal Article
Shavadia, JS; Granger, CB; Alemayehu, W; Westerhout, CM; Povsic, TJ; Brener, SJ; van Diepen, S; Defilippi, C; Armstrong, PW
Published in: Am Heart J
February 2020

BACKGROUND: Although spontaneous reperfusion (SR) prior to primary percutaneous coronary intervention (pPCI) is associated with improved outcomes, its pathophysiology remains unclear. The objective of the study was to explore associations between SR in ST-segment elevation myocardial infarction (STEMI) using a multimarker cardiovascular proteins strategy METHODS: We evaluated STEMI patients from the Assessment of Pexelizumab in Acute Myocardial Infarction trial treated with pPCI within 6 hours from symptom onset. SR was core laboratory-defined as pre-PCI Thrombolysis in Myocardial Infarction flow 2 or 3. Ninety-one cardiovascular disease-related serum biomarkers drawn prior to PCI were analyzed using a high-throughput "targeted discovery" panel. Expression levels for individual biomarkers were compared between patients with/without SR. A hierarchical clustering method of biomarkers identified clusters of biomarkers that differentiated the 2 groups. Associations between individual biomarkers and clusters with SR were further evaluated by multivariable logistic regression. RESULTS: Of 683 patients studied, 290 had spontaneous reperfusion; those with compared to without SR were more likely noninferior STEMI and had lower clinical acuity and lower baseline levels of troponin and creatine kinase. SR was associated with a lower occurrence of 90-day composite of death, heart failure, or cardiogenic shock. Fifty-two of 91 individual biomarkers were significantly univariably associated with SR. Forty-five remained significant with adjustment for false discovery rate. Using cluster analysis, 26 biomarkers clusters were identified, explaining 72% of total covariance, and 13 biomarker clusters were significantly associated with SR after multivariable adjustment. SR was associated with higher mean expression levels of proteins in all 13 clusters. The cluster most strongly associated with SR consisted of novel proteins across various distinct, yet interlinked, pathobiological processes (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin). CONCLUSIONS: Spontaneous reperfusion prior to pPCI in STEMI was associated with a lower risk of adverse clinical events. These exploratory data from a targeted discovery proteomics platform identifies novel proteins across diverse, yet complementary, pathobiological axes that show promise in providing mechanistic insights into spontaneous reperfusion in STEMI. CONDENSED ABSTRACT: Spontaneous reperfusion has been established with improved STEMI outcomes, yet its pathobiology is unclear and appears to involve diverse physiological processes. Using a 91-biomarker high-throughput proteomics platform, we studied 683 STEMI patients in the APEX AMI trial (290 had core laboratory-adjudicated pre-PCI TIMI 2/3 flow) and identified 52 proteins that univariably associate with spontaneous reperfusion. Cluster analysis identified 26 biomarker clusters (explaining 72% of total variance), 13 of which, after multivariable adjustment, were significantly associated with spontaneous reperfusion. Four proteins (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3, and elafin) across diverse, yet complementary, pathways appear to be associated most strongly with spontaneous reperfusion.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2020

Volume

220

Start / End Page

137 / 144

Location

United States

Related Subject Headings

  • Troponin
  • Single-Chain Antibodies
  • ST Elevation Myocardial Infarction
  • Proteomics
  • Percutaneous Coronary Intervention
  • Patient Acuity
  • Middle Aged
  • Male
  • Logistic Models
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shavadia, J. S., Granger, C. B., Alemayehu, W., Westerhout, C. M., Povsic, T. J., Brener, S. J., … Armstrong, P. W. (2020). High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction. Am Heart J, 220, 137–144. https://doi.org/10.1016/j.ahj.2019.09.015
Shavadia, Jay S., Christopher B. Granger, Wendimagegn Alemayehu, Cynthia M. Westerhout, Thomas J. Povsic, Sorin J. Brener, Sean van Diepen, Christopher Defilippi, and Paul W. Armstrong. “High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction.Am Heart J 220 (February 2020): 137–44. https://doi.org/10.1016/j.ahj.2019.09.015.
Shavadia JS, Granger CB, Alemayehu W, Westerhout CM, Povsic TJ, Brener SJ, et al. High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction. Am Heart J. 2020 Feb;220:137–44.
Shavadia, Jay S., et al. “High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction.Am Heart J, vol. 220, Feb. 2020, pp. 137–44. Pubmed, doi:10.1016/j.ahj.2019.09.015.
Shavadia JS, Granger CB, Alemayehu W, Westerhout CM, Povsic TJ, Brener SJ, van Diepen S, Defilippi C, Armstrong PW. High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction. Am Heart J. 2020 Feb;220:137–144.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2020

Volume

220

Start / End Page

137 / 144

Location

United States

Related Subject Headings

  • Troponin
  • Single-Chain Antibodies
  • ST Elevation Myocardial Infarction
  • Proteomics
  • Percutaneous Coronary Intervention
  • Patient Acuity
  • Middle Aged
  • Male
  • Logistic Models
  • Humans