Investigating known and novel biomarkers for risk stratification in cardiovascular disease

Student thesis: Doctoral Thesis

Abstract

Biomarker research in cardiovascular disease (CVD) is increasingly challenging with very few biomarkers being adopted into clinical practice. CVD risk assessment scores are in place to guide primary and secondary prevention however, they require considerable improvement. At present, there is no blood test that can predict who is at higher risk of first or recurrent cardiovascular events. Since CVD is a complex inflammatory disease with several underlying biological pathways, one biomarker is unlikely to define an individual’s cardiovascular risk. However, it is possible to improve the current risk assessment scores using a multimarker approach. To date no one has investigated the many known and potentially novel markers in individuals at various levels of CVD risk. Therefore, in this present work, 344 participants at various levels of CVD risk (according to the European Society of Cardiology risk score), were recruited to explore potential biomarkers for risk stratification.

Proteins belonging to the tumour necrosis factor alpha (TNFα) inflammatory pathway, which has previously been shown to play a major role in CVD initiation and complications, as well as novel proteins associated with atherosclerosis, plaque rupture and thrombosis were explored using ELISA, multiplex proximity extension assays (PEA) developed by Olink Proteomics®, MSD® MULTI-SPOT Assay System and quantitative real-time PCR. Results reveal a complex panel of markers that were able to identify individuals at very high risk of CVD. Furthermore, more specific panels of markers were discovered that were able to further stratify patients at very high risk of CVD according to their cardiac history and co-morbidities. The present investigation overall demonstrates that a combination of proteins from several inflammatory pathways are necessary to evaluate an individual’s risk of first or recurrent cardiovascular events as well as the risk of developing CVD-associated co-morbidities and treatment response. The blood biomarker panels discovered in this present work can be used to establish a unique proteomic disease signature for each individual recruited to the study. This will aid future long term prospective longitudinal studies in evaluating the clinical utility of such panels alone or in combination with current risk prediction tools.
Date of AwardMay 2018
LanguageEnglish
Awarding Institution
SupervisorVictoria Mc Gilligan (Supervisor), Tony Bjourson (Supervisor) & Aaron Peace (Supervisor)

Keywords

  • Heart Disease
  • Coronary Artery Disease
  • Atherosclerosis

Cite this

Investigating known and novel biomarkers for risk stratification in cardiovascular disease
Chemaly, M. (Author). May 2018

Student thesis: Doctoral Thesis