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New markers and mechanisms of atherosclerosis

University of Sydney

Grant:
  • Cardiovascular Clinician Scientist Grant
Organ System:
  • Cardiovascular
Date Funded:
  • 31 May, 2019
Chief Investigator/s:
  • Professor Gemma Figtree

Project summary

Discovering and translating new markers and mechanisms of atherosclerosis.

What is the issue for NSW?

Professor Figtree is a clinician researcher whose integrated program of research extends from fundamental discovery through to clinical trials, interventional cardiology and implementation. She coordinates a team of multi-disciplinary researchers, driven by the increasing number of heart attack patients who are asking “why me”? While it is imperative that we treat established risk factors, this approach “misses” a substantial group of patients who are not identified as “at risk”.

Indeed, the proportion of patients presenting with life-threatening heart attacks to Professor Figtree’s hospital with 0 standard modifiable risk factors [SMuRFs] has increased from 13% 10 years ago to ~30% in 2014. Her driving hypothesis is that major residual mechanisms for atherosclerosis can be unravelled by comprehensive molecular characterisation of such “athero-vulnerable” and “athero-resilient” patients.

What does the research aim to do and how?

Professor Figtree has established and continues to expand a suite of biobanks that combine state-of-the-art imaging of the heart with a panel of high-technology “omics” measures and clinical data. Through novel computational bioinformatics approaches she plans to unravel new mechanisms and biomarkers of both coronary artery disease susceptibility and resilience.

Given coronary artery disease kills approximately 3x more Australians than the leading individual cancer, the expanding group with “SMuRFless” coronary artery disease has enormous public health significance. Furthermore, new mechanistic pathways will likely have broad relevance, bringing improved risk stratification and targeted preventative management to all patients at risk of atherosclerosis. She has established a collaboration with Professor Alex Brown to ensure novel markers can be tested for efficacy in the Indigenous population.

Discoveries made during the proposed program of work will guide the design of dedicated trials testing the ability of new markers to guide clinician decision making above and beyond traditional risk factor profiling, with beneficial outcomes on health. Existing intellectual property (USA14/069913), a formal research agreement with NSW Health Pathology and CDA with Abbott Diagnostics highlights Professor Figtree’s commitment to commercialisation and translation. Her position in national and international clinical leadership groups and extensive network of collaborators leading cardiovascular advances and practices will ensure rapid translation and benefit to international patient populations.

In addition to the risk identification and prognostic value of Professor Figtree’s study, her team is well positioned to discover completely novel pathophysiological pathways relevant to atherosclerosis. These will pave the way for testing new therapeutic targets. Her team are well placed to capitalise on such discoveries, with an established pipeline for drug development that progresses from preclinical disease models to humans.