Up to 27% of heart attack patients experience life-threatening events having shown no risk factors – hypertension, cholesterol, diabetes and smoking – at all.
A large group of “low risk” young people are developing coronary artery disease with no warning symptoms or way of knowing. Some patients go on to experience recurrent heart attacks despite good medical management, reflecting “residual risk”1 and areas of unknown biology. Clearly there’s more at play.
Our biggest killer
Humans are the only animal on our planet to suffer from coronary artery disease and subsequent heart attack. Yet it is our biggest killer. Chimpanzees, despite being our closest relative with over 96% shared DNA and 50% higher “bad” cholesterol than the average human, do not suffer this form of heart disease. We urgently need to find out why humans are so susceptible to coronary atherosclerosis.
There is an unmet need for quantifiable markers of vascular health to guide personalised primary prevention.
The “holy grail” of the cardiovascular field
A blood-based biomarker to detect and treat CAD before a heart attack, is the “holy grail”.
To date, efforts to detect these biomarkers have defined disease based on cardiac events such as heart attack, an approach that ignores the frequent presence of “silent”, subclinical disease in the “healthy” control group.
Because the early disease is the very condition we want to detect, our team has been working to quantify subclinical CAD by CT coronary angiography (CTCA) and pairing this with analysis of blood samples and clinical data.
We seek to prevent heart attack by discovering and translating:
new blood biomarkers that identify silent CAD that are relevant to our entire community
new drugs that target the individual’s CAD susceptibility and halt disease
Heart attacks could virtually be eliminated if we identify CAD early, and “hit it hard” with effective therapies.
What can Core 1 offer our partners?
National CAD data platform - ACDC; coordinating and harmonizing established cohorts with > 50,000 Australians with genomics/lipidomics and clinical outcomes
BioHEART – up to 15,000 participants with detailed coronary imaging, clinical data, bloods and linked outcomes.
Innovative handling and storage/analysis of raw imaging data
Novel biomarkers and risk algorithms - licensing opportunities
Dataset and blood samples to validate diagnostic tools for CAD
Dataset and blood samples to define “normal” values in patients with angiographically defined absence of CAD
BioHEART is one of our flagship studies that is still recruiting participants who are undergoing advanced imaging of their coronary arteries with CT coronary angiography. After providing informed consent, individuals provide a blood sample, along with their de-identified clinical and imaging data. Unprecedented depth of molecular phenotyping on the blood allows for machine learning experts to identify new biomarkers of coronary artery disease. Further information is provided here: short animated video
What can Core 2 offer our partners?
New risk assessment and prevention pathways in primary care in rigorous and innovative prospective studies with long term linkage outcome data
Deep engagement with community and consumers, including with detailed PROMs and PREMs
Novel endpoints to accelerate prospective testing of new blood-based markers, focussing on detection of early and treatable CAD (measured by CT) to guide treatment decisions and heart attack prevention
Joint-venture opportunities, including with our established national pathology providers and regulatory experts, to accelerate navigation of regulatory pathway for new diagnostic tools
Access to emerging risk algorithms (polygenic and multi-omic scores) aimed at detecting subclinical CAD in large number of individuals where community risk algorithms fail
Direct to consumer/patient communication tools and gamification strategies
What can Core 3 offer our partners?
Novel CAD therapeutic targets, informed by machine learning integration of clinical, imaging and multi-omic molecular data
CAD patient-derived cell and organoid models with unique phenotyping for drug library screening
Molecules with preclinical evidence to support efficacy in CAD
Novel preclinical pipeline for CAD drug development with direct consideration of unique features of human atherosclerosis
– phase II studies utilising advanced serial imaging of CAD
– phase Ill studies embedded into health with experienced and coordinated clinical trial network.
Novel approaches to prevention and application of therapies: SMuRFless CAD clinic and hitting CAD "early and hard" in primary care
An engaged international call to action CAD drug discovery and translation expert group