Meet the team detecting heart disease before it strikes

Many are familiar with the most commonly known risk factors for cardiovascular disease, such as high blood pressure, high cholesterol, obesity, diabetes and history of smoking.

However, approximately one-quarter of first-time heart attack patients do not have any of these risk factors, and develop ‘silent’ coronary artery disease (CAD) with no symptoms at all.

CAD Frontiers, an international research team led by cardiologist Professor Gemma Figtree from the Faculty of Medicine and Health, is getting straight to the heart of the matter. Professor Figtree and her team are working on a new approach to heart attack prevention that does not rely on risk factors and symptoms to predict an individual’s heart attack risk.

CAD Frontiers has a vision of ‘a world without heart attacks’. They are aiming to do so by addressing the unmet clinical needs of people traditionally considered at low risk who suffer sudden death or heart attack due to undetected coronary artery disease.

The team is developing precision diagnostic tools to detect preclinical coronary artery disease early, shifting the focus from assessing risk factors to determine a person’s ‘probability’ of heart attack to precisely identifying their actual disease burden, allowing for more informed and proactive prevention and treatment decisions.

In parallel, CAD Frontiers is developing advanced pharmaceutical therapies that target such early coronary artery disease directly, to prevent it from progressing to heart attack.

“Heart attacks could virtually be eliminated if we could identify disease – including ‘silent’ coronary artery disease – early, and ‘hit it hard’ with established and emerging therapeutics,” says Professor Figtree.

“We hypothesise that previously unrecognised molecules exist in the blood that can be powerful biomarkers to inform us of the burden and activity of ‘silent’ coronary artery disease. Our overarching aim is to develop a series of blood-based coronary artery disease biomarkers to transform primary prevention of heart attack. At the same time, we will identify causal metabolic and regulatory pathways driving coronary artery disease, and therapeutic targets within these pathways.”

Known risk factors do help to predict the development of atherosclerosis (restriction of the blood flow through the coronary arteries); however, a major challenge is to target preventive therapy to the right individual at the right time.

“While traditional risk factors help to predict events, it is difficult to motivate patients to commit to lifelong drugs based on the probability of suffering a heart attack without knowing that they are susceptible or already have asymptomatic coronary artery disease,” says Professor Figtree.

“In fact, a substantial proportion (14–27 percent) of heart attack patients have developed their atherosclerosis silently over many years in the absence of apparent risk factors. There is clearly more at play.”

Early detection at individual level of the actual presence of plaque in the arteries – the causal factor in heart attack – would be a precision-focused approach, and one with flow-on implications for subsequent treatment decisions.

“Most drugs currently used for coronary artery disease and heart attack prevention target the modifiable risk factors, such as statins (which target cholesterol) and angiotensin-converting enzyme inhibitors (which target blood pressure),” says Professor Figtree.

“However, individual susceptibility or resilience to developing atherosclerosis against a particular ‘load’ of risk factors is poorly understood.”

CAD Frontiers’ drug development program takes a novel approach, incorporating the relevant expertise, resources and partners to advance and share new knowledge regarding causal factors of coronary artery disease, identify diagnostic targets, and develop new treatments through to commercialisation – traversing what Professor Figtree describes as “the complete translational pathway from patient bedside to the bench and back again”.

“We hypothesise that, by applying strategies informed by factors driving individual susceptibility as well as resilience to coronary artery disease, we will continue to discover and translate new therapeutic pathways and drugs with relevance to all individuals at risk of heart attack and sudden death.

“The new armoury of drugs for treating coronary artery disease emerging from and accelerated by this program will result in improved heart health for all Australians and, by extension, all global citizens, as well as building capacity for the next generation of Australian cardiovascular researchers and the Australian med-tech ecosystem.

“Australia already has a well-deserved reputation for the quality of its health and medical research. CAD Frontiers is uniquely positioned to make a major contribution to improving cardiovascular health, reducing premature cardiovascular death and human suffering, increasing productivity and reducing direct healthcare costs.”

The University of Sydney is a founding partner of CAD Frontiers and has contributed significant support towards the first stage of its research program and will continue to extend its support to the next stage. This includes generous contributions through the University’s core research facilities and its Cardiovascular Initiative; philanthropic support; bioinformatics capacity building and linkage to the translational omics and bioinformatics hub within the Charles Perkins Centre’s integrative systems and modelling theme and the Faculty of Science’s Centre of Precision Data Science; commercialisation strategy; and significant contributions from academic and professional staff.

Learn more about about CAD Frontiers here.