How mutations in blood cells affect plaque build-up in the heart arteries after heart attack

Professor Peter Psaltis, Adelaide University

Vanguard Grant

Years funded: 2026 - 2028

Heart attacks are still Australia’s biggest killer. They are caused by sudden blockages to blood flow in the heart arteries, typically from accelerated build-up and disruption of inflamed, fatty, atherosclerotic plaques. When a person has a heart attack, they usually undergo a coronary angiogram to identify and treat the culprit plaque (e.g., by stenting) and are prescribed long-term medication to prevent recurrences. However, despite this many heart attack survivors still go on to have at least one other event, such as another life-threatening heart attack, within just a few years. A major reason why this occurs is because most patients have other “non-culprit” plaques that are left behind after their first heart attack. Even with current treatment, these residual plaques can grow and disrupt to cause new heart attacks.

Inflammation is a major driver of this ongoing risk. Among factors that link inflammation and uncontrolled growth of plaque, clonal haematopoiesis of indeterminate potential (CHIP) has emerged as an intriguing new player. CHIP occurs when mutations develop in the bone marrow to cause expansion of white blood cells and increased inflammation. Recent studies suggest that CHIP mutations are common in patients with heart attack and double the risk of recurrent events, including death and repeat heart attacks. However, it is unclear how CHIP does this and how to prevent it.

This project will address an important knowledge gap by studying whether CHIP mutations, even at low quantities, lead to more aggressive growth of coronary plaques after heart attack. To do this in a timely and cost-efficient manner, we will use blood samples from an ongoing study of 300 patients in whom we are tracking residual plaque growth over the first year after heart attack by repeat imaging with photon-counting coronary computed tomography angiography. Supported by this grant, we will perform CHIP gene sequencing from blood DNA to detect and measure CHIP mutations, along with other blood-based measurements of inflammation.

Our results will inform if, and how, CHIP associates with plaque progression and uncontrolled inflammation after heart attack to help explain why it is linked to worse outcomes. This could provide impetus for future trials to test whether new treatments (e.g., anti-inflammatory drugs) can prevent plaque progression in patients with CHIP and pave the way for CHIP testing in clinical practice to identify people at higher risk after heart attack who would benefit from more personalised, targeted therapies to improve outcomes.