Using genetics improve prevention of heart disease

Dr Chenglong Yu, Monash University

Vanguard Grant - 2 Year

Years funded: 2025 - 2026

Using genomics to personalise heart disease prevention

Primary prevention strategies aim to deter the development of cardiovascular disease (CVD) in asymptomatic individuals. However, effective primary prevention strategies remain elusive. Low-dose aspirin has been a popular option but has recently become controversial due to its bleeding risks, especially in older adults. Recent aspirin primary prevention trials, including the ASPREE trial in Australia, have shown more harm than benefit in the general community, owing to these bleeding risks.

Targeted strategies through genomic risk profiling

However, we hypothesize that certain high-risk subgroups of the general population (identifiable through genomics) may still derive more benefit than harm from aspirin, in the primary prevention setting - with the benefits outweighing bleeding risks. If we can identify and target aspirin and other preventive interventions to these subgroups using genomics, it represents an innovative opportunity to develop and optimize “precision prevention” strategies - moving the field beyond traditional “one-size-fits-all” population methods.

Our group has shown proof-of-concept of this genomic-driven approach, by stratifying the ASPREE trial population using lipoprotein(a) genotypes, then showing that aspirin benefits outweigh the harms of bleeding in certain subgroups - based on the prevention of major adverse cardiovascular events. Our proposed Vanguard project now seeks to expand this impactful work, by using polygenic risk scores to further stratify the ASPREE population, examining other outcomes including atrial fibrillation, stroke and type 2 diabetes, whilst more rigorously investigating the genetics of bleeding risk.

Our project will also train young scientists in the highly sought-after skills of genomic epidemiology in CVD. The study is supported by an exceptionally large randomized controlled trial cohort (ASPREE), experienced investigators and robust research infrastructure at Monash University, to ensure future success, feasibility, and return on investment. The expected outcomes include high-impact research outputs, building capacity in ""genomic-driven"" clinical trials and targeted preventive strategies, and enabling the application of genomics to preventive cardiology.