Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE)

Health Research BC is providing match funds for the Master’s Studentship 2023 Award, supported by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN). As part of my work, I will be conducting the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study. The ACCURATE, BC-based study is also funded by Genome British Columbia and Vancouver Coastal Health Research Institute (VCHRI).  

Familial hypercholesterolemia (FH) is one of the most common genetic diseases, affecting 1 in 250 individuals and elevating the risk of early onset heart disease. About 1 in 14 individuals who have a heart attack under 60 years old have FH, but 99% of them were not aware of it before their heart attack. In British Columbia, over 85% of individuals with FH remain undiagnosed due to the lack of genetic testing, leading to missed opportunities for early intervention.  

The ACCURATE study aims to investigate how genetic testing for patients hospitalized with acute coronary syndrome (ACS) can improve the diagnosis of FH, influence physicians’ treatment approaches, patients’ medication use, and ultimately reduce the disease burden for these patients.  

The outcomes will contribute to understanding how genetic diagnosis influences patient care in acute cardiac settings, with the hope of influencing healthcare practices in the entire province. This will improve the health of British Columbians and enhance the reputation of BC as a leader in genomic clinical care. 

End of Award Update – December 2024

Results

The ACCURATE study found that 8% of young acute coronary syndrome (ACS) patients with untreated LDL-C >4 mmol/L had a genetic diagnosis of Familial Hypercholesterolemia (FH). This is a prevalence 24 times higher than in the general population. Importantly, genetic testing reclassified 88% of these patients initially categorized as “unlikely” or “possible” FH to a confirmed diagnosis of “definite” FH. These findings show that genetic testing can identify FH in patients who would otherwise be missed using traditional clinical criteria alone. Additionally, 24% of patients were identified as having polygenic hypercholesterolemia. These patients did not carry variants in the known FH-causing genes but had a high LDL polygenic risk score (PRS), indicating that other genetic factors contribute to their elevated cholesterol and heart disease risk. Altogether, our current results highlight the value of both genetic testing and polygenic risk scoring in detecting, diagnosing and understanding FH in young high-risk patient populations.  

Impact

The ACCURATE study has addressed a significant gap in care by diagnosing FH-positive patients in an acute cardiac care setting where genetic testing is not currently performed and therefore, these patients would likely remain undiagnosed. By providing treating physicians with genetic test results within 1 month of their patients’ ACS event, this study has raised awareness of the genetic basis underlying their patients’ premature cardiovascular events. While it is too early to measure changes in long-term outcomes, this approach ensures physicians are better informed to consider these insights in real-time clinical decision making and follow-up care. The rationale for conducting this research and the early results from ACCURATE has also inspired conversations with policy makers, industry experts, and healthcare providers in BC about the importance of integrating clinical FH genetic testing in the province. 

Potential Influence 

This study has the potential to change the standard of care for young patients with heart attacks by making FH genetic testing routine, especially for those with high LDL levels. This would lead to earlier detection of FH and may also highlight the importance of tailoring treatment intensity based on genetic findings, thus allowing physicians to identify those who may require more aggressive interventions to achieve lipid targets and prevent further cardiovascular events. Over time, this approach could help lower the rates of heart attacks and other cardiovascular events caused by undiagnosed or undertreated FH in British Columbia. Beyond its local impact, the study may provide a clear model for integrating genetic testing into acute cardiac care that can be adopted nationally and internationally.  

Next Steps

ACCURATE is ongoing as patients in the Active Testing Phase are still being followed to assess outcomes including treatment intensification, lowest LDL-C achieved, guideline lipid target attainment at 15-months post ACS, and the rate of recurrent cardiovascular events. Next steps include assessing how these genetic results for FH impact physicians and their patients, particularly how they are integrated into clinical care. For this reason, we plan to conduct a survey to explore physicians’ reactions to and concerns regarding FH genetic results, assess the influence on clinical workflow, changes in treatment plans, and identify ways to support physicians in better diagnosing FH and delivering optimal care for patients. Additionally, exploring genetic testing for first-degree relatives may be a future direction to help identify more individuals with FH, therefore extending the reach and impact of the study.