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What’s the signature of a healthy heart?

Instead of treating the “average person,” the Courtois Cardiovascular Signature Program aims to treat every person as a unique individual

The Courtois Cardiovascular Signature Program ─ a research project led by Dr. Matthias Friedrich and Dr. Nadia Giannetti at the Research Institute of the McGill University Health Centre (RI-MUHC) ─aims at developing personalized medicine in cardiology in a cohort of 4,000 participants who will be followed for at least 10 years. It will collect extensive amounts of genomic, microbiomic, imaging and lifestyle data, and use advanced machine learning to identify what part of their individual cardiovascular signature is linked to their good or poor health.

In common usage, a signature is the distinctive and personal inscription of one’s name. It’s an arrangement of a series of letters handwritten and stylized in a unique way. In the context of this research initiative, a signature refers to the unique combination of a multitude of markers that may have an influence on the cardiovascular health of an individual.

“This project is about wiring a lot of quantifiable data points that are not necessarily targeted by physicians in their medical history-taking to discover what makes a healthy heart, and what markers are associated with an increased risk of cardiovascular disease,” explains Dr. Friedrich, a cardiologist at the Royal Victoria Hospital of the MUHC and an investigator in the Cardiovascular Health Across the Lifespan (CHAL) Program at the RI-MUHC, with a particular interest in magnetic resonance imaging. “The idea is to have a more holistic data set for each individual and not just focus on assumptions that may or may not be true.”

The research team plans to enroll 4,000 participants, aged 35 to 79, one third of them healthy, one third considered at risk for heart disease, and one third with known heart disease. All participants will provide blood samples and undergo various tests, like an electrocardiogram and a walk test, as well as cardiac and cerebrovascular magnetic resonance imaging (MRI). In addition, they will complete online questionnaires about their lifestyle, family history, medications and nutrition, and they will use wearable digital health devices to monitor their physical activity, heart rate, temperature and similar markers. The data collected will be used to discover the unique profile of each participant – their cardiovascular signature.

“In the context of that project, we look at the genes and epigenomes – and how behaviours and environmental factors may induce changes that affect how the genes work,” explains Dr. Friedrich. “We also analyze the microorganisms present in the gut, as there is growing evidence that interactions in the microbiome can play a role in cardiovascular disease. Finally, we look at images of the heart, blood vessels and arteries. For that purpose, we are lucky to have access to a research MRI scanner, and to a dedicated team to interpret the images.”

Because nobody can wrap their mind around all these aspects, the researchers will use artificial intelligence to analyze the data and discover unsuspected connections between all the data points included in the signatures. The researchers will also work with industry partners who, for example, might want to measure the impact of tracking certain vital markers with wearable devices, in order to determine if people with certain lifestyles or conditions have an increased benefit in using them. In return, the partners will leave their data within the platform so that it can be used by other research teams to understand future questions.

“We call it a program, but what we are building is a platform that will allow for performing an infinite number of studies,” says Dr. Friedrich. “There are a huge number of possibilities, not only for academic partners to make progress in research, but also for the industry to use it as a study environment to contribute to advancing our knowledge on cardiovascular health.”

Dr. Friedrich and his team believe that in addition to facilitating the identification of new therapeutic targets, this model will help us understand why some people respond to interventions and others not. It may also serve as a model for truly personalized preventative medicine. “It’s one of the most forward-thinking research initiatives I could think of,” he says.

“We want to find out why some people with unhealthy life habits or environmental factors remain healthy and why other people with healthy behaviours develop heart disease,” he adds. “If we can identify the critical parts in the individual signatures that are associated with a protective effect or an increased risk for illness, we might eventually be able to target at-risk individuals and give them preventative advice to lower their risk.”

Co-led by Dr. Nadia Giannetti, Associate Physician-in-Chief, MUHC Department of Medicine, this research initiative is supported by the MUHC Foundation and was made possible thanks to a 18M$ donation from the Family Courtois Foundation. It also involves Dr. George Thanassoulis, Lead in Genomics, and Dr. Abhinav Sharma, Lead in the Digital Health Initiative, both members of the CHAL Program at the RI-MUHC, as well as a dozen research staff members.

So far, the research team has reached approximately 25% of its recruitment target. If you are interested in participating, please visit cvsignature.ca.

Dr. Matthias Friedrich,  Scientific and Imaging Director, Courtois Cardiovascular Signature Program
Dr. Matthias Friedrich,  Scientific and Imaging Director, Courtois Cardiovascular Signature Program