Leaders in Cardiovascular Research: Nilesh J. Samani Free

Biography: Professor Sir Nilesh J. Samani is Professor of Cardiology at the University of Leicester, Consultant Cardiologist at the Cardiac Centre, Glenfield Hospital, Leicester and Medical Director of the British Heart Foundation. Previously, he was Head of the Department of Cardiovascular Sciences at the University of Leicester and Director of the Leicester National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease. Professor Samani’s clinical practice is in adult cardiology. His research interests are focused around understanding the inherited basis of common cardiovascular diseases, especially coronary artery disease and hypertension. He is a Fellow of the UK Academy of Medical Sciences, is an emeritus NIHR Senior Investigator and holds fellowships of the Royal College of Physicians, the American College of Cardiology, the American Heart Association, and the European Society of Cardiology.

Summary of interview

Q: What is your secret of success—is it ambition, or talent?

An interesting question to start with! I think it is both, not one or the other.

Actually, it is more than that. I think there is also commitment. And to some extent, luck. I think people will agree that what you do in life somewhat depends on where you are, the people and mentors around you and the circumstances you find yourself in. So, it is a mixture of these things.

Q: What would you say is the force that pushes you on?

Ultimately, it is patient care and benefit. For most doctors, it is the same. I do not think this is anything special. You enter this profession, whether you do research or clinical practice, or a combination, to enrich the lives of the people and the patients you look after.

Q: Among your many scientific and clinical achievements, which would you identify as the one you are the most proud of?

I think the importance of my achievements are for others to judge. I am of course proud of the discoveries we have made on genetic determinants of cardiovascular diseases, especially coronary artery disease (CAD) as these are beginning to pay dividends in terms of new therapeutic targets and earlier identification of people at risk through polygenic risk scores.

However, reflecting on it, the thing I have found most satisfying is my work on telomeres. This research was really prompted by observations in the cath lab (catheterization laboratory). You cath an 80-year-old woman with aortic stenosis and find her arteries are completely clean. No CAD. Then you ask: ‘why is that the case? Although CAD is age-related why do some people never develop CAD and why do some people develop it at a very early age?’.

A lot of this variation relates of course to known risk factors. However, because CAD is age-associated, I started to wonder whether what we are seeing was signs of accelerated biological ageing in some people. In the late 1990s, that led me to looking at telomere length as a marker for biological ageing and its relationship to CAD at a time when nobody else was looking at this. We published our first paper in The Lancet showing that people with CAD had shorter telomeres. This could, of course, be due to a lot of reasons. Over the last 20 years, we have explored this in greater detail and shown that variation in telomere length is a causal risk factor for CAD using genetic and other evidence.

Part of the reason for my pride here is that it opened up a new area of research, around biological ageing, which did not exist in cardiovascular medicine. Lots of groups are now working on this. Recently, my team achieved the major task of measuring telomere length in almost half a million people from the UK Biobank. A singularly terrific achievement, to open up this field even more and provide a resource for the community at-large to exploit.

Q: As a scientist, how do you identify what is an important question for science?

This is an interesting question without a single answer. To some extent it must start with your passions. Mine were in genomics and genetics. Then you think about what the most important questions are depending on the topic you want to study. For me dissecting the genetics of complex cardiovascular diseases and traits seemed both challenging and rewarding, thinking about new treatments, as well as better prognostics.

Q: Switching topics, what is the role of a mentor in the life of a young scientist?

I would say to young people reading this, identifying a good mentor and someone who supports you is critically important. Throughout all phases of my career, even until recently, I have found someone to act as a mentor. I was very lucky when I was a medical student and a junior doctor to have Professor John Swales, Foundation Professor and Chairman of Medicine at the University of Leicester and a world leader in hypertension, who guided me. Then Professor David De Bono, who was Professor of Cardiology at the University of Leicester and who did a lot of work on thrombolytics, supported me as I trained in interventional cardiology at the same time as tried to maintain my research.

A good mentor is somebody who advises but does not order. Someone who supports and guides you while giving you the independence to do things.

When they do their mentoring well it is almost unnoticeable until much later on.

Q: Cardiovascular Research is a basic and translational science journal, and we always ask—how can we convince people of the importance of basic science?

Let me illustrate it with an example and then expand on it a bit more. Think about the CRISPR-Cas9 story. The people that were working on it were looking at a bacterial system—completely unrelated to medicine. It was about how bacteria manipulate their DNA. Look at what this basic science discovery is achieving now. It has rapidly translated into vast areas of application in medicine, and we are talking about gene editing as a possible reality in the future for curing inherited heart diseases. I am pretty sure the people who discovered it had no idea that it would have that broad an application, particularly for cardiovascular diseases.

As Medical Director of the British Heart Foundation (BHF), I can tell you that about 60% of our funding currently goes into discovery science, because it is so vital. Clinical advances would not exist without basic discovery. So, supporting basic science research for its own sake is very important.

Q: When you look at the landscape of basic discoveries in the last five years, which do you see as giving hope for novel therapies?

I already alluded to CRISPR-Cas9, which is revolutionizing research and medicine in so many ways. The other thing related to my own field of research is better understanding of the genes that affect risk of cardiovascular diseases—this is providing a plethora of new therapeutic targets with the additional certainty that the targets are causal.

Perhaps the discovery that has excited me most in recent months is the evidence that some of the newer drugs developed for diabetes have profound effects on weight loss, independent of diabetes. Obesity is such a big problem for us. That we may now have relatively safer drugs to tackle it, I think, is a big breakthrough. This is of course not to downgrade lifestyle and other efforts to prevent obesity in the first place.

Q: Looking at research funding, why do you think cardiovascular diseases fall so short of cancer in terms of investment?

That is a great question. As Medical Director of the BHF, you would expect me to think about this a lot. Even in the UK, Cancer Research UK, our equivalent charity-based funder, has four to five times the funding power that we do, despite disease prevalence for cardiovascular diseases being higher than for many cancers. Why this is the case is in my view complex.

First of all, cancer has that sense of it happening to you rather than you being responsible and the possibility of curative treatment. It is also a single word, whereas cardiovascular disease is very broad—there is stroke, heart attacks, heart arrhythmias, and heart failure. There is a sort of more diffuse nature of cardiovascular disease rather than a single all-encompassing word that you can immediately relate to.

The second issue, which concerns me, is that many people and politicians consider cardiovascular diseases to have been ‘solved’, because of the successes we have achieved in the last 40 years. Or that some people consider it to be a disease of lifestyle. It is your problem, rather than something that happens to you.

At the BHF, we obviously look at how we can bring a greater focus on funding for research into cardiovascular diseases. We hope we can inject urgency into the cardiovascular cause. What other disease means you can leave home in the morning, and not return in the evening? Cardiovascular diseases have been not solved, they devastate more families than any other diseases and we need to get these messages across.

Q: Much of the importance of cardiovascular health has been brought into focus recently by the COVID-19 pandemic. How do you think COVID-19 will change cardiology?

In a number of different ways. In the practice of cardiology, things had already started to change around the use of digital technology and COVID-19 has accelerated that change. We need to harness the potential of providing better care for patients using digital technology—without exacerbating inequalities. That is the challenge.

The other thing that COVID-19 has illustrated is the power of people coming together and collaborating: industry, academia, and government. Particularly around data. A lot of the understanding around COVID-19 came about by assimilating large-scale data. There has been a willingness to share data which had been a problem previously. Through COVID-19, the barriers have come down. And I hope we do not go back to where we were before.

So there are changes, both for research, and for clinical practice.

Q: And the BHF has participated in the effort to use this opportunity to utilize access to data, generation of data and support for on-going trials, is that right?

Our ambition to harness the value of routinely collected healthcare data for research, and to facilitate more efficient digitally based clinical trials, predates the pandemic. The UK with its single healthcare provider is a fantastic place to do this. That is why we established the BHF Data Science Centre in partnership with Health Data Research UK (HDR UK) and with strong patient and public engagement and involvement.

The pandemic has also demonstrated the value of such an infrastructure. The BHF Data Science Centre, working with NHS Digital, rapidly set up a trusted research environment that has linked COVID-19 data with other healthcare data on 55 million people. This is facilitating and supporting a whole series of large-scale projects on COVID-19 and cardiovascular health. For example, by bringing all the data together they have quantified the small excess risk of arterial and venous thrombosis in people from different COVID-19 vaccines. This really illustrates the power of data if you can bring it together.

Q: Thinking about your work within the BHF, what would say was your greatest success?

The BHF is a wonderful organization. It has a fantastic sixty-year track record history of promoting better health through research. So when I joined it almost 5 years ago now, it already had a well-established and respected system for funding research mainly as a response mode funder. Which means we ask people to come to us with their ideas, and we try to fund the best.

I was not going to change this because in my view in the end it leads to the best discoveries and progress. But I also felt we could do a bit more in terms of strategic initiatives to support science. The BHF Data Science Centre, which I mentioned earlier, is one of these initiatives. We have also set up the BHF Clinical Research Collaborative to support and facilitate clinical research groups in different areas of cardiovascular medicine coming together and identify and prioritize the most important research questions in their area and prepare compelling applications to address these questions and deliver them. We also recognized the overlap between the infrastructure that the BHF supports through our chairs, Centers of Excellence and our Accelerator Awards and the infrastructure that the NIHR supports through their Biomedical Research Centers. So we have established the NIHR-BHF Cardiovascular Partnership to leverage this great capability to address important cross-cutting and multi-disciplinary research questions at scale. Indeed, the Partnership has been the forefront of setting up some national Flagship Projects on Covid-19 which has brought the CVS community and others together.

Looking more widely, and based on my own research ethos, I am keen to support more international collaborations for BHF funded researchers. I am therefore very proud of the joint funding scheme we now have with the DZHK and the Dutch Heart Foundation, which is now in its third cycle of funding. Recently, we have also announced the setting up of the Global Cardiovascular Research Funders Forum which brings several major cardiovascular research funders together for the first time to promote joint working. One of the early initiatives of the forum is to establish a platform to facilitate multi-national academically initiated clinical trials.

Finally, I am sure you are aware of the BHF’s Big Beat Challenge which we announced at the ESC Congress in 2018. This is an international competition with a 30-million-pound award for a transformational programme of research in any area of cardiovascular medicine. We had enormous interest in this with 75 fantastic outline applications form round the world. The international advisory panel shortlisted four teams to develop full applications. COVID-19 has delayed consideration of these, but we are back on track and hope to announce the winner soon.

Q: Listening to all of this, how do you find time to pursue all these aspects of your work?

[Laughs] I could probably turn the question to you: how do you find the time to do all the things that you do?

I think it is driven by passion, really. Maybe my wife will not agree with me completely when I say this but, of course, if you enjoy what you are doing then you do not partition your time between work life and home life. However, seriously I should probably do this better. I tell my patients to do it better!

But if it is passion-driven, then it is easy to cope with. Every bit of my work, I enjoy thoroughly, so that is why it is easy to do.

Q: Do you still have time for additional passions?

Sports. I am an avid sports fan. Particularly football, but other sports as well—cricket and rugby. I am a big supporter of my local team, Leicester City Football Club, which many of your readers may know about now, because as one of the ‘smaller’ clubs we have done very well lately.

I have always wanted to be the club doctor, at least their cardiologist, but I do not think the invitation is going to come. I hope the owners will read this article!

Conflict of interest: none declared.