Leaders in Cardiovascular Research: Salim Yusuf

Watch the interview here:https://youtu.be/mmuTMOcW-yw Biography: Dr Salim Yusuf is Distinguished Professor of Medicine and Clinical Epidemiology & Biostatistics at McMaster University in Canada. He is also Executive Director of the Population Health Research Institute at McMaster University, Chief Scientist at Hamilton Health Sciences, Past-President of the World Heart Federation, and Senior Advising Editor of Cardiovascular Research. Q: What is the secret of success in science—is it ambition, or talent? I wouldn’t put either at the top. You need many things; but the most important thing is to ask important questions that make a difference to people. Then, it is often a long journey. It takes a long time to answer those questions. So a serious researcher needs to put in the necessary efforts, which can often be for a decade or longer. It is important to get the big picture right, but to also get the details right—then work very hard to tackle the questions you have set out to address. Q: And how do you know the question is important? There are different ways that you try to make an assessment. If something is more common, it’s likely more important than something less common because of the human impact. If you’re trying to make a difference to people’s lives, dying or living or having a heart attack or a stroke—that is more important than changing parameters like a blood marker, such as glucose or lipids. So, it’s what health outcome that you try to impact, and how many people would be affected that makes a question more important. However, sometimes something can be very important even when it doesn’t conform to these parameters. This could be work that leads to a fundamental conceptual change or a major improvement in our understanding of disease. There are different kinds of questions and often people must make up their own minds about what is important, which questions they are interested in and for which questions they have the skills to address. Q: Having addressed many important questions throughout the years, can you identify which of these made the biggest difference? Doing the large simple trials in acute infarction with beta-blockers, thrombolytics, and aspirin in the ISIS trials made a big difference. But the key thing was to change the culture of clinical research and the way people worked selflessly and collaboratively to address important questions that improved the health of millions worldwide. It brought hundreds of thousands of investigators to work together to answer important questions at little personal gain. When I moved to the United States, establishing the SOLVD studies was important. They were the first major trials which showed we could actually change the course of heart failure. When I came to McMaster University, our studies which showed ACE inhibitors work in people without heart failure are also important, as they demonstrated a new way of avoiding heart attacks, strokes or deaths in high-risk people. Conceptually, our studies of dual antiplatelet therapy demonstrated the value of blocking different platelet activation pathways and this was further expanded in the recent COMPASS trial where low-dose rivaroxaban, a factor Xa inhibitor, combined with low-dose ASA reduced CVD events substantially. The INTERHEART and INTERSTROKE studies were the first to study the impact of risk factors on CVD globally as well as whether their impact varied in different parts of the world. This has now been followed by the PURE study. So, there are different studies, they’re all important, but I am most proud of developing a global collaboration through global friendships, addressing important questions with a team and building global capacity to do good research. Q: You mentioned the PURE study. It is changing, and it for a number of years has changed, our view of cardiovascular risk. What question led to the creation of such a large effort? The idea of PURE was born in the late 1990s, although some kernels existed even before then. It emerged from the INTERHEART study as it was happening, when we realized that the risk factors more or less behaved the same worldwide. The next question we asked was: do risk factors explain the differences in heart attack rates and stroke rates between different countries and societies? Our thinking was that it was urbanization and increasing development that led to more risk factors and therefore, more cardiovascular disease. And indeed, we found that with urbanization and in richer countries, risk factors were higher compared to poorer countries or people living in rural areas. But we found that cardiovascular disease and mortality did not track with it—in fact, if anything, although rich countries had more risk factors, they had less cardiovascular disease. This paradox emphasized to us that modern health care and health systems had a much larger benefit than what we had suspected. We are now looking at new risk factors or syndromes such as frailty, which we think is a big issue as people age and in vulnerable populations, especially in poor countries. Frailty may be a marker of vulnerability to dying when someone has a health issue, but it may also be influenced by early life factors and other factors that play a role throughout a person’s life. I think our current concepts on the causation of CVD are incomplete and have to evolve; and that risk factors alone are not responsible for disease, or death. It’s the importance of the health care and health systems, as well as other factors like frailty that may be equally relevant. We are also looking at societal factors as they influence health behaviours and risk factors but also how care is delivered in different healthcare settings and societies. Q: What other aspects of cardiovascular biology and epidemiology are now the main topics in the PURE study? I think understanding societal factors and the impact of health systems is very important because the use of simple, proven therapies like anti-platelet agents, statins, getting people to stop smoking and healthy diets is very, very low. Practically, every proven therapy, even in rich countries, is not used by more than 40% or 50% of the people who should be receiving them. So it’s not just a matter of telling people what to do or having the evidence, there are societal and systems related barriers we need to overcome. Understanding those barriers at a societal, health systems and individual level becomes very important. I believe that the next decade, or next 20 years, is not a time where health is primarily improved by personalized medicine. It’s going to be improved by understanding why we cannot translate what we already know into practice. And we need to improve our understanding at all three levels: a societal, a health systems and an individual level. Q: Many people say the pharmaceutical industry is no longer that interested in developing new therapies in the cardiovascular field. What is the reason for this? Cardiovascular disease is still the number one killer, or at least a cause of premature deaths worldwide—but the disease pattern is shifting. It has shifted from younger to older people. It has shifted from richer to not-so-rich people. It has shifted from rich countries to poorer countries. In some of the rich countries today, cancer is more common as a cause of death than heart disease. Canada is an example of that. I think we’re going to start to see a transition from one type of non-communicable disease (cardiovascular) decreasing, to other forms increasing, like cancers. Since the investment of the pharmaceutical companies is almost always in regions of the world where they can generate a reasonable return on investment, they’re going to invest in diseases that are more common in the rich countries. Because cardiovascular disease is coming down in richer countries due to the substantial progress that we have made, there is a need to pay greater attention to other diseases. Not surprisingly that is where industry is shifting its attention to. Having said that, there are still companies investing in cardiovascular disease and new pathways to prevent clotting, lower blood pressure, and reduce cholesterol. So it’s not to say investment has come to a standstill, but certainly more new drug discoveries and work is being done in diseases outside cardiovascular disease. We have made so many advances in cardiovascular disease that, as a society, we need to make advances in other common diseases as well. It’s not inappropriate to have a shift. Again, when we have this large body of evidence that we’re not putting into practice fully, surely that’s got to be a priority. We shouldn’t think of research in cardiovascular disease as being entirely pharmacologically oriented. It’s got to be health systems, structural, social. Those are the things we have to emphasize. Q: What’s the future for Salim Yusuf? What’s your next ambition? Now my next ambition is to promote research worldwide, especially on conditions that affect people in poor countries. Building capacity to help and mentor younger people in our group and in other countries is a priority. When I say, ‘our group’, I don’t just mean in Hamilton—but around the world that we collaborate with, to help them answer big questions by empowering them. Hopefully such an approach will help them overcome local problems in their own countries. And hopefully they learn something from my experiences that they can use to emulate me. I’d like the next generation to have a greater impact than I have had. Doing the same is not good enough. I think there are a lot of wonderful people out there who are truly committed, and I’ve been fortunate to work with so many of them. I won’t mention names because there are so many of them. Many are here in Hamilton, but many more are around the world. Q: As a former and current leader of the World Heart Federation (WHF), where do you feel is the best place of convergence between this institution and the European Society of Cardiology (ESC)? I think there is already a good convergence between the two organizations. The ESC is a partner of the WHF, as is the American Heart Association (AHA), American College of Cardiology (ACC), and several other mid-sized national foundations like the British Heart Foundation, the Canadian Heart and Stroke Foundation, and a few others. So that convergence in goals is important. The WHF is really quite a modest organization in terms of funds. It doesn’t have huge resources, so it has to work through member organizations and in partnership with other leading likeminded organizations such as the 190 cardiology societies and foundations around the world. I see a role in empowering these people to do the right thing in their own country. The WHF has limited resources and manpower, but it does have a grand and noble vision. I think the AHA, ESC, ACC—the three big groups—are important, Japan is important, China is important, India is important but hasn’t organized itself as well; along with the UK, Canada, and a few others. Many major societies in Europe are not formal members of the WHF, like France or Germany—they ought to be. These are important countries that can make a difference. The Scandinavian countries are part of the WHF but could do more. I think creating a global coalition of key societies and foundations around the world will be critical. I am really pleased that Professor Barbara Casadei, the current President of the ESC, has highlighted global efforts as one of her priorities. Q: Returning to more personal matters: what is your personal plan in the nearest future? I think if you now ask me, I would say my personal plan is to catch up on certain things in life that I have not paid enough attention to. In that, the most important thing is family. I want to spend more time with my family, with my wife and children—and now I have three grandchildren. To spend more time with them than I did in the past. This doesn’t mean that work won’t still be important, but it’s no longer as important as it was 10 or 20 years back. That’s my personal goal. And to continue to work in science and help a lot of younger people be successful. My personal ambition is to continue the path of discovery. And I think the best way I can do that is to have a multiplier effect by helping other people to be successful. Then the collective impact will be much bigger.

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