What first made you interested in cardiology?
My internship was primarily focused on nephrology, but I also studied hypertension and went on to complete my post-doctoral studies in the laboratory of Victor Dzau in Boston, USA. It was ultimately this experience that led to me achieving my aim of getting a position in the cardiology department at Universitätsklinikum Regensberg, Germany, at a time when competition for such positions was extremely high. I then became fascinated by the genetic foundation of CVD and that is where my interest has been ever since. Over the years, I have witnessed enormous improvements in the understanding and treatment of the diseases of the heart. I feel extremely fortunate to have been a spectator and to some extent, a participant, in these developments – I was at the right place at the right time.
What are the key themes of your lecture?
During my presentation, I will explore how findings from genetic research in CVD, mainly coronary artery disease, may find their way into clinical decision making. Specifically, looking at the relationship between genetics and modifiable risk factors and discussing how these complex interactions can be used to improve disease prevention and management.
When I started out in cardiology in the early 1990s, family history was really the only indication that there was an inherited component of CVD. With the possible exception of mutations in the low-density lipoprotein receptor and familial hypercholesterolaemia, little was known about the genetic basis of CVD. In order to find out more, I became involved in the study of thousands of families in which at least two members had myocardial infarction at a young age. Taking advantage of the successive developments in technology, our research progressed from using microsatellite studies to array studies then whole exome and whole genome sequencing to gain a much better understanding of the inherited basis of these diseases. We now know from the human genome that everyone has a predisposition for atherosclerosis. But this is only part of the story. It is the interaction between the inherited component and modifiable risk factors that completes the picture.1 And a clear mathematical exponential relationship has emerged that describes an individual’s risk of disease. This will allow us to more precisely identify those individuals who are at a particularly high risk of CVD and to select effective management options. Given the potentially damaging consequences associated with the accrual of multiple events, we also need to look beyond high-risk individuals to find strategies for those in so-called lower-risk groups.
What are the current challenges in your field?
A considerable number of genetic variants have been identified to play a causative role and it is now important to understand their cellular mechanisms. Once determined, these variants can be used to describe different disease aetiologies and to develop novel preventive and treatment approaches. Regarding (preventive) treatment, the immediate challenge facing us is how to design studies – which likely need to enrol large numbers of patients – to document clinically relevant benefits. Academia, patient and disease societies and industry will need to work together if this is to be achieved.
Where do you think research in your field is heading in the future?
Right now, I am hoping that we will find ways to bring genetic risk scores into the types of risk prediction models that already exist, such as the ESC’s Systematic COronary Risk Evaluation 2 (SCORE2) algorithm. To that end, I will continue in my work with the ESC Council of Cardiovascular Genomics to encourage the academic community that there is an important role for these polygenic risk scores in improving both prediction and treatment of CVD.