After obtaining a PhD in Biophysics in London, UK, Janet Powell, professor of Vascular Biology & Medicine at Imperial College, London, studied medicine in the United States, before returning to the UK where she completed clinical training in pathology, specialising in cardiovascular risk. In this interview, Powell tells why the cause and management of abdominal aortic aneurysms are her major research interest and speaks about her early career, her mentors, the IMPROVE randomised controlled trial, and also her interests outside medicine.
How did you come to choose medicine as a career? And why pathology and cardiovascular risk?
I was envious of the clinicians’ understanding of the integration of the physiology and pathophysiology of the body: only with such understanding and collaborative research can one obtain the evidence for improvements in patient care. So there always was a strong interest in pathophysiology. However, the choice of pathology, rather than an interventional speciality, was driven mainly by the need for work-family balance, since I had two small children at home throughout my training period. The choice of cardiovascular risk, or endocrinology, as a speciality allowed for continued patient contact and care.
Who were your mentors and what advice from them do you still remember?
Professor Donald Massaro, a pulmonary physician, who thought about pathophysiology in big pictures, was definitely a mentor. He was convinced that better science would lead to better clinical care.
How did you develop your interest in vascular biology and clinical trials?
I was interested in the pathophysiology of elastic tissues and working with Roger Greenhalgh, the aorta became the key vessel of interest. These horizons expanded after a sabbatical year at the Red Cross Laboratories in Amsterdam, where Jan van Mourik was a fantastic adviser. Science is based on experiments and evidence and I soon appreciated how randomised clinical trials were the best “experiments” to gain new evidence in clinical medicine and the best outcomes for patients.
The cause and management of abdominal aortic aneurysms are your major research interests. How did it all begin and what was your first piece of work in this field?
It began through my interest in the pathophysiology of elastic tissues. The first piece of work was a comparison of the concentration of acute phase reactants (including CRP) in the serum of patients with abdominal aortic aneurysm and patients with occlusive aortic atheromatous disease, pursuing evidence for the hypothesis that inflammation played an important role in the development of aortic aneurysms. The death of my father from aortic dissection sharpened my focus on degenerative disorders of the aorta.
The one-year results of the IMPROVE randomised controlled trial were published in the European Heart Journal in April. How do you interpret the data and what does the trial add to the literature?
The outcomes important to patients are not necessarily the same outcomes as those using to evaluate the success of treatments in clinical trials. Before we designed the trial, Rob Hinchliffe and I discussed with several patients and their families what they viewed as the most important outcomes to evaluate after aneurysm rupture. The focus was not on who lived and who died but on who came back home, how quickly and without any added disability. Accordingly, we started planning a trial using in-hospital mortality as the primary outcome, with patient disposal and quality of life as secondary outcomes. In contrast, surgical reporting standards focus on 30-day mortality and to get the trial funded we had to use this as the primary outcome measure.
Interestingly, our one-year results show that the patient-preferred outcomes are all better using an endovascular strategy, even though there was no significant survival advantage. In addition, the endovascular strategy appeared to be cost-effective. Through the trial we saw more and more centres becoming eligible to join the trial (ie. have credentialed experience in elective and emergency EVAR). Some of them were at an early stage of teamwork using emergency EVAR. So the question has been asked, did we do the trial too early? Of course not, if we had left it longer it might have been too late, with very experienced centres preferring EVAR. There was also the risk of surgeons losing equipoise by listening to the apples versus oranges comparisons from the likes of Frank Veith. The IMPROVE trial has shown how influential aortic neck length is in predicting mortality: the easy EVAR cases with long proximal aneurysm necks have low mortality after both EVAR and open repair, whilst those with short necks are predominantly treated with open repair and do much worse. So comparing observational data for emergency EVAR versus emergency open repair compares patients with long necks versus patients with short necks: apples and oranges. The results from emergency EVAR may improve with time and if so, this will be an added reason to encourage the wider use of emergency EVAR. Overall the current findings from IMPROVE lead to encouragement for the increasing use of endovascular repair. With survival of discharged patients being so good at one year, with so few delayed reinterventions, we need the three-year results to confirm or refute such encouragement.
Critics often say a trial comparing EVAR and open repair for ruptured abdominal aortic aneurysms is not needed. How do you respond to criticism towards IMPROVE?
Mainly with the fallacy of the apples and oranges comparison described earlier. In addition, we needed to know whether organisational changes to provide more widespread emergency endovascular repair might be necessary.
What piece of research are you most proud of and why?
Anything that improves outcomes for patients, including all the randomised trials of abdominal aortic aneurysm management, as well as an early piece of pathology research which showed the importance of inflammation in the developing aneurysm… a theme still being investigated by vascular biologists and evaluated in randomised trials.
The rate of abdominal aortic aneurysm is falling. In your opinion, why is this happening? Do you see it as a continuous trend?
This is largely due to the changes in smoking prevalence and practice. In men it appears to be a continuous trend but the same is not true in younger women. So in the future we might see the prevalence increasing in women.
You are participating in the AARDVARK clinical trial, which is assessing the use of an ACE inhibitor in abdominal aortic aneurysms. What are your expectations with regards to the results of this trial and other potential medical therapy approaches for the condition?
I wish that I was more optimistic but the RESCAN study suggests that single therapeutic agents are unlikely to have large enough effects on aneurysm growth. But wait and see, we shall have the results very soon.
What advice do you usually give to young vascular surgeons starting their research careers?
Do something you enjoy and believe in something that will enhance your standing beyond your research period eg. learning how to measure things properly, test new ideas and technologies, do a systematic review, assess the grey areas in vascular surgery.
What is the most interesting paper you have come across recently?
The ROX CONTROL HTN trial, using endovascular implantation of an arteriovenous coupler device to reduce blood pressure (Lancet 2015;385:1634).
What are your interests outside of medicine?
Outside of work, I spend time with my son, daughters, grandchildren and friends. I also enjoy trekking and maintenance of local area footpaths, growing my own vegetables (I have a large garden), bird-watching, contemporary cinema and theatre (last play seen was View from the Bridge, which was excellent—I am an Arthur Miller fan). Also, I am a local school governor. So nothing very extraordinary!
Professor of Vascular Biology & Medicine at Imperial College, London, UK
- BSc in Chemistry, 1968, Oxford, UK
- PhD in Biophysics, 1972, London, UK
- MD Medicine, 1981, University of Miami School of Medicine, USA
- FRCPath Pathology, specialising in cardiovascular risk
- UK Small Aneurysm Trial
- EVAR trials 1 and 2
- Cochrane reviews (2 published in 2012 with one 2014 update)
- 2011 ESVS guidelines for clinical practice relating to abdominal aortic aneurysm
- In total, more than 200 original papers listed in PubMed, including one in Nature and 3 in the New England Journal of Medicine
- Either chief investigator or a co-investigator on four Health Technology Assessment projects
- Associate editor of the Arteriosclerosis, Thrombosis & Vascular Biology
- Editorial Board, Circulation
- Ex-associate editor of the European Journal of Vascular & Endovascular Surgery
- 2012, Life time achievement award, Vascular Society of Great Britain and Ireland