In Conversation With ... Professor Stuart Cobbe
Professor Jeremy Pearson's 'In Conversation With...' series continues; in June, our Associate Medical Director spoke to former BHF Professor Stuart Cobbe. A (virtual) guest at Tighanoisinn, Stuart's home in the heart of Scotland close to the River Tay and the Cairngorms National Park, Jeremy walked with him through his remarkable career, from landing in Glasgow - via Cambridge, Oxford, London and Heidelberg - to energise their clinical cardiology research programme, to launching the landmark WOSCOPS study, all while training his PhDs.
Professor Cobbe was the BHF Walton Professor of Cardiology at the University of Glasgow from 1985-2008. He is now retired.
'I started by noting that our paths had first crossed, though we did not know each other then, when Stuart was a Medical Sciences student in Cambridge carrying out a final year project in the department of Pathology (which led to his first publication) while I was in my first year studying for a PhD in the same department (which led to no publications). Alarmingly, we realised this was just over half a century ago. Cambridge’s School of Clinical Medicine did not open until 1976 and students then had to complete their medical degree elsewhere: Stuart went to St. Thomas’ in London. It was here that he came into contact with Professor Philip Poole-Wilson, who was recruited in 1976 as a senior lecturer to the Cardiothoracic Institute at the Royal Brompton Hospital. Poole-Wilson went on to be the BHF Professor of Cardiology there in 1988 (when the institute was renamed as the National Heart and Lung Institute). Stuart became Philip’s first clinical research training fellow on completing his general medical training in 1977, funded by the BHF and working on the development and consequences of acidosis in the heart after myocardial infarction. Stuart pioneered the adaptation of pH electrodes to be suitable for catheter insertion for continuous measurement of local pH in the blood in preclinical experiments and then in patients, leading to his first highly cited publication.
Having completed his MD Stuart moved to Oxford to continue his specialty training in cardiology. Here he became particularly interested in how drugs could alleviate arrhythmias and spent a year as a Humboldt Fellow working on this topic in animal models at the cardiology department in Heidelberg led by Professor Wolfgang Kübler. This again was fruitful, with five substantial papers (two now well-cited) as the product.
Continuing his clinical training in Oxford, Professor Peter Sleight (head of the cardiology department and BHF Professor of Cardiovascular Medicine) appointed Stuart to a “Clinical Readership” – in reality a non-tenured senior lecturer role. Stuart recounts that even at this stage in his career he was uncertain he ought to pursue an academic route, but Sleight was highly supportive that he should, though not in Oxford, where a suitable vacancy was unlikely! He also recalls that Professor Sleight was widely known alternatively (but affectionately) as the BA Professor of Cardiovascular Medicine, thanks to his frequent flying for international collaborations.
So with Peter Sleight’s backing Stuart began to apply for chairs in cardiology, and in 1985 was successful in being appointed to the endowed BHF Walton Chair of Medical Cardiology at the University of Glasgow on the retirement of Professor Veitch Lawrie.
Stuart arrived to find several challenges. First, to balance his new role as head of clinical cardiology at the Royal Infirmary (one of the two hospitals responsible for advanced cardiovascular medicine across Glasgow) with the re-establishment of his own research career. Second, to find ways to energise high quality clinical cardiology research in Glasgow, which by comparison with Oxford was poorly developed. He set about ensuring that clinicians could have protected research time and encouraged research fellowship applications.
Stuart’s firm belief that clinical trainees should benefit from basic science experience during their research (just as he had done) led to his supervision of a long string of BHF funded research fellows completing PhDs, many working with Dr Godfrey Smith as the second supervisor. Godfrey, who arrived in Glasgow in 1988 (as a BHF Intermediate Fellow) and is now Professor of Cardiovascular Physiology there, remembers Stuart’s efficient and productive management of regular, usually weekly, progress meetings with each student presenting their results or reviewing recently published papers in the field. Though somewhat intimidating for the students at first they soon realised how valuable these meetings were. Stuart and Godfrey’s collaboration was enhanced by their joint leadership of part of a successful large application on basic and clinical aspects of heart failure to the MRC’s Clinical Research Initiative, funded in 1994, which subsequently led to successful joint programme grants from the BHF for 10 years from 1999. Stuart’s contribution was substantial, not just in introducing rabbit models of hypertension and heart failure to Godfrey’s lab that are still in use today but also deploying his BHF chair funding to develop pioneering optical mapping techniques for cardiac conduction in isolated hearts. Despite his busy clinical load Stuart managed to make time to take part in experimental work, training new PhD students in techniques he had learned during his MD, rolling up his sleeves to do so.
One of Stuart’s early tasks as a trainee in Oxford was to teach ambulance crews CPR – this being before automated defibrillators were widely available. On arrival in Glasgow he was influential in driving the introduction of automated defibrillators in ambulances across Scotland, pioneering this in the UK. He persuaded Professor Brian Pentecost, then BHF Medical Director, to set up a BHF fund-raising campaign, Heartstart Scotland, for £2.5m. Stuart’s powers of persuasion were impressive: the campaign was seeking over £6m in today’s money, at a time when the BHF’s total research budget was £7.5m. The funds were to pay for the defibrillators for all 407 Scottish ambulances and for the rapid training of ambulance staff. Within a year 268 defibrillators had been purchased, used over 600 times, and had resulted in 30% of cases surviving to reach hospital admission. Stuart estimated that if fully deployed in all ambulances defibrillators could reduce death from heart attack in Scotland by 4%, at that time at least as important as the effect of long-term blood pressure control. Productive collaboration with Dr Jill Pell (now Professor of Public Health in Glasgow and a BHF Trustee since 2020) over the next few years led to further valuable insights for improving the strategic management of out of hospital cardiac arrest.
Stuart’s research focus on arrhythmia and cardiac arrest remained undimmed throughout his career, with international recognition of his expertise. He was a member of the European Society of Cardiology (ESC) Task Force on Sudden Cardiac Death set up in 2001 and later of the ESC Euro Heart Survey working group on the management of atrial fibrillation.
However, a new clinical research avenue opened shortly after Stuart’s arrival in Glasgow by collaboration with Professor James (Jim) Shepherd, a senior lecturer in clinical biochemistry when Stuart took up his Chair. Stuart supported Jim’s promotion to professor and head of the Department of Pathological Biochemistry in 1988. In 1989 Shepherd, with Cobbe and six colleagues, launched WOSCOPS (the West of Scotland Coronary Disease Prevention Study) – the first study ever to test whether cholesterol lowering with a statin would reduce risk of a future heart attack in men with hypercholesterolemia but no previous clinical history of cardiac disease. The results of the 5 year trial on over 6000 men were spectacularly successful, with more than 25% risk reduction. This landmark study, which reported its findings in the New England Journal of Medicine in 1995 (and has been cited more times than the number of trial participants), shifted the paradigm for statin use to include it as a valuable tool for primary as well as secondary prevention of heart attack. Remarkably, 10 years after the completion of the study the risk of heart attack or death from any cause remained significantly lower in those who had been in the statin-treatment arm of the trial – despite equal use of statins in the original treatment and placebo groups over the subsequent decade. Though the authors didn’t elaborate on the possible explanation, Stuart agreed with me that the results are a powerful indication that statin treatment put the brakes on the development of atherosclerosis (and modified the composition of the plaques) over 5 years, permanently providing risk reduction compared with age-matched controls.
WOSCOPS firmly secured an international reputation for Stuart and led to his involvement in a series of further important studies, including PROSPER, the first large trial of statin safety and efficacy in the elderly. Pravastatin was shown to lower event risk substantially in men and women with an average age of 75. Another young senior lecturer appointment at the Royal Infirmary, fresh from his PhD in 1998, was Naveed Sattar, who had a particular interest in diabetes and cardiovascular risk. His analysis of metabolic syndrome as a risk factor in the WOSCOPS population in collaboration with Stuart led to another highly cited publication. Naveed’s career then blossomed in Glasgow: he rose rapidly to be appointed as professor of metabolic medicine in 2005 and is now an acknowledged world leader in his field.
A further example of Stuart’s unobtrusive but effective and valuable contributions to the careers of junior staff at this time is his joint supervision of a PhD student, Colette Jackson, with Dr John McMurray (then recently recruited to Glasgow; now professor of medical cardiology and like Sattar a world leader in his research field, in McMurray’s case treatment for heart failure). The topic of the PhD was microvolt T-wave alternans (MTWA) measurement and its value (or not) in risk stratification in heart failure, thus combining the complementary expertise of the supervisors. The BHF turned down their application, the reviewers apparently considering the value of MTWA assessment obvious – but fortunately they found funding elsewhere. The data collected by Jackson led to a series of papers that effectively discredited the MTWA hypothesis, while she continues to publish successfully with McMurray, combining her consultant cardiology post in Glasgow with an honorary senior lectureship.
Stuart decided to end his academic career in 2008 after suffering (ironically) a heart attack at a relatively young age. He recovered fully from this and took up the role of regional clinical director for cardiology until 2012, which doubtless reflects the esteem his clinical colleagues held for him as an effective manager (though Stuart described it to me as a penance!), before retiring.
In conversation Stuart was characteristically modest about his achievements, but tributes from his colleagues are uniformly fulsome. He very clearly achieved his goal to energise cardiac research in Glasgow and did so by creating an environment in which it could flourish, consistently supporting young talent (often using his BHF chair discretionary fund to underpin the development of fellowship applications) and helping to catalyse the unification of clinical and preclinical cardiovascular research across Glasgow despite political and geographical difficulties. Naveed Sattar told me he is indebted to Stuart, who helped him get his first grant (from the BHF) and provided experienced guidance thereafter for important decisions about his career. John McMurray notes Stuart’s “super brightness” leavened with a gentle wit and a twinkle in his eye. Godfrey Smith was amazed by how efficiently Stuart managed a huge and diverse workload and meeting schedule armed solely with a pocket diary (the hand-written kind, for those who can remember pre-electronic diaries). Jill Pell has fond memories of Stuart’s charm – and attention to detail not only in research but also in other important ways: he always provided coffee and biscuits for their research meetings; however, he also provided detailed advanced homework on the rare ceilidh dances to be performed at a celebratory party, which to her chagrin Jill failed to read and so arrived unprepared.
Though not Scottish born, Stuart is clearly happy and settled there. He has now lived in Scotland for more than half his life and has children and grandchildren not far away. He enjoys whisky. He remains a serious cyclist, with wonderful countryside outside his door. And he can be very proud of his own contributions to cardiovascular research and nurturing its success in Glasgow. It was a real pleasure to catch up with him.'