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Michael Oliver

Year: March 17th, 2004
Interviewed by: Blackburn, Henry

Abstract

Michael Oliver of Edinburgh and London has been a leader in CVD prevention research since the origins of formal epidemiolology and trials, dating from his direction of the first major cholesterol-lowering trial of clofibrate, the WHO Trial, and his early studies of hormonal relations to blood lipids. His major lifetime interest as a clinical investigator has been in mechanisms, making particular contributions to the understanding of the role of hormones, free fatty acids, and lipoproteins. As seen in this questionnaire interview and the reference to his 2000 historical review of the field in the UK, he has maintained a wide interest in all issues surrounding the etiology and prevention of atherosclerosis.

Oliver’s view is clear that epidemiology’s main finding, the risk paradigm, is established, so that the science should now move on to mechanisms, leaving medical and public health applications to non-scientist health educators; here he evinces pique over ‘epidemiologists who educate.’ (Henry Blackburn)

Quotes

[ed. The entire questionnaire is quoted here]

Interview by Questionnaire

Q: What do you see as the formative influence on the eruption of interest in the epidemiology and prevention of cardiovascular disease (CVD) in many places in the mid-20th century?

MO: The recognition after World War 2 that there had been a massive increase during the previous 30 years in CVD and particularly in coronary heart disease (CHD) in many western countries. At that time, the data were not structured and it was essential to learn how uniform was this increase in incidence, to identify factors likely to be contributory, whether such influences applied equally in all populations with ‘advanced’ economies only, and whether populations with a continuing low incidence (i.e. Japan) had some protective factors in their way of life. International statistics lacked agreed diagnostic categories with, for example, inclusion of ‘cardiovascular or myocardial degeneration’ as a major entity.

Q: What persons and events do you think most influenced this development early and how independent or interrelated were their efforts?

MO: In the USA

Jack Gofman with his seminal identification of lipoproteins and their relation to CHD (1950)

Ancel Keys proposed in 1950 that the concentration of plasma cholesterol is proportional to the intake of saturated fat;

Paul Dudley White was the first cardiologist in the early 1950s to become concerned with the pathogenesis of CHD;

descriptionKatz, Pick and Stamler were pioneers in experimental atherosclerosis but they used the wrong species (chicks) to induce atherosclerosis;

Keys and the Seven Countries Study (1956)

In the UK [ed. see Oliver, M. ‘Pioneer research in Britain into atherosclerosis and coronary heart disease – an historical review” Atherosclerosis 2000, 150, 1-12],

Ryle and Russell (Oxford), Jerry Morris (London), and Jack Duguid (Newcastle) demonstrating that there was no parallel increase in coronary atherosclerosis and hence a focus on thrombosis (Duguid, Newcastle; also, Florey and McFarlane, Oxford);

Morris (London) focused on the inverse relation between physical exercise and CHD. Doll (Oxford) and Hill established the link with cigarette smoking.

Geoffrey Rose (London) recognized the inverse relation between CHD and social opportunity.

Henry Blackburn (Minneapolis), with Rose, compiled the first diagnostic vocabulary for CHD and hypertension. Cardiovascular Survey Methods (WHO 1968) became a ‘vade mecum’ for all population studies.

In South Africa

Jack Brock and Brian Bronte-Stewart studied nutrition [and cultural differences].

In Scandinavia

Nicolaysen and Malmros studied nutrition and lipids;

descriptionBjork set the clinical scene in Sweden;

and Puska and his team established the North Karelia Project;

Kalevi Pyorala was perhaps the first – at least in Europe – to embrace the risk factor concept and the potential of prevention of CHD.

In Geneva,

Zdenek Fejfar and WHO initiative in classification of diseases and

establishment in 1955 of a Cardiovascular Unit.

Initially, in 1950, these investigators were independent; by 1955 an international ‘polylogue’ had developed [ed.catalyzed by Ancel Keys’ Conference on Atherosclerosis in Minneapolis, 1955].

Q. What were the major scientific issues and public health needs at the outset?

MO: The relevance of cholesterol/lipoprotein abnormalities, hypertension, cigarette smoking. This led to the Pooling Project, mostly stimulated by Jserry Stamler (Chicago), and to the establishment of the quantitative and algebraic importance of risk factors.

Q. What do you see as major contributions of CVD epidemiology and prevention to understanding of cardiovascular diseases and to public policy?

MO: The fact that most governments round the world have now recognized that CVD and CHD are major causes of death in their countries, particularly death in early middle age, and that these are economically serious. This is a direct result of successful international CVD epidemiology. It has followed that many governments have initiated public health campaigns to alert doctors and the public as to the risks of CVD, provided preventive advice and, in some, funded institutions for fundamental research [ed. e.g. NHLBI in the USA, MRC and British Heart Foundation initiatives in the UK, INSERM programmes in France].

Q. What evidence from CVD epidemiology has been ignored or insufficiently applied or distorted in practice and policy, and why?

MO: There are three problems in my view. One is that the risk factors aggregate as causal factors only to less than half of CHD. Epidemiologists seem unwilling to accept this — even to the point of adding minor risk factors in order to ‘explain’ everything.

Another is that the epidemiology of thrombosis has been inadequately studied. Atherosclerosis is ubiquitous and only causes morbidity and mortality when there is co-existing thrombosis. Related to this is the paucity of data concerning a thrombogenic tendency, possibly because it is a transient phenomenon but nonetheless vital.

A third is that the proportion of sudden cardiac deaths has not changed even although the overall incidence of CHD had decreased over the last 20 years. While the mechanisms may be primarily electrophysiological and metabolic, this should be no reason for not focusing on its prevalence.

Q: What do you see as the important unanswered scientific questions and policy and program needs today for CVD prevention, both individual and population-wide?

Thrombosis and sudden cardiac death [ed. see above].

MO It is unfortunate that many epidemiologists are allowing themselves to become health educators. There is more to learn about CVD from classic epidemiological studies. While it is true that education of the public (and of doctors) is a huge problem, this should be left more to the emerging professional cohort of health educators. They need to tackle the fact that the more health programmes are promulgated, the less the public follows. In the UK, a nanny-state is developing and the public is confused and resistant to advice.

Another emerging issue is the misinformation available on Web sites and the failure of these to give uniform advice.

Q: What things were missed or false starts made in CVD prevention research and policy and what might have been done differently?

MO: Our collective ignorance as to how to design and pursue clinical trials was a serious deterrent. I started the first major trial (the WHO Clofibrate Trial) in 1966 with fairly rudimentary knowledge and understanding of the issues involved. Now, the science of randomized clinical trials is well understood.

Q. What might we and our institutions learn and use from the history and contribution of research in CVD epidemiology and prevention?

MO: In my view, as a non-epidemiologist, the worldwide programmes have been tremendously successful. But now epidemiologists should lead, rather than resist, more fundamental studies of particularly vulnerable groups, for example, the genetically susceptible and the genetically resistant to CHD. Because of the successes, too many repetitive population studies seem to be ongoing. Many lack new ideas and measurements.

Q. How do you respond to the frequent general commentary today about the “inherent limitations” of epidemiology as a research discipline?

MO: Epidemiology is an entirely satisfactory research discipline but it is not and should not be independent of biology. Some epidemiologists do not care about the pathophysiology of CVD and, worse, do not want to know. Too much of epidemiology seems to have been taken over by health educationalists and too little has been given to exploring root causes of CVD.

Q. What historical aspects and shifts of research priorities and funding policy of governmental and private funding organizations do you consider to have influenced the field of CVD epidemiology and prevention, and in what way?

MO: The intrusion of pharmaceutical company interests is worrying and distorting in many ways. The profit motive is becoming stronger. Financing of fundamental research into the pathogenesis and epidemiology of CHD is less. For example, studies of lipoprotein subgroup differences have been too dominant because, of course, drugs can be devised with foreseeable commercial profits. Until recently, the field of (endothelial) inflammation has been ignored. The correlation of inflammatory disorders with CHD is surely an ideal epidemiological project.

Q. Please recount favourite anecdotes about yourself and others who have worked in CVD epidemiology and prevention!

MO: At the 10th anniversary meeting in Stockholm of Brown and Goldstein’s Nobel Prize, I quoted Maynard Keynes statement after the 1929 financial crisis: “When the facts change, I change my mind. What do you do?” Such flexibility in thinking might be applied more widely.

Q. What other events, persons, findings, milestones, turning points, or controversies do you think should be explored in a history of CVD?

MO: While the relationship of diet with CHD was recognized in 1950, the analysis of dietary composition was slow, possibly because of the focus of the Seven Countries Study on saturated fat.

In the 1950s it was thought that CHD was a disease of the affluent and educated classes. The recognition that the reverse is true took a long time and possibly was not identified until Rose and Marmot’s Whitehall Civil Servant Studies were published.

Mention might be made of the delay in recognizing the importance of lowering raised plasma cholesterol (and LDL cholesterol) because of the equivocal results of the first major trial -the WHO trial. This used the only available drug (a fibrate). Statins were not introduced until 1988.

Q: Please enclose and label any documents or photographs you think relevant to the history and development of the field that you would allow to be reproduced in a publication and archive!

MO: I enclose a photograph taken in 1955 in Minneapolis at the first meeting on CHD. The characters are Louis Katz (Chicago), Jack Brock (Cape Town), Michael Oliver (Edinburgh), Irvine Page (Cleveland) and Paul Dudley White (Boston).

I also enclose a reprint of ‘Pioneer research in Britain into atherosclerosis and coronary heart disease – an historical review”. Atherosclerosis 2000, 150, 1-12

 

oliverJohn Brock, Michael Oliver, and Irvine Page pictured at the first international conference on diet-lipid-heart issues, held in Minneapolis in 1955.

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