AAS Quarterly E-Newsletter

April 2010

Now four months into 2010 and those four letters, RGMS, seemed to occupy our thoughts more than we could possibly have imagined, during the heat-filled days of an almost distant summer. Mostly it’s was “Will I get on? Or “How slow will it be today?” Not to mention, the midnight snapshot reports and the dreaded deadline that thankfully got extended… But something far more enjoyable has been occupying my and my co-editor Alison’s mind lately. Our burning issue has been how we are going to fill the rather large vacant shoes left behind by the very capable and very likable previous AAS editor, David van Reyk. Our first foray into newsletter editorial-ship saw us chasing down the Director of the BakerIDI to obtain his views on where “the money is” (see Garry Jennings’ wonderful Exposé in the feature article of this newsletter) with respect to new treatments for cardiovascular disease. We hope that you find this article of interest along with our other regular news and information segments highlighting “Whats-on” in 2010. Now that grant writing and RGMS are behind us, maybe we can begin to relax and enjoy 2010!

Judy de Haan and Alison Heather, April 2010.

President's Report – “A picture is worth a thousand words”

For those members who are not aware of the AAS activities in the education field, since 2008 AAS has been involved in a partnership with drug companies (the Australian Education Partnership - AEP) to run educational programs for GPs and specialists and young scientists. This will run again in 2010 with a 2 day specialist educational forum in Sydney and a one day session in Cairns for young scientists (the SCOLAR program). The funds of the AEP fund speaker travel, student travel grants and student prizes as well as the educational activities noted above. In addition in 2010 for the specialists program we hope to have the assistance of the USA National Lipid Association in the program with the provision of 2 speakers and course materials.

Don’t forget the next annual meeting is the Asian Pacific Society of Atherosclerosis and Vascular Diseases in Cairns from 26-29th of October which AAS is hosting and which will incorporate the AAS annual scientific meeting with special sessions run in partnership with the Australian Diabetes Society and the European Atherosclerosis Society. Don’t forget to book flights early to get the cheapest deals.

Finally AAS has been invited to have a representative on the Corresponding Group of the National Vascular Disease Prevention Alliance to provide advice to their expert working group on new guidelines for the management of cardiovascular disease risk. I will be the AAS representative.

The AAS Education Subcommittee plans to develop interim guidance on lipid management by updating Australian Public Position Documents such as NHF guidelines. It aims to do this by considering the implications of recently completed lipid trials. If you would like to be a member of the committee established to develop these documents, please contact the Secretariat ASAP.

Peter Clifton

FEATURE ARTICLE - Sutton’s law of Atherosclerosis

As attendance at any meeting of our society will testify we know a lot about atherosclerosis. Yet in many ways we act as if we do not, especially in the delivery of clinical services and in clinical research. We know that the beginnings are in our genes. GWAS studies are defining a range of associations and although the effect of most genetic variations is very small, collectively they remain important and may point to fruitful new areas of research on pathophysiology. Environmental influences begin before birth and carry on through life and the real propensity for atherosclerosis and its clinical complications depends on gene environmental interactions. It is not so much the cards we are dealt with but those that we deal ourselves. Epigenomics promises the means to examine the mechanisms and consequences of gene- environmental interactions but the science is in its infancy and, like peeling an onion there are no doubt many layers beneath.

The classical risk factors are important and have generally stood the test of time, both as markers of risk, and as targets for therapy. To date the tools we have beyond lifestyle optimization are limited. Statins have been outstandingly successful in reducing risk in those with elevated LDL-cholesterol but more people in the world today are at risk due to other forms of dyslipidaemia, especially low HDL syndromes for which we have no effective therapy. We have safe and effective antihypertensive drugs but single agents rarely achieve optimum levels of blood pressure and patients are left with complicated regimens. Diabetes treatment remains problematic and it seems that not everything that controls blood glucose levels controls cardiovascular outcomes.

These risk factors have, in common an association with impairment of the many functions of the vascular endothelium. Endothelial cells last about one month each and turn over erratically in the face of adverse lifestyle so the balance of apoptosis and replacement of cells seems important in the long term. We use these classical risk factors to evaluate and define absolute risk. The method is derived from cohort studies so it is risk of an event that is being defined, even though our understanding of the role of the classical risk factors suggests that the relationship is to atherosclerosis in both its indolent form and as the substrate for plaque disruption and acute events. Perhaps that is why age is such an important factor in risk equations- the longer an individual with atherosclerosis lives, the more time for other processes to develop and cause plaque disruption.

Inflammatory diseases such as obesity, metabolic syndrome, diabetes, HIV, rheumatoid and autoimmune diseases and populations with a high inflammatory burden such as many of our indigenous communities are associated with a high rate of cardiovascular events. In general this is not all explained by classical risk factors, and presentations with acute coronary events or sudden cardiac death are more common providing a clinical hint that whatever the role of inflammation in early development of atherosclerotic plaques it is key to the transition from stable to unstable plaque. Once this occurs of course thrombosis becomes the dominant feature and target for therapy.

What does this have to do with Sutton’s Law? Willie Sutton was of course the bank robber who was quoted in response to a question on why he robbed banks as saying ‘That’s where the money is.’ It is actually more likely that he did not and the famous quote was fashioned by a creative reporter. In fact he was more like us and our approach to scientific enquiry, telling another reporter "Why did I rob banks? Because I enjoyed it. I loved it. I was more alive when I was inside a bank, robbing it, than at any other time in my life. I enjoyed everything about it so much that one or two weeks later I'd be out looking for the next job. But to me the money was the chips, that's all." By appropriating the quote as a title for his second book, Sutton started a chain reaction that continues to this day.

No one can accuse current practice in interventional cardiology of not going where the money is, or those involved in marketing another lipid or blood pressure lowering agent with the same mechanism of action as its predecessors. We may be guilty in clinical research of using techniques that provide surrogate markers of vascular structure or function that can never tell us more than that, as a systemic disease, manifestations of atherosclerosis in one part of the vasculature are likely to be associated with similar changes elsewhere.

But where is the plaque that matters, when will it matter and how should we specifically intervene? The two biggest killers worldwide, heart attack and stroke have the same parent. Our challenges include the development of useful experimental models of unstable plaque; smart clinical trial design that allows us to compare mechanisms involved in the maintenance of lifelong stability of some plaques with instability in others before an event occurs; biomarkers and/or imaging techniques to distinguish vulnerable plaques and much better ways of evaluating risks that take into account our knowledge of characteristics involved causally in events beyond blood pressure, cholesterol and age. Add to that some new therapeutics that address known targets like, say HDL, matrix metalloproteinases, tissue factor and we may at last be going where the ‘money’ is. Above all we need to start younger and go harder at defining interventions at all stages of the disease, rather than considering atherosclerosis as a single monotonal lump of yellow.

Garry Jennings

Membership News

If you have not renewed your membership, please click here to visit the Meetings First website and renew online. Alternatively, please click here to download a copy of the paper registration form.

The Australian Atherosclerosis Society always welcomes new members. Please encourage your students and work colleagues to join the AAS. Remember, that members receive the following:

- A monthly email that includes, job opportunities, information on meetings relating to atherosclerosis and regular updates on similar interests.

- A new quarterly newsletter that will feature different articles each quarter.

- Discounted rates to attend AAS Annual Scientific Meetings.

- Networking opportunities and involvement.

- Opportunity to receive student travel grants and present your research at the Annual Scientific Meeting.

- Opportunity to apply for AAS Trust travel grants

FH Corner – Gerald Watts

A National Symposium of Stakeholders on ‘Facing the Challenge of Familial Hypercholesterolaemia in Australia ‘

Royal Prince Alfred Hospital, Sydney, 19th March, 2010

Familial hypercholesterolaemia (FH) is a lethal cardiometabolic disorder, characterized by marked elevation in plasma cholesterol and premature coronary artery disease, that remains largely undetected and untreated worldwide, including Australia. To meet this demand we are working on a model of care (MoC) for FH in Australia. This MoC is based on clinical experience, expert opinion and published evidence, and is being informed be experience in Western Australia. The MoC is also being developed in consultation with a wide spectrum of stakeholders from the disciplines of lipidology, nursing, primary care, pharmacy, cardiology, health economics, genetics, and patient support groups who met in Sydney on March 19th at a symposium to discuss ‘Facing the Challenge of Familial Hypercholesterolaemia in Australia.‘

The MoC for FH will be presented as a series of algorithms focusing on identifying index cases, diagnosis and management, cascade screening, DNA testing, and an integrated clinical service. The MoC aims to provide a standardized, cost-effective system of care that is likely to have the highest impact on patient outcomes.

The proposed protocols are not prescriptive and need to be complemented by good clinical judgment. The MoC is an evolving entity that will need periodic review and modification. The preliminary MoC for FH has been presented to The National Heart Foundation for ratification.

Forthcoming Meetings

IAS-Sponsored 2010 Workshop on HDL

17 – 20 May 2010, Whistler, BC, Canada

Please direct your questions and comments to Dr. Francis at gfrancis@mrl.ubc.ca or to the Workshop Secretariat at hdl@venuewest.com

9th Conference of the International Society for the Study of Fatty Acids and Lipids (ISSFAL)

29 May – 2 June 2010, Maastricht, Netherlands