Lipid hypothesis proves its case at HEART UK conference

Br J Cardiol 2009;16:223-225 Leave a comment
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HEART UK – The Cholesterol Charity held its 23rd annual conference in Liverpool in June, focussing on understanding clinical trials and the evidence base for the theories that underpin current cardiovascular disease prevention strategies

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Introduction

The language of the 23rd annual HEART UK conference resembled a courtroom debate rather than a medical discussion platform. This was because the UK’s leading cholesterol charity had given their event the evocative title ‘The Lipid Hypothesis on Trial’ and invited speakers, throughout three days of conference, to probe the hypotheses behind current cardiovascular disease prevention strategies – many of which HEART UK has successfully campaigned for over recent years.

Proven beyond reasonable doubt?

Professor James Shepherd was in sparkling form when he came to the defence of the lipid hypothesis in the main Myant lecture on the first full day of conference. Head of the Vascular Biochemistry Department at the University of Glasgow Royal Infirmary, Professor Shepherd held the floor with a convincing case to support Rudolph Virchow’s work that the accumulation of plasma cholesterol in the artery wall is the root cause of atherosclerosis.1 Professor Shepherd revealed that his evidence was a result of some unique work applying Koch’s postulates2 to cholesterol. This is the first time that these postulates have been used in relation to cholesterol, as previously, a generic set of postulates have only been used with regard to infection and bacteria. Koch stated that a suspected agent can be considered causal for a disease if it is present and isolable from all cases of the condition; the condition can be reproduced in animals by inoculation; the agent is recoverable from the affected animal; epidemiological evidence should support the hypothesis and experimental intervention should retard or arrest the disease.

Professor Shepherd was able to show, by using Koch’s postulates plus the weight of evidence that has been collected in parallel with the growth of cardiovascular disease (CVD) in the population, that Virchow was correct. This topic generated several questions from the audience, including some from patient members of HEART UK, who were invited to attend the annual conference for the first time this year. Professor Shepherd responded to all the queries in clear language that was understood by medics and lay delegates alike. By the close of his session, the auditorium had wholeheartedly agreed that Professor Shepherd had proved, beyond reasonable doubt, that the lipid hypothesis is true.

Making the right choices

So the conference may have established that the UK’s lipid specialists are following the right path for predicting the onset of CVD, but the following day’s keynote lecture showed that there is still plenty of work needed from both government and business to help the consumer make the right choices with regard to their diet – the first step in cardiovascular prevention. The Director of Consumer Choice at the Food Standards Agency (FSA), Ms Gill Fine, explained that the FSA’s nutrition programme aims to make it easier for consumers to make healthier choices, working with businesses to encourage them to produce better food and with government agencies to provide the consumers with the information they need. She revealed that the FSA’s work with a number of leading food outlets had stimulated others to seek changes to their products. This was in addition to a drive from the general public, and she praised pressure groups and charities, including HEART UK, for helping to raise awareness of issues, such as the cardiovascular health risks caused by high salt and saturated fat intake. Ms Fine agreed that the UK was ahead of many other countries around the world with regard to food labelling, but reported that as long as “around 75% of our salt intake is already in foods we buy” there is still plenty of work to do. She added that just reducing our daily salt intake from 9.5 g per day to 8.5 g per day would save 3,000 lives per year.

Saturated fat and calorie balance is also a target for the FSA, and Ms Fine announced that the agency was already working alongside those sectors of the food industry that contribute the most saturated fat in the diet. “The FSA is nearing completion of developing voluntary recommendations, with a consultation period following shortly,” she said. Ms Fine stated that working in partnership with charities, including HEART UK, has enabled the FSA to deliver key messages of its ‘sat fat’ campaign to diverse audiences in a meaningful way. However, despite moves in the right direction by the food industry in general, she concluded that “partnership can work but it needs realistic time frame for sustained change”.

Baldeesh Rai, dietetic advisor to HEART UK, had already told the conference that small changes to the diet can successfully augment cholesterol management. Mrs Rai finished her session, which was part of a nurses and dietitians workshop, with several practical tips and approaches to achieve cholesterol reduction, and also gave invaluable advice on how the medical community can support their patients in making these life-saving changes.

New findings on body fat in South Asians

One section of the UK population that is more susceptible to CVD than any other is the South Asian community. This was the subject of two abstracts on the last day of the conference. The team from the Department of Clinical Biochemistry at the Royal Free Hospital in London, including Dr Devi Nair, who founded HEART UK’s Family Support Centre in London, carried out an observational study looking at the body fat distribution in men and women of South Asian origin. Dr N Rao presenting for the team, showed data from some 215 people (96 men and 119 women) who were screened at two Hindu temples – in London and Leicester.

After measurement of total body fat by bioelectrical impedance, the results showed that 63% of the men and 65% of the women had a body mass index (BMI) >25 kg/m2, but 55% of men and 93% of women had a total body fat (TBF) >30%, and 17% of men and 55% of women had a TBF reading >40%. The desirable TBF range is 10–20% for men and 18–22% for women. The major surprise was that TBF was excessively high in a large proportion of those with normal BMI. Furthermore, women had three times more TBF than the men despite similar BMI. This led the team to conclude that the high TBF percentage may well reflect the South Asian population’s increased risk for CVD and diabetes, and this may be due to lack of physical activity.

To respond to this finding, the team has secured a community grant to develop a bicycle exercise programme for the temple, and Bollywood dancing classes are also planned. Discussion of this study highlighted limitations with the reliability of the TBF analyser methodology, although it was acknowledged that this can be a very good ‘engagement tool’ as people are motivated to try to improve their results and do return for follow-up measurements.

This same team, with the addition of Dr B Persaud, then presented an abstract that looked at the comparison of a point-of-care cholesterol device and laboratory analysis in the prediction of CVD. The team undertook a pilot scheme screening the South Asian population attending a temple in Neasden, North London. The screening included lipid measurements using point-of-care testing equipment (Cholestech, LDX) and a routine laboratory method to compare the risks assigned using the Joint British Societies’ (JBS 2) CVD chart. Some 49 paired samples were analysed immediately using the LDX system test cassettes, which offered a full lipid profile in just seven minutes. Serum samples from the same patients were also transported at room temperature and analysed by the Roche modular method (Roche Diagnostics). The only significant difference in lipid variables were the high-density lipoprotein (HDL) cholesterol where the LDX measured 1.06 ± 0.29 mmol/L versus the Roche result which was 1.24 ± 0.24 mmol/L (p=0.001). Dr Rao reported that the LDX system over-estimated high CVD risk using both JBS 2 charts and the JBS 2 calculator compared with the laboratory method due to the lower HDL-cholesterol reading. Discussion highlighted that the laboratory analysis methods are not completely accurate and, therefore, it was concluded that the LDX analyser performed quite well in this study.

Implementing the NICE guidance

The conference concluded with Dr Jonathan Morrell, Chair of HEART UK’s Familial Hypercholesterolaemia (FH) Guideline Implementation Team (FHGIT), hosting a session to update delegates on the charity’s activities to support commissioning of the National Institute for Health and Clinical Excellence (NICE) FH guideline, and giving a preview of what is to be included in the much needed implementation toolkit – which is scheduled to be made available to healthcare teams later this year via the FHGIT web page: www.heartuk.org/fhgit. Despite progress in Wales, Northern Ireland and Scotland, so far there has been no progress with commissioning the guideline in England and Dr Morrell described the sensation of “walking through treacle” when trying to move this activity forward.

Professor Steve Humphries, Chief Executive Officer of the UCL Genetics Institute, presented the results of the Royal College of Physicians’ pilot audit project on implementation of the NICE FH guideline in 14 UK hospitals, showing that, while care for individual patients with FH was of a consistently high quality, systematic cascade testing within families was seldom completed. In summarising, he quoted from the report’s foreword by Professor Roger Boyle, National Clinical Director for Heart Disease and Stroke, who wrote: “While it is reassuring that those with hypercholesterolaemia are being well managed [by the sites in the pilot] the results do indicate a great missed opportunity if cascade testing is not being effectively implemented.”

Information technology support for FH cascade testing was the focus of the presentation by Dr Ian McDowell of University Hospital of Wales, Cardiff, who described the Welsh experience with the English language version of the Dutch FH database software from PassClinical. The new software included pedigree drawing and task management in a flexible, user-friendly package that is purpose-designed for cascade testing and appeared well suited to FH management in Wales. Dr Diego Tejedor of Progenika, Bilbao, Spain, then presented the results of the first UK evaluation of the LipoChip system in screening for genetic mutations in FH patients from the DNA Cascade Screening Pilot Study. Previously screened samples were available from 126 of 145 index cases from the Newcastle clinic and, using a ‘chip and sequence’ strategy with the microarray system, all the mutations found by conventional methods were reliably detected and three additional positive cases were identified in intronic ‘primer blind spots’. With a rapid turnaround time of less than four weeks and a UK-specific ‘Brit-Chip’ now under consideration, Dr Tejedor and his team believe that new technology could help address the logistic challenges of FH cascade testing in the UK.

In the final presentation, Dr Dermot Neely, Royal Victoria Hospital, Newcastle Upon Tyne, gave a brief account of progress with commissioning FH cascade testing in the North East, with ‘do once and share’ principles being applied to facilitate the parallel development of the implementation toolkit. Using local pilot data from the Department of Health funded DNA Cascade Screening Study, a business case had been submitted and accepted, but a final decision on funding for the all-important genetics components was still awaited, after nearly six months of deliberations. The most important thing that was still missing, according to Dr Neely, was Department of Health recognition of the NICE FH Guideline as a national priority for implementation – as for the much larger Vascular Health Checks programme.

Dr Morrell and Dr Neely concluded by encouraging those interested in obtaining HEART UK support for their local implementation efforts to contact the FHGIT – who hope to organise a series of regional focus meetings and a national focus meeting in the autumn – and visit the website regularly for updates.

References

  1. Virchow R. Phlogose und thromboseim gefassystem. In: Gesammelte abhandlungen zur wissenschaftlichen medizin. Staatsdruckerel Frankfurt, 1856.
  2. Grimes DJ. Koch’s postulates – then and now. Microbe 2006;1:223–8.
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