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Controversies in cardiovascular disease

Prevention


This 08.30 session started with a smallish (25% full) select audience but soon filled up during the first session. Relatively ‘early’ starts are always a problem in a country like Spain where restaurants open at 2200 for dinner and you are unlikely to have added significantly to your personal risk factors through over-eating much before 1 am. It was deserved that the session was well attended because the 4 sessions were extremely fit for purpose with genuinely stellar speakers. One characteristic of joint sessions between the ESC and the European Primary Care Cardiovascular Society (EPCCS) is their breadth and variety – sessions ranged from risk assessment, through evidence for treatment targets, to young adults perceptions of health education. I suppose such sessions will never appeal to all card-carrying cardiologists who needs the ‘ESC fix’ of new data and little else, but update and evidence reflective sessions such as this should be also the core of the ESC – practical resumes of where recent data fit with established data and how the busy clinician translates this into their updated clinical practise. On second thoughts, such sessions should appeal to all clinicians who attend ESC who see patients in any generalist primary or secondary care settings.

Text of your report The first session was on ‘Predicting cardiovascular disease: does C-Reactive Protein (hsCRP) add anything?’ and was delivered by Tom Pearson from Rochester USA. As author of the 2004 AHA/ACC recommendations on hsCRP use we were well served by his comprehensive review of the evidence base. He started by showing how hsCRP is a good risk marker, as opposed to a risk factor, with repeated and large retrospective and prospective cohort studies showing a close and ‘dose dependent’ relationship between elevated hsCRP levels and subsequent cardiovascular events. He moved onto whether hsCRP met the characteristics for a ‘useable’ risk marker, such as stable and affordable assays, which were largely achieved. However, the evidence that hsCRP adds value over and above traditional risk scores was not demonstrated in repeated analyses. Having dismissed e role for hsCRP in the generality, he produced more speculative data on the ability of hsCRP to provide additional information in certain sub-groups of the at risk population ie to re-classify risk in some of the population defined as moderate risk using traditional risk factors. Adding to the precision of CVD risk prediction tools may be an important future role for hsCRP aided by its incorporation into ‘second generation’ tools scores such as the Reynolds CVD risk score. Finally, Pearson reflected that what was most needed by hsCRP if it is to gain wider adoption is evidence of cost effectiveness, and that requires a trial of patient management triaged by hsCRP categorisation versus treatment based on standard risk scoring, with clinical outcomes as primary endpoints. Now that would end speculation and provide finally justification, or not, for adding hsCRP to routine patient assessment. An interesting series of audience questions focussed mainly around the results of JUPITER and its interpretation.

The second session focused on treatment on one of the three principal risk factors for CVD, namely hypertension. Specifically Bryan Williams, Professor of Medicine from Leicester UK, spoke on treatment targets in hypertension in a session entitled ‘current blood pressure targets: are we at the limits of benefit?’ This was a fascinating and detailed review of the evidence for differential management targets in the commonest risk factor prevalent in developed economies. Although the evidence is incomplete, of all major risk factors and chronic diseases, hypertension has the greatest evidence base for how low we should attempt to go. Showing data for epidemiological longitudinal studies and observational cohort follow up, Williams convincingly demonstrated the linear relationship (or to be more precise log linear and therefore curvilinear association) between recorded blood pressure values and adverse clinical outcomes. However, once he produced data on outcomes related to achieved blood pressure, the picture became less clear. Few differential treatment target trials exist and none until 2009 relate to systolic targets. Presenting data from a recent sub-analysis of ON-TARGET, he showed that blood pressure reductions below an achieved 140 systolic and 90 diastolic showed no incremental further benefit in terms of outcomes, and probably none below 150/90 in those over the age of 75 based on HYVET. Indeed, the re-emergence of the ‘J curve’ became observed with evidence if anything for harm with the groups where achieved blood pressure reduction was much below 140/90. The only outcome exception was stroke where additional benefits were observed however low the achieved blood pressure. He also showed that, similarly, there was no evidence for the more intensive targets all guidelines recommend for diabetes and established cardiovascular disease – targets of 130/80 were a step too far? Importantly, alongside these lack of data on evidence for blood pressure targets below 140/90, he showed data from the recent Zanchetti review in J Hypertens which showed that even within the confines of randomised controlled trials, with all the extra investment in achieving target blood pressure reductions, virtually all studies failed to average blood pressure in the trial below 140 systolic in general or diabetic hypertensive populations ie in the most favourable of circumstances, blood pressure targets below 140/90 were not achievable. The audience questions further debated this ‘real world’ question and the potential adverse impact on quality of life with (over) intensive blood pressure targets.

The third session, delivered by Jonathan Mant Professor of Primary Care Research at the University of Cambridge, UK, shifted emphasis to ‘Stroke prevention in atrial fibrillation’ posing the question ‘Who should be on more than aspirin?’. This was a tour de force on this critical and expanding evidence base, where there is much conflicting recommendation. He started by summarising the main recommendations in clinical guidelines, pointing out the current inconsistency in stating age over 75 as both a risk factor for higher stroke risk ie needing anticoagulation beyond aspirin, and then advising age over 75 as a precaution against the use of warfarin (on perceived higher bleeding risk). He also contrasted the relative uselessness of guidance which states add warfarin to high risk people (based on scores such as CHADS 2), leave on aspirin alone in low risk, but either are options in the one third of people at lower stroke risk (who are also at lower bleed risk). What is the busy clinician to do?! Running through the recent data from the BAFTA trial, showing the unequivocal efficacy benefit of warfarin target INR of 2.5 in people over 75 with a bleeding risk of just over 2% a year that was the same as aspirin, Mant clearly showed that those over 75, who represent approaching 60% of those with AF, should and could receive warfarin, even the very elderly over 80 (25% of the BAFTA population). The only caveat, highlighted by Hyleck’s observational data on warfarin use in real life Boston hospital discharges (ie warfarin in stroke secondary prevention), is that INR control is important with no gain if INRs are below 2 and risk if above 3/3.5. In terms of moderate risk, then Mant echoed the views of Williams that physicians need to acknowledge that guidelines are just that – guidance not mandate, and that we need to contextualise recommendations perhaps more in clinical settings where evidence is less clear and involve the patient more in balancing potential benefits over potential risks in seeking the best treatment option for the individual. He also provided this as a major justification for the continued search for newer and possibly safer anticoagulation options to the 50 year old warfarin, citing the impressive results of the RE-LY trial of at the ESC showing 46% superiority of Dabigratan 150 mg over warfarin with similar serious bleeding risk and no current monitoring requirements. The audience questions further explored the difficulties of achieving good INR control and issues around clinical equipoise in clinicians.

The final session changed tempo to explore recent data on ‘What’s the quality of cardiovascular care in European primary care?’ delivered by Sabine Ludt from Heidelberg University in Germany. Based on the recently completed EPA-Cardio study this large series of linked surveys across 12 European countries provides complementary and contemporary data to the EURO-ASPIRE surveys which, until the III survey only examined quality of care in secondary care settings. The EPA-Cardio study established a series of quality indicators for provision of preventive cardiovascular care through an international iterative DELPHI technique and then conducted clinical casenote reviews amongst 12 practices per country to examine adherence of the indicators within at risk and established disease populations. The results form this survey demonstrated a good uptake of risk factor identification and management in most countries, with rates generally above 60%, with particular success in countries including Belgium, England, France, and Slovenia and weakest performance (sorry) in Spain. Ludt speculated on the reasons for the variance citing itarget incentives in England (QOF) and prevention initiatives in France and Slovenia. She finally introduced some fascinating data on surveys of young adults (aged 18-45) on their perception son the usefulness of health education – generally this showed extremely low (under 10%) perceived value of such advise. Clearly young adults are not interested per se in information on healthier living, at least from primary care sources. However, she then presented data showing that young adults with established risk factors, namely abnormal BMI, smokers and those who were inactive, were most likely to have received some health advice from their general practitioner, and the type most likely to have been received was personalised care consultation as opposed to leaflets of general strategies.. Further, and surprisingly given the earlier nihilism, the young adults with adverse risk factors who received such advise rated this highly, with over 80% stating that they found it useful. A promising note to end on and the audience questions further explored this terribly important and under-researched subject.

Conclusion:

So a positive smorgasbord of clinical topics provided up to the minute data in the context of the huge evidence base in vascular risk prediction, hypertension, atrial fibrillation thromboprophylaxis, and novel data on public perceptions on CVD risk, with practical recommendations on how to utilise all this in clinical practice. Joint ESC/EPCCS meetings are clearly worth attending.

References


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Controversies in cardiovascular disease

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.