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News: Congress

EAS2018 Tuesday's Plenary: Detection and management of atherosclerosis

Friday 11 May 2018   (0 Comments)
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Improving strategies to detect and treat atherosclerosis: What does the future offer?

Atherothrombosis is the major cause of acute coronary syndromes and the leading cause of mortality in the industrialized world.  Thus, the focus of this Plenary was aligned with the need to detect and manage atherosclerosis to impact this global burden.

Thrombus formation can be divided into three phases: adhesion, activation, and thirdly, aggregation of platelets with the platelet membrane receptors (glycoprotein [GP]Ib-V-IX, GPVI, and GPIIbIIIa]) which are involved in all these steps. Professor Steffen Massberg (Ludwig-Maximilians University, Germany) discussed novel opportunities for intervention in this process. One approach may be via inhibition of glycoprotein VI, which has been shown to reduce platelet activation, with minimal effect on bleeding risk. Additionally, the neutrophil may represent a potential target. Not only are neutrophils early mediators of the innate immune defense, but they also play a role in amplifying intravascular coagulation by stimulating the tissue factor-dependent extrinsic pathway via inactivation of endogenous anticoagulants, enhancing factor XII activation or decreasing plasmin generation.1   Accumulation of neutrophils at the site of the lesion is predictive of cardiovascular outcomes.2  Recent evidence suggests that neutrophils may be also involved in reciprocal activation of platelets, mediated by cathelicidins.3 Immunothrombosis and thrombo-inflammation may therefore offer a number of targets for intervention to prevent thrombosis.

Additionally, Mendelian randomization studies may provide important insights for potential therapeutic targets and may help to inform the design of randomized controlled trials to test interventions directed against these targets, as discussed by Professor Brian Ference (University of Cambridge, and University of Bristol, UK). Importantly, this approach may help in estimating the magnitude of change needed in a biomarker to provide a clinically meaningful reduction in cardiovascular risk. Such an approach has been validated for trials investigating the effect of PCSK9 inhibition on clinical outcomes. Genetic studies may also have a role in improving the precision or even individualizing risk prediction, which would be entirely consistent with a personalized precision medicine approach.

Novel therapeutic approaches have shown promise. Professor Joseph L. Witztum (University of California, San Diego, USA) discussed possibilities for the use of antisense inhibition, which have been made feasible by advances in medicinal chemistry to improve potency and tolerability. This has been critical to the development of novel agents targeting elevated lipoprotein(a), a casual risk factor for ischaemic heart disease.4 Indeed, given the estimated prevalence of lipoprotein(a) levels in excess of the 80th percentile, thought to affect up to 750 million people in the EU and 7 billion people globally,5 there is a clear unmet need for new treatments specific to this lipoprotein. Additionally, beyond the development of second generation antisense oligonucleotides targeting apo(a) to lower lipoprotein(a), gene silencing (as for example used for the development of the novel liver-targeted intracellular PCSK9 inhibitor inclisiran) also offers new therapeutic potential.

Finally, new approaches to the detection of vulnerable plaque are needed. As discussed by Professor David Erlinge (Lund University, Sweden) there are a number of intracoronary imaging methods that may offer potential. As the majority of plaques causing sudden death have a lipid core or lipid pool, the combination of near-infrared spectroscopy and intravascular ultrasound, which is practical, simple to use and has shown prospective validity at the patient level, may offer potential. Segment-level studies, such as PROSPECT II, are ongoing.

Of course, the next question will be how to treat such vulnerable plaques, which merits separate discussion.


1. Pfeiler S, Stark K, Massberg S, Engelmann B. Propagation of thrombosis by neutrophils and extracellular nucleosome networks. Haematologica 2017;102:206-213.

2. Mangold A, Alias S, Scherz T et al. Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res 2015;116:1182-92.

3. Pircher J, Czermak T, Ehrlich A et al. Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. Nat Commun 2018;9:1523.

4. Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res 2016;57:1953-1975.

5. Varvel S, McConnell JP, Tsimikas S. Prevalence of elevated Lp(a) mass levels and patient thresholds in 532 359 patients in the United States. Arterioscler Thromb Vasc Biol 2016;36:2239-2245.

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