87th EAS Congress
Let's look at the highlights of the 87th Congress of the European Society for Atherosclerosis.
Remembering the 4th day of Congress EAS in Maastricht, 2019
From the plenary session on Wednesday May 29
Looking to the future – novel treatment strategies
The final Plenary session gave a dynamic overview of the future for therapeutic strategies,
in which both the immune system and lipoproteins feature.
Opening this session, Professor Laszlo Nagy (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA)
discussed researches implicating the immune system in muscle regeneration and repair. Macrophages
play a pivotal role in this process, initially as inflammatory mediators that help to clear
necrotic debris, and subsequently transitioning to repair macrophages involved in the tissue
repair and remodelling processes.1System level approaches, involving a combination of epigenomics,
transcriptomics and lipidomics, helped to define critical effectors of this macrophage plasticity
that occurs in response to specific environmental cues. Studies identified BACH1 and PPAR? as key
transcription factors involved in this phenotypic switch mediated via lipid signalling that controls
the expression of final effectors such as HOX1 (via BACH1) and GFD3 (via PPAR?). Shotgun and targeted
lipidomics also identified resolvin D2 as critically involved in in promoting muscle repair process.
Taken together, these findings implicate innate immune cells with dynamic lipid mediator signatures in
the muscle repair process. Targeting key effectors of this metabolic regulation may offer therapeutic
potential not only in muscle regeneration disorders, but also in diabetes, the latter possibly via the involvement
Back to lipids…
The third day of the Congress EAS 2019, Tuesday, May 28
With the advent of the PCSK9 inhibitors, attainment of very low LDL-C levels now becomes feasible,
implying that the time has now come for researchers to turn their attention to other novel targets.
Professor Erik Stroes (Amsterdam Medical Center, University of Amsterdam, the Netherlands)
discussed apolipoprotein-B containing lipoproteins worthy of contention. Mendelian randomisation
studies have validated three potential targets: apo-CIII for triglyceride-rich lipoproteins, apo(a)
contained within lipoprotein(a) and angiopoietin like protein 3 (ANGPTL3).
Recent data have established that the clinical benefit from lowering apoB-containing lipoproteins
is directly related to the absolute reduction in apoB. However, there appears to be a discordance
between the magnitude of reduction of triglycerides observed in clinical trials (ranging from 15% to 80%,
depending on the drug) and that observed for apoB (5-10%). An exception to this is represented by
early clinical trials targeting ANGPTL3, where a comparable and extensive reduction in apoB and
triglycerides was observed with the anti ANGPTL3 monoclonal antibody evinacumab in a pilot study
in patients with homozygous familial hypercholesterolaemia.7 The mechanism of this effect merits
further investigation, but appears to involve lowering of both triglycerides and cholesterol.
In a setting of finite healthcare resources, it will be become increasingly important to target these
costly treatments to patients at highest absolute cardiovascular risk who are likely to benefit most
from these treatments. Clinicians will require an improved framework to optimise clinical decision-making,
integrating information from biomarkers, genetics and imaging. Ultimately, implementation will require
the combination of machine learning, to achieve cost-effective use of highly efficacious but costly
therapies in cardiovascular medicine.
From the plenary session on Tuesday
Preventing cardiovascular disease risk – where do we stand?
Expanding knowledge about a myriad of risk factors including biomarkers, genetics and imaging,
together with recognition that there is unite funding for healthcare systems, argues for new thinking about
cardiovascular disease risk prevention. This background provided the basis for pertinent discussions around
key issues in this plenary.
Leading the session, Professor Chris Packard (University of Glasgow, UK) made a case
for reconsidering the framework of biomarkers based on their utility. He proposed that
biomarkers should be categorised as either 1) causal, with low-density lipoprotein
cholesterol (LDL-C), the benchmark for this group,1 2) systems biomarkers such as
C-reactive protein, fibrinogen, apolipoprotein (apo) CIII, nonfasting triglycerides
and insulin resistance, which report on the state of a system but may not be directly
involved in atherogenesis; or 3) disease progression biomarkers such as high-sensitivity
troponin T and I and NT-proB-type Natriuretic Peptide which inform about the state of
the myocardium, and when combined with classical biomarkers improve the ability to
predict coronary disease, heart failure and peripheral vascular disease.2 Using this
framework, he suggested a new paradigm for cardiovascular disease prevention similar
to that used in other disciplines such as oncology and infection, involving episodic
intensive lowering of plasma LDL-C specifically targeting younger adults in the primary
prevention setting to drive down levels until early atherosclerotic lesions have resolved,
followed by a subsequent ‘maintenance phase’ in which LDL-C levels <2.6 mmol/L are tolerated.
Such an approach has the potential to limit clinical atherosclerotic cardiovascular disease
events later in life and confer socioeconomic benefit. This approach would also obviate
the need for adherence to lifelong lipidlowering drug therapy in most individuals and minimise
However, there are other components of risk that need to be incorporated as discussed by Professor Heribert Schunkert
(Technische Universitaet Munich,Germany). Genetic risk may be attributed to both rare variants
with large effects and common small-effect variants. The latter has a profound impact on risk at the
population level, and therefore prevention strategies should aim to neutralise these risk alleles.
Incorporation of polygenic risk scores which identify those individuals with risk equivalent to
monogenic mutations was suggested.3 Genetic information will also help in resolving causal
mechanisms implicated in atherosclerosis, even lifestyle which is at least partly determined by genetics.
Failure to diagnose familial hypercholesterolaemia results in worse outcome
Results from an analysis of more than 1.7 million patient records show that patients who are
likely to have familial hypercholesterolaemia (FH, inherited high cholesterol) based on cholesterol
and family history criteria, but are not diagnosed as FH, are twice as likely to die earlier
than individuals who have a FH diagnosis.1 The study was reported by Professor Kausik Ray
(Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health,
Imperial College London, UK).
Professor Paul Ridker discusses inflammation inhibition and atherothrombosis.
Whether systemic inflammation is a marker or mediator of atherothrombosis has engendered much
debate in the past. However, the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study)
changed this.1 In patients managed with best evidence-based therapy, including very well controlled
low-density lipoprotein cholesterol (LDL-C) levels at baseline, treatment with canakinumab, a
monoclonal antibody to interleukin-1? (IL-1?), resulted in profound reduction in the high-sensitivity
C-reactive protein levels (by 37 and 41% with the two higher doses, 150 mg and 300 mg), and this was
associated with significant reduction in major adverse cardiovascular events. Importantly, this benefit
was independent of any change in plasma LDL-C levels. CANTOS was truly a proof-of-concept study
that irrevocably changed thinking about inflammatory risk.
Secondary analyses of the CANTOS study showed that patients who achieved lower levels of hs-CRP or IL-6
following the therapy with canakinumab derived greater cardiovascular benefit, also in terms of
cardiovascular and all-cause mortality.
Remembering the 2nd day of Congress EAS in Maastricht, 2019
Plenary meeting on Monday May 27, 2019:
Novel insights into metabolic dysfunction in cardiovascular disease
The Monday plenary focused on metabolic dysfunction, with ensuing discussion of potential
targets in that may offer potential for therapeutic intervention.
Opening the session, Professor Klaus Ley (La Jolla Institute for Allergy and Immunology
and Adjunct Professor of Bioengineering at the University of California, San Diego, USA)
suggested a role for olfactory receptors in mediating atherosclerosis.
Following on, Professor Peter Carmeliet (Katholieke Universiteit Leuven, Belgium), a past Anitschkow Award
recipient (Innsbruck 2016), revisited angiogenesis, specifically focusing on the role of endothelial metabolism
Read the full report on Monday's plenary :
Section sessions on familial hypercholesterolemia, PCSK9 inhibitors and bempedoic acid feature
The first late breaking session on Monday highlighted new therapeutic approaches focused on lowering
low-density lipoprotein cholesterol (LDL-C). Among the studies reported was the ORION-2 study with
inclisiran in homozygous familial hypercholesterolaemia (FH, inherited high cholesterol), a novel
anti-PCSK9 agent LIB003, and a fixed combination of bempedoic acid and ezetimibe. In addition,
there were important insights from a new analysis of the Scandinavian Simvastatin Survival Study (4S),
a gamechanger for statin therapy in the secondary prevention.
Read the full report on the sessions Monday:
The first day, May 26, 2019.
Opening the Congress, EAS President Professor Lale Tokgozoglu (Ankara, Turkey) highlighted the role of the Society in research,
education and collaboration. The new Joint Dyslipidaemia Guidelines with the European
Society of Cardiology are eagerly anticipated later this year, in the light of recent findings from major trials
of innovative therapies.
The pinnacle of the Opening Ceremony, however, is the Anitschkow Lecture,
which this year was given by Anitschkow Award recipient, Professor Helen
Hobbs, an international leader in research defining the genetic determinants of
plasma lipid levels and cardiovascular risk. Professor Hobbs’ lecture was a
tour de force of her research career, illustrating the value of the rare genetic
concept, initially from work within the Dallas Heart Study, and then extending to collaborations around the world.
The main result of the study was the discovery of the genetic and population
relationship of the formation of atherosclerosis and non-alcoholic fatty liver
disease in patients with obesity.
The Anitschkow Lecture - Helen Hobbs
Lipids in the wrong places ...
The value of lipoprotein (a)
The difference in the levels of LDL cholesterol
in men in the United States and China
From genetics to public health
Dallas Heart Study
Post-meal dislipidemia (Nonfasting)
and fasting dislipidemia
The pathway for the formation of non-alcoholic
fatty liver disease –
obesity and insulin resistance
Parallels between non-alcoholic fatty liver
disease and coronary pathology
Genetic marking of atherosclerosis and
non-alcoholic fatty liver disease
Let us inform you about the next scientific and informational events of the Ukrainian Atherosclerosis
Society scheduled in 2019 as well.
We invite you to meet the Ukrainian Lipid School:
- April 19 in Chernivtsy (venue - Academy Palace).
- Two subsequent meetings of the Lipid School
will take place in the fall of 2019 (additional information will be provided).
Also, let us announce events of the Ukrainian Atherosclerosis Society included in the general
register of congresses and conferences in Ukraine at 2019:
- On October 17, 2019, the Conference "Gender aspects of cardiometabolic risk in women" will be held
in Dnipro City.
- On November 13, 2019, the XIII Annual Meeting of the Ukrainian Atherosclerosis Society "Diagnosis,
prevention and treatment of atherosclerosis and coronary heart disease: modern approaches and new achievements"
will take place in Kyiv.