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EAS2019 - From the plenary session on Tuesday May 28

Wednesday 29 May 2019   (0 Comments)
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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 finite 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 lipid‐lowering drug therapy in most individuals and minimise safety considerations.

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 [Eur Heart J 2019 in press].

The question is how to integrate information from biomarkers and genetics in standardised risk estimation. Professor Ian Graham (Trinity College Dublin, Ireland) recognised that the current approach for global risk estimation in Europe – SCORE – requires revision. This is because SCORE is based on historic cohorts which are not representative of current populations, does not estimate risk reliably in younger individuals, and does not adequately take account of the complex biological interaction of risk factors. There is ongoing revision of SCORE, including extension of the upper age limit to 70 years, and setting the cholesterol range from 4 to 7 mmol/L (values above this would indicate an inherited hypercholesterolaemia and therefore high risk). Evidence from Mendelian randomisation studies should also be incorporated, as well as exposure duration, the gradient of the rise in the risk factor, environmental factors. Moreover, retargeting SCORE to younger individuals is warranted.

Professor Kausik Ray (Imperial College London, UK) emphasised the importance of considering the trajectory of cardiovascular disease for risk-based approaches to add-on costly lipid modifying treatments. Such therapies should be best directed to high risk groups, such as those with pre-existing clinical atherosclerotic cardiovascular disease or familial hypercholesterolaemia. Currently, risk estimation in these high-risk groups needs further refinement and validation, as a “one size fits all” is not appropriate.

Concluding this plenary, Professor Thomas Lüscher (Royal Brompton and Harefield Hospitals, Imperial College, London, UK) highlighted the role of the microbiome, especially relevant in the concept that long-term susceptibility to disease originates early in life. Further understanding of the molecular mechanisms that drive linkages between the microbiome and cardiovascular disease is needed, as the metabolites of the microbiota have prognostic value.4 Many challenges remain in integrating the components of risk – from biomarkers, genetics, the environment and the microbiome – to develop a new paradigm for prevention of cardiovascular disease risk.  

References

1. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017;38:2459-72.

2. Matsushita K, Kwak L, Yang C, et al. High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study. Eur Heart J 2018;39:2412-9.

3. Khera AV, Chaffin M, Aragam KG et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 2018;50:1219-24.

4. Li XS, Obeid S, Wang Z et al. Trimethyllysine, a trimethylamine N-oxide precursor, provides near- and long-term prognostic value in patients presenting with acute coronary syndromes. Eur Heart J 2019. pii: ehz259.


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