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News: EAS Academy - Lecture of the week

Biomarkers predicting CVD

Thursday 2 July 2020   (0 Comments)
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About the presenter: Professor Chris Packard

Chris Packard is Professor of Vascular Biochemistry and a Senior Research Fellow at the University of Glasgow.
His research has focused on lipoprotein metabolism and how it is affected by diets and drugs, and he has played a key role in large scale clinical trials of lipid lowering agents.
More recently, his research interests have extended to the study of emerging risk factors for coronary heart disease, the metabolic consequences of insulin resistance and the causes of the dyslipidaemia in metabolic syndrome, the health consequences of social deprivation, as well as exploration of the mechanism of action of novel lipid lowering drugs.

Key contributions from his research include evaluation of the role of the low-density lipoprotein (LDL) receptor in vivo, the discovery of metabolic channelling in the apolipoprotein B lipoprotein delipidation cascade, and the formulation of models to explain the generation of small, dense LDL. Outside the laboratory,

Professor Packard is active in local and national initiatives to promote health gains from medical research. He was founding chairman of NEXXUS, the West of Scotland Bioscience Network which promoted community building and knowledge exchange between life sciences industry, academia and the UK National Health Service.

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About the topic: Biomarkers predicting CVD

The morbidity and disability associated with nonfatal cardiovascular complications are major contributors to the societal burden of cardiovascular disease. With increasing financial pressures on healthcare systems, it is therefore critical to identify susceptible individuals so as to prevent new events. Much of the focus of previous guidelines for cardiovascular disease prevention has been on traditional modifiable risk factors; however, it is evident that these risk factors do not explain all risk, as there are individuals who have events who do not fit the traditional definition of “high risk”. Consequently, there has been a drive to identify and validate novel biomarkers that may be of relevance.

Investigation of this question has offered a diversity of biomarker candidates. One example is troponin I, a specific marker of myocardial injury and an independent predictor of cardiovascular mortality in patients with and without cardiovascular disease. Analyses from the West of Scotland Coronary Prevention Study also showed that serial troponin I measurement has therapeutic potential as a dynamic biomarker of cardiovascular disease risk. To date, however, there is no ‘one’ biomarker that can be recommended. Furthermore, while incorporation of multiple biomarkers in one multimodal marker can improve predictive ability, the costs entailed can limit the gains of this approach.

More recently, attention has also focused on the potential of small non-coding microRNAs (miR) as biomarkers of disease, given their regulatory roles in gene expression. For example, miR-30 has been suggested as one possibility given evidence of a positive association with total- and low-density lipoprotein cholesterol, implicating regulatory functions in lipid homeostasis. Studies also implicate miR 30c-5p as a promoter of early atherosclerosis. These novel miR may therefore offer promise as non-invasive biomarkers in diagnosis and cardiovascular disease risk stratification, providing information complementary to traditional markers and established clinical variables. As with other potential biomarker candidates, however, there are a range of issues to consider, including changes in the utility of the biomarker in different clinical settings, the extent of intra-individual variability over time, as well as practical requirements. If validated, the use of such novel biomarkers, either alone or in combination, may offer opportunities for tailoring treatment to the individual, as well as monitoring efficacy, consistent with the concept of personalized cardiovascular disease medicine.

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Key references

Annemans L, Packard CJ, Briggs A, Ray KK. ‘Highest risk-highest benefit’ strategy: a pragmatic, cost-effective approach to targeting use of PCSK9 inhibitor therapies. Eur Heart J 2018;39:2546-50.

Packard CJ, Young R, Ross K, Ford I, Ambegaonkar BM, Brudi P, McCowan C. Modelling total coronary heart disease burden and long-term benefit of cholesterol lowering in middle aged men with and without a history of cardiovascular disease. Eur Heart J Qual Care Clin Outcomes 2017;3:281-8.

Sodi R, Eastwood J, Caslake M, Packard CJ, Denby L. Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins. Clin Chim Acta 2017;466:13-19.


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