Abstract
Purpose of Review
Conventional risk stratification algorithms that rely on age, clustered phenotypic traits, and biomarkers under-recognize the sizeable subgroup of individuals at high polygenic risk for atherosclerotic cardiovascular disease (ASCVD). This review provides perspective on the promising role of genetic testing in cardiovascular prevention through the lens of lipid metabolism.
Recent Findings
Recent advances in cardiovascular genetics identified a number of common and rare variants affecting ASCVD risk. This genetic susceptibility can be assessed by polygenic risk scores (PRS) which quantify risk conferred by the cumulative impact of common variants. This results in a normally distributed spectrum of risk for coronary artery disease that is present at birth and amplifies the effects of modifiable risk factors including lipids.
Summary
Polygenic risk is a significant determinant of ASCVD risk that is below the discrimination level of conventional guideline-based clinical frameworks. Genetic risk scores thus hold potential to refine phenotypic screening in cardiovascular prevention, identify subsets of the population that might derive particular benefit from early lifestyle and pharmaceutical interventions, and guide treatment eligibility. This might pave the way to personalized prevention aimed at reducing the unacceptable global burden of ASCVD.
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Open Access funding provided by Projekt DEAL. The authors acknowledge the support of the Bavarian State Ministry of Health and Care within the framework of DigiMed Bayern (grant No: DMB-1805-0001), the German Federal Ministry of Education and Research (BMBF) within the framework of ERA-NET on Cardiovascular Disease (Druggable-MI-genes: 01KL1802), within the scheme of target validation (BlockCAD: 16GW0198K), within the framework of the e:Med research and funding concept (AbCD-Net: 01ZX1706C), and within the British Heart Foundation (BHF)/German Centre of Cardiovascular Research (DZHK) collaboration. Further support was granted by the German Research Foundation (DFG) as part of the Sonderforschungsbereich SFB 1123 (B02) and the Sonderforschungsbereich SFB TRR 267 (B05) as well as the Corona-Foundation (Junior Research Group Translational Cardiovascular Genomics).
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K.L. did the literature search and drafted the manuscript. T.K. and H.S. critically revised and edited the manuscript. All authors approved the final version of the manuscript.
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Katharina Lechner has received speaker’s honoraria from Goerlich Pharma, Novo Nordisk, Sanofi, and Amgen.
Thorsten Kessler declares no conflict of interest.
Heribert Schunkert has received an institutional grant and honorarium from AstraZeneca; a travel grant from Vifor Pharma; and honoraria from MSD Sharpe & Dohme, Sanofi-Aventis, Brahms, Boehringer-Ingelheim, Novartis, Amgen, Synlab, Daiichi-Sankyo, Servier, Bristol-Myers Squibb, Medtronic, Pfizer, and Bayer Vital.
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Lechner, K., Kessler, T. & Schunkert, H. Should We Use Genetic Scores in the Determination of Treatment Strategies to Control Dyslipidemias?. Curr Cardiol Rep 22, 146 (2020). https://doi.org/10.1007/s11886-020-01408-9
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DOI: https://doi.org/10.1007/s11886-020-01408-9