Should We Use Genetic Scores in the Determination of Treatment Strategies to Control Dyslipidemias?
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LIPID ABNORMALITIES AND CARDIOVASCULAR PREVENTION (G. DE BACKER, SECTION EDITOR)
Should We Use Genetic Scores in the Determination of Treatment Strategies to Control Dyslipidemias? Katharina Lechner 1,2 & Thorsten Kessler 1,2 & Heribert Schunkert 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Conventional risk stratification algorithms that rely on age, clustered phenotypic traits, and biomarkers underrecognize 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. Keywords Dyslipidemias . Genetic scores . Risk stratification . Cardiovascular prevention . Genome-wide association study . Myocardial infarction . Coronary artery disease
Introduction Despite major technological and pharmacological advances in cardiovascular medicine, atherosclerosis and its clinical
Topical Collection on Lipid Abnormalities and Cardiovascular Prevention * Heribert Schunkert [email protected] Katharina Lechner [email protected] Thorsten Kessler [email protected] 1
Department of Cardiology, German Heart Centre Munich, Technical University Munich, Lazarettstraße 36, 80636 Munich, Germany
2
DZHK (German Centre for Cardiovascular Research), Partner site Munich, Munich Heart Alliance, Munich, Germany
manifestations remain the leading causes of death worldwide. Atherosclerosis is a multifactorial, systemic process that progresses at various rates in many vascular territories. It is a consequence of genetic predisposition and exogenous risk factors, whose cumulative effects become evident in the arterial wall over a lifetime and are best reflected by chronological aging, the strongest “risk factor” [1–3]. Acute clinical manifestations of atherosclerotic cardiovascular disease (ASCVD) are triggered by subsets of atherosclerotic lesions [4]. Such lesions are often found in individuals with a genetic di
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