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CARDIOVASCULAR PREVENTION / CLINICAL RESEARCH
Risk of adverse cardiovascular events based on common genetic variants in 8-year follow-up of the LIPIDOGEN2015 population using the polygenic risk score (PRS): study design and methodology
1
Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
2
Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland
3
Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, USA
4
Liverpool Centre for Cardiovascular Science (LCCS), Liverpool, UK
5
Department of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
6
Department of Genetics, Polish Mother’s Memorial Hospital-Research Institute (PMMHRI), Lodz, Poland
7
Biobank Lab, Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Poland
8
Institute of Medical Sciences, Department of Biology and Genetics, Faculty of Medicine, University of Opole, Poland
9
Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, and Liverpool Heart and Chest Hospital, Liverpool, UK
10
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
11
Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK
12
Department of Preventive Cardiology, CGH Medical Center, Sterling, Illinois, USA
13
Clinical Pharmacy & Therapeutics Research Group, School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
14
Department of Family Medicine and Public Health, Faculty of Medicine, University of Opole, Poland
Submission date: 2024-05-07
Final revision date: 2024-07-23
Acceptance date: 2024-08-08
Online publication date: 2024-08-08
Corresponding author
Maciej Banach
Department of Preventive Cardiology and Lipidology, Medical University of Lodz, 281/289 Rzgowska St, 93-338 Lodz, Poland, Phone: +48422711124
Department of Preventive Cardiology and Lipidology, Medical University of Lodz, 281/289 Rzgowska St, 93-338 Lodz, Poland, Phone: +48422711124
KEYWORDS
TOPICS
CardiologyGeneticsPublic HealthCoronary artery diseaseAtherosclerosisLipid disordersAcute Coronary Syndrome
ABSTRACT
Introduction:
Classical risk factors such as hypertension, hypercholesterolemia, pre-diabetes, diabetes and obesity can predict adverse cardiovascular events, but they are less prognostic in patients aged < 60 years. Polygenic risk scores (PRS) can be effective in predicting adverse coronary events in younger and middle-aged patients. Our main aim is to assess the utility of a new PRS created for the Polish population in predicting mortality during an 8-year follow-up in the nationwide LIPIDOGEN2015 population.
Material and methods:
All DNA samples of 1779 patients were genotyped using Infinium Global Screening Array-24+ v3.0 Kit microarrays. The samples were amplified, fragmented, and hybridized to BeadChips. The BeadChips were scanned using iScan and converted to genotypes using Genome Studio 2.0.
Results:
We will develop a PRS based on the identified single nucleotide polymorphisms (SNPs) in the LIPIDOGEN2015 project’s studied population and determine the analyzed group’s risk of death due to cardiovascular diseases (CVD) based on data obtained from 8 years of patient-follow-up. Using the developed PRS scale and biochemical analyses, we will assess the effectiveness of lipid-lowering therapy with statins in patients with high and low genetic risk of sudden CVD events (secondary endpoints).
Conclusions:
The developed PRS scale, combined with clinical covariates, will facilitate the creation of an algorithm to predict long-term mortality. This will enable us to stratify CVD risk more precisely, which may result in earlier implementation of lifestyle changes and dietary adjustments and potentially initiate earlier pharmacotherapy for at-risk individuals.
Classical risk factors such as hypertension, hypercholesterolemia, pre-diabetes, diabetes and obesity can predict adverse cardiovascular events, but they are less prognostic in patients aged < 60 years. Polygenic risk scores (PRS) can be effective in predicting adverse coronary events in younger and middle-aged patients. Our main aim is to assess the utility of a new PRS created for the Polish population in predicting mortality during an 8-year follow-up in the nationwide LIPIDOGEN2015 population.
Material and methods:
All DNA samples of 1779 patients were genotyped using Infinium Global Screening Array-24+ v3.0 Kit microarrays. The samples were amplified, fragmented, and hybridized to BeadChips. The BeadChips were scanned using iScan and converted to genotypes using Genome Studio 2.0.
Results:
We will develop a PRS based on the identified single nucleotide polymorphisms (SNPs) in the LIPIDOGEN2015 project’s studied population and determine the analyzed group’s risk of death due to cardiovascular diseases (CVD) based on data obtained from 8 years of patient-follow-up. Using the developed PRS scale and biochemical analyses, we will assess the effectiveness of lipid-lowering therapy with statins in patients with high and low genetic risk of sudden CVD events (secondary endpoints).
Conclusions:
The developed PRS scale, combined with clinical covariates, will facilitate the creation of an algorithm to predict long-term mortality. This will enable us to stratify CVD risk more precisely, which may result in earlier implementation of lifestyle changes and dietary adjustments and potentially initiate earlier pharmacotherapy for at-risk individuals.
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