Banach Maciej, Fronczek Martyna, Osadnik Tadeusz, Gach Agnieszka, Strapagiel Dominik, Słomka Marcin, Lejawa Mateusz, Goc Anna, Boniewska-Bernacka Ewa, Pańczyszyn Anna, Lip Gregory Y H, Mikhailidis Dimitri P, Toth Peter P, Penson Peter E, Jóźwiak Jacek
Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland.
Arch Med Sci. 2024 Aug 8;20(5):1452-1460. doi: 10.5114/aoms/192147. eCollection 2024.
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.
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.
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).
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.
高血压、高胆固醇血症、糖尿病前期、糖尿病和肥胖等经典风险因素可预测不良心血管事件，但在60岁以下患者中其预后价值较低。多基因风险评分（PRS）在预测中青年患者的不良冠状动脉事件方面可能有效。我们的主要目的是评估为波兰人群创建的一种新的PRS在全国LIPIDOGEN2015人群8年随访期间预测死亡率的效用。
使用Infinium Global Screening Array - 24 + v3.0试剂盒微阵列对1779例患者的所有DNA样本进行基因分型。样本进行扩增、片段化，并与BeadChips杂交。使用iScan对BeadChips进行扫描，并使用Genome Studio 2.0将其转换为基因型。
我们将基于LIPIDOGEN2015项目研究人群中鉴定出的单核苷酸多态性（SNP）开发一个PRS，并根据8年患者随访获得的数据确定分析组因心血管疾病（CVD）死亡的风险。使用开发的PRS量表和生化分析，我们将评估他汀类药物降脂治疗对CVD事件突发遗传风险高和低的患者的有效性（次要终点）。
开发的PRS量表与临床协变量相结合，将有助于创建一种预测长期死亡率的算法。这将使我们能够更精确地分层CVD风险，这可能导致更早地实施生活方式改变和饮食调整，并可能为高危个体更早地启动药物治疗。
