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Bioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases.
European Heart Journal. Cardiovascular Pharmacotherapy 2023 August 11
Although bioinformatic methods gained a lot of attention in the latest years, their use in real-world studies for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD) is still lacking. Bioinformatic resources have been applied to thousands of individuals from the Framingham Heart Study as well as health care-associated biobanks such as the UK Biobank, the Million Veteran Program, and the CARDIoGRAMplusC4D Consortium and randomized controlled trials (i.e. ODYSSEY, FOURIER, ASPREE, PREDIMED). These studies contributed to the development of polygenic risk scores (PRS) which emerged as novel potent genetic-oriented tools able to calculate the individual risk of ASCVD and to predict the individual response to therapies such as statins and PCSK9i. ASCVD are the first cause of death around the world including coronary heart disease (CHD), peripheral artery disease, and stroke. To achieve the goal of precision medicine and personalized therapy, advanced bioinformatic platforms are set to link clinically useful indices to heterogeneous molecular data, mainly epigenomics, transcriptomics, metabolomics and proteomics. The DIANA study found that differential methylation of ABCA1, TCF7, PDGFA, and PRKCZ significantly discriminated patients with acute coronary syndrome from healthy subjects and their expression levels positively associated with CK-MB serum concentrations. The ARIC Study revealed several plasma proteins, acting or not in lipid metabolism, with a potential role in determining the different pleiotropic effects of statins in each subject. The implementation of molecular high-throughput studies and bioinformatic techniques into traditional cardiovascular risk prediction scores is emerging as a more accurate practice to stratify patients earlier in life and to favour timely and tailored risk reduction strategies. Of note, radiogenomics aims to combine imaging features extracted for instance by coronary computed tomography angiography and molecular biomarkers to create CHD diagnostic algorithms useful to characterize atherosclerotic lesions and myocardial abnormalities. The current view is that such platforms could be of clinical value for prevention, risk stratification, and treatment of ASCVD.
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