Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction

Graphical Abstract Graphical Abstract Proteomics and lipidomics improve traditional ASCVD risk prediction. Plasma proteomics and lipidomics hold a major promise in improving ASCVD risk prediction offering high-throughput assessment using different techniques. Albeit retrospectively, large proteomic and lipidomic studies have consistently demonstrated improved ASCVD risk prediction in terms of discrimination and reclassification benefit compared to risk scoring with clinical characteristics. Future studies into clinical utility are needed for widespread clinical implementation. ASCVD, atherosclerotic cardiovascular disease; AUC, area under the receiver operating curve; non-HDL-C, non-high-density lipoprotein cholesterol; SCORE2, Systematic COronary Risk Evaluation 2 system; SMART2, Second Manifestations of ARTerial disease 2; LC-MS, liquid chromatography–mass spectrometry; MS, mass spectrometry. Abstract Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual’s susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual’s ASCVD risk.