Liquid biopsy based on whole blood transcriptome and artificial intelligence for the prediction of coronary artery calcification: a pilot study.

Abstract

Aims: Whole blood RNA expression is modulated in response to signals from tissues, including the vessel wall. The primary objective of this study was to explore the ability of whole blood transcriptomes, analysed using artificial intelligence (AI), to predict coronary artery calcifications (CAC).

Methods and results: A total of 196 subjects [men aged 40-70 years and women aged 50-70 years without known cardiovascular disease (CVD)] were non-consecutively enrolled for CAC assessment via chest computed tomography. Whole blood RNA was isolated and sequenced. Different AI models were trained using clinical and transcriptomic variables as distinctive features to identify the presence of CAC (Agatston score >0). Finally, we compared the predictive performance of these models. The prevalence of CAC was 43.9%. The combined AI model, incorporating transcriptome data along with age, sex, body mass index, smoking status, diabetes, and hypercholesterolaemia, achieved an area under the curve (AUC) of 0.92 (95% CI, 0.88-0.95) for predicting the presence of CAC, with a sensitivity of 92%, specificity of 80%, positive predictive value of 81%, negative predictive value of 91%, and an overall accuracy of 86%. The combined AI model demonstrated significantly improved discrimination compared with the transcriptomic model (AUC 0.79; P = 0.009), the clinical variables model (AUC 0.72; P < 0.001), and the CVD risk model (AUC 0.68; P < 0.001).

Conclusion: In this pilot study, an AI model integrating whole blood transcriptome data with clinical risk factors demonstrated the ability to predict CAC, providing incremental value over clinical models. Further studies are needed to achieve more robust validation.