AI Article Synopsis

  • - This study aimed to assess the predictive power of coronary artery calcification (CAC) genetic risk scores (GRSs) for coronary artery disease (CAD), suggesting existing GRSs may overlook important genetic factors related to intermediate phenotypes like CAC.
  • - Researchers analyzed data from three different studies involving a total of 3,535 participants, comparing CAC GRSs to traditional cardiovascular disease (CVD) risk factors and a broader CAD GRS constructed from 1.7 million genetic variants.
  • - Results indicated that CAC GRS is significantly linked to CAD across multiple cohorts and provides additional predictive value beyond traditional risk factors, enhancing risk assessment and precision in predicting CAD.

Article Abstract

Aim: The modest added predictive value of the existing genetic risk scores (GRSs) for coronary artery disease (CAD) could be partly due to missing genetic components, hidden in the genetic architecture of intermediate phenotypes such as coronary artery calcification (CAC). In this study, we investigated the predictive ability of CAC GRS for CAD.

Materials And Methods: We investigated the association of CAC GRSs with CAD and coronary calcification among the participants in the Ludwigshafen Risk and Cardiovascular Health study (LURIC) ( = 2742), the Tampere Vascular Study (TVS) ( = 133), and the Tampere Sudden Death Study (TSDS) ( = 660) using summary data from the largest multi-ancestry GWAS meta-analysis of CAC to date. Added predictive value of the CAC GRS over the traditional CVD risk factors as well as metaGRS, a GRS for CAD constructed with 1.7 million genetic variants, was tested with standard train-test machine learning approach using the LURIC data, which had the largest sample size.

Results: CAC GRS was significantly associated with CAD in LURIC (OR=1.41, 95 % CI [1.28-1.55]), TVS (OR=1.79, 95 % CI [1.05-3.21]) as well as in TSDS (OR=4.20, 95 % CI [1.74-10.52]). CAC GRS showed strong association with calcification areas in left (OR=1.78, 95 % CI [1.16-2.74]) and right (OR=1.71, 95 % CI [1.98-2.67]) coronary arteries. There was statistically significant added predictive value of the CAC GRS for CAD over the used traditional CVD risk factors (AUC 0.734 vs 0.717, p-value = 0.02). Furthermore, CAC GRS improved the prediction accuracy for CAD when combined with metaGRS.

Conclusions: This study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525111PMC
http://dx.doi.org/10.1016/j.ajpc.2024.100884DOI Listing

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