Coronary artery calcification score and 19 biomarkers on cardiovascular events; a 10-year follow-up DanRisk substudy

Abstract Background SCORE2 is recommended for the estimation of the 10-year risk of cardiovascular disease (CVD), and guideance of medical therapy. However, the prediction is deficient. Coronary artery calcification (CAC) score has been proven to improve the risk assessment in primary prevention of CVD, however, it is also resource-intensive. Biomarkers may be an advantageous alternative. Purpose This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction. Methods Classic cardiovascular (CV) risk factors, CAC-score, and a wide range of blood samples (including lipids, calcium-phosphate metabolism, troponin, inflammation, and kidney function), were collected from 1,211 randomly selected middle-aged men and women in this multicentre prospective cohort in 2009-2010. 10-year follow-up data on CV-events (death from CVD, stroke, myocardial infarction, heart failure or coronary artery revascularization) were obtained from the Danish Health Registries. The association between SCORE2, CAC-score, biomarkers, and CV-events was displayed in Kaplan Meier diagrams, assessed using cox proportional hazard rates (HR) and compared using area under the curve (AUC) calculation of receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) for CAC-score compared to SCORE2 was also calculated. Results 92 participants had CV-events. Events were seen in 29.3% of 41 participants with a very high risk (SCORE2 ≥10%) and 24.2% of 66 participants with CAC-score ≥400. Adjusted for risk factors, CAC-score was significantly associated with events adjusted HR 1.91 (95%CI: 1.10;3.31), 3.61 (95%CI: 1.93;6.76), and 5.2 (95%CI: 2.63;10.29) for CAC-score 1-99, CAC-score 100-399 and CAC-score ≥400, respectively. HR for the highest quartile of C-reactive protein (CRP) was 2.34 (95%CI: 1.15;4.47), while none of the remaining biomarkers improved HR. CAC-score improved AUC of the SCORE2 model (AUC_CAC+SCORE2: 0.72, AUC_SCORE2: 0.67, p