Abstract Background Metabolic syndrome (MetS) is a well-established risk factor for major adverse cardiovascular events (MACE). Previous studies have shown the relationship between MetS, computed tomography derived epicardial fat volume (EFV), non-alcoholic fatty liver disease (NAFLD) status and coronary artery calcium score (CACS) in asymptomatic patients. Objective To assess the prognostic value of coronary computed tomography angiography (CCTA) derived EFV, NAFLD status, CACS and the number of plaques (NoP) in symptomatic patients with and without MetS and to design a new risk score for predicting MACE. Methods We conducted a single-centre, cross-sectional study on 2038 patients with intermediate risk of CAD, which underwent CCTA between March 2019 and May 2022. Data regarding MetS status and other comorbidities were assessed at the moment of the inclusion in the study. CCTA assessment included: CACS, NoP, EFV and NAFLD status. The endpoint was the occurrence of MACE (late revascularization, myocardial infarction, sudden cardiac death). Cox regression was used to assess the relationship between MetS and CCTA derived variables on the occurrence of MACE. Receiver operating characteristic curve analysis was used to determine the prediction value of CCTA derived parameters and of the new risk score. Net reclassification improvement was used to compare the risk score with CACS ability to predict MACE. Results Patients were prospectively followed up during a mean time of 26.9 (standard deviation: 9.5) months. 361 (17.7%) patients developed a MACE (myocardial infarction, n=67; late revascularization, n=282; sudden cardiac death, n=12). More events were seen in MetS+ patients (n=244) versus MetS- patients (n=117) (p<0.001). MetS, age, male gender, CACS, NoP, EFV and NAFLD were all associated with the occurrence of MACE: unadjusted hazard ratios (HR) of: 1.56, 1.25, 1.87, 1.0013, 1.16, 1.053 and 1.67 (p<0.001 for all). However, in the multivariate analysis only the CCTA derived variables showed a significant association with MACE: CCS HR=1.001, NoP HR=1.097, EFV HR=1.035, NAFLD HR=1.843 (p<0.001 for all). Our risk score for predicting MACE included CACS, NoP, EFV and NAFLD. It had an area under the curve (AUC) of 0.948, a sensitivity of 89.7%, a specificity of 92.9% and a negative predicting value of 97.7%. When compared to CCS alone, the risk score correctly reclassified 24 (6.6%) events and 101 (6.2%) non-events, with a net reclassification index of 0.128 (p<0.001). Conclusion MetS is associated with an increased risk for MACE, but not after adjustment for CCS, NoP, EFV, and NAFLD. Adding NoP, EFV and NAFLD to CCS in a risk score further improves the accuracy in predicting MACE, when compared to CCS alone.
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