A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: The use of association, discrimination and reclassification

Abstract

Background: Computed tomography (CT) biomarkers claim to improve cardiovascular risk stratification. This review focuses on significant differences in incremental measures between adequate and inadequate reporting practise. Methods: Studies included were those that used Framingham Risk Score as a baseline and described the incremental value of adding calcium score or CT coronary angiogram in predicting cardiovascular risk. Searches of MEDLINE, EMBASE, Web of Science and Cochrane Central were performed with no language restriction. Results: Thirty five studies consisting of 206,663 patients (men=118,114, 55.1%) were included. The baseline Framingham Risk Score included the 1998, 2002 and 2008 iterations. Selective reporting, inconsistent reference groupings and thresholds were found. Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and the respective AUC were significantly different (p=0.015). When the baseline model performed well, the AUC was relatively lower with the addition of a CT biomarker (Spearman coefficient=-0.46, p<0.0001; n=33; 76 pairs of data). Other factors that influenced AUC performance included exploration of data analysis, calibration, validation, multivariable and AUC documentation (all p<0.05). Most studies (68.7%) that reported categorical NRI (n=16; 46 pairs of data) subjectively drew strong conclusions along with other poor reporting practices. However, no significant difference in values of NRI was found between adequate and inadequate reporting. Conclusions: The widespread practice of poor reporting particularly association, discrimination, reclassification, calibration and validation undermines the claimed incremental value of CT biomarkers over the Framingham Risk Score alone. Inadequate reporting of discrimination inflates effect estimate, however, that is not necessarily the case for reclassification.