The mediation of coronary calcification in the association between risk scores and cardiac troponin T elevation in healthy adults: Is atherosclerosis a good prognostic precursor of coronary disease?

Antonio Ivan Lazzarino,Mark Hamer,Livia Carvalho,David Gaze,Paul Collinson,Andrew Steptoe

doi:10.1016/j.ypmed.2015.05.025

Abstract

BackgroundConventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease. In UK in 2006–2008 (Whitehall II study) we tested the ability of several risk scores to identify individuals with cardiac cell damage and assessed to what extent their estimates were mediated by the presence of atherosclerosis. Methods430 disease-free, low-risk participants were tested for high-sensitivity cardiac troponin-T (HS-CTnT) and for coronary calcification using electron-beam, dual-source, computed tomography (CAC). We analysed the data cross-sectionally using ROC curves and mediation tests. ResultsWhen the risk scores were ranked according to the magnitude of ROC areas for HS-CTnT prediction, a score based only on age and gender came first (ROC area=0.79), followed by Q-Risk2 (0.76), Framingham (0.70), Joint-British-Societies (0.69) and Assign (0.68). However, when the scores were ranked according to the extent of mediation by CAC (proportion of association mediated), their order was essentially reversed (age&gender=6.8%, Q-Risk2=9.7%, Framingham=16.9%, JBS=17.8%, Assign=17.7%). Therefore, the more accurate a score is in predicting detectable HS-CTnT, the less it is mediated by CAC; i.e. the more able a score is in capturing atherosclerosis the less it is able to predict cardiac damage. The P for trend was 0.009. ConclusionsThe dynamics through which cardiac cell damage is caused cannot be explained by ‘classic’ heart disease risk factors alone. Further research is needed to identify precursors of heart disease other than atherosclerosis.

Highlights

Conventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease
Coronary atherosclerosis, indicated as the fundamental precursor of coronary artery disease, was previously considered as a passive cholesterol storage disease whereas we currently view it as an inflammatory disorder and modern views of the dynamics underlying acute cardiac events highlight the role of inflammation
In spite of our constant progress in the comprehension of coronary artery disease (CAD) pathophysiology, standard risk algorithms are based on the idea that cardiac events arise through the accumulation of coronary atherosclerosis and widely-used tools like the Framingham, the Joint British Societies & British National Formulary, the Assign, and the Q-Risk scores are still based on variables such as age, gender, blood lipids, blood pressure, and other ‘classic’ risk factors associated with atherosclerosis, as it was traditionally conceived (D'Agostino et al, 2008; British Cardiac Society et al, 2005; Woodward et al, 2007; Hippisley-Cox et al, 2008)

Summary

Introduction

Conventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease. In spite of our constant progress in the comprehension of CAD pathophysiology, standard risk algorithms are based on the idea that cardiac events arise through the accumulation of coronary atherosclerosis and widely-used tools like the Framingham, the Joint British Societies & British National Formulary, the Assign, and the Q-Risk scores are still based on variables such as age, gender, blood lipids, blood pressure, and other ‘classic’ risk factors associated with atherosclerosis, as it was traditionally conceived (D'Agostino et al, 2008; British Cardiac Society et al, 2005; Woodward et al, 2007; Hippisley-Cox et al, 2008). The standard risk algorithms may not be completely accurate in predicting cardiac events, rather than coronary stenosis, because they only include factors associated with ‘passive’ atherosclerosis, considered as the main mediator for CAD events

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