title: 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?
abstract: BACKGROUND
  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 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.
  
  
  METHODS
  430 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.
  
  
  RESULTS
  When 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom. Electronic address: a.lazzarino@ucl.ac.uk.
authors.forename: Antonio Ivan
authors.initials: AI
authors.lastname: Lazzarino
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Hamer
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Livia
authors.initials: L
authors.lastname: Carvalho
authors.affiliation: Chemical Pathology, Clinical Blood Sciences, St. George's Healthcare NHS Trust, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Gaze
authors.affiliation: Chemical Pathology, Clinical Blood Sciences, St. George's Healthcare NHS Trust, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Collinson
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Steptoe
mesh_terms: D000367:Age Factors; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000150:complications*; D002114:Calcinosis / Q000000981:diagnostic imaging*; D002318:Cardiovascular Diseases; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D012737:Sex Factors; D014057:Tomography, X-Ray Computed; D020107:Troponin T / Q000097:blood*
chemical_list: D020107:Troponin T
keywords: Acute coronary syndrome; Aetiology; Coronary artery disease; Physiopathology; Risk assessment; Risk factors; Routine Diagnostic tests; Tomography; Troponin T; X-ray computed