title: Quantification of coronary atherosclerosis and inflammation to predict coronary events and all-cause mortality.
abstract: OBJECTIVE
  This study sought to determine whether the evaluation of the combined presence of coronary artery calcium (CAC) and high-sensitivity C-reactive protein (hsCRP) improves discrimination and stratification of hard coronary events and all-cause mortality in the general population.
  
  
  BACKGROUND
  Coronary atherosclerosis is a chronic inflammatory disease. Both hsCRP as a measure of inflammation and CAC as a measure of coronary plaque burden have been shown to improve risk appraisal.
  
  
  METHODS
  Framingham risk variables, hsCRP, and CAC were measured in 3,966 subjects without known coronary artery disease or acute inflammation. After 5 years, incident coronary deaths, nonfatal myocardial infarction, and all-cause mortality were determined.
  
  
  RESULTS
  CAC and hsCRP independently predicted 91 coronary events (adjusted hazard ratios [HRs]: log(2)(CAC+1) = 1.25 [95% confidence interval (CI): 1.16 to 1.34], p < 0.0001; hsCRP = 1.11 [95% CI: 1.02 to 1.21], p = 0.019) and 130 deaths (adjusted HRs: log(2)(CAC+1) = 1.12 [95% CI: 1.06 to 1.19], p < 0.0001; hsCRP = 1.11 [95% CI: 1.04 to 1.19], p = 0.004). For coronary events, net reclassification improvement (NRI) was 23.8% (p = 0.0007) for CAC and 10.5% (p = 0.026) for hsCRP. Adding CAC to Framingham risk variables and hsCRP further improved discrimination of coronary risk but not vice versa. Among persons without CAC, those with hsCRP >3 mg/l versus <3 mg/l had a significantly higher coronary risk (p = 0.006). For all-cause mortality, integrated discrimination improvement (IDI) was positive when CAC or hsCRP were added to age and sex (+0.51%, p < 0.001 and +0.43%, p = 0.012, respectively). Adjusted HRs in the highest versus lowest category of a risk index derived from established CAC and hsCRP thresholds (i.e., CAC = 100 and hsCRP = 3 mg/l) were 5.92 (95% CI: 3.14 to 11.16) for coronary events and 3.02 (95% CI: 1.82 to 5.01) for all-cause mortality (p < 0.0001 each). The adjusted HR for coronary events in intermediate risk subjects was 6.98 (95% CI: 2.47 to 19.73), p < 0.001.
  
  
  CONCLUSIONS
  The risk of coronary events and all-cause mortality that is mediated by the presence of coronary atherosclerosis and systemic inflammation can be estimated by CAC and hsCRP. An improvement in coronary risk prediction and discrimination was predominantly driven by CAC, whereas hsCRP appears to have a role especially in persons with very low CAC scores.
authors: Clinic of Cardiology, West-German Heart Center Essen, University Clinic Duisburg-Essen, Hufelandstrasse 55, Essen, Germany. stefan.moehlenkamp@uk-essen.de
authors: Stefan
authors: S
authors: Möhlenkamp
authors: Nils
authors: N
authors: Lehmann
authors: Susanne
authors: S
authors: Moebus
authors: Axel
authors: A
authors: Schmermund
authors: Nico
authors: N
authors: Dragano
authors: Andreas
authors: A
authors: Stang
authors: Johannes
authors: J
authors: Siegrist
authors: Klaus
authors: K
authors: Mann
authors: Karl-Heinz
authors: KH
authors: Jöckel
authors: Raimund
authors: R
authors: Erbel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis*; D002114:Calcinosis / Q000000981:diagnostic imaging* / Q000453:epidemiology; D015331:Cohort Studies; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology*; D018570:Risk Assessment; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein