title: Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial.
abstract: OBJECTIVE
  We tested whether on-statin C-reactive protein is associated with cardiovascular (CV) outcome in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).
  
  
  RESULTS
  ASCOT randomized a subset of 4853 patients with total cholesterol ≤6.5 mmol/L (250 mg/dL) to atorvastatin or placebo. In a case-control study during 5.5-year follow-up, 485 CV cases were age- and sex-matched with 1367 controls. Baseline LDL-cholesterol (LDL-c) and log-transformed C-reactive protein predicted CV events [odds ratio (OR) per 1 standard deviation (SD) 1.31 (95% confidence interval {CI}: 1.10, 1.56), P = 0.002 and OR 1.19 (1.05, 1.34), P = 0.006, respectively]. Including baseline C-reactive protein into a Framingham risk model very modestly improved risk prediction. Baseline C-reactive protein did not indicate the magnitude of the atorvastatin effect on CV outcome (P = 0.54). At 6 months, atorvastatin reduced median LDL-c by 40.3% and median C-reactive protein by 27.4%. In those randomized to atorvastatin, lower on-treatment LDL-c at 6 months was associated with a significant reduction in subsequent CV events [OR 0.41 (0.22, 0.75), P = 0.004] comparing those above and below the median (2.1 mmol/L). In contrast, C-reactive protein below the median (1.83 mg/L) compared with C-reactive protein above the median was not associated with a significant reduction in CV events [OR 0.86 (0.49, 1.51), P = 0.60]. Consequently, addition of on-treatment C-reactive protein to LDL-c did not improve prediction of statin efficacy.
  
  
  CONCLUSIONS
  Among these hypertensive patients selected on the basis of traditional CV risk factors, C-reactive protein did not usefully improve the prediction of CV events and, critically, reduction in C-reactive protein associated with statin therapy was not a predictor of CV outcome alone or in combination with LDL-c.
authors.affiliation: International Centre for Circulatory Health, Imperial College London, 59 North Wharf Road, London, UK. p.sever@imperial.ac.uk
authors.forename: Peter S
authors.initials: PS
authors.lastname: Sever
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
authors.forename: Choon L
authors.initials: CL
authors.lastname: Chang
authors.forename: Aroon
authors.initials: A
authors.lastname: Hingorani
authors.forename: Simon A
authors.initials: SA
authors.lastname: Thom
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D018570:Risk Assessment; D020521:Stroke / Q000097:blood / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin