title: C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study.
abstract: BACKGROUND
  It has been suggested that inflammation status, as assessed by C-reactive protein (CRP) concentration, modifies the vascular protective effects of statin therapy. In particular, there have been claims that statins might be more beneficial in people with raised CRP concentrations, and might even be ineffective in people with low concentrations of both CRP and LDL cholesterol. This study aimed to test this hypothesis.
  
  
  METHODS
  In 69 UK hospitals, 20,536 men and women aged 40-80 years at high risk of vascular events were randomly assigned to simvastatin 40 mg daily versus matching placebo for a mean of 5·0 years. Patients were categorised into six baseline CRP groups (<1·25, 1·25-1·99, 2·00-2·99, 3·00-4·99, 5·00-7·99, and ≥8·00 mg/L). The primary endpoint for subgroup analyses was major vascular events, defined as the composite of coronary death, myocardial infarction, stroke, or revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN48489393.
  
  
  RESULTS
  Overall, allocation to simvastatin resulted in a significant 24% (95% CI 19-28) proportional reduction in the incidence of first major vascular event after randomisation (2033 [19·8%] allocated simvastatin vs 2585 [25·2%] allocated placebo). There was no evidence that the proportional reduction in this endpoint, or its components, varied with baseline CRP concentration (trend p=0·41). Even in participants with baseline CRP concentration less than 1·25 mg/L, major vascular events were significantly reduced by 29% (99% CI 12-43, p<0·0001; 239 [14·1%] vs 329 [19·4%]). No significant heterogeneity in the relative risk reduction was recorded between the four subgroups defined by the combination of low or high baseline concentrations of LDL cholesterol and CRP (p=0·72). In particular, there was clear evidence of benefit in those with both low LDL cholesterol and low CRP (27% reduction, 99% CI 11-40, p<0·0001; 295 [15·6%] vs 400 [20·9%]).
  
  
  CONCLUSIONS
  Evidence from this large-scale randomised trial does not lend support to the hypothesis that baseline CRP concentration modifies the vascular benefits of statin therapy materially.
  
  
  BACKGROUND
  UK Medical Research Council, British Heart Foundation, Merck, Roche Vitamins, and GlaxoSmithKline.
authors.lastname: Jonathan Emberson
authors.lastname: Derrick Bennett
authors.lastname: Emma Link
authors.lastname: Sarah Parish
authors.lastname: John Danesh
authors.lastname: Jane Armitage
authors.lastname: Rory Collins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis*; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000401:mortality; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D019821:Simvastatin / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D019821:Simvastatin