title: Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?
abstract: BACKGROUND
  Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.
  
  
  RESULTS
  In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).
  
  
  CONCLUSIONS
  In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.
authors: Division of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, Scotland, UK. nsattar@clinmed.gla.ac.uk
authors: Naveed
authors: N
authors: Sattar
authors: Heather M
authors: HM
authors: Murray
authors: Paul
authors: P
authors: Welsh
authors: Gerard J
authors: GJ
authors: Blauw
authors: Brendan M
authors: BM
authors: Buckley
authors: Stuart
authors: S
authors: Cobbe
authors: Anton J M
authors: AJ
authors: de Craen
authors: Gordon D
authors: GD
authors: Lowe
authors: J Wouter
authors: JW
authors: Jukema
authors: Peter W
authors: PW
authors: Macfarlane
authors: Michael B
authors: MB
authors: Murphy
authors: David J
authors: DJ
authors: Stott
authors: Rudi G J
authors: RG
authors: Westendorp
authors: James
authors: J
authors: Shepherd
authors: Ian
authors: I
authors: Ford
authors: Chris J
authors: CJ
authors: Packard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000401:mortality; D015850:Interleukin-6 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality*; D017035:Pravastatin / Q000627:therapeutic use; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000401:mortality*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein; D017035:Pravastatin