C-reactive protein and all-cause mortality--the Copenhagen City Heart Study

Eur Heart J. 2010 Jul;31(13):1624-32. doi: 10.1093/eurheartj/ehq103. Epub 2010 Apr 27.


Aims: We tested whether elevated levels of C-reactive protein is robustly and causally associated with all-cause mortality.

Methods and results: We studied 10 388 white persons from the general population. During 16 years 3124 persons died. We measured baseline high-sensitivity C-reactive protein and fibrinogen levels and genotyped for four C-reactive protein polymorphisms and two apolipoprotein E polymorphisms. Levels of C-reactive protein >3 mg/L vs. <1 mg/L associated with a multi-factorially adjusted two-fold increased risk of all-cause mortality. Stratifying C-reactive protein into tertiles, quintiles, or octiles resulted in step-by-step increased risk of all-cause mortality, even after fibrinogen adjustment. Finally, genetically elevated C-reactive protein levels associated with a causal hazard ratio of 0.94 (95% CI: 0.64-1.39) for all-cause mortality per doubling of C-reactive protein levels on instrumental variable analysis, for which the corresponding hazard ratio on Cox regression for a doubling in measured plasma C-reactive protein levels was 1.25 (1.21-1.29). As a positive control, a doubling in genetically elevated cholesterol levels via apolipoprotein E associated with a hazard ratio of 6.3 (1.8-22) for all-cause mortality.

Conclusion: A single C-reactive protein measurement robustly associates with increased risk of all-cause mortality; however, this does not appear to be a causal association. Therefore, elevated C-reactive protein levels more likely are a marker of hidden, potentially fatal inflammatory disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cause of Death*
  • Denmark / epidemiology
  • Female
  • Fibrinogen / metabolism
  • Genotype
  • Heart Diseases / blood
  • Heart Diseases / genetics
  • Heart Diseases / mortality
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • Fibrinogen
  • C-Reactive Protein