title: Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections: Results from 2 Large Danish Population Cohorts.
abstract: BACKGROUND
  The acute-phase reactant C-reactive protein (CRP) increases rapidly during an infection. We tested the hypothesis that chronic low-level increases in CRP are associated with an increased risk of infectious disease.
  
  
  METHODS
  We studied 9660 individuals from a prospective general population cohort, including 3592 in whom infectious disease developed, and another 60 896 individuals from a cross-sectional general population study, of whom 13 332 developed infectious disease; 55% were women, and the mean age was 57 years. Hospital diagnoses of infections in 1977-2010 were based on International Classification of Diseases-coded discharge records from the national Danish Patient Registry. We measured CRP concentrations and conducted genotyping for 4 CRP polymorphisms that increase CRP. Individuals with CRP >10 mg/L were excluded because of possible ongoing infection at the time of testing.
  
  
  RESULTS
  Individuals with CRP >3 mg/L had 1.2 and 1.7 times increased risk of infectious disease, in the prospective general population cohort and the cross-sectional general population study, respectively, compared with individuals with CRP <1 mg/L. In the combined populations, individuals in the highest CRP tertile (compared with the lowest) had an increased risk of bacterial diseases (hazard ratio 1.7, 95% CI 1.6-1.8), but not viral, mycosis, and parasitic diseases. The increased risk was mainly carried by pneumonia, sepsis, and particularly gram-negative infections. None of the genotype combinations examined conferred an increased risk of infectious disease.
  
  
  CONCLUSIONS
  Chronic low-level CRP increases were associated with increased risk of bacterial infections, gram-negative infections in particular. Genotypes associated with increases in CRP were not associated with increased risk of infection.
authors.affiliation: Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark;
authors.forename: Jeppe
authors.initials: J
authors.lastname: Zacho
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, Copenhagen University Hospital, Copenhagen, Denmark;
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
authors.affiliation: The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. boerge.nordestgaard@regionh.dk.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000097:blood / Q000209:etiology* / Q000235:genetics; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003718:Denmark; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000097:blood; D014777:Virus Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics
chemical_list: D002097:C-Reactive Protein