TY - JOUR

T1 - Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections

T2 - Results from 2 Large Danish Population Cohorts

AU - Zacho, Jeppe

AU - Benfield, Thomas

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G

N1 - © 2015 American Association for Clinical Chemistry.

PY - 2016/2

Y1 - 2016/2

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Bacterial Infections

KW - C-Reactive Protein

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Denmark

KW - Female

KW - Gram-Negative Bacterial Infections

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Genetic

KW - Prospective Studies

KW - Risk Factors

KW - Sepsis

KW - Virus Diseases

KW - Journal Article

U2 - 10.1373/clinchem.2015.249680

DO - 10.1373/clinchem.2015.249680

M3 - Journal article

C2 - 26721294

VL - 62

SP - 335

EP - 342

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 2

ER -