Dataset Information

Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy Men: Results from the Danish Blood Donor Study (DBDS).

ABSTRACT:

Introduction

The aim of this study was to examine whether low-grade inflammation (LGI) is associated with a subsequently increased risk of infection.

Methods

We included 15,754 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. LGI was defined as a C-reactive protein level between 3 and 10 mg/L. Infections were identified by ICD-10 codes in the Danish National Patient Register and ATC-codes in the Danish Prescription Register. Multivariable Cox proportional hazard analysis was used as the statistical model.

Results

During 53,302 person-years of observation, 571 participants were hospitalized for infection. Similarly, during 26,125 person-years of observation, 7,276 participants filled a prescription of antimicrobials. LGI was associated with increased risk of hospital-based treatment for infection only among men (hazard ratio = 1.60, 95% confidence interval (CI): 1.10-2.34) and specifically infections were abscesses and infections of the skin and subcutaneous tissue. Similarly, LGI was associated with the overall use of antimicrobials among men, and particularly with phenoxymethylpenicillin and broad-spectrum antimicrobials for treatment of urinary tract infections. The difference between men and women was not statistically significant.

Conclusions

In a large cohort of healthy individuals, LGI was associated with an increased risk of infection among healthy male blood donors.

SUBMITTER: Kaspersen KA

PROVIDER: S-EPMC5049789 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy Men: Results from the Danish Blood Donor Study (DBDS).

Kaspersen Kathrine Agergård KA Dinh Khoa Manh KM Erikstrup Lise Tornvig LT Burgdorf Kristoffer Sølvsten KS Pedersen Ole Birger OB Sørensen Erik E Petersen Mikkel Steen MS Hjalgrim Henrik H Rostgaard Klaus K Nielsen Kaspar Rene KR Ullum Henrik H Erikstrup Christian C

PloS one 20161004 10

<h4>Introduction</h4>The aim of this study was to examine whether low-grade inflammation (LGI) is associated with a subsequently increased risk of infection.<h4>Methods</h4>We included 15,754 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. LGI was defined as a C-reactive protein level between 3 and 10 mg/L. Infections were identified by ICD-10 codes in the Danish National Patient Register and ATC-codes in the Danish Prescription Regi ...[more]

PMID: 27701463

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Project description:BACKGROUND:Health-Related Quality of Life (HRQL) represent individuals' subjective assessment of their mental and physical well-being, and is highly predictive of future health. C-reactive protein (CRP) is a well-established marker of inflammation. Low-grade inflammation (LGI), defined as slightly increased CRP levels, is associated with increased risk of several diseases. LGI may reflect subclinical pathology, which could affect individual's subjective health assessment. This study aimed to examine whether LGI has an independent impact on self-reported health or rather is a mediator of a confounder in a large population of healthy individuals. METHODS:Plasma CRP levels were measured in 17,024 participants from the Danish Blood Donor Study (DBDS). All participants completed a standard questionnaire including smoking status, and the 12-item short-form health survey (SF-12), which is a widely used scale for HRQL. SF-12 is reported as a mental (MCS) and physical (PCS) score. The relationship between LGI (defined as a plasma CRP level between 3 mg/L and 10 mg/L) and MCS or PCS was explored by mediation analysis and adjusted multivariable linear regression analysis. Multiple imputation modelling was used to remedy missing values. The analyses were stratified according to sex and use of combined oral contraception (OC). RESULTS:In the study, 1,542 (10.3%) participants had LGI. PCS was associated with LGI in all strata, i.e. women using OC: RC = -0.36 points lower PCS in participants with LGI vs no LGI, CI: -0.94 to -0.19, women not using OC: RC = -0.63, CI: -1.05 to -0.21 and men: RC = -0.76, CI: -1.10 to -0.42. But LGI had no impact on MCS. Predictors of lower PCS included obesity, current smoking, and waist circumference in all strata. Physical activity in leisure time was the only factor positively associated with PCS. Age and physical activity in leisure time was associated with increased MCS in all strata whereas current smoking was the only strong predictor of a reduction in MCS. Only a small effect of smoking on PCS was mediated through LGI. CONCLUSION:In this population of healthy individuals, LGI had independent impact on lower self-rated physical health score in HRQL in both sexes, but was not associated with self-rated mental health score. A small and significant effect of smoking on physical health score was mediated through LGI.

Project description:Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers.Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis.HsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83).Comprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.

Dataset Information

Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy Men: Results from the Danish Blood Donor Study (DBDS).

Introduction

Methods

Results

Conclusions

Publications

Low-Grade Inflammation Is Associated with Susceptibility to Infection in Healthy Men: Results from the Danish Blood Donor Study (DBDS).

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