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Published in: Intensive Care Medicine 8/2018

01-08-2018 | Original

Association of iron status with the risk of bloodstream infections: results from the prospective population-based HUNT Study in Norway

Authors: Randi Marie Mohus, Julie Paulsen, Lise Gustad, Åsa Askim, Arne Mehl, Andrew T. DeWan, Jan Egil Afset, Bjørn Olav Åsvold, Erik Solligård, Jan Kristian Damås

Published in: Intensive Care Medicine | Issue 8/2018

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Abstract

Purpose

As iron is essential for both immune function and microbial growth, alterations in iron status could influence the risk of infections. We assessed the associations of iron status with risk of bloodstream infections (BSIs) and BSI mortality.

Methods

We measured serum iron, transferrin saturation (Tsat) and total iron-binding capacity (TIBC) in 61,852 participants in the population-based HUNT2 study (1995–97). Incident BSIs (1995–2011) were identified through linkage with the Mid-Norway Sepsis Register, which includes prospectively registered information on BSI from local and regional hospitals. We assessed the risk of a first-time BSI and BSI mortality with the iron indices using Cox proportional hazards regression analysis.

Results

During a median follow-up of 14.8 years, 1738 individuals experienced at least one episode of BSI, and 370 died within 30 days after a BSI. In age- and sex-adjusted analyses, BSI risk was increased among participants with indices of iron deficiency, serum iron ≤ 2.5th percentile (HR 1.72, 95% CI 1.34–2.21), Tsat ≤ 2.5th percentile (HR 1.48, 95% CI 1.12–1.96) or TIBC ≥ 97.5th percentile (HR 1.46, 95% CI 1.06–2.01). The associations remained similar after adjusting for comorbidities and exclusion of BSI related to cancer, rheumatic illnesses and inflammatory bowel disease. BSI mortality showed similar associations.

Conclusion

Indices of severe iron deficiency are associated with an increased risk of a future BSI.
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Literature
1.
go back to reference Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC et al (2015) Sepsis: a roadmap for future research. Lancet Infect Dis 15:581–614CrossRefPubMed Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC et al (2015) Sepsis: a roadmap for future research. Lancet Infect Dis 15:581–614CrossRefPubMed
2.
go back to reference Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M et al (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43:304–377CrossRefPubMed Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M et al (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43:304–377CrossRefPubMed
3.
go back to reference Henriksen DP, Pottegard A, Laursen CB, Jensen TG, Hallas J et al (2015) Risk factors for hospitalization due to community-acquired sepsis—a population-based case-control study. PLoS One 10:e0124838CrossRefPubMedPubMedCentral Henriksen DP, Pottegard A, Laursen CB, Jensen TG, Hallas J et al (2015) Risk factors for hospitalization due to community-acquired sepsis—a population-based case-control study. PLoS One 10:e0124838CrossRefPubMedPubMedCentral
4.
go back to reference Paulsen J, Askim A, Mohus RM, Mehl A, Dewan A et al (2017) Associations of obesity and lifestyle with the risk and mortality of bloodstream infection in a general population: a 15-year follow-up of 64 027 individuals in the HUNT Study. Int J Epidemiol 46:1573–1581CrossRefPubMed Paulsen J, Askim A, Mohus RM, Mehl A, Dewan A et al (2017) Associations of obesity and lifestyle with the risk and mortality of bloodstream infection in a general population: a 15-year follow-up of 64 027 individuals in the HUNT Study. Int J Epidemiol 46:1573–1581CrossRefPubMed
8.
go back to reference Perner A, Gordon AC, De Backer D, Dimopoulos G, Russell JA et al (2016) Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med 42:1958–1969CrossRefPubMed Perner A, Gordon AC, De Backer D, Dimopoulos G, Russell JA et al (2016) Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med 42:1958–1969CrossRefPubMed
9.
go back to reference Hussain SQ, Ashraf M, Wani JG, Ahmed J (2014) Low hemoglobin level a risk factor for acute lower respiratory tract infections (ALRTI) in children. J Clin Diag Res 8:Pc01–Pc03 Hussain SQ, Ashraf M, Wani JG, Ahmed J (2014) Low hemoglobin level a risk factor for acute lower respiratory tract infections (ALRTI) in children. J Clin Diag Res 8:Pc01–Pc03
10.
go back to reference Gwamaka M, Kurtis JD, Sorensen BE, Holte S, Morrison R et al (2012) Iron deficiency protects against severe Plasmodium falciparum malaria and death in young children. Clin Infect Dis 54:1137–1144CrossRefPubMedPubMedCentral Gwamaka M, Kurtis JD, Sorensen BE, Holte S, Morrison R et al (2012) Iron deficiency protects against severe Plasmodium falciparum malaria and death in young children. Clin Infect Dis 54:1137–1144CrossRefPubMedPubMedCentral
11.
12.
go back to reference Bassetti M, Poulakou G, Ruppe E, Bouza E, Van Hal SJ et al (2017) Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach. Intensive Care Med 43:1464–1475CrossRefPubMed Bassetti M, Poulakou G, Ruppe E, Bouza E, Van Hal SJ et al (2017) Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach. Intensive Care Med 43:1464–1475CrossRefPubMed
13.
go back to reference Askim A, Mehl A, Paulsen J, DeWan AT, Vestrheim DF et al (2016) Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993–2011: an observational study. BMC Infect Dis 16:223CrossRefPubMedPubMedCentral Askim A, Mehl A, Paulsen J, DeWan AT, Vestrheim DF et al (2016) Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993–2011: an observational study. BMC Infect Dis 16:223CrossRefPubMedPubMedCentral
14.
go back to reference Paulsen J, Mehl A, Askim A, Solligard E, Asvold BO et al (2015) Epidemiology and outcome of Staphylococcus aureus bloodstream infection and sepsis in a Norwegian county 1996–2011: an observational study. BMC Infect Dis 15:116CrossRefPubMedPubMedCentral Paulsen J, Mehl A, Askim A, Solligard E, Asvold BO et al (2015) Epidemiology and outcome of Staphylococcus aureus bloodstream infection and sepsis in a Norwegian county 1996–2011: an observational study. BMC Infect Dis 15:116CrossRefPubMedPubMedCentral
16.
go back to reference Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K et al (2013) Cohort Profile: the HUNT study, Norway. Int J Epidemiol 42:968–977CrossRefPubMed Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K et al (2013) Cohort Profile: the HUNT study, Norway. Int J Epidemiol 42:968–977CrossRefPubMed
17.
go back to reference Holmen JM, Krüger K, Langhammer Ø, Holmen A, Bratberg TL et al (2003) The Nord-Trøndelag Health Study 1995–97 (HUNT 2): objectives, contents, methods and participation. Norsk Epidemilogi 13:14 Holmen JM, Krüger K, Langhammer Ø, Holmen A, Bratberg TL et al (2003) The Nord-Trøndelag Health Study 1995–97 (HUNT 2): objectives, contents, methods and participation. Norsk Epidemilogi 13:14
18.
go back to reference Hallan S, Astor B, Lydersen S (2006) Estimating glomerular filtration rate in the general population: the second Health Survey of Nord-Trondelag (HUNT II). Nephrol Dial Transplant 21:1525–1533CrossRefPubMed Hallan S, Astor B, Lydersen S (2006) Estimating glomerular filtration rate in the general population: the second Health Survey of Nord-Trondelag (HUNT II). Nephrol Dial Transplant 21:1525–1533CrossRefPubMed
20.
go back to reference Ihlebaek C, Brage S, Natvig B, Bruusgaard D (2010) Occurrence of musculoskeletal disorders in Norway. Tidsskr Nor Legeforen 130:2365–2368CrossRef Ihlebaek C, Brage S, Natvig B, Bruusgaard D (2010) Occurrence of musculoskeletal disorders in Norway. Tidsskr Nor Legeforen 130:2365–2368CrossRef
21.
go back to reference Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W et al (2018) Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390:2769–2778CrossRefPubMed Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W et al (2018) Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390:2769–2778CrossRefPubMed
22.
go back to reference Thiebaut AC, Benichou J (2004) Choice of time-scale in Cox’s model analysis of epidemiologic cohort data: a simulation study. Stat Med 23:3803–3820CrossRefPubMed Thiebaut AC, Benichou J (2004) Choice of time-scale in Cox’s model analysis of epidemiologic cohort data: a simulation study. Stat Med 23:3803–3820CrossRefPubMed
24.
go back to reference Tansarli GS, Karageorgopoulos DE, Kapaskelis A, Gkegkes I, Falagas ME (2013) Iron deficiency and susceptibility to infections: evaluation of the clinical evidence. Eur J Clin Microbiol Infect Dis 32:1253–1258CrossRefPubMed Tansarli GS, Karageorgopoulos DE, Kapaskelis A, Gkegkes I, Falagas ME (2013) Iron deficiency and susceptibility to infections: evaluation of the clinical evidence. Eur J Clin Microbiol Infect Dis 32:1253–1258CrossRefPubMed
26.
go back to reference Jonker FA, Boele van Hensbroek M (2014) Anaemia, iron deficiency and susceptibility to infections. J Infect 69(Suppl 1):S23–S27CrossRefPubMed Jonker FA, Boele van Hensbroek M (2014) Anaemia, iron deficiency and susceptibility to infections. J Infect 69(Suppl 1):S23–S27CrossRefPubMed
27.
go back to reference Ekiz C, Agaoglu L, Karakas Z, Gurel N, Yalcin I (2005) The effect of iron deficiency anemia on the function of the immune system. Hematol J 5:579–583CrossRefPubMed Ekiz C, Agaoglu L, Karakas Z, Gurel N, Yalcin I (2005) The effect of iron deficiency anemia on the function of the immune system. Hematol J 5:579–583CrossRefPubMed
28.
go back to reference Sipahi T, Akar N, Egin Y, Cin S (1998) Serum interleukin-2 and interleukin-6 levels in iron deficiency anemia. Pediatr Hematol Oncol 15:69–73CrossRefPubMed Sipahi T, Akar N, Egin Y, Cin S (1998) Serum interleukin-2 and interleukin-6 levels in iron deficiency anemia. Pediatr Hematol Oncol 15:69–73CrossRefPubMed
29.
go back to reference Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC (2004) Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 104:2263–2268CrossRefPubMed Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC (2004) Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 104:2263–2268CrossRefPubMed
30.
go back to reference Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L (2016) Iron deficiency anaemia. Lancet 387:907–916CrossRefPubMed Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L (2016) Iron deficiency anaemia. Lancet 387:907–916CrossRefPubMed
31.
go back to reference Peyrin-Biroulet L, Williet N, Cacoub P (2015) Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review. Am J Clin Nutr 102:1585–1594CrossRefPubMed Peyrin-Biroulet L, Williet N, Cacoub P (2015) Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review. Am J Clin Nutr 102:1585–1594CrossRefPubMed
32.
go back to reference Hawkins RC (2007) Total iron binding capacity or transferrin concentration alone outperforms iron and saturation indices in predicting iron deficiency. Clin Chim Acta 380:203–207CrossRefPubMed Hawkins RC (2007) Total iron binding capacity or transferrin concentration alone outperforms iron and saturation indices in predicting iron deficiency. Clin Chim Acta 380:203–207CrossRefPubMed
33.
go back to reference Johansson L, Solvoll K (1999) Norkost 1997 Landsomfattende kostholdsundersøkelse blant menn og kvinner i alderen 16-79 år. Statens ernæringsråd 2:1–84 Johansson L, Solvoll K (1999) Norkost 1997 Landsomfattende kostholdsundersøkelse blant menn og kvinner i alderen 16-79 år. Statens ernæringsråd 2:1–84
34.
go back to reference Fonseca C, Marques F, Robalo Nunes A, Belo A et al (2016) Prevalence of anaemia and iron deficiency in Portugal: the EMPIRE study. Intern Med J 46:470–478CrossRefPubMed Fonseca C, Marques F, Robalo Nunes A, Belo A et al (2016) Prevalence of anaemia and iron deficiency in Portugal: the EMPIRE study. Intern Med J 46:470–478CrossRefPubMed
35.
go back to reference de Silva A, Atukorala S, Weerasinghe I, Ahluwalia N (2003) Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka. Am J Clin Nutr 77:234–241CrossRefPubMed de Silva A, Atukorala S, Weerasinghe I, Ahluwalia N (2003) Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka. Am J Clin Nutr 77:234–241CrossRefPubMed
36.
go back to reference Litton E, Xiao J, Ho KM (2013) Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ 347:f4822CrossRefPubMedPubMedCentral Litton E, Xiao J, Ho KM (2013) Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ 347:f4822CrossRefPubMedPubMedCentral
Metadata
Title
Association of iron status with the risk of bloodstream infections: results from the prospective population-based HUNT Study in Norway
Authors
Randi Marie Mohus
Julie Paulsen
Lise Gustad
Åsa Askim
Arne Mehl
Andrew T. DeWan
Jan Egil Afset
Bjørn Olav Åsvold
Erik Solligård
Jan Kristian Damås
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 8/2018
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-018-5320-8

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