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Randomized Controlled Trial
. 2020 Nov 16;17(11):e1003413.
doi: 10.1371/journal.pmed.1003413. eCollection 2020 Nov.

Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study

Tormod Rogne  1   2   3 , Erik Solligård  1   3 , Stephen Burgess  4   5 , Ben M Brumpton  6   7   8 , Julie Paulsen  9 , Hallie C Prescott  10   11 , Randi M Mohus  1   3 , Lise T Gustad  1   12 , Arne Mehl  12 , Bjørn O Åsvold  6   13 , Andrew T DeWan  1   2 , Jan K Damås  1   14   15
Affiliations
Randomized Controlled Trial

Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study

Tormod Rogne et al. PLoS Med. .

Abstract

Background: In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI.

Methods and findings: We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study [HUNT]), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m2. During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m2, a genetically predicted BMI of 30 kg/m2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p < 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered.

Conclusions: Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the "obesity paradox," where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: SB is a paid statistical reviewer for PLOS Medicine. HCP has current or prior grant funding from the NIH, AHRQ, and the US Department of Veterans Affairs. The other authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Mendelian randomization analysis of body mass index and bloodstream infection incidence.
The association between genetically predicted body mass index and risk of contracting a bloodstream infection (BSI), with a body mass index of 25 kg/m2 as reference (red dot). Gray lines represent 95% confidence intervals.
Fig 2
Fig 2. Mendelian randomization analysis of body mass index and bloodstream infection mortality in the general population.
The association between genetically predicted body mass index and risk of dying from a bloodstream infection (BSI) in the general population, with a body mass index of 25 kg/m2 as reference (red dot). Gray lines represent 95% confidence intervals.
Fig 3
Fig 3. Mendelian randomization analysis of body mass index and bloodstream infection mortality among patients with bloodstream infection.
The association between genetically predicted body mass index and risk of dying from a bloodstream infection (BSI) among patients with a bloodstream infection, with a body mass index of 25 kg/m2 as reference (red dot). The analysis was weighted for the inverse probability of contracting a bloodstream infection. Gray lines represent 95% confidence intervals.
See this image and copyright information in PMC

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