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

Tormod Rogne,Hallie C Prescott,Jan K Damås,Julie Paulsen,Ben M Brumpton,Lise T Gustad,Erik Solligård,Randi M Mohus,Bjørn O Åsvold,Arne Mehl,Andrew T Dewan,Stephen Burgess,Cosetta Minelli

doi:10.1371/journal.pmed.1003413

Abstract

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. 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. 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.

Highlights

Bloodstream infection (BSI) is caused by bacteria entering the bloodstream as a severe complication of an infection, and may in turn lead to sepsis, representing a dysregulated immune response to infection resulting in organ dysfunction and high mortality rate [1]
Supportive of a causal relationship, genetically predicted body mass index (BMI) was positively associated with bloodstream infection (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

Summary

Introduction

Bloodstream infection (BSI) is caused by bacteria entering the bloodstream as a severe complication of an infection, and may in turn lead to sepsis, representing a dysregulated immune response to infection resulting in organ dysfunction and high mortality rate [1]. Studies restricted to patients with BSI or sepsis have observed a considerable reduced mortality risk with increasing BMI [12,13,14,15,16,17], including a systematic review from 2017 [18]. It has been advocated that one should study in what way obesity is protective for sepsis mortality, and that this may help inform new therapeutic strategies [17,18]. 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. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI

Objectives

Methods

Results

Conclusion