Repository logo
 

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

Published version
Peer-reviewed

Change log

Authors

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.

Description

Funder: US-Norway Fulbright Commission


Funder: Stiftelsen Kristian Gerhard Jebsen; funder-id: http://dx.doi.org/10.13039/100007793


Funder: The Liaison Committee for education, research and innovation in Central Norway


Funder: The Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU


Funder: The Research Council of Norway


Funder: Samarbeidsorganet Helse Midt-Norge

Keywords

Research Article, Biology and life sciences, Medicine and health sciences

Journal Title

PLOS Medicine

Conference Name

Journal ISSN

1549-1277
1549-1676

Volume Title

17

Publisher

Public Library of Science
Sponsorship
Medical Research Council and the University of Bristol (MC_UU_12013/1)
National Institutes of Health (K08 GM115859)