PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort

Kellie A. Mitchell, Justin Xavier Moore, Robert S. Rosenson, Ryan Irvin, Faheem W. Guirgis, Nathan Shapiro, Monika Safford, Henry E. Wang

Research output: Contribution to journalArticle

Abstract

Background Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been associated with adverse outcomes in patients hospitalized for sepsis. PCSK9 loss-of-function (LOF) variants area associated with lower low-density lipoprotein cholesterol (LDL-C) levels. Decreased LDL-C is a biomarker of acute and chronic infection and sepsis risk. We examined the association between presence of two genetic PCSK9 LOF variants and risk of infection and sepsis in community-dwelling adults. Methods We analyzed data from 10,924 Black participants tested for PCSK9 LOF variants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary endpoint was hospitalization for a serious infection. Within serious infection hospitalizations, we defined sepsis as 2 system inflammatory response syndrome criteria. Using multivariable Cox and logistic regression, we investigated the association between LOF variants and hospitalization for infection and sepsis events, adjusting for sociodemographics, health behaviors, chronic medical conditions and select biomarkers. Results Among 10,924 Black participants, PCSK9 LOF variants were present in 244 (2.2%). Serious infection hospitalizations occurred in 779 participants (14 with PCSK9 variants and 765 without). The presence of PCSK9 variants was not associated with infection risk (adjusted HR 0.68; 95% CI: 0.38–1.25). Among participants hospitalized for a serious infection, the presence of PCSK9 variants was not associated with sepsis (adjusted OR 7.31; 95% CI = 0.91–58.7). Conclusions PCSK9 LOF variants are not associated with increased risk of hospitalization for a serious infection. Among those hospitalized for a serious infection, PCSK9 LOF variants was not associated with odds of sepsis.

Original languageEnglish (US)
Article numbere0210808
JournalPloS one
Volume14
Issue number2
DOIs
StatePublished - Feb 2019
Externally publishedYes

Fingerprint

Proprotein Convertases
Subtilisin
sepsis (infection)
subtilisin
stroke
Sepsis
Stroke
Infection
infection
Hospitalization
Biomarkers
low density lipoprotein cholesterol
LDL Cholesterol
biomarkers
Proprotein Convertase 9
Association reactions
Independent Living
Health Behavior
endpoints
Logistics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. / Mitchell, Kellie A.; Moore, Justin Xavier; Rosenson, Robert S.; Irvin, Ryan; Guirgis, Faheem W.; Shapiro, Nathan; Safford, Monika; Wang, Henry E.

In: PloS one, Vol. 14, No. 2, e0210808, 02.2019.

Research output: Contribution to journalArticle

Mitchell, Kellie A. ; Moore, Justin Xavier ; Rosenson, Robert S. ; Irvin, Ryan ; Guirgis, Faheem W. ; Shapiro, Nathan ; Safford, Monika ; Wang, Henry E. / PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. In: PloS one. 2019 ; Vol. 14, No. 2.
@article{f3056d63ae654d0c96da960a30f43989,
title = "PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort",
abstract = "Background Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been associated with adverse outcomes in patients hospitalized for sepsis. PCSK9 loss-of-function (LOF) variants area associated with lower low-density lipoprotein cholesterol (LDL-C) levels. Decreased LDL-C is a biomarker of acute and chronic infection and sepsis risk. We examined the association between presence of two genetic PCSK9 LOF variants and risk of infection and sepsis in community-dwelling adults. Methods We analyzed data from 10,924 Black participants tested for PCSK9 LOF variants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary endpoint was hospitalization for a serious infection. Within serious infection hospitalizations, we defined sepsis as 2 system inflammatory response syndrome criteria. Using multivariable Cox and logistic regression, we investigated the association between LOF variants and hospitalization for infection and sepsis events, adjusting for sociodemographics, health behaviors, chronic medical conditions and select biomarkers. Results Among 10,924 Black participants, PCSK9 LOF variants were present in 244 (2.2{\%}). Serious infection hospitalizations occurred in 779 participants (14 with PCSK9 variants and 765 without). The presence of PCSK9 variants was not associated with infection risk (adjusted HR 0.68; 95{\%} CI: 0.38–1.25). Among participants hospitalized for a serious infection, the presence of PCSK9 variants was not associated with sepsis (adjusted OR 7.31; 95{\%} CI = 0.91–58.7). Conclusions PCSK9 LOF variants are not associated with increased risk of hospitalization for a serious infection. Among those hospitalized for a serious infection, PCSK9 LOF variants was not associated with odds of sepsis.",
author = "Mitchell, {Kellie A.} and Moore, {Justin Xavier} and Rosenson, {Robert S.} and Ryan Irvin and Guirgis, {Faheem W.} and Nathan Shapiro and Monika Safford and Wang, {Henry E.}",
year = "2019",
month = "2",
doi = "10.1371/journal.pone.0210808",
language = "English (US)",
volume = "14",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort

AU - Mitchell, Kellie A.

AU - Moore, Justin Xavier

AU - Rosenson, Robert S.

AU - Irvin, Ryan

AU - Guirgis, Faheem W.

AU - Shapiro, Nathan

AU - Safford, Monika

AU - Wang, Henry E.

PY - 2019/2

Y1 - 2019/2

N2 - Background Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been associated with adverse outcomes in patients hospitalized for sepsis. PCSK9 loss-of-function (LOF) variants area associated with lower low-density lipoprotein cholesterol (LDL-C) levels. Decreased LDL-C is a biomarker of acute and chronic infection and sepsis risk. We examined the association between presence of two genetic PCSK9 LOF variants and risk of infection and sepsis in community-dwelling adults. Methods We analyzed data from 10,924 Black participants tested for PCSK9 LOF variants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary endpoint was hospitalization for a serious infection. Within serious infection hospitalizations, we defined sepsis as 2 system inflammatory response syndrome criteria. Using multivariable Cox and logistic regression, we investigated the association between LOF variants and hospitalization for infection and sepsis events, adjusting for sociodemographics, health behaviors, chronic medical conditions and select biomarkers. Results Among 10,924 Black participants, PCSK9 LOF variants were present in 244 (2.2%). Serious infection hospitalizations occurred in 779 participants (14 with PCSK9 variants and 765 without). The presence of PCSK9 variants was not associated with infection risk (adjusted HR 0.68; 95% CI: 0.38–1.25). Among participants hospitalized for a serious infection, the presence of PCSK9 variants was not associated with sepsis (adjusted OR 7.31; 95% CI = 0.91–58.7). Conclusions PCSK9 LOF variants are not associated with increased risk of hospitalization for a serious infection. Among those hospitalized for a serious infection, PCSK9 LOF variants was not associated with odds of sepsis.

AB - Background Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been associated with adverse outcomes in patients hospitalized for sepsis. PCSK9 loss-of-function (LOF) variants area associated with lower low-density lipoprotein cholesterol (LDL-C) levels. Decreased LDL-C is a biomarker of acute and chronic infection and sepsis risk. We examined the association between presence of two genetic PCSK9 LOF variants and risk of infection and sepsis in community-dwelling adults. Methods We analyzed data from 10,924 Black participants tested for PCSK9 LOF variants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary endpoint was hospitalization for a serious infection. Within serious infection hospitalizations, we defined sepsis as 2 system inflammatory response syndrome criteria. Using multivariable Cox and logistic regression, we investigated the association between LOF variants and hospitalization for infection and sepsis events, adjusting for sociodemographics, health behaviors, chronic medical conditions and select biomarkers. Results Among 10,924 Black participants, PCSK9 LOF variants were present in 244 (2.2%). Serious infection hospitalizations occurred in 779 participants (14 with PCSK9 variants and 765 without). The presence of PCSK9 variants was not associated with infection risk (adjusted HR 0.68; 95% CI: 0.38–1.25). Among participants hospitalized for a serious infection, the presence of PCSK9 variants was not associated with sepsis (adjusted OR 7.31; 95% CI = 0.91–58.7). Conclusions PCSK9 LOF variants are not associated with increased risk of hospitalization for a serious infection. Among those hospitalized for a serious infection, PCSK9 LOF variants was not associated with odds of sepsis.

UR - http://www.scopus.com/inward/record.url?scp=85061147190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061147190&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0210808

DO - 10.1371/journal.pone.0210808

M3 - Article

C2 - 30726226

AN - SCOPUS:85061147190

VL - 14

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e0210808

ER -