1. PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
- Author
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Mitchell KA, Moore JX, Rosenson RS, Irvin R, Guirgis FW, Shapiro N, Safford M, and Wang HE
- Subjects
- Black or African American statistics & numerical data, Aged, Biomarkers blood, Cholesterol, LDL blood, Cholesterol, LDL metabolism, Cohort Studies, Female, Hospitalization statistics & numerical data, Humans, Independent Living statistics & numerical data, Loss of Function Mutation, Male, Middle Aged, Proprotein Convertase 9 metabolism, Sepsis blood, Sepsis genetics, Sepsis therapy, United States epidemiology, Proprotein Convertase 9 genetics, Sepsis epidemiology
- 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., Competing Interests: Dr. Safford reports the following potential conflicts of interest: Amgen - salary support to study patterns of statin use in Medicare and other large databases; diaDexus - salary support for a research grant on lipids and CAD outcomes; diaDexus - consulting to help with FDA application; NIH, AHRQ - salary support for research grants. Dr. Rosenson receives research support from Akcea, Amgen, Astra Zeneca, Esperion, Medicines Company, and Regeneron, fees for participation in Advisory Boards from Amgen, C5, CVS Caremark, EasyVitals, Regeneron and Sanofi, honoraria from Akcea and Kowa, royalties from UpToDate, Inc, and has stock holdings in MediMergent. Dr. Wang – methodological consultant for Shire, Inc. The remaining authors do not report any related conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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