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Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein

Paroxonase-1 (PON1) is a key enzyme that inhibits low-density lipoprotein oxidation and consequently atherogenesis. Here, we assessed whether low serum PON1 activity associates with incident cardiovascular disease (CVD) in subjects with high levels of high-density cholesterol (HDL-C) and C-reactive...

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Autores principales: Corsetti, James P., Sparks, Charles E., James, Richard W., Bakker, Stephan J. L., Dullaart, Robin P. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780415/
https://www.ncbi.nlm.nih.gov/pubmed/31480611
http://dx.doi.org/10.3390/jcm8091357
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author Corsetti, James P.
Sparks, Charles E.
James, Richard W.
Bakker, Stephan J. L.
Dullaart, Robin P. F.
author_facet Corsetti, James P.
Sparks, Charles E.
James, Richard W.
Bakker, Stephan J. L.
Dullaart, Robin P. F.
author_sort Corsetti, James P.
collection PubMed
description Paroxonase-1 (PON1) is a key enzyme that inhibits low-density lipoprotein oxidation and consequently atherogenesis. Here, we assessed whether low serum PON1 activity associates with incident cardiovascular disease (CVD) in subjects with high levels of high-density cholesterol (HDL-C) and C-reactive protein (CRP), a marker of low-grade systemic inflammation. Cox proportional-hazards modeling of incident CVD risk (11 years mean follow-up) adjusted for relevant clinical and biomarker covariates was performed on a population-based study (N = 7766) stratified into three groups: low CRP—(LR; event rate 4.9%); low HDL-C/high CRP—(HR1; event rate 14.4%); and high HDL-C/high CRP—(HR2; event rate 7.6%). Modeling results for PON1 activity in HR2 were significant and robust (hazard ratio/SD unit—0.68, 95% CI 0.55–0.83, p = 0.0003), but not so for LR and HR1. Analyses in HR2 of the interaction of PON1 with HDL-C, apoA-I, apoA-II, and apoE levels were significant only for PON1 with apoE (hazard ratio—1.77, 95% CI 1.29–2.41, p = 0.0003). Subsequent subgroup analysis revealed inverse risk dependence for apoE at low PON1 levels. In conclusion, in a population-based study of subjects with concurrently high HDL-C and CRP levels, low serum PON1 activity associates with incident CVD risk with risk accentuated at low apoE levels.
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spelling pubmed-67804152019-10-30 Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein Corsetti, James P. Sparks, Charles E. James, Richard W. Bakker, Stephan J. L. Dullaart, Robin P. F. J Clin Med Article Paroxonase-1 (PON1) is a key enzyme that inhibits low-density lipoprotein oxidation and consequently atherogenesis. Here, we assessed whether low serum PON1 activity associates with incident cardiovascular disease (CVD) in subjects with high levels of high-density cholesterol (HDL-C) and C-reactive protein (CRP), a marker of low-grade systemic inflammation. Cox proportional-hazards modeling of incident CVD risk (11 years mean follow-up) adjusted for relevant clinical and biomarker covariates was performed on a population-based study (N = 7766) stratified into three groups: low CRP—(LR; event rate 4.9%); low HDL-C/high CRP—(HR1; event rate 14.4%); and high HDL-C/high CRP—(HR2; event rate 7.6%). Modeling results for PON1 activity in HR2 were significant and robust (hazard ratio/SD unit—0.68, 95% CI 0.55–0.83, p = 0.0003), but not so for LR and HR1. Analyses in HR2 of the interaction of PON1 with HDL-C, apoA-I, apoA-II, and apoE levels were significant only for PON1 with apoE (hazard ratio—1.77, 95% CI 1.29–2.41, p = 0.0003). Subsequent subgroup analysis revealed inverse risk dependence for apoE at low PON1 levels. In conclusion, in a population-based study of subjects with concurrently high HDL-C and CRP levels, low serum PON1 activity associates with incident CVD risk with risk accentuated at low apoE levels. MDPI 2019-09-01 /pmc/articles/PMC6780415/ /pubmed/31480611 http://dx.doi.org/10.3390/jcm8091357 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Corsetti, James P.
Sparks, Charles E.
James, Richard W.
Bakker, Stephan J. L.
Dullaart, Robin P. F.
Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein
title Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein
title_full Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein
title_fullStr Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein
title_full_unstemmed Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein
title_short Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein
title_sort low serum paraoxonase-1 activity associates with incident cardiovascular disease risk in subjects with concurrently high levels of high-density lipoprotein cholesterol and c-reactive protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780415/
https://www.ncbi.nlm.nih.gov/pubmed/31480611
http://dx.doi.org/10.3390/jcm8091357
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