Cargando…

PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR

BACKGROUND: Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship...

Descripción completa

Detalles Bibliográficos
Autores principales: Rogacev, Kyrill S., Heine, Gunnar H., Silbernagel, Günther, Kleber, Marcus E., Seiler, Sarah, Emrich, Insa, Lennartz, Simone, Werner, Christian, Zawada, Adam M., Fliser, Danilo, Böhm, Michael, März, Winfried, Scharnagl, Hubert, Laufs, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723078/
https://www.ncbi.nlm.nih.gov/pubmed/26799206
http://dx.doi.org/10.1371/journal.pone.0146920
_version_ 1782411456498630656
author Rogacev, Kyrill S.
Heine, Gunnar H.
Silbernagel, Günther
Kleber, Marcus E.
Seiler, Sarah
Emrich, Insa
Lennartz, Simone
Werner, Christian
Zawada, Adam M.
Fliser, Danilo
Böhm, Michael
März, Winfried
Scharnagl, Hubert
Laufs, Ulrich
author_facet Rogacev, Kyrill S.
Heine, Gunnar H.
Silbernagel, Günther
Kleber, Marcus E.
Seiler, Sarah
Emrich, Insa
Lennartz, Simone
Werner, Christian
Zawada, Adam M.
Fliser, Danilo
Böhm, Michael
März, Winfried
Scharnagl, Hubert
Laufs, Ulrich
author_sort Rogacev, Kyrill S.
collection PubMed
description BACKGROUND: Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored. METHODS: Lipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2–4 Patients—The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m(2)) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m(2) enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths. RESULTS: PCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8–4.1] years and 10.0 [7.3–10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results. CONCLUSION: In two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function.
format Online
Article
Text
id pubmed-4723078
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-47230782016-01-30 PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR Rogacev, Kyrill S. Heine, Gunnar H. Silbernagel, Günther Kleber, Marcus E. Seiler, Sarah Emrich, Insa Lennartz, Simone Werner, Christian Zawada, Adam M. Fliser, Danilo Böhm, Michael März, Winfried Scharnagl, Hubert Laufs, Ulrich PLoS One Research Article BACKGROUND: Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored. METHODS: Lipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2–4 Patients—The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m(2)) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m(2) enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths. RESULTS: PCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8–4.1] years and 10.0 [7.3–10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results. CONCLUSION: In two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function. Public Library of Science 2016-01-22 /pmc/articles/PMC4723078/ /pubmed/26799206 http://dx.doi.org/10.1371/journal.pone.0146920 Text en © 2016 Rogacev et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rogacev, Kyrill S.
Heine, Gunnar H.
Silbernagel, Günther
Kleber, Marcus E.
Seiler, Sarah
Emrich, Insa
Lennartz, Simone
Werner, Christian
Zawada, Adam M.
Fliser, Danilo
Böhm, Michael
März, Winfried
Scharnagl, Hubert
Laufs, Ulrich
PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR
title PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR
title_full PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR
title_fullStr PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR
title_full_unstemmed PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR
title_short PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR
title_sort pcsk9 plasma concentrations are independent of gfr and do not predict cardiovascular events in patients with decreased gfr
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723078/
https://www.ncbi.nlm.nih.gov/pubmed/26799206
http://dx.doi.org/10.1371/journal.pone.0146920
work_keys_str_mv AT rogacevkyrills pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT heinegunnarh pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT silbernagelgunther pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT klebermarcuse pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT seilersarah pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT emrichinsa pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT lennartzsimone pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT wernerchristian pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT zawadaadamm pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT fliserdanilo pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT bohmmichael pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT marzwinfried pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT scharnaglhubert pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr
AT laufsulrich pcsk9plasmaconcentrationsareindependentofgfranddonotpredictcardiovasculareventsinpatientswithdecreasedgfr