title: PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR.
abstract: 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 m2) 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 m2 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany.|Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.affiliation: Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital, Bern, Switzerland.
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.affiliation: Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Insa
authors.initials: I
authors.lastname: Emrich
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Lennartz
authors.affiliation: Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Synlab Academy, Synlab Services GmbH, Mannheim and Augsburg, Germany.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Medical Center, Homburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D015415:Biomarkers; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases