title: Association of vascular endothelial factors with cardiovascular outcome and mortality in chronic kidney disease patients: a 4-year cohort study.
abstract: BACKGROUND
  Angiogenic cytokines fms-like tyrosine kinase-1(sFlt-1) and placental growth factor (PlGF) are associated with increased risk for cardiovascular disease (CVD) in the general population. In this study we examine the association between these vascular endothelial factors and atherosclerosis, cardiovascular outcome, and mortality in chronic kidney disease (CKD) patients.
  
  
  METHODS
  Serum level of PlGF and sFlt-1 were measured in 301 patients with CKD, who were followed for up to 4 years. Primary outcomes were CV events and all-cause mortality. Carotid-intima media thickness (CIMT) was used as marker of atherosclerosis. Kaplan-Meier survival curves and the Cox proportional hazard model were used to assess the association of biomarkers and clinical outcomes.
  
  
  RESULTS
  Mean (SD) PlGF and sFlt-1 were 5.45 ng/ml (3.76) and 68.6 (28.0) pg/ml, respectively. During the follow up time, 60 patients (19.9%) experienced CV events and 22 patients (7.3%) died. Compared with low PlGF, patients with PlGF above median level had higher CV events (12.7% vs. 27.2%, p = 0.002) and mortality (2.0% vs. 12.6%, p < 0.001). The associations of PlGF and sFlt-1 with CV events were not statistically significant in the fully adjusted model. Higher PlGF was associated with greater death risk (HR = 5.22, 95% CI: 1.49-18.33, p = 0.01), which was robust to adjustment for sFlt-1 and other risk factors. Elevated sFlt-1 level was also an independent predictor of mortality (HR 3.41, 95% CI: 1.49-9.51, p = 0.019).
  
  
  CONCLUSIONS
  In CKD patients not yet on dialysis, higher serum level of PlGF and sFlt-1 are associated with increased mortality, but not CV events.
authors.affiliation: Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rambod
authors.affiliation: Saarland University Medical Center and Saarland University Faculty of Medicine, Internal Medicine IV - Nephrology and Hypertension, Homburg, Saar, Germany.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.affiliation: Saarland University Medical Center and Saarland University Faculty of Medicine, Internal Medicine IV - Nephrology and Hypertension, Homburg, Saar, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler
authors.affiliation: The George Washington University, Washington, DC, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dominic
authors.affiliation: Saarland University Medical Center and Saarland University Faculty of Medicine, Internal Medicine IV - Nephrology and Hypertension, Homburg, Saar, Germany.
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.affiliation: Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA; Division of Cardiovascular and Renal Products, Office of New Drugs, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Rama
authors.initials: R
authors.lastname: Dwivedi
authors.affiliation: Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Ramezani
authors.affiliation: Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Wing
authors.affiliation: Biostatistics Core, The George Washington University, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Amdur
authors.affiliation: Saarland University Medical Center and Saarland University Faculty of Medicine, Internal Medicine IV - Nephrology and Hypertension, Homburg, Saar, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA. Electronic address: draj@mfa.gwu.edu.
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Raj
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D059168:Carotid Intima-Media Thickness; D002423:Cause of Death; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009026:Mortality; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; C098069:PIGF protein, human; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Placental growth factor; Survival; Vascular endothelial growth factors; sFlt