title: Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia.
abstract: OBJECTIVE
  Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt-1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.
  
  
  METHODS
  Serum sFlt-1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22-MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum.
  
  
  RESULTS
  During pregnancy, higher levels of sFlt-1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt-1 and the sFlt-1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt-1 and the sFlt-1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt-1 and the sFlt-1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum.
  
  
  CONCLUSIONS
  Higher sFlt-1 levels and sFlt-1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt-1 levels and the sFlt-1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
authors.affiliation: Department of Women's and Children's Health, Section of Obstetrics and Gynaecology, Uppsala University, Uppsala, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Akhter
authors.affiliation: Department of Women's and Children's Health, Section of Obstetrics and Gynaecology, Uppsala University, Uppsala, Sweden.
authors.forename: A-K
authors.initials: AK
authors.lastname: Wikström
authors.affiliation: Department of Women's and Children's Health, Section of Obstetrics and Gynaecology, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Wikström
authors.affiliation: Department of Women's and Children's Health, Section of Obstetrics and Gynaecology, Uppsala University, Uppsala, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Naessen
mesh_terms: D000328:Adult; D000375:Aging; D015415:Biomarkers / Q000097:blood*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood / Q000000981:diagnostic imaging* / Q000503:physiopathology; D011247:Pregnancy; D016216:Ultrasonography, Prenatal; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: cardiovascular disease; common carotid artery; fms-like tyrosine kinase-1; fms-like tyrosine kinase-1:placental growth factor ratio; high-frequency ultrasonography; intima:media ratio; placental growth factor; pre-eclampsia