title: Subclinical signs of vascular damage relate to enhanced platelet responsiveness among nonpregnant formerly preeclamptic women.
abstract: OBJECTIVE
  In nonpregnant formerly preeclamptic women, the prevalence of occult cardiovascular abnormalities is increased. These high-risk women mildly benefit from low-dose aspirin in the prevention of recurrent disease. How this effect is mediated, either by affecting platelet or vascular function, is still unsettled. In this study, we tested the hypothesis that in these nonpregnant women, enhanced platelet responsiveness is common and related to microvascular damage.
  
  
  METHODS
  At least 6 months' postpartum we evaluated in 66 formerly preeclamptic women platelet count, volume, and in vitro response to low-dose ADP (0.5 microg/mL). Peripheral levels of fibronectin (microg/mL), von Willebrand factor antigen (%), C-reactive protein (high-sensitive CRP, mg/L), urinary albumin, and protein (24-hour collection, g/mol creatinine) served as markers of vascular damage. Hemodynamic function was determined by plasma volume (iodine I 125 HSA indicator dilution method, mL/kg lean body mass), cardiac index (Doppler, mL/min/m2), blood pressure and heart rate (Dinamap [Critikon, Tampa, FL], mm Hg and beats/min, respectively). Thereafter, we subdivided these 66 women into 2 subgroups either with (n = 10, 15%) or without increased platelet responsiveness (n = 56, 85%). Both groups were compared nonparametrically.
  
  
  RESULTS
  Groups were comparable with respect to age, blood pressure, body mass index, parity, plasma volume, and cardiac index. Women with enhanced platelet responsiveness had higher levels of circulation fibronectin and CRP, and displayed more often albuminuria and proteinuria. In addition, even though platelet count was comparable between groups, the mean platelet volume was higher among women with enhanced platelet responsiveness.
  
  
  CONCLUSIONS
  Fifteen percent of formerly preeclamptic women had enhanced platelet responsiveness, which was associated with elevated levels of various markers for (micro) vascular damage. We speculate that in these women platelets are presensitized on a relatively dysfunctional endothelium. Although this association does not prove causality, these results may indicate a subgroup of women who benefit from low-dose aspirin in the prevention of recurrent disease in a next pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Marc E A
authors.initials: ME
authors.lastname: Spaanderman
authors.forename: Marianne
authors.initials: M
authors.lastname: Schippers
authors.forename: Fedde
authors.initials: F
authors.lastname: van der Graaf
authors.forename: Henricus J M
authors.initials: HJ
authors.lastname: Thijssen
authors.forename: Ing Han
authors.initials: IH
authors.lastname: Liem
authors.forename: Louis L H
authors.initials: LL
authors.lastname: Peeters
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D005260:Female; D006801:Humans; D008833:Microcirculation; D011225:Pre-Eclampsia; D011247:Pregnancy; D014652:Vascular Diseases / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology