title: Microvesicle protein levels are associated with increased risk for future vascular events and mortality in patients with clinically manifest vascular disease.
abstract: OBJECTIVE
  Microvesicles (MVs) are small membrane vesicles that are involved in atherotrombotic processes. In the present study, we evaluated the risk of MV protein levels on the occurrence of new vascular events in patients with clinically manifest vascular disease.
  
  
  METHODS
  In this cohort study 1060 patients were prospectively followed for the occurrence of a new vascular event or death (median follow up 6.4 years, interquartile range 5.2-7.3 years). MVs were isolated from plasma and MV protein levels of Cystatin C, Serpin G1, Serpin F2 and CD14 were measured. Multivariable Cox proportional hazards models were used to estimate the risk for new vascular events, vascular mortality and all-cause mortality. During follow up 136 vascular events occurred, 65 vascular mortality and 114 all-cause mortality.
  
  
  RESULTS
  An increase in 1 standard deviation (SD) of Cystatin C MV level was related to an increased risk for myocardial infarction (HR 1.49; 95%CI 1.20-1.86), vascular mortality (HR 1.48; 95%CI 1.17-1.86), vascular events (HR 1.27; 1.07-1.52) and all-cause mortality (HR 1.41; 95%CI 1.18-1.69). Serpin F2 MV levels were related to an increased risk for myocardial infarction (HR 1.22; 95%CI 1.00-1.51), vascular mortality (HR 1.25; 95%CI 1.00-1.56), and all-cause mortality (HR 1.22; 95% CI 1.03-1.45). CD14 MV levels were related to an increased risk for myocardial infarction (HR 1.55; 95%CI 1.27-1.91), vascular mortality (HR 1.37; 95%CI 1.10-1.70), vascular events (HR 1.32; 95%CI 1.12-1.55), all-cause mortality (HR 1.36; 95%CI 1.15-1.62) and occurrence of ischemic stroke (HR 1.32; 95%CI 1.00-1.74).
  
  
  CONCLUSIONS
  Cystatin C, Serpin F2 and CD14 MV levels are related to an elevated risk for future vascular events and mortality in patients with clinically manifest vascular disease.
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht (UMC Utrecht), Utrecht, The Netherlands.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Kanhai
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: Arjan H
authors.initials: AH
authors.lastname: Schoneveld
authors.forename: Louise M
authors.initials: LM
authors.lastname: Catanzariti
authors.forename: Leo
authors.initials: L
authors.lastname: Timmers
authors.forename: L Jaap
authors.initials: LJ
authors.lastname: Kappelle
authors.forename: Cuno S P M
authors.initials: CS
authors.lastname: Uiterwaal
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
mesh_terms: D002423:Cause of Death / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D015843:Serpins / Q000378:metabolism* / Q000648:ultrastructure; D015996:Survival Rate / Q000639:trends; D014652:Vascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000473:pathology
chemical_list: D015843:Serpins; C434683:serpin-2
keywords: Epidemiology; Microvesicles; Mortality; Proteins; Vascular events