title: Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management.
abstract: BACKGROUND
  Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. These pathophysiologic processes are assessable by measurement of plasma levels of von Willebrand factor (vWf), and by vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). We hypothesized that these markers would correlate with the Framingham cardiovascular risk score and would be responsive to treatment.
  
  
  METHODS
  We measured these markers by enzyme-linked immunosorbent assay in 286 patients with hypertension (239 men; mean age 63 years; mean systolic blood pressure [BP]/diastolic BP 162/89 mm Hg) and additional risk factors, and related them to the patient's cardiovascular disease (CVD) and cerebrovascular accident (CVA) risk, using the Framingham equation. Patients were compared with 60 healthy normotensive controls. In 248 patients, the effects of 6 months of intensified cardiovascular risk factor management, including BP and (where appropriate) lipid-lowering treatment, were investigated.
  
  
  RESULTS
  Plasma VEGF and vWf levels were higher, but sFlt-1 levels lower (all P <.001), in the hypertensive patients compared with the controls. The VEGF and vWf levels correlated significantly with age, systolic and diastolic BP, 10-year CVD risk, and CVA risk scores (all P <.01), whereas sFlt-1 was negatively correlated with these risk scores (P <.01). After intensified cardiovascular risk factor management, total cholesterol, BP, VEGF, and vWf levels were all reduced, yet sFlt-1 levels increased (all P <.05).
  
  
  CONCLUSIONS
  In hypertension, the processes of endothelial damage and angiogenesis are abnormal, and correlate with overall cardiovascular risk. Indices of endothelial damage and angiogenesis are beneficially changed by intensive cardiovascular risk factor management.
authors.affiliation: Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
authors.forename: Dirk C
authors.initials: DC
authors.lastname: Felmeden
authors.forename: Charles G C
authors.initials: CG
authors.lastname: Spencer
authors.forename: Funmi M
authors.initials: FM
authors.lastname: Belgore
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blann
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Beevers
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016228:Endothelial Growth Factors / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology / Q000473:pathology / Q000628:therapy; D006973:Hypertension / Q000453:epidemiology* / Q000473:pathology* / Q000628:therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000453:epidemiology* / Q000473:pathology*; D012307:Risk Factors; D040242:Risk Reduction Behavior; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D040281:Vascular Endothelial Growth Factor Receptor-1