title: IGF-I and IGFBP2 in peripheral artery disease: results of a prospective study.
abstract: OBJECTIVE
  The search for novel risk factors of cardiovascular disease (CVD) has provided valuable clinical data concerning underlying mechanism of disease. Increasing evidence indicates a possible involvement of insulin-like growth factor-I (IGF-I) and its binding protein 2 (IGFBP-2) in the pathogenesis of CVD disorders. The aim of this study was to examine the relationship between levels of IGF-I and IGFBP-2 with all-cause and CVD mortality in a prospective study of patients with lower-extremity peripheral artery disease (PAD).
  
  
  METHODS
  Serum IGF-I and IGFBP-2 levels were obtained in 440 patients (257 males) with symptomatic PAD. Patients were followed for a median of 6.1 (IQ 5.1-7.2) years. The relationship between times to lethal outcome and baseline serum IGF-I and IFGBP-2 levels were examined by Cox proportional hazard analysis. The role of IFGBP-2 for prognosis of CVD death was assessed with c-statistic.
  
  
  RESULTS
  During follow-up 115 (26%) patients (48 females and 67 males) died, and 53 (12%) died from CVD-related causes. Cox regression analysis revealed that an increase of 100 μg/l of baseline IFGBP-2 were significantly associated with an increased risk for CVD mortality [crude hazard ratio (HR) 1.14 (95% CI (1.05-1.23)), and adjusted HR 1.12 (95% CI (1.01-1.24))]. The receiver operating characteristic (ROC) analysis yielded area under curve of 0.61 (95% CI: 0.51-0.67, p = 0.022). However, the model including IFGBP-2 did not show a significant improvement in accuracy of CVD death prediction [the area under ROC curve 0.73 (0.66-0.80) vs. 0.75 (0.69-0.82), p = 0.696], and net reclassification improvement was 10.3% (p = 0.23).
  
  
  CONCLUSIONS
  Increased IFGBP-2 concentration was significantly and independently associated with long-term CVD mortality in patients with lower-extremity PAD. However, risk prediction of CVD mortality did not improve by adding IFGBP-2 to a model containing conventional CVD risk factors.
authors.affiliation: Diagnostic Center, Regional Hospital Silkeborg , Silkeborg , Denmark.
authors.forename: Grazina
authors.initials: G
authors.lastname: Urbonaviciene
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Sigitas
authors.initials: S
authors.lastname: Urbonavicius
authors.forename: Jes S
authors.initials: JS
authors.lastname: Lindholt
mesh_terms: D000368:Aged; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000401:mortality; D011446:Prospective Studies
chemical_list: C583557:IGF1 protein, human; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I