title: Endothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related to peripheral arterial disease: a prospective analysis.
abstract: OBJECTIVE
  Endothelial dysfunction plays a key role in the development, progression, and clinical manifestation of atherosclerosis, and in symptomatic peripheral arterial disease, endothelial dysfunction and enlarged intima-media thickness might be associated with increased cardiovascular risk. Flow-mediated dilatation and serologic parameters are used to evaluate individual endothelial function. Brachial intima-media thickness, a less recognized parameter of cardiovascular risk, is independently associated with coronary artery disease. The aim of this study was to evaluate the prognostic value of ultrasound and serologic parameters of endothelial function in relation to cardiovascular mortality in peripheral arterial disease.
  
  
  METHODS
  monocentric, prospective cohort study.
  
  
  METHODS
  Flow mediated dilatation and brachial intima-media thickness were assessed in 184 (124 male) patients with peripheral arterial disease (Rutherford stages 2-3). Serologic parameters of endothelial function included asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine. Cardiovascular events were recorded during a follow-up of 99.1±11.1 months. Subjects who died of noncardiovascular causes were excluded from further analysis.
  
  
  RESULTS
  Eighty-two patients (44.6%) died during follow-up after a mean duration of 49.7±28.3 months. There were 49 cardiovascular deaths (59.8%) and 33 other deaths (40.2%). Flow mediated dilatation was associated with cardiovascular death [1.17% (0.0, 4.3) vs. 4.1% (1.2, 6.4), p<0.001]. Intima-media thickness was greater in patients who succumbed to cardiovascular disease [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p<0.001]. Brachial intima-media thickness above 0.345 mm was most predictive of cardiovascular death, with sensitivity and specificity values of 0.714 and 0.657, respectively (p<0.001). Furthermore, ADMA levels above 0.745 µmol/l and SDMA levels above 0.825 µmol/l were significantly associated with cardiovascular death (p<0.001 and 0.030).
  
  
  CONCLUSIONS
  In symptomatic peripheral arterial disease, decreased flow mediated dilatation, enlarged intima-media thickness, and elevated levels of ADMA and SDMA were associated with increased cardiovascular risk.
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Hafner
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kieninger
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gary
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Froehlich
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Haas
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hackl
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Marianne
authors.initials: M
authors.lastname: Brodmann
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Seinost
mesh_terms: D050197:Atherosclerosis / Q000150:complications / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D058729:Peripheral Arterial Disease / Q000150:complications / Q000000981:diagnostic imaging*; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis
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