title: Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study.
abstract: OBJECTIVE
  Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies.
  
  
  RESULTS
  In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for.
  
  
  CONCLUSIONS
  Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.
authors.affiliation: Wolfson Unit for Prevention of Peripheral Vascular Diseases, Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. i.tzoulaki@sms.ed.ac.uk
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tzoulaki
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Murray
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lee
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: F Gerald R
authors.initials: FG
authors.lastname: Fowkes
mesh_terms: D000368:Aged; D001167:Arteritis / Q000175:diagnosis; D015415:Biomarkers / Q000378:metabolism*; D001809:Blood Viscosity / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000175:diagnosis*; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules