title: Cadmium exposure, intercellular adhesion molecule-1 and peripheral artery disease: a cohort and an experimental study.
abstract: OBJECTIVE
  Cadmium exposure has been found to be associated with atherosclerotic plaques in the carotid arteries and with circulating levels of the proatherogenic intercellular adhesion molecule-1 (ICAM-1). The research questions were (1) if blood and urinary cadmium levels are associated with low ankle-brachial index (ABI) as a measure of peripheral artery disease in a longitudinal study and (2) if ICAM-1 mediates proatherogenic effects of cadmium exposure.
  
  
  METHODS
  A prospective, observational cohort study with a 5-year follow-up and an experimental study of cultured human aortic endothelial cells exposed to cadmium.
  
  
  METHODS
  Research unit at a university hospital.
  
  
  METHODS
  A cohort of 64-year-old women (n=489) recruited by stratified sampling of similarly sized groups with normal, impaired and diabetic glucose tolerance as assessed in a population-based screening examination.
  
  
  METHODS
  ABI (ratio of the systolic blood pressures in the tibial and brachial arteries ≤0.9 in any artery) in relation to cadmium exposure; ICAM-1 concentrations in the cell culture medium after cadmium incubation.
  
  
  RESULTS
  High (tertile 3 vs 1) concentrations of blood (B-Cd) or creatine-adjusted urinary cadmium (U-Cd) at baseline were found to predict low ABI after adjustment for smoking and other cardiovascular risk factors at baseline. For U-Cd the OR was 2.5 (95% CI 1.1 to 5.8). After exclusion of participants with ultrasound-assessed femoral atherosclerosis at baseline the OR for U-Cd was unchanged, and for B-Cd it was 3.7 (95% CI 1.05 to 13.3). Inclusion of serum ICAM-1 levels did not affect the cadmium-related ORs in multivariate analyses. The experimental study did not show any cadmium-induced increase of the production of ICAM-1 from human endothelial cells.
  
  
  CONCLUSIONS
  Cadmium exposure was associated with future peripheral artery disease, supporting the concept that cadmium exposure in the population has proatherogenic effects, although ICAM-1 mediated effects do not seem to be involved.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Lars
authors.initials: L
authors.lastname: Barregard