BMJ Open. 2013 Mar 06;3(3). doi: 10.1136/bmjopen-2012-002489.

Cadmium exposure, intercellular adhesion molecule-1 and peripheral artery disease: a cohort and an experimental study.

BMJ open

Björn Fagerberg, Göran Bergström, Jan Borén, Lars Barregard

PMID: 23471610 PMCID: PMC3612796 DOI: 10.1136/bmjopen-2012-002489

Abstract

OBJECTIVES: 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.

DESIGN: A prospective, observational cohort study with a 5-year follow-up and an experimental study of cultured human aortic endothelial cells exposed to cadmium.

SETTING: Research unit at a university hospital.

PARTICIPANTS: 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.

PRIMARY AND SECONDARY OUTCOME MEASURES: 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.

References

1. Circulation. 2004 Jun 29;109(25):3196-201 - PubMed
2. Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):971-7 - PubMed
3. Life Sci. 2006 Sep 13;79(16):1493-506 - PubMed
4. Angiology. 2010 Nov;61(8):780-3 - PubMed
5. Biochem Biophys Res Commun. 2004 Jul 30;320(3):887-92 - PubMed
6. Circ J. 2011;75(10):2491-5 - PubMed
7. Toxicol Appl Pharmacol. 2009 Aug 1;238(3):201-8 - PubMed
8. Toxicology. 1992 Dec 4;76(3):257-70 - PubMed
9. Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1392-8 - PubMed
10. Biometals. 2010 Oct;23(5):811-22 - PubMed
11. J Intern Med. 2012 Dec;272(6):601-10 - PubMed
12. Circulation. 2004 Feb 17;109(6):733-9 - PubMed
13. Environ Health Perspect. 2009 Feb;117(2):190-6 - PubMed
14. Am J Public Health. 2002 Feb;92(2):284-7 - PubMed
15. J Cell Physiol. 1994 Jul;160(1):154-62 - PubMed
16. Environ Health Perspect. 2008 Oct;116(10):1338-43 - PubMed
17. Environ Health Perspect. 2012 Jul;120(7):1017-22 - PubMed
18. Angiology. 2009 Feb-Mar;60(1):108-14 - PubMed
19. Environ Res. 2010 Feb;110(2):199-206 - PubMed
20. J Cell Sci. 1992 Dec;103 ( Pt 4):1073-81 - PubMed
21. J Vasc Surg. 2006 Sep;44(3):531-6 - PubMed
22. Environ Health Perspect. 1994 Dec;102(12):1058-66 - PubMed
23. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):833-8 - PubMed
24. Diabet Med. 1998 Jul;15(7):539-53 - PubMed
25. Environ Health Perspect. 2005 Feb;113(2):164-9 - PubMed
26. Diabetes Care. 2006 Feb;29(2):363-7 - PubMed
27. Atherosclerosis. 2008 Feb;196(2):817-22 - PubMed
28. Arterioscler Thromb Vasc Biol. 1997 Jul;17(7):1193-202 - PubMed
29. Am J Epidemiol. 2010 Sep 15;172(6):671-81 - PubMed

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