Peripheral arterial disease and metals in urine and blood.

Navas-Acien et al. (2005) recently analyzed the data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES). They suggested that blood lead and blood and urinary cadmium, at levels well below safety standards, were associated with an increased prevalence of peripheral arterial disease (PAD) and that cadmium might partly mediate the detrimental arterial effects of smoking. The authors recognized that their findings needed confirmation and support from mechanistic studies. In line with their suggestion, we analyzed data from 428 participants in the Flemish Study on Environment, Genes, and Health Outcomes (Staessen et al. 1994). As described by Navas-Acien et al. (2005), we included only subjects who were at least 40 years of age and we defined PAD as an ankle brachial index of > 0.9 in at least one leg. Blood lead and blood and urinary cadmium were measured by atomic absorption spectrometry. The geometric mean concentrations were 0.43 nmol/L [5th-95th percentile interval (PI), 0.19-1.03] for blood lead and 11.6 nmol/L (PI, 3.6-31.1) for blood cadmium. The urinary cadmium excretion averaged 11.6 nmol/24 hr (PI, 3.8-35.5).

We adjusted for demographic and cardiovascular risk factors. For blood lead and cadmium, the odds ratios of PAD comparing quartiles 2-4 with the lowest quartile were in line with those of Navas-Acien et al. (2005). However, for the 24-hr urinary cadmium excretion the p-value for trend was only 0.72. Urinary cadmium is a more precise biomarker of exposure than blood cadmium, because urinary cadmium reflects lifetime exposure and blood cadmium reflects more recent exposure. Navas-Acien et al. (2005) measured only metal concentrations in spot urine samples (Navas-Acien et al. 2005), whereas we measured the 24-hr excretion of cadmium. We could not demonstrate any relation between cardiovascular disease or the incidence of hypertension in relation to environmental exposure to lead and cadmium (Staessen et al. 2000). We therefore concur with their conclusion that the role of cadmium in the pathogenesis of atherosclerosis needs further research. However, not only are mechanistic studies required but also population studies, for example, that relate pulse wave velocity to biomarkers of cadmium exposure. We currently have similar experiments in progress.

The authors declare they have no competing financial interests.

Michelle Plusquin

Tim S. Nawrot

Jan A. Staessen

Katholieke Universiteit Leuven 

Leuven, Belgium

E-mail: [e-mail]

REFERENCES

Navas-Acien A, E K Silbergeld, R Sharrett, E Calderon-Aranda, E Selvin, E Guallar. 2005. Metals in urine and peripheral arterial disease. Environ Health Perspect 113:164?169.

Staessen JA, T Kuznetsova, H A Roels, D Emelianov, R Fagard, for the Public Health and Environmental Exposure to Cadmium Study Group. 2000. Exposure to cadmium and conventional and ambulatory blood pressures in a prospective population study. American Journal of Hypertension 13:146-156.

Staessen JA, R Lauwerys, G Ide, H A Reels, G Vyncke, A Amery. 1994. Renal function and historical environmental cadmium pollution from zinc smelters. Lancet 343:1523-1527.