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Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease

Journal article
Authors Björn Fagerberg
Y. Borné
Lars Barregård
Gerd Sällsten
N. Forsgard
B. Hedblad
M. Persson
G. Engström
Published in Environmental Research
Volume 152
ISSN 0013-9351
Publication year 2017
Published at Wallenberg Laboratory
Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Keywords Biomarker, Cadmium, Inflammation, Neutrophil to lymphocyte ratio, Soluble urokinase-type plasminogen activator receptor
Subject categories Clinical chemistry, Environmental medicine


Background Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. ©

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