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

Environ Res. 2017 Jan:152:185-191. doi: 10.1016/j.envres.2016.10.019. Epub 2016 Oct 26.

Abstract

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.

Keywords: Biomarker; Cadmium; Inflammation; Neutrophil to lymphocyte ratio; Soluble urokinase-type plasminogen activator receptor.

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cadmium / blood*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology*
  • Cross-Sectional Studies
  • Environmental Exposure*
  • Environmental Pollutants / blood*
  • Female
  • Humans
  • Inflammation / chemically induced
  • Inflammation / epidemiology*
  • Leukocyte Count
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Neutrophils / metabolism
  • Receptors, Urokinase Plasminogen Activator / blood*
  • Sweden / epidemiology

Substances

  • Biomarkers
  • Environmental Pollutants
  • PLAUR protein, human
  • Receptors, Urokinase Plasminogen Activator
  • Cadmium
  • C-Reactive Protein
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PLA2G7 protein, human