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Biomarkers of blood cadmium and incidence of cardiovascular events in non-smokers : Results from a population-based proteomics study

Borné, Yan LU ; Fagerberg, Björn; Sallsten, Gerd; Hedblad, Bo LU ; Persson, Margaretha LU ; Melander, Olle LU ; Nilsson, Jan LU ; Orho-Melander, Marju LU ; Barregard, Lars and Engström, Gunnar LU (2019) In Clinical Proteomics 16(1).
Abstract

Background: Cadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD. Methods: B-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet and Cancer study. The primary analysis was performed in never smokers (n = 1725). Multiple linear regression was used with adjustments for age and sex, and correction for multiple comparisons using the false discovery rate method. Proteins significantly associated with B-Cd were replicated in long-term former smokers (n = 782). Significant... (More)

Background: Cadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD. Methods: B-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet and Cancer study. The primary analysis was performed in never smokers (n = 1725). Multiple linear regression was used with adjustments for age and sex, and correction for multiple comparisons using the false discovery rate method. Proteins significantly associated with B-Cd were replicated in long-term former smokers (n = 782). Significant proteins were then studied in relation to incidence of CVD (i.e., coronary events or ischemic stroke) in never smokers. Results: Fifteen proteins were associated with B-Cd in never smokers. Eight of them were replicated in long-term former smokers. Kidney injury molecule-1, fibroblast growth factor-23 (FGF23), tumor necrosis factor receptor-2, matrix metalloproteinase-12, cathepsin L1, urokinase plasminogen activator receptor, C-C motif chemokine-3 (CCL3), and chemokine (C-X3-C motif) ligand-1 were associated with B-Cd both in never smokers and long-term former smokers. Except for CCL3 and FGF23, these proteins were also significantly associated with incidence of CVD. Conclusions: B-Cd in non-smokers was associated with eight potential plasma biomarkers of CVD and kidney injury. The results suggest pathways for the associations between B-Cd and CVD and kidney injury.

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@article{33821a7d-622d-4b80-a6f7-c78bd6336ee1,
  abstract     = {<p>Background: Cadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD. Methods: B-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet and Cancer study. The primary analysis was performed in never smokers (n = 1725). Multiple linear regression was used with adjustments for age and sex, and correction for multiple comparisons using the false discovery rate method. Proteins significantly associated with B-Cd were replicated in long-term former smokers (n = 782). Significant proteins were then studied in relation to incidence of CVD (i.e., coronary events or ischemic stroke) in never smokers. Results: Fifteen proteins were associated with B-Cd in never smokers. Eight of them were replicated in long-term former smokers. Kidney injury molecule-1, fibroblast growth factor-23 (FGF23), tumor necrosis factor receptor-2, matrix metalloproteinase-12, cathepsin L1, urokinase plasminogen activator receptor, C-C motif chemokine-3 (CCL3), and chemokine (C-X3-C motif) ligand-1 were associated with B-Cd both in never smokers and long-term former smokers. Except for CCL3 and FGF23, these proteins were also significantly associated with incidence of CVD. Conclusions: B-Cd in non-smokers was associated with eight potential plasma biomarkers of CVD and kidney injury. The results suggest pathways for the associations between B-Cd and CVD and kidney injury.</p>},
  articleno    = {21},
  author       = {Borné, Yan and Fagerberg, Björn and Sallsten, Gerd and Hedblad, Bo and Persson, Margaretha and Melander, Olle and Nilsson, Jan and Orho-Melander, Marju and Barregard, Lars and Engström, Gunnar},
  issn         = {1542-6416},
  keyword      = {Cadmium,Cohort study,CVD,Non-smokers,Proteomics study},
  language     = {eng},
  month        = {05},
  number       = {1},
  publisher    = {Humana Press},
  series       = {Clinical Proteomics},
  title        = {Biomarkers of blood cadmium and incidence of cardiovascular events in non-smokers : Results from a population-based proteomics study},
  url          = {http://dx.doi.org/10.1186/s12014-019-9231-7},
  volume       = {16},
  year         = {2019},
}