Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study

Shohreh F. Farzan, Caitlin G. Howe, Michael S. Zens, Thomas Palys, Jacqueline Y. Channon, Zhigang Li, Yu Chen, Margaret R. Karagas

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Arsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations.

OBJECTIVES: We investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418).

METHODS: Associations between toenail As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models.

RESULTS: Covariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2). Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15-F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a 2.98% decrease in 15-F2t-IsoP [(95% CI: -6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3% decrease (95% CI: -4.3, -0.3) in MMP-9, and a 5% increase in %uMMA was associated with a 7.7% decrease (95% CI: -12.6, -2.5) in PAI-1.

CONCLUSION: In a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062.

Original languageEnglish (US)
Number of pages1
JournalEnvironmental Health Perspectives
Volume125
Issue number12
DOIs
StatePublished - Dec 15 2017

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Arsenic
Oxidative Stress
Cross-Sectional Studies
Biomarkers
Urine
Inflammation
Nails
Cardiovascular Diseases
Vascular Cell Adhesion Molecule-1
Plasminogen Activator Inhibitor 1
Matrix Metalloproteinase 9
Linear Models
Intercellular Adhesion Molecule-1
Population
Blood Vessels
Tumor Necrosis Factor-alpha
15-F2t-isoprostane

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction : A Cross-Sectional Study. / Farzan, Shohreh F.; Howe, Caitlin G.; Zens, Michael S.; Palys, Thomas; Channon, Jacqueline Y.; Li, Zhigang; Chen, Yu; Karagas, Margaret R.

In: Environmental Health Perspectives, Vol. 125, No. 12, 15.12.2017.

Research output: Contribution to journalArticle

Farzan, Shohreh F. ; Howe, Caitlin G. ; Zens, Michael S. ; Palys, Thomas ; Channon, Jacqueline Y. ; Li, Zhigang ; Chen, Yu ; Karagas, Margaret R. / Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction : A Cross-Sectional Study. In: Environmental Health Perspectives. 2017 ; Vol. 125, No. 12.
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title = "Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study",
abstract = "BACKGROUND: Arsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations.OBJECTIVES: We investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418).METHODS: Associations between toenail As, total urine As (uAs), and {\%}uAs metabolites [monomethyl ({\%}uMMAV), dimethyl ({\%}uDMAV), and inorganic ({\%}iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models.RESULTS: Covariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8{\%} increase in 15-F2t-IsoP (95{\%} CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7{\%} increase in VCAM-1 (95{\%} CI: 0.2, 3.2). Additionally, a 5{\%} increase in {\%}uMMA was associated with a 7.9{\%} increase in 15-F2t-IsoP (95{\%} CI: 2.1, 14.1), and a 5{\%} increase in {\%}uDMA was associated with a 2.98{\%} decrease in 15-F2t-IsoP [(95{\%} CI: -6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3{\%} decrease (95{\%} CI: -4.3, -0.3) in MMP-9, and a 5{\%} increase in {\%}uMMA was associated with a 7.7{\%} decrease (95{\%} CI: -12.6, -2.5) in PAI-1.CONCLUSION: In a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062.",
author = "Farzan, {Shohreh F.} and Howe, {Caitlin G.} and Zens, {Michael S.} and Thomas Palys and Channon, {Jacqueline Y.} and Zhigang Li and Yu Chen and Karagas, {Margaret R.}",
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TY - JOUR

T1 - Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction

T2 - A Cross-Sectional Study

AU - Farzan, Shohreh F.

AU - Howe, Caitlin G.

AU - Zens, Michael S.

AU - Palys, Thomas

AU - Channon, Jacqueline Y.

AU - Li, Zhigang

AU - Chen, Yu

AU - Karagas, Margaret R.

PY - 2017/12/15

Y1 - 2017/12/15

N2 - BACKGROUND: Arsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations.OBJECTIVES: We investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418).METHODS: Associations between toenail As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models.RESULTS: Covariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2). Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15-F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a 2.98% decrease in 15-F2t-IsoP [(95% CI: -6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3% decrease (95% CI: -4.3, -0.3) in MMP-9, and a 5% increase in %uMMA was associated with a 7.7% decrease (95% CI: -12.6, -2.5) in PAI-1.CONCLUSION: In a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062.

AB - BACKGROUND: Arsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations.OBJECTIVES: We investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418).METHODS: Associations between toenail As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models.RESULTS: Covariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2). Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15-F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a 2.98% decrease in 15-F2t-IsoP [(95% CI: -6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3% decrease (95% CI: -4.3, -0.3) in MMP-9, and a 5% increase in %uMMA was associated with a 7.7% decrease (95% CI: -12.6, -2.5) in PAI-1.CONCLUSION: In a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062.

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