Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

BACKGROUND: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic. OBJECTIVE: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. METHODS: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. RESULTS: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UAs tertiles (<47 ng/mL: reference, 47-72 ng/mL: 48.7 pg/mL, >72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT-proBNP were significantly related to arsenic exposure or echocardiographic parameters. CONCLUSIONS: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life.

Evaluation of vascular and kidney injury biomarkers in Mexican children exposed to inorganic fluoride.

Exposure to inorganic fluoride (F) has been implicated in cardiovascular and kidney dysfunction mainly in adult populations. However, limited epidemiological information from susceptible populations, such as children, is available. In this study we evaluated the relationship of F exposure with some vascular and kidney injury biomarkers in children. A cross-sectional study was conducted in 374 Mexican schoolchildren. Dental fluorosis and F concentrations in the water and urine were evaluated. The glomerular filtration rate (eGFR) and the urinary concentrations of kidney injury molecule 1 (KIM-1) and cystatin-C (uCys-C) were examined to assess kidney injury. The carotid intima media thickness (cIMT) and serum concentrations of vascular adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), endothelin 1(ET-1) and cystatin-C (sCys-C) were measured to assess vascular alterations. High proportions of children exposed to F were observed (79.7% above 1.2 ppm F in urine) even in the low water F exposure regions, which suggested additional sources of F exposure. In robust multiple linear regression models, urinary F was positively associated with eGFR (ß = 1.3, p = 0.015), uCys-C (ß = -8.5, p = 0.043), VCAM-1 (ß = 111.1, p = 0.019), ICAM-1 (ß = 57, p = 0.032) and cIMT (ß = 0.01, p = 0.032). An inverse association was observed with uCys-C (ß = -8.5, p = 0.043) and sCys-C (ß = -9.6, p = 0.021), and no significant associations with ET-1 (ß = 0.069, p = 0.074) and KIM-1 (ß = 29.1, p = 0.212) were found. Our findings revealed inconclusive results regarding F exposure and kidney injury. However, these results suggest that F exposure is related to early vascular alterations, which may increase the susceptibility of cardiovascular diseases in adult life.

Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic.

BACKGROUND: Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure-related cardiovascular disease in children. OBJECTIVE: In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children. METHODS: A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation-cryotrapping-atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography. RESULTS: U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 µg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: -7.14, -0.20) and 3.41% (95% CI: -6.44, -0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL. CONCLUSION: Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Carotid intima-media thickness and plasma asymmetric dimethylarginine in Mexican children exposed to inorganic arsenic.

BACKGROUND: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk. OBJECTIVES: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs). METHODS: We conducted a cross-sectional study in 199 children 3-14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry. RESULTS: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-µmol/L increase in ADMA per 1-mm increase in cIMT). CONCLUSIONS: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water.