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Arsenic is a ubiquitous toxic metalloid causing serious health problems. Speciation analysis of arsenic in human urine provides valuable insights for large-scale epidemiological studies and informs on sources of exposure as well as human metabolism. The Multi-Ethnic Study of Atherosclerosis (MESA) is a valuable cohort for assessing chronic low-moderate arsenic exposure and health effects in an ethnically diverse US population. We present a state-of-the-art arsenic speciation analysis methodology and its application to 7677 MESA spot urine samples based on high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. This method is fast, robust and detects a total of 11 individual As species at method detection limits of 0.02-0.03 µg arsenic/L urine for each individual species. Our analytical approach features excellent mean method accuracy (98%) and precision (5%) for the main arsenic species in urine (arsenobetaine, methylarsonic acid, dimethylarsinic acid, and total inorganic As); intra- (3-6%) and inter-day coefficients of variability (5-6%); column recovery (96 ± 7%); and spike recovery (97 ± 6%). The main arsenic species were detectable in ≥95% of urine samples due to the implementation of an oxidation step. Each individual minor arsenic species was detectable in ≤25% of all urines, although at least one of them was detected in almost half the participants. We identified two minor urinary arsenic species as dimethylarsinoylacetic acid and dimethylarsinoylpropionic acid, potential metabolites of seafood-related arsenicals. We observed differences in individual As species excretion by race/ethnicity, with Asian-American participants featuring 3-4 times higher concentrations compared to other participants. We also found differences by site, body mass index, smoking status, rice intake, and water arsenic levels, potentially indicating different exposures or related to individual bio-metabolism. The proposed approach is suitable for epidemiological studies and the collected data will constitute the base for future research on potential health effects of chronic low-level arsenic exposure.
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BACKGROUND: American Indian populations have experienced marked disparities in respiratory disease burden. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) are a novel class of biomarkers that may improve recognition of lung damage in indigenous populations. RESEARCH QUESTION: Are plasma EV-miRNAs viable biomarkers of respiratory health in American Indian populations? STUDY DESIGN AND METHODS: The Strong Heart Study is a prospective cohort study that enrolled American Indians aged 45-74 years. EV-miRNA expression was measured in plasma (1993-1995). Respiratory health outcomes including pre-bronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and respiratory symptom burden were ascertained in the same study visit. Club cell secretory protein (CC-16), an anti-inflammatory pneumoprotein implicated in COPD pathogenesis, was measured in serum. Linear and logistic regression were used for statistical analyses. Biological pathway analyses were used to elucidate gene targets of significant EV-miRNAs. RESULTS: Among 853 American Indian adults, three EV-miRNAs were associated with FEV1, four EV-miRNAs were associated with FVC, and one EV-miRNA was associated with FEV1/FVC (P<0.05). Increased miR-1294 expression was associated with higher odds of airflow limitation (OR 1.29, 95% CI 1.07-1.55), while increased expression of miR-1294 (OR 1.32, 95% CI 1.07-1.63) and miR-532-5p (OR 1.57, 95% CI 1.02-2.40) was associated with higher odds of restriction. Increased miR-451a expression was associated with lower odds of exertional dyspnea (OR 0.71, 95% CI 0.59-0.85). Twenty-two EV-miRNAs were associated with serum CC-16 levels (q<0.05), suggesting EV-miRNAs may play a role in the pathway linking CC-16 to COPD pathogenesis. A pathway analysis showed key EV-miRNAs targeted biological pathways that modulate inflammation, immunity, and structural integrity in the lungs. INTERPRETATION: Circulating EV-miRNAs are novel mechanistic biomarkers of respiratory health and may facilitate the early detection and treatment of lung damage in American Indian populations that have been disproportionately affected by chronic lung diseases.
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Background Arsenic-related cardiovascular effects at exposure levels below the US Environmental Protection Agency's standard of 10 µg/L are unclear. For these populations, food, especially rice, is a major source of exposure. We investigated associations of rice intake, a marker of arsenic exposure, with subclinical cardiovascular disease (CVD) markers in a multiethnic population. Methods and Results Between 2000 and 2002, MESA (Multi-Ethnic Study of Atherosclerosis) enrolled 6814 adults without clinical CVD. We included 5050 participants with baseline data on rice intake and markers of 3 CVD domains: inflammation (hsCRP [high-sensitivity C-reactive protein], interleukin-6, and fibrinogen), vascular function (aortic distensibility, carotid distensibility, and brachial flow-mediated dilation), and subclinical atherosclerosis at 3 vascular sites (carotid intima-media thickness, coronary artery calcification, and ankle-brachial index). We also evaluated endothelial-related biomarkers previously associated with arsenic. Rice intake was assessed by food frequency questionnaire. Urinary arsenic was measured in 310 participants. A total of 13% of participants consumed ≥1 serving of rice/day. Compared with individuals consuming <1 serving of rice/week, ≥1 serving of rice/day was not associated with subclinical markers after demographic, lifestyle, and CVD risk factor adjustment (eg, geometric mean ratio [95% CI] for hsCRP, 0.98 [0.86-1.11]; aortic distensibility, 0.99 [0.91-1.07]; and carotid intima-media thickness, 0.98 [0.91-1.06]). Associations with urinary arsenic were similar to those for rice intake. Conclusions Rice intake was not associated with subclinical CVD markers in a multiethnic US population. Research using urinary arsenic is needed to assess potential CVD effects of low-level arsenic exposure. Understanding the role of low-level arsenic as it relates to subclinical CVD may contribute to CVD prevention and control.