@article{9b5c640a1b2643c8bdaae1decede02dd,
title = "Urinary arsenic and heart disease mortality in NHANES 2003–2014",
abstract = "Background: Evidence evaluating the prospective association between low-to moderate-inorganic arsenic (iAs) exposure and cardiovascular disease in the general US population is limited. We evaluated the association between urinary arsenic concentrations in National Health and Nutrition Examination Survey (NHANES) 2003–2014 and heart disease mortality linked from the National Death Index through 2015. Methods: We modeled iAs exposure as urinary total arsenic and dimethylarsinate among participants with low seafood intake, based on low arsenobetaine levels (N = 4990). We estimated multivariable adjusted hazard ratios (HRs) for heart disease mortality per interquartile range (IQR) increase in urinary arsenic levels using survey-weighted, Cox proportional hazards models, and evaluated flexible dose-response analyses using restricted quadratic spline models. We updated a previously published relative risk of coronary heart disease mortality from a dose-response meta-analysis per a doubling of water iAs (e.g., from 10 to 20 μg/L) with our results from NHANES 2003–2014, assuming all iAs exposure came from drinking water. Results: A total of 77 fatal heart disease events occurred (median follow-up time 75 months). The adjusted HRs (95% CI) of heart disease mortality for an increase in urinary total arsenic and DMA corresponding to the interquartile range were 1.20 (0.83, 1.74) and 1.18 (0.68, 2.05), respectively. Restricted quadratic splines indicate a significant association between increasing urinary total arsenic and the HR of fatal heart disease for all participants at the lowest exposure levels <4.5 μg/L. The updated pooled relative risk of coronary heart disease mortality per doubling of water iAs (μg/L) was 1.16 (95% CI 1.07, 1.25). Conclusions: Despite a small number of events, relatively short follow-up time, and high analytical limits of detection for urinary arsenic species, iAs exposure at low-to moderate-levels is consistent with increased heart disease mortality in NHANES 2003–2014 although the associations were only significant in flexible dose-response models.",
keywords = "Arsenic, Cardiovascular disease, Epidemiology, NHANES",
author = "Nigra, {Anne E.} and Moon, {Katherine A.} and Jones, {Miranda R.} and Sanchez, {Tiffany R.} and {Navas Acien}, Ana",
note = "Funding Information: This study was supported by NIEHS grants P42ES010349 , P30ES009089 , R01ES028758 , and R21ES029668 . Anne Nigra is also supported by NIEHS grants 2T32ES007322 and F31ES029799 . Funding Information: Although the current analysis was limited by the small number of events, short follow-up time (median time from NHANES examination to end of NDI follow-up 75 months), and high analytical limits of detection for urinary arsenic species, our reported effect estimates are similar to those estimated in other prospective US cohorts for incident fatal and non-fatal cardiovascular disease with low-to moderate-levels of iAs exposure (Moon et al. 2013, 2018a). Across the studies included in the original meta-analysis by Moon et al. relative risk estimates for fatal coronary heart disease comparing arsenic exposure at 20 ?g/L to 10 ?g/L in drinking water ranged from 1.06 (0.99, 1.13) (Wade et al., 2009) to 1.27 (1.09, 1.48) (D'Ippoliti et al., 2015), with a pooled relative risk across six studies of 1.16 (1.07, 1.26). In two prospective US-based studies included in this meta-analysis, iAs exposure at low-to moderate-levels in drinking water was significantly associated with coronary heart disease (James et al., 2015; Moon et al., 2013). In a prospective analysis of a case-control study of adults from New Hampshire, the association between estimated water arsenic concentrations and fatal coronary heart disease was positive but non-significant (relative risk 1.14, 95% CI 0.87, 1.50, N = 154 events) (Farzan et al., 2015). Similarly, our current study found a HR of fatal heart disease per increase in urinary total arsenic corresponding to the interquartile range of 1.20 (0.83, 1.74, N = 77 events) for all participants. Pooling our study results with those included in Moon et al.?s recent meta-analysis resulted in similar RR estimate per doubling of water arsenic from 10 to 20 ?g/L (1.16, 95% CI 1.07, 1.25), with lower estimates of heterogeneity, providing further support for the association between low-to moderate-exposure to iAs and cardiovascular disease at exposure levels relevant for the general US population. In pooling our study results, we assumed that all iAs exposure came from drinking water (as in a previously published dose-response meta analysis), which is not true in the US population where diet is the major source for those with water arsenic concentrations below 10 ?g/L (Moon et al., 2018a). The main rationale for doing this is to enable pooling across studies with different metrics of arsenic exposure. Water and dietary arsenic may have different associations with cardiovascular disease because of differences in absorption, metabolism, and the arsenic species present in water versus food. Because low-to moderate-iAs exposure is relevant for the entire US population (Nachman et al., 2017; Nigra et al., 2020), even modest effect estimates of the association between iAs exposure and cardiovascular disease indicate that elevated iAs exposure may result in high burden of cardiovascular disease for the US population.This study was supported by NIEHS grants P42ES010349, P30ES009089, R01ES028758, and R21ES029668. Anne Nigra is also supported by NIEHS grants 2T32ES007322 and F31ES029799. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = sep,
doi = "10.1016/j.envres.2021.111387",
language = "English (US)",
volume = "200",
journal = "Environmental research",
issn = "0013-9351",
publisher = "Academic Press Inc.",
}