Katherine A Moon1,2, Shilpi Oberoi3, Aaron Barchowsky3, Yu Chen4, Eliseo Guallar1, Keeve E Nachman2, Mahfuzar Rahman5, Nazmul Sohel6, Daniela D'Ippoliti7, Timothy J Wade8, Katherine A James9, Shohreh F Farzan10, Margaret R Karagas11, Habibul Ahsan12, Ana Navas-Acien1,2,13. 1. Department of Epidemiology. 2. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 3. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA. 4. Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA. 5. Research and Evaluation Division, BRAC, Dhaka, Bangladesh. 6. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. 7. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy. 8. United States Environmental Protection Agency, Office of Research and Development, Chapel Hill, NC, USA. 9. Department of Family Medicine, University of Colorado, Denver, CO, USA. 10. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. 11. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. 12. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA. 13. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.
Abstract
Background: Consistent evidence at high levels of water arsenic (≥100 µg/l), and growing evidence at low-moderate levels (<100 µg/l), support a link with cardiovascular disease (CVD). The shape of the dose-response across low-moderate and high levels of arsenic in drinking water is uncertain and critical for risk assessment. Methods: We conducted a systematic review of general population epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary heart disease (CHD) and stroke) with three or more exposure categories. In a dose-response meta-analysis, we estimated the pooled association between log-transformed water arsenic (log-linear) and restricted cubic splines of log-transformed water arsenic (non-linear) and the relative risk of each CVD endpoint. Results: Twelve studies (pooled N = 408 945) conducted at high (N = 7) and low-moderate (N = 5) levels of water arsenic met inclusion criteria, and 11 studies were included in the meta-analysis. Compared with 10 µg/l, the estimated pooled relative risks [95% confidence interval (CI)] for 20 µg/l water arsenic, based on a log-linear model, were 1.09 (1.03, 1.14) (N = 2) for CVD incidence, 1.07 (1.01, 1.14) (N = 6) for CVD mortality, 1.11 (1.05, 1.17) (N = 4) for CHD incidence, 1.16 (1.07, 1.26) (N = 6) for CHD mortality, 1.08 (0.99, 1.17) (N = 2) for stroke incidence and 1.06 (0.93, 1.20) (N = 6) for stroke mortality. We found no evidence of non-linearity, although these tests had low statistical power. Conclusions: Although limited by the small number of studies, this analysis supports quantitatively including CVD in inorganic arsenic risk assessment, and strengthens the evidence for an association between arsenic and CVD across low-moderate to high levels.
Background: Consistent evidence at high levels of water arsenic (≥100 µg/l), and growing evidence at low-moderate levels (<100 µg/l), support a link with cardiovascular disease (CVD). The shape of the dose-response across low-moderate and high levels of arsenic in drinking water is uncertain and critical for risk assessment. Methods: We conducted a systematic review of general population epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary heart disease (CHD) and stroke) with three or more exposure categories. In a dose-response meta-analysis, we estimated the pooled association between log-transformed water arsenic (log-linear) and restricted cubic splines of log-transformed water arsenic (non-linear) and the relative risk of each CVD endpoint. Results: Twelve studies (pooled N = 408 945) conducted at high (N = 7) and low-moderate (N = 5) levels of water arsenic met inclusion criteria, and 11 studies were included in the meta-analysis. Compared with 10 µg/l, the estimated pooled relative risks [95% confidence interval (CI)] for 20 µg/l water arsenic, based on a log-linear model, were 1.09 (1.03, 1.14) (N = 2) for CVD incidence, 1.07 (1.01, 1.14) (N = 6) for CVD mortality, 1.11 (1.05, 1.17) (N = 4) for CHD incidence, 1.16 (1.07, 1.26) (N = 6) for CHD mortality, 1.08 (0.99, 1.17) (N = 2) for stroke incidence and 1.06 (0.93, 1.20) (N = 6) for stroke mortality. We found no evidence of non-linearity, although these tests had low statistical power. Conclusions: Although limited by the small number of studies, this analysis supports quantitatively including CVD in inorganic arsenic risk assessment, and strengthens the evidence for an association between arsenic and CVD across low-moderate to high levels.
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