Background: Epidemiologic studies have related chronic exposure to high arsenic levels to cardiovascular disease, despite methodologic limitations of the available literature. At low-to-moderate arsenic levels, the evidence is inconclusive. Aims: We updated a previous systematic review (Am J Epidemiol 2005;162:1037-49) examining the association between arsenic exposure and cardiovascular disease. Methods: We evaluated all studies published before July 23, 2012 that assessed the relationship between arsenic exposure and clinical cardiovascular disease in the general population. Measures of association and their standard errors or 95% confidence intervals (CI) were abstracted or derived using the data reported in the publications. Combining the 13 studies from the previous review with 18 new studies, we calculated pooled relative risks by comparing the highest versus the lowest exposure category across studies. We also assessed study quality and evaluated dose-response trends. Results: For high exposure (arsenic in drinking water ＞50 μg/L), the pooled relative risks (95% CI) for cardiovascular disease, coronary heart disease, stroke, and peripheral arterial disease were 1.32 (95% CI: 1.05-1.67), 1.89 (95% CI: 1.33-2.69), 1.08 (95% CI: 0.98-1.19), and 2.17 (95% CI: 1.47-3.20), respectively. For low-moderate exposure (arsenic in drinking water ＜50 μg/L), the corresponding pooled relative risks (95% CI) for cardiovascular disease, coronary heart disease, stroke, and peripheral arterial disease were 1.06 (95% CI: 0.99-1.14), 1.06 (95% CI: 0.89-1.26), 1.07 (95% CI: 0.96-1.20) and 1.13 (95% CI: 0.77-1.66), respectively. Conclusions: This review strengthens the evidence for a causal association between high-chronic arsenic exposure and clinical cardiovascular endpoints. At low-moderate arsenic levels affecting most general populations, the evidence remains inconclusive. Additional high quality prospective studies are needed at low-moderate arsenic levels.
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