Arsenic Exposure and Cardiovascular Disease: An Updated Systematic Review

Abstract

In epidemiologic studies, high-chronic arsenic exposure has been associated with cardiovascular disease, despite methodological limitations. At low-moderate arsenic levels, the evidence was inconclusive. Here, we update a previous systematic review (Am J Epidemiol 2005;162: 1037-49) examining the association between arsenic exposure and cardiovascular disease. Eighteen studies published since 2005 were combined with 13 studies from the previous review. We calculated pooled relative risks by comparing the highest versus the lowest exposure category across studies. For high exposure (arsenic in drinking water > 50 μg/L), the pooled relative risks (95 % confidence interval) 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. At low-moderate arsenic levels, the evidence was inconclusive. Our review strengthens the evidence for a causal association between highchronic arsenic exposure and clinical cardiovascular endpoints. Additional high quality studies are needed at low-moderate arsenic levels.

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

“…Although there is a strong evidence of arsenic‐induced cardiotoxicity, many epidemiological studies reporting potential associations relate to highly exposed populations. The scientific evidence of causal association with low level exposure is inconclusive . From a recent investigation, Sidhu et al concluded that the available evidence does not show a robust mechanism of action of i As in CVD incidence, nor does it show a linear dose‐response relationship; indicating that this relationship has a threshold.…”

“…i As‐induced kidney tumors arise from the kidney pelvis urothelium and are essentially related to the urinary bladder tumors . Some of these tumors, such as myeloma, prostate, bladder, and peripheral lymphocytes show very weak and inconsistent evidence of carcinogenicity when exposure is low . Hence, i As modes of action as well as its possible carcinogenic effects at low exposures are not clearly understood.…”

Environmental Risk Factors for Stroke and Cardiovascular Disease

“…This is consistent with a role for high arsenic exposure in atherosclerosis. This review and a later one (Moon et al, 2012) pointed to the inconclusiveness of the chronic low-dose exposure to arsenic. Risk assessment, based on epidemiological studies (cohort, case-control cross-sectional, and ecological studies) from the United States, Taiwan, Bangladesh, and China, proposes a no-observed-adverse-effect level of 100 mg/L for arsenic in water, equivalent to an iAs dose of 0.009 mg/kg-day (Tsuji et al, 2014).…”

Low concentration arsenite activated JAK2/STAT3 signal and increased proliferative factor expressions in SV‐HUC‐1cells after short and long time treatment

“…Arsenic is a naturally occurring metalloid and ubiquitously available in the earth's environment. Arsenic exposure has been through the drinking water, occupational inhalation, diet and pharmaceuticals and an estimation of about 100 million population all around the world was exposed to arsenic level more than 50 μg/L . Epidemiological studies have indicated that ingestion of inorganic arsenic resulted in increased risks of internal cancers, including carcinomas of the skin, urinary bladder, lung, and possibly other tissues .…”