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 high-chronic arsenic exposure and clinical cardiovascular endpoints. Additional high quality studies are needed at low-moderate arsenic levels.

Fig. 1. Relative risks (RR) for coronary heart disease (CHD) comparing the highest to lowest arsenic exposure categories

The area of each black square (individual study) is proportional to the inverse of the variance of the estimated log relative risk. Horizontal lines represent 95 % confidence intervals.

Fig. 2. Dose-response relationship of arsenic exposure and coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD)

Solid lines represent studies conducted in high exposure areas (Taiwan, Bangladesh, Chile, Inner Mongolia, and Pakistan) and dashed lines represent studies conducted in low to moderate exposure areas (U.S., Spain, Slovakia, Hungary, and Japan). Studies of CHD: Chen et al. 2011 [28••] (red); Tseng et al. 2003 [23] (light brown); Chen et al. 1996 [56] (light pink); Wu et al. 1989 [58] (light green); Medrano et al. 2010 [32•] (gray); Zierold et al. 2004 [59] (black); Lewis et al. 1999 [60] (gold); Engel & Smith 1994 [62] (dark green). Studies of stroke: Chen et al. 2011 [28] (red); Wade et al. 2009 [30] (blue); Chiou et al. 1997 [57] (orange); Wu et al. 1989 [58] (light green); Lisabeth et al. 2010 [31•] (pink); Medrano et al. 2010 [32•] (gray); Yoshikawa et al. 2008 [43] (turquoise); Zierold et al. 2004 [59] (black); Lewis et al. 1999 [60] (gold); Engel & Smith 1994 [62] (dark green). Studies of PAD: Tseng et al. 2005 [24] (purple); Wu et al. 1989 [58] (light green); Chen et al. 1988 [55] (light blue); Lewis et al. 1999 [60] (gold); Engel & Smith 1994 [62] (dark green). The reference categories were as follows: Chen et al. 2011 [28••]: 6.6–105.9 μg/g creatinine (urine); Wade et al. 2009 [30]: 0–5 μg/L; Tseng et al. 2005 [24]: 0 CAE (cumulative arsenic exposure) mg/L × year; Tseng et al. 2003 [23]: 0 mg/L-years; Chiou et al. 1997 [57]: <0.1 mg/L - year; Chen et al. 1996 [56]: 0 mg/L - years; Wu et al. 1989 [58]: <0.3 mg/L; Chen et al. 1988 [55]: 0 years; Lisabeth et al. 2010 [31•]: 0.3–4.5 μg/L; Medrano et al. 2010 [32•]: <1 μg/L; Yoshikawa et al. 2008 [43]: <0.77 ng/m³; Zierold et al. 2004 [59]: <2 μg/L; Lewis et al. 1999 [60]: < 1 mg/L-year; Engel & Smith 1994 [62]: 5–10 μg/L.