Exposure to Metal-Mixtures and Coronary Heart Disease Across Diverse Populations

Coronary heart disease (CHD) is the leading cause of mortality and disability worldwide, and accounts for 13% of global deaths and 370,000 deaths annually in the US. Accumulating evidence suggests exposure to inorganic arsenic (As) and other (often co-occurring) toxic metals may be an independent risk factor for CHD. Although most individuals are simultaneously exposed to different metals, most studies focused on the toxicity of individual metals. Combinations of exposures may have different, and possibly stronger, effects than each exposure separately. However, there were no large epidemiologic studies on either the effects of metal mixtures (specific combinations of metals) or metal–metal interactions on CHD risk. Moreover, the inadequacy of data on genetic susceptibility masks the effects of environmental exposures. Conversely, genetic studies often ignore that effects of genetic factors on CHD are modulated by varying levels of environmental factors. Data on gene–metal interactions can identify population subgroups with much higher disease risks. However, the few studies focused on gene–metal interactions in CHD had limited sample sizes (n = ~200), tested a single exposure only, considered only