Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between environmental chemicals with DNA methylation levels in adults. After excluding arsenic, recently evaluated in a systematic review, we identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic hydrocarbons). The selected articles reported quantitative methods to determine DNA methylation including immunocolorimetric assays for total content of genomic DNA methylation, and microarray technologies, methylation-specific quantitative PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA methylation content of genomic sites such as gene promoters, LINE-1, Alu elements, and others. Considering consistency, temporality, strength, dose-response relationship, and biological plausibility, we concluded that the current evidence is not sufficient to provide inference because differences across studies and limited samples sizes make it difficult to compare across studies and to evaluate sources of heterogeneity. Important questions for future research include the need for larger and longitudinal studies, the validation of findings, and the systematic evaluation of the dose-response relationships. Future studies should also consider the evaluation of epigenetic marks recently in the research spotlight such as DNA hydroxymethylation and the role of underlying genetic variants.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0055-7) contains supplementary material, which is available to authorized users.

Published systematic reviews concluded that there is moderate to strong evidence to infer a potential role of lead and cadmium, widespread metal exposures, as cardiovascular risk factors. For other non-essential metals, the evidence has not been appraised systematically. Our objective was to systematically review epidemiologic studies on the association between cardiovascular disease in adults and the environmental metals antimony, barium, chromium, nickel, tungsten, uranium, and vanadium. We identified a total of 4 articles on antimony, 1 on barium, 5 on chromium, 1 on nickel, 4 on tungsten, 1 on uranium and 0 on vanadium. We concluded that the current evidence is not sufficient to inform on the cardiovascular role of these metals because the small number of studies. Few experimental studies have also evaluated the role of these metals in cardiovascular outcomes. Additional epidemiologic and experimental studies, including prospective cohort studies, are needed to understand the role of metals, including exposure to metal mixtures, in cardiovascular disease development.

Environmental declines in lead and cadmium exposures were associated with reductions in cardiovascular mortality in US adults. Given the fact that lead and cadmium remain associated with cardiovascular disease at relatively low levels of exposure, prevention strategies that further minimize exposure to lead and cadmium may be needed.