2013 Articles

A Prospective Study of Arsenic Exposure, Arsenic Methylation Capacity, and Risk of Cardiovascular Disease in Bangladesh

Chen, Yu; Wu, Fen; Liu, Mengling; Parvez, Muhammad F.; Slavkovich, Vesna N.; Eunus, Mahbub; Ahmed, Alauddin; Argos, Maria; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane K.; Graziano, Joseph; Ahsan, Habibul

Millions of persons worldwide, including 13 million Americans (U.S. Environmental Protection Agency 2009) and over 50 million in Bangladesh (British Geological Survey 2007), have been chronically exposed to arsenic, a group 1 human carcinogen (International Agency for Research on Cancer 2004), through contaminated drinking water. Arsenic exposure from drinking water has been associated with cardiovascular disease (CVD) (Chen CJ et al. 1996; Chen Y et al. 2011; Chiou et al. 1997; Liao et al. 2012; Tseng et al. 2003; Yuan et al. 2007). However, prospective studies assessing susceptibility to CVD due to arsenic exposure are rare. Arsenic in drinking water is present as inorganic arsenic (iAS). Once ingested, iAs is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The relative distribution of urinary arsenic metabolites varies from person to person and has been interpreted to reflect arsenic methylation capacity (Hopenhayn-Rich et al. 1996; Vahter 1999). Mechanistic studies have shown that MMAIII is more toxic than iAs or any of the pentavalent metabolites (Petrick et al. 2000; Styblo et al. 2000). Incomplete methylation, indicated by a high percentage of urinary MMA (MMA%), has been consistently related to cancers (Chen YC et al. 2003; Pu et al. 2007; Steinmaus et al. 2006; Yu et al. 2000), and there is some evidence of stronger associations among smokers than nonsmokers (Pu et al. 2007; Steinmaus et al. 2006). However, the association between urinary MMA% and CVD risk is unknown, and research on the combined effects of arsenic and biomarkers of arsenic susceptibility on CVD risk is needed. We conducted a prospective case–cohort study nested in a large prospective cohort to assess associations of arsenic exposure from drinking water and arsenic methylation capacity, indicated using relative distribution of urinary arsenic metabolites, with CVD risk.