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

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

Association between number of children and carotid intima-media thickness in Bangladesh

Previous studies on the association between number of children and carotid intima-media thickness (cIMT) were limited to Western populations. Pregnancy in women is associated with physiologic changes that may influence the risk of cardiovascular disease. Comparing the association between number of children and cIMT in men and women can provide insights on whether the association may be due to pregnancy. We investigated the association between number of children and cIMT among 718 female (mean age 37.5 years) and 417 male participants (mean age 41.3 years), randomly selected from the Health Effect of Arsenic Longitudinal Study (HEALS), a population-based cohort study in Bangladesh. Multivariate linear regression was used to assess the association and to control for education attainment, history of diabetes, age, smoking, betel use, BMI, systolic blood pressure, and diastolic blood pressure. The average number of children was 4.43 for women and 3.74 for men. There were no nulliparous women. We observed a positive association between number of children and cIMT in women. Mean cIMT increased by 4.5 μm (95% CI, 0.8–8.1) per increment of one birth (P = 0.02). Compared to women with two children, cIMT in women with 4 children and ≥5 children was 23.6μm (95%CI, 2.6–44.7; P = 0.03) and 25.1 μm (95%CI, 3.5–46.6; P = 0.02) greater, respectively. The association was not modified by BMI, SBP, betel use or age. Data in men showed no evidence of association (P = 0.4). The finding suggests a role of high parity in atherosclerosis in women of a low-income, high parity population

Association between number of children and carotid intima-media thickness in Bangladesh.

Previous studies on the association between number of children and carotid intima-media thickness (cIMT) were limited to Western populations. Pregnancy in women is associated with physiologic changes that may influence the risk of cardiovascular disease. Comparing the association between number of children and cIMT in men and women can provide insights on whether the association may be due to pregnancy. We investigated the association between number of children and cIMT among 718 female (mean age 37.5 years) and 417 male participants (mean age 41.3 years), randomly selected from the Health Effect of Arsenic Longitudinal Study (HEALS), a population-based cohort study in Bangladesh. Multivariate linear regression was used to assess the association and to control for education attainment, history of diabetes, age, smoking, betel use, BMI, systolic blood pressure, and diastolic blood pressure. The average number of children was 4.43 for women and 3.74 for men. There were no nulliparous women. We observed a positive association between number of children and cIMT in women. Mean cIMT increased by 4.5 μm (95% CI, 0.8-8.1) per increment of one birth (P = 0.02). Compared to women with two children, cIMT in women with 4 children and ≥5 children was 23.6μm (95%CI, 2.6-44.7; P = 0.03) and 25.1 μm (95%CI, 3.5-46.6; P = 0.02) greater, respectively. The association was not modified by BMI, SBP, betel use or age. Data in men showed no evidence of association (P = 0.4). The finding suggests a role of high parity in atherosclerosis in women of a low-income, high parity population

Reduction of household air pollution through clean fuel intervention and recovery of cellular immune balance

Background: We conducted a clean fuel intervention trial (Bangladesh Global Environmental and Occupational Health (GEOHealth) (NCT02824237) with liquefied petroleum gas (LPG) for 26 months among rural Bangladeshi women chronically exposed to household air pollution (HAP) from biomass fuel (BMF) use. We aimed to evaluate the effect of HAP reduction following LPG intervention on immune response outcome. Methods: We supplied LPG cook stove and refills in cylinder in 200 households for 26 months. We measured personal exposure to HAP [particulate matter 2.5 (PM2·5), black carbon (BC) and carbon monoxide (CO)] in 200 women (main cook) by personal monitors at pre- and post-intervention. Immune function was assessed before and after intervention, in blood collected within 2 weeks of HAP measurements. Primary endpoints included reduction in HAP, lymphocyte proliferation and oxidative stress response, and alterations in T and B cell proportions. Findings: Exclusive LPG use for 26 months resulted in significant reduction in PM2·5 (43.5%), BC (13%) and CO (48%) exposure in the women. For one unit decrease in BC, Treg cells and memory B cells increased by 7% and 34% respectively, in the peripheral circulation. One unit decrease in CO was significantly associated with increase in early B cells and plasmablasts by 66% and 5% respectively. For one unit decrease in BC, percent-dividing cells, proliferation and expansion indices increased by 2%, 0.4%, and 1%, respectively. Interpretation: Reduced personal exposure to HAP through clean fuel intervention was related to a return towards cellular immune balance.</p

The association between smoking and gut microbiome in Bangladesh

Introduction Epidemiological studies that investigate alterations in the gut microbial composition associated with smoking are lacking. This study examined the composition of the gut microbiome in smokers compared with non-smokers. Methods Stool samples were collected in a cross-sectional study of 249 participants selected from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Microbial DNA was extracted from the fecal samples and sequenced by 16S rRNA gene sequencing. The associations of smoking status and intensity of smoking with the relative abundance or the absence and presence of individual bacterial taxon from phylum to genus levels were examined. Results The relative abundance of bacterial taxa along the Erysipelotrichi-to-Catenibacterium lineage was significantly higher in current smokers compared to never smokers. The odds ratio comparing the mean relative abundance in current smokers with that in never smokers was 1.91 (95% confidence interval [CI] = 1.36 to 2.69) for the genus Catenibacterium and 1.89 (95% CI = 1.39 to 2.56) for the family Erysipelotrichaceae, the order Erysipelotrichale, and the class Erysipelotrichi ((FDR-adjusted p-values = 0.0008 to 0.01). A dose-response association was observed for each of these bacterial taxa. The presence of Alphaproteobacteria was significantly greater comparing current with never smokers (OR = 4.85, FDR-adjusted p-values = 0.04). Conclusions Our data in a Bangladeshi population are consistent with evidence of an association between smoking status and dosage with change in the gut bacterial composition. Implications This study for the first time examined the relationship between smoking and the gut microbiome composition. The data suggest that smoking status may play an important role in the composition of the gut microbiome, especially among individuals with higher levels of tobacco exposure