Rabiul Hasan

Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study

BACKGROUND Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. METHODS In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. FINDINGS 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. INTERPRETATION Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. FUNDING US National Institutes of Health.

Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study

Objective To evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association. Design Prospective cohort study with arsenic exposure measured in drinking water from wells and urine. Setting General population in Araihazar, Bangladesh. Participants 11 746 men and women who provided urine samples in 2000 and were followed up for an average of 6.6 years. Main outcome measure Death from cardiovascular disease. Results 198 people died from diseases of circulatory system, accounting for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100 000 person years in people drinking water containing <12.0 µg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with ≥12.0 µg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease; the hazard ratios in increasing quarters of arsenic concentration in well water (0.1-12.0, 12.1-62.0, 62.1-148.0, and 148.1-864.0 µg/L) were 1.00 (reference), 1.22 (0.65 to 2.32), 1.35 (0.71 to 2.57), and 1.92 (1.07 to 3.43) (P=0.0019 for trend), respectively, after adjustment for potential confounders including age, sex, smoking status, educational attainment, body mass index (BMI), and changes in urinary arsenic concentration since baseline. Similar associations were observed when baseline total urinary arsenic was used as the exposure variable and for mortality from ischaemic heart disease specifically. The data indicate a significant synergistic interaction between arsenic exposure and cigarette smoking in mortality from ischaemic heart disease and other heart disease. In particular, the hazard ratio for the joint effect of a moderate level of arsenic exposure (middle third of well arsenic concentration 25.3-114.0 µg/L, mean 63.5 µg/L) and cigarette smoking on mortality from heart disease was greater than the sum of the hazard ratios associated with their individual effect (relative excess risk for interaction 1.56, 0.05 to 3.14; P=0.010). Conclusions Exposure to arsenic in drinking water is adversely associated with mortality from heart disease, especially among smokers.

A Prospective Study of Arsenic Exposure From Drinking Water and Incidence of Skin Lesions in Bangladesh

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000-2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1-50.0, 50.1-100.0, 100.1-200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (P(trend) = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).

A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh.

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk. Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk. Method: We conducted a case–cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity—indicated by higher urinary MMA% or lower urinary DMA%—with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking. Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk.

A prospective study of body mass index and mortality in Bangladesh

BACKGROUND Body mass index (BMI) (kg/m(2)) has a U- or J-shaped relationship with all-cause mortality in Western and East Asian populations. However, this relationship is not well characterized in Bangladesh, where the BMI distribution is shifted towards lower values. METHODS Using data on 11,445 individuals (aged 18-75 years) participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, we prospectively examined associations of BMI (measured at baseline) with all-cause mortality during approximately 6 years of follow-up. We also examined this relationship within strata of key covariates (sex, age, smoking, education and arsenic exposure). Cox proportional hazards models adjusted for these covariates and BMI-related illnesses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for BMI categories defined by the World Health Organization. RESULTS Low BMI was strongly associated with increased mortality in this cohort (P-trend < 0.0001). Severe underweight (BMI < 16 kg/m(2); HR 2.06, CI 1.53-2.77) and moderate underweight (16.0-16.9 kg/m(2); HR 1.39, CI 1.01-2.90) were associated with increased all-cause mortality compared with normal BMI (18.6-22.9 kg/m(2)). The highest BMI category (> or =23.0 kg/m(2)) did not show a clear association with mortality (HR 1.10, CI 0.77-1.53). The BMI-mortality association was stronger among individuals with <5 years of formal education (interaction P = 0.02). CONCLUSIONS Underweight (presumably due to malnutrition) is a major determinant of mortality in the rural Bangladeshi population.

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study

BACKGROUND Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. METHODS We evaluated the association between As exposure from drinking water and proteinuria in 11,122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. RESULTS At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤ 7, 8-39, 40-91, 92-179 and 180-864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77-1.27], POR 1.23 (95% CI 0.97-1.57), POR 1.50 (95% CI 1.18-1.89) and POR 1.59 (95% CI 1.26-2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67-1.03) and POR 0.91 (95% CI 0.74-1.12) for participants with a decreasing level of >70 and 17-70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97-1.42) and POR 1.42 (95% CI 1.16-1.73) for participants with an increasing level of 16-68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As -16 to 15 µg/l). CONCLUSION The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure.

Arsenic exposure and impaired lung function. Findings from a large population-based prospective cohort study.

RATIONALE Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. OBJECTIVES To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. METHODS In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator-administered pulmonary function assessed during follow-up. MEASUREMENTS AND MAIN RESULTS For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (-46.5 ml; P < 0.0005) and FVC (-53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (-48.3 ml; P < 0.005) and FVC (-55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (-74.4 ml, P < 0.01; and -116.1 ml, P < 0.05) and FVC (-72.8 ml, P = 0.02; and -146.9 ml, P = 0.004), respectively. CONCLUSIONS This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range.

Betel quid chewing in rural Bangladesh: prevalence, predictors and relationship to blood pressure

BACKGROUND Betel quid is chewed by 600 million people worldwide and it has been linked to obesity and cardiovascular disease. The purpose of our study was to examine the prevalence and predictors of betel quid chewing in a rural area of Bangladesh, and determine its effects on body mass index (BMI) and blood pressure. METHODS In this population-based prospective study, we analysed data on 19 934 Bangladeshi adults. Linear and multivariate logistic regression was used to determine the socio-demographic predictors of betel quid chewing and the effect of betel quid on change in BMI and on systolic and diastolic blood pressure, pulse pressure, arterial pressure, overweight or obesity, and hypertension. RESULTS At baseline, betel quid was chewed by 33.2% of the cohort (35.5% of men, 31.6% of women). In a subsample in which we collected methods of use, 17.5% chewed it without tobacco and 82.5% chewed it with tobacco. In multivariate analysis, betel quid chewing was associated with female sex, older age, tobacco smoking and lower socio-economic status, as measured by fewer years of formal education and not owning land. Betel quid was chewed more times per day among women and older persons. At follow-up, persons who chewed betel quid without tobacco had higher systolic blood pressure, diastolic blood pressure and arterial pressure in comparison with never users. After controlling for other explanatory variables, chewing betel quid without tobacco was associated with general hypertension [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.04-2.10] and systolic hypertension (OR 1.55, 95% CI 1.01-2.37). We did not observe associations of betel quid chewing with BMI or overweight. CONCLUSIONS Betel quid chewing is likely contributing to high blood pressure in Bangladesh, particularly among women.

A prospective study of tobacco smoking and mortality in Bangladesh.

Background Limited data are available on smoking-related mortality in low-income countries, where both chronic disease burden and prevalence of smoking are increasing. Methods Using data on 20, 033 individuals in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, we prospectively evaluated the association between tobacco smoking and all-cause, cancer, and cardiovascular disease mortality during ∼7.6 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for deaths from all-cause, cancer, CVD, ischemic heart disease (IHD), and stroke, in relation to status, duration, and intensity of cigarette/bidi and hookah smoking. Results Among men, cigarette/bidi smoking was positively associated with all-cause (HR 1.40, 95% CI 1.06 1.86) and cancer mortality (HR 2.91, 1.24 6.80), and there was a dose-response relationship between increasing intensity of cigarette/bidi consumption and increasing mortality. An elevated risk of death from ischemic heart disease (HR 1.87, 1.08 3.24) was associated with current cigarette/bidi smoking. Among women, the corresponding HRs were 1.65 (95% CI 1.16 2.36) for all-cause mortality and 2.69 (95% CI 1.20 6.01) for ischemic heart disease mortality. Similar associations were observed for hookah smoking. There was a trend towards reduced risk for the mortality outcomes with older age at onset of cigarette/bidi smoking and increasing years since quitting cigarette/bibi smoking among men. We estimated that cigarette/bidi smoking accounted for about 25.0% of deaths in men and 7.6% in women. Conclusions Tobacco smoking was responsible for substantial proportion of premature deaths in the Bangladeshi population, especially among men. Stringent measures of tobacco control and cessation are needed to reduce tobacco-related deaths in Bangladesh.

Arsenic exposure from drinking water and QT-interval prolongation: results from the Health Effects of Arsenic Longitudinal Study.

Background: Arsenic exposure from drinking water has been associated with heart disease; however, underlying mechanisms are uncertain. Objective: We evaluated the association between a history of arsenic exposure from drinking water and the prolongation of heart rate–corrected QT (QTc), PR, and QRS intervals. Method: We conducted a study of 1,715 participants enrolled at baseline from the Health Effects of Arsenic Longitudinal Study. We assessed the relationship of arsenic exposure in well water and urine samples at baseline with parameters of electrocardiogram (ECG) performed during 2005–2010, 5.9 years on average since baseline. Results: The adjusted odds ratio (OR) for QTc prolongation, defined as a QTc ≥ 450 msec in men and ≥ 460 msec in women, was 1.17 (95% CI: 1.01, 1.35) for a 1-SD increase in well-water arsenic (108.7 µg/L). The positive association appeared to be limited to women, with adjusted ORs of 1.24 (95% CI: 1.05, 1.47) and 1.24 (95% CI: 1.01, 1.53) for a 1-SD increase in baseline well-water and urinary arsenic, respectively, compared with 0.99 (95% CI: 0.73, 1.33) and 0.86 (95% CI: 0.49, 1.51) in men. There were no apparent associations of baseline well-water arsenic or urinary arsenic with PR or QRS prolongation in women or men. Conclusions: Long-term arsenic exposure from drinking water (average 95 µg/L; range, 0.1–790 µg/L) was associated with subsequent QT-interval prolongation in women. Future longitudinal studies with repeated ECG measurements would be valuable in assessing the influence of changes in exposure.