Faculty Bibliography

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 microg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with >/=12.0 microg/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 microg/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 microg/L, mean 63.5 microg/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

BACKGROUND: Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS: We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS: In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS: Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

Dietary factors are believed to modulate arsenic toxicity, potentially influencing risk of arsenical skin lesions. The authors evaluated associations among dietary patterns, arsenic exposure, and skin lesion risk using baseline food frequency questionnaire data collected in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000-2009). They identified dietary patterns and estimated dietary pattern scores using factor analysis. Scores were tested for association with incident skin lesion risk and interaction with water arsenic exposure by using approximately 6 years of follow-up data (814 events among 9,677 individuals) and discrete time hazards models (adjusting for key covariates). The authors identified 3 clear dietary patterns: the "gourd and root," "vegetable," and "animal protein" patterns. The gourd and root pattern score was inversely associated with skin lesion risk (P(trend) = 0.001), with hazard ratios of 0.86, 0.73, and 0.69 for the second, third, and fourth highest quartiles. Furthermore, the association between water arsenic and skin lesion incidence was stronger among participants with low gourd and root scores (multiplicative P(interaction) < 0.001; additive P(interaction) = 0.05). The vegetable pattern and animal protein pattern showed similar but weaker associations and interactions. Eating a diet rich in gourds and root vegetables and increasing dietary diversity may reduce arsenical skin lesion risk in Bangladesh.

Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond.

BACKGROUND: The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia. METHODS AND FINDINGS: A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5-24.9 Kg/m(2) as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m(2) to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m(2). The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction<0.001), in cohorts from India and Bangladesh (p<0.001), in individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no differences were observed by gender, urban residence, or alcohol drinking. CONCLUSIONS: This study estimated the shape and the strength of the association between BMI and prevalence of diabetes in Asian populations and identified patterns of the association by age, country, and other risk factors for diabetes

PURPOSE: The objective of this analysis was to evaluate the effects of dietary B vitamin intakes on creatinine-adjusted urinary total arsenic concentration among individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Araihazar, Bangladesh. Arsenic exposure is a major public health problem in Bangladesh, where nearly 77 million people have been chronically exposed to arsenic through the consumption of naturally contaminated groundwater. Dietary factors influencing the metabolism of ingested arsenic may potentially be important modifiers of the health effects of arsenic in this population. METHODS: Daily average B vitamin intakes from a validated food frequency questionnaire and laboratory data on drinking water and urinary arsenic concentrations among 9,833 HEALS cohort participants were utilized. Statistical analyses were conducted using generalized estimating equations incorporating knotted spline linear regression. RESULTS: Increasing dietary intakes of thiamin, niacin, pantothenic acid, and pyridoxine were found to significantly increase urinary total arsenic excretion, adjusted for daily arsenic intake from drinking water and other potential confounders. CONCLUSIONS: These results suggest that higher intakes of certain B vitamins may enhance the excretion of arsenic from the body. This study offers new insights into modifiable dietary factors that relate to arsenic excretion and thus provides potential avenues for the prevention of arsenic-related health effects

Because the human skin microbiota may play roles in the causation or modification of skin diseases, we sought to provide initial quantitative analysis from different cutaneous locations. We developed quantitative PCRs to enumerate the total bacterial and fungal populations, as well as the most common bacterial and fungal genera present in six locales, in eight healthy subjects. We used a set of primers and TaqMan MGB probes based on the bacterial 16S rRNA and fungal internally transcribed spacer region, as well as bacterial genus-specific probes for Propionibacterium, Corynebacterium, Streptococcus, and Staphylococcus and a fungal genus-specific probe for Malassezia. The extent of human DNA contamination of the specimen was determined by quantitating the human housekeeping GAPDH gene. The highest level of 16S rRNA copies of bacteria was present in the axilla (4.44 +/- 0.18 log(10) copies/mul [mean +/- standard error of the mean]), with normalization based on GAPDH levels, but the other five locations were similar to one another (range, 2.48 to 2.89 log(10) copies/mul). There was strong symmetry between the left and right sides. The four bacterial genera accounted for 31% to 59% of total bacteria, with the highest percent composition in the axilla and the lowest in the forearm. Streptococcus was the most common genus present on the forehead and behind the ear. Corynebacterium spp. were predominant in the axilla. Fungal levels were 1 to 2 log(10) lower than for bacteria, with Malassezia spp. accounting for the majority of fungal gene copies. These results provide the first quantitation of the site and host specificities of major bacterial and fungal populations in human skin and present simple methods for their assessment in studies of disease