Faculty Bibliography

The effect of dietary composition on mortality in low-income countries is largely unknown. We evaluated whether percentages of dietary energy derived from protein, fat and carbohydrates were associated with all-cause and cancer mortalities in a Bangladeshi population. Data from a prospective population-based cohort study of 17,244 men and women were used. Percentages of dietary energy derived from protein, fat and carbohydrates, assessed using a validated food-frequency questionnaire at baseline, were analyzed in relation to mortality over an average of 9 years (155,126 person-years) of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios for all cause, all cancer and cancers of the digestive organs mortalities. Percentage of dietary energy from protein appeared to be significantly associated with cancer mortality. Fully adjusted hazard ratios for cancer mortality in increasing tertiles of percentage of dietary energy from protein were 1.0 (reference), 1.21 (0.73, 2.00) and 1.84 (1.08, 3.15) (p for trend = 0.023). These associations were much stronger for deaths from cancers of the digestive organs with fully adjusted hazard ratios in increasing tertiles of percentage of dietary energy from protein being 1.0 (reference), 2.25 (0.91, 5.59) and 4.85 (1.88, 12.51) (p for trend = 0.001). No significant associations in relation to cancer-related mortality were observed for percentage of dietary energy from fat. Novel findings from this prospective study show protein is an important risk factor or proxy to an important risk factor for cancer mortality especially from digestive organ cancers in Bangladesh.

BACKGROUND: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. OBJECTIVES: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. METHODS: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms "arsenic", "in utero", "transplacental", "prenatal" and "fetal". DISCUSSION: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. CONCLUSIONS: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels.

OBJECTIVE: To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. DESIGN: Pooled analyses of 20 prospective cohorts in Asia, including data from 835,082 east Asians and 289,815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. SETTING: General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). PARTICIPANTS: 1,124,897 men and women (mean age 53.4 years at baseline). MAIN OUTCOME MEASURES: Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. RESULTS: 49,184 cardiovascular deaths (40,791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). CONCLUSIONS: Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

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.

BACKGROUND & AIMS: Despite appropriate passive and active immunization, perinatal transmission of hepatitis B virus (HBV) still occurs in 5%-10% of infants born to women with high levels of viremia who test positive for the hepatitis B e antigen (HBeAg). We evaluated the effects of cesarean section delivery on perinatal transmission of HBV from women who tested positive for the hepatitis B surface antigen (HBsAg). METHODS: We analyzed data from 1409 infants born to HBsAg-positive mothers through vaginal delivery (VD) (n = 673), elective caesarean section (ECS) (n = 496), or urgent cesarean section (UCS) (n = 240) who completed appropriate immunization against HBV. The prevention was assumed to have failed for infants who were HBsAg positive when they were 7-12 months old; this information was used to assess transmission rates. RESULTS: HBV infection was transmitted to a smaller percentage of infants born by ECS (1.4%) than by VD (3.4%, P < .032) or UCS (4.2%, P < .020). UCS had no effect on vertical transmission, compared with VD (4.2% vs 3.4%, P = .593). Infants born by ECS had a significantly lower rate of vertical transmission than those born by non-ECS (1.4% vs 3.6%, P = .017). Women with HBV DNA levels <1,000,000 copies/mL did not transmit the infection to their infants, regardless of method of delivery. There were no differences in maternal or infant morbidity and mortality among the groups. CONCLUSIONS: There is a significantly lower rate of vertical transmission of HBV infection to infants delivered by ECS, compared with those delivered vaginally or by UCS. Elective cesarean sections for HBeAg-positive mothers with pre-delivery levels of HBV DNA >/=1,000,000 copies/mL could reduce vertical transmission.

BACKGROUND: Total or red meat intake has been shown to be associated with a higher risk of mortality in Western populations, but little is known of the risks in Asian populations. OBJECTIVE: We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia. DESIGN: We used ecological data from the United Nations to compare country-specific meat consumption. Separately, 8 Asian prospective cohort studies in Bangladesh, China, Japan, Korea, and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause, 9558 cancer, and 6373 cardiovascular disease (CVD) deaths. We estimated the study-specific HRs and 95% CIs by using a Cox regression model and pooled them by using a random-effects model. RESULTS: Red meat consumption was substantially lower in the Asian countries than in the United States. Fish and seafood consumption was higher in Japan and Korea than in the United States. Our pooled analysis found no association between intake of total meat (red meat, poultry, and fish/seafood) and risks of all-cause, CVD, or cancer mortality among men and women; HRs (95% CIs) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 (0.91, 1.15) in men and 0.93 (0.86, 1.01) in women. CONCLUSIONS: Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.

OBJECTIVE: Persistent colonisation by Helicobacter pylori, and especially by cagA-positive strains, has been related to several health outcomes with effects in opposite directions. Thus, it is important to evaluate its influence on total and category-specific mortality. DESIGN: We conducted prospective cohort analyses in a nationally representative sample of 9895 participants enrolled in the National Health and Nutrition Examination Survey III to assess the association of H pylori status with all-cause and cause-specific mortality. Analyses for the association of H pylori cagA positivity with mortality were conducted in 7384 subjects with data on H pylori cagA status. RESULTS: In older people (>40.1 years), H pylori was not associated with all-cause mortality (HR 1.00; 95% CI 0.84 to 1.18). There was an inverse association of H pylori status with stroke mortality (HR 0.69; 95% CI 0.44 to 1.08), and the inverse association was stronger for H pylori cagA positivity, with the HR of 0.45 (95% CI 0.27 to 0.76). H pylori was also strongly positively related to gastric cancer mortality. After we adjusted p values using the Benjamini-Hochberg false discovery rate method to account for multiple comparisons, these associations remained, and H pylori status was not related to other outcomes. CONCLUSIONS: Our findings suggest that H pylori has a mixed role in human health, but is not a major risk factor for all-cause mortality.

BACKGROUND: Dietary pattern analysis is emerging as a practical, effective tool for relating comprehensive dietary intake to risk of cardiovascular disease mortality. However, no studies have applied this technique to a population outside of the developed world. METHODS: We conducted prospective cohort analyses in 11,116 participants enrolled in the Health Effects of Arsenic Study in Araihazar, Bangladesh, measuring deaths attributable to disease of circulatory system, heart disease, and cerebrovascular disease. Participants were enrolled in 2000 and followed up for an average of 6.6years. Dietary information was obtained through a previously validated food-frequency questionnaire at baseline. RESULTS: Principal component analysis based on our comprehensive, 39 item FFQ yielded 3 dietary patterns: (i) a "balanced" pattern, comprised of steamed rice, red meat, fish, fruit and vegetables; (ii) an "animal protein" diet, which was more heavily weighted towards eggs, milk, red meat, poultry, bread, and vegetables; and (iii) a "gourd and root vegetable" diet that heavily relied on a variety of gourds, radishes, pumpkin, sweet potato, and spinach. We observed a positive association between increasing adherence to the animal protein diet and risk of death from both disease of the circulatory system and heart disease; the hazard ratios were 1.13 (95% CI, 1.00-1.28, p=0.05) and 1.17 (95% CI, 0.99-1.38, p=0.07), respectively, in relation to one standard deviation increase in the factor scores for the animal protein diet pattern, after controlling for age, sex, body mass index, smoking status, and energy intake. The positive association was more significant among ever smokers; the hazard ratios (95% CI) for deaths from disease of the circulatory system and heart disease were 1.17 (1.02-1.34) and 1.20 (1.00-1.45), respectively, in relation to one standard deviation increase in the factor scores for the animal protein diet pattern. CONCLUSIONS: An animal protein-rich diet in rural Bangladesh may increase risk of heart disease mortality, especially among smokers. This emphasizes the need to further explore and address the impact of dietary patterns on cardiovascular disease in populations undergoing epidemiologic transition.

We conducted a cross-sectional study to evaluate the interrelationships between past arsenic exposure, biomarkers specific for susceptibility to arsenic exposure, and carotid intima-media thickness (cIMT) in 959 subjects from the Health Effects of Arsenic Longitudinal Study in Bangladesh. We measured cIMT levels on average 7.2 years after baseline during 2010-2011. Arsenic exposure was measured in well water at baseline and in urine samples collected at baseline and during follow-up. Every 1-standard-deviation increase in urinary arsenic (357.9 microg/g creatinine) and well-water arsenic (102.0 microg/L) concentration was related to a 11.7-microm (95% confidence interval (CI): 1.8, 21.6) and 5.1-microm (95% CI: -0.2, 10.3) increase in cIMT, respectively. For every 10% increase in monomethylarsonic acid (MMA) percentage, there was an increase of 12.1 microm (95% CI: 0.4, 23.8) in cIMT. Among participants with a higher urinary MMA percentage, a higher ratio of urinary MMA to inorganic arsenic, and a lower ratio of dimethylarsinic acid to MMA, the association between well-water arsenic and cIMT was stronger. The findings indicate an effect of past long-term arsenic exposure on cIMT, which may be potentiated by suboptimal or incomplete arsenic methylation capacity. Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes.