Faculty Bibliography

BACKGROUND: Anthropometric measures such as waist-hip-ratio (WHR), waist-height-ratio (WHtR), waist circumference, Mid-upper arm circumference (MUAC), and upper thigh circumference, have been linked to the risk of cardiovascular disease (CVD). However, their relationships with subclinical atherosclerosis are unclear. Studies in normal-weight populations, especially in Asian countries where leanness is prevalent, are lacking. METHODS: We conducted a cross-sectional study to assess the associations of WHR, WHtR, waist circumference, hip circumference, body mass index (BMI), MUAC and upper thigh circumference with carotid intima-media thickness (cIMT) among 562 middle-aged participants free of CVD in rural Bangladesh. RESULTS: After adjusting for age and sex, WHR and waist circumference but not BMI showed a positive significant association with cIMT. In multivariate analysis, each standard deviation (SD) increase of WHR (0.08) or WHtR (0.07) was associated with an 8.96 mum (95% CI, 1.12-16.81) or 11.45 mum (95%CI, 0.86-22.04) difference in cIMT, respectively, after controlling for age, sex, BMI, smoking status, education level, and systolic blood pressure (SBP). The associations of WHR and WHtR with cIMT were independent of the influence of other anthropometric measures. The associations of other anthropometric measures and cIMT were not apparent. CONCLUSIONS: In our relatively lean, healthy Asian population, WHR and WHtR appear to be better predictors of early atherosclerosis than other common surrogates of adiposity.

OBJECTIVES: To estimate global, regional (21 regions) and national (187 countries) sodium intakes in adults in 1990 and 2010. DESIGN: Bayesian hierarchical modelling using all identifiable primary sources. DATA SOURCES AND ELIGIBILITY: We searched and obtained published and unpublished data from 142 surveys of 24 h urinary sodium and 103 of dietary sodium conducted between 1980 and 2010 across 66 countries. Dietary estimates were converted to urine equivalents based on 79 pairs of dual measurements. MODELLING METHODS: Bayesian hierarchical modelling used survey data and their characteristics to estimate mean sodium intake, by sex, 5 years age group and associated uncertainty for persons aged 20+ in 187 countries in 1990 and 2010. Country-level covariates were national income/person and composition of food supplies. MAIN OUTCOME MEASURES: Mean sodium intake (g/day) as estimable by 24 h urine collections, without adjustment for non-urinary losses. RESULTS: In 2010, global mean sodium intake was 3.95 g/day (95% uncertainty interval: 3.89 to 4.01). This was nearly twice the WHO recommended limit of 2 g/day and equivalent to 10.06 (9.88-10.21) g/day of salt. Intake in men was approximately 10% higher than in women; differences by age were small. Intakes were highest in East Asia, Central Asia and Eastern Europe (mean >4.2 g/day) and in Central Europe and Middle East/North Africa (3.9-4.2 g/day). Regional mean intakes in North America, Western Europe and Australia/New Zealand ranged from 3.4 to 3.8 g/day. Intakes were lower (<3.3 g/day), but more uncertain, in sub-Saharan Africa and Latin America. Between 1990 and 2010, modest, but uncertain, increases in sodium intakes were identified. CONCLUSIONS: Sodium intakes exceed the recommended levels in almost all countries with small differences by age and sex. Virtually all populations would benefit from sodium reduction, supported by enhanced surveillance.

OBJECTIVE: Limited studies suggest that blood pressure variability over time is a risk factor of long-term cardiovascular outcomes. However, most of these were in populations with pre-existing cardiovascular diseases (CVD) and studies in general population are lacking. METHODS: The study included 11,153 participants in a population-based, prospective cohort study in Araihazar, Bangladesh. Resting blood pressure was measured at baseline and every two years thereafter. Participants were followed up for an average of 6.5years (2002-2009). RESULTS: Male gender, older age, baseline systolic blood pressure (SBP), and absence of betel leaf use were independently positively associated with greater SBP variability over time. There was a significant association between SBP variability and the risk of death from overall CVD, especially from major CVD events. The positive association with the risk of death from any cause and stroke in age- and sex-adjusted models was attenuated in fully-adjusted models. In addition, the hazard ratio (HR) of stroke mortality was greater for individuals with both high baseline and high SBP variability. Similar patterns of HRs were observed for all-cause and CVD mortalities. CONCLUSION: In this rural Bangladeshi population, variability in SBP contributes to the risk of death from CVD and may further potentiate the increased mortality risk associated with high SBP.

BACKGROUND: Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. METHODS: Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. RESULTS: Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). CONCLUSIONS: We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

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.