Faculty Bibliography

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: 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.

BACKGROUND: Prospective studies that evaluate the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk are lacking. OBJECTIVE: To evaluate 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 non-fatal cases of CVD, including 148 stroke cases and 211 cases of heart disease, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study. RESULTS: The adjusted hazard ratio (HR) for all CVD, heart disease, and stroke in association with a standard deviation increase in baseline well arsenic (112 microg/L) was 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. Adjusted HRs for the second and third tertiles of 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 (HR=0.54; 95% CI: 0.34, 0.85) and heart disease (HR=0.54; 95% CI: 0.33, 0.88). There was no apparent association between arsenic metabolite indices and stroke risk. The joint effects of incomplete arsenic methylation capacity, indicated by higher urinary MMA% or lower urinary DMA%, with higher levels of well 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 incomplete methylation capacity of arsenic were adversely associated with heart disease risk.

We aimed to examine the association between BMI and the risk of death from pancreas cancer in a pooled analysis of data from the Asia Cohort Consortium. The data for this pooled analysis included 883 529 men and women from 16 cohort studies in Asian countries. Cox proportional-hazards models were used to estimate the hazard ratios and 95% confidence intervals for pancreas cancer mortality in relation to BMI. Seven predefined BMI categories (<18.5, 18.5-19.9, 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, >/= 30) were used in the analysis, with BMI of 22.5-24.9 serving as the reference group. The multivariable analyses were adjusted for known risk factors, including age, smoking, and a history of diabetes. We found no statistically significant overall association between each BMI category and the risk of death from pancreas cancer in all Asians, and obesity was unrelated to the risk of mortality in both East Asians and South Asians. Age, smoking, and a history of diabetes did not modify the association between BMI and the risk of death from pancreas cancer. In planned subgroup analyses among East Asians, an increased risk of death from pancreas cancer among those with a BMI less than 18.5 was observed for individuals with a history of diabetes; hazard ratio=2.01 (95% confidence interval: 1.01-4.00) (P for interaction=0.07). The data do not support an association between BMI and the risk of death from pancreas cancer in these Asian populations.

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 microg/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 microg/L; range, 0.1-790 microg/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.