Faculty Bibliography

BACKGROUND: Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies, conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy. OBJECTIVES: To evaluate the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a US population. METHODS: The New Hampshire Birth Cohort Study is an ongoing prospective cohort study, in which over 10% of participant household wells exceed the arsenic maximum contaminant level of 10 mug/L established by the US EPA. Total urinary arsenic measured at 24-28 weeks gestation was measured in 514 pregnant women, ages 18-45, who used a private well in their household and used as a biomarker of exposure during pregnancy. Outcomes were repeated blood pressure measurements (systolic, diastolic and pulse pressure) recorded during pregnancy. RESULTS: Using linear mixed effects models, we estimated that, on average, each 5 microg/L increase in urinary As was associated with a 0.15 mmHg (95% CI: 0.02, 0.29, p = 0.022) increase in systolic blood pressure per month and a 0.14 mmHg (95% CI: 0.02, 0.25; p=0.021) increase in pulse pressure per month over the course of pregnancy. CONCLUSIONS: In our US cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications as even modest increases in blood pressure impact cardiovascular disease risk.

OBJECTIVE:To quantify global intakes of key foods related to non-communicable diseases in adults by region (n=21), country (n=187), age and sex, in 1990 and 2010. DESIGN/METHODS:We searched and obtained individual-level intake data in 16 age/sex groups worldwide from 266 surveys across 113 countries. We combined these data with food balance sheets available in all nations and years. A hierarchical Bayesian model estimated mean food intake and associated uncertainty for each age-sex-country-year stratum, accounting for differences in intakes versus availability, survey methods and representativeness, and sampling and modelling uncertainty. SETTING/POPULATION/METHODS:Global adult population, by age, sex, country and time. RESULTS:In 2010, global fruit intake was 81.3 g/day (95% uncertainty interval 78.9-83.7), with country-specific intakes ranging from 19.2-325.1 g/day; in only 2 countries (representing 0.4% of the world's population), mean intakes met recommended targets of ≥300 g/day. Country-specific vegetable intake ranged from 34.6-493.1 g/day (global mean=208.8 g/day); corresponding values for nuts/seeds were 0.2-152.7 g/day (8.9 g/day); for whole grains, 1.3-334.3 g/day (38.4 g/day); for seafood, 6.0-87.6 g/day (27.9 g/day); for red meats, 3.0-124.2 g/day (41.8 g/day); and for processed meats, 2.5-66.1 g/day (13.7 g/day). Mean national intakes met recommended targets in countries representing 0.4% of the global population for vegetables (≥400 g/day); 9.6% for nuts/seeds (≥4 (28.35 g) servings/week); 7.6% for whole grains (≥2.5 (50 g) servings/day); 4.4% for seafood (≥3.5 (100 g) servings/week); 20.3% for red meats (≤1 (100 g) serving/week); and 38.5% for processed meats (≤1 (50 g) serving/week). Intakes of healthful foods were generally higher and of less healthful foods generally lower at older ages. Intakes were generally similar by sex. Vegetable, seafood and processed meat intakes were stable over time; fruits, nuts/seeds and red meat, increased; and whole grains, decreased. CONCLUSIONS:These global dietary data by nation, age and sex identify key challenges and opportunities for optimising diets, informing policies and priorities for improving global health.

High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with>/=31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), >/= 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality.

OBJECTIVE:Baseline, persistent, incident, and remittent dipstick proteinuria have never been tested as predictors of mortality in an undeveloped country. The goal of this study was to determine which of these four types of proteinuria (if any) predict mortality. METHODS:Baseline data was collected from 2000 to 2002 in Bangladesh from 11,121 adults. Vital status was ascertained over 11-12years. Cox models were used to evaluate proteinuria in relation to all-cause and cardiovascular disease (CVD) mortality. CVD mortality was evaluated only in those with baseline proteinuria. Persistent, remittent, and incident proteinuria were determined at the 2-year exam. RESULTS:Baseline proteinuria of 1+ or greater was significantly associated with all-cause (hazard ratio (HR) 2.87; 95% C.I., 1.71-4.80) and CVD mortality (HR: 3.55; 95% C.I., 1.81-6.95) compared to no proteinuria, adjusted for age, gender, arsenic well water concentration, education, hypertension, BMI, smoking, and diabetes mellitus. Persistent 1+ proteinuria had a stronger risk of death, 3.49 (1.64-7.41)-fold greater, than no proteinuria. Incident 1+ proteinuria had a 1.87 (0.92-3.78)-fold greater mortality over 9-10years. Remittent proteinuria revealed no increased mortality. CONCLUSIONS:Baseline, persistent, and incident dipstick proteinuria were predictors of all-cause mortality with persistent proteinuria having the greatest risk. In developing countries, those with 1+ dipstick proteinuria, particularly if persistent, should be targeted for definitive diagnosis and treatment. The two most common causes of proteinuria to search for are diabetes mellitus and hypertension.

BACKGROUND: Cross-sectional studies have shown associations between arsenic exposure and prevalence of high BP; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking. METHOD: We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every two years after baseline. Mixed effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with blood pressure annual change during follow-up (median, 6.7 years). RESULT: In the HEALS population, the median water arsenic concentration at baseline was 62 microg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in SBP compared with those in the reference group (beta=0.48 mmHg/year; 95% CI: 0.35-0.61, and beta=0.43 mmHg/year; 95% CI: 0.29-0.56) for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in DBP (beta=0.39 mmHg/year; 95% CI: 0.30, 0.49, and beta=0.45 mmHg/year; 95% CI: 0.36, 0.55) for water arsenic and urinary creatinine-adjusted arsenic, respectively) compared with those in the lowest quartile. CONCLUSION: Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease.

BACKGROUND: In laboratory experiments, omega-3 polyunsaturated fatty acids (PUFAs) have been found to reduce inflammatory eicosanoids resulting from omega-6 PUFA metabolism via competitive inhibition, and the omega-3-induced cytotoxic environment increases apoptosis and reduces cell growth in breast cancer cells. To the authors' knowledge, epidemiologic investigations regarding whether dietary omega-3 PUFA intake benefits survival after breast cancer are limited and inconsistent. METHODS: The authors used resources from a population-based follow-up study conducted on Long Island, New York, among 1463 women newly diagnosed with first primary breast cancer who were interviewed an average of approximately 3 months after diagnosis to assess risk and prognostic factors, including dietary intake (using a food frequency questionnaire). Vital status was determined through 2011, yielding a median follow-up of 14.7 years and 485 deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regression. RESULTS: All-cause mortality was reduced among women with breast cancer reporting the highest quartile of intake (compared with never) for tuna (HR, 0.71; 95% CI, 0.55-0.92), other baked/broiled fish (HR, 0.75; 95% CI, 0.58-0.97), and the dietary long-chain omega-3 PUFAs docosahexaenoic acid (HR, 0.71; 95% CI, 0.55-0.92) and eicosapentaenoic acid (HR, 0.75; 95% CI, 0.58-0.97). CONCLUSIONS: All-cause mortality was reduced by 16% to 34% among women with breast cancer who reported a high intake of fish and long-chain omega-3 PUFAs. Long-chain omega-3 PUFA intake from fish and other dietary sources may provide a potential strategy to improve survival after breast cancer. Cancer 2015. (c) 2015 American Cancer Society.

BACKGROUND:: Observational studies and clinical trials have shown associations of diet and high blood pressure (BP). However, prospective studies on the association between dietary patterns and longitudinal BP change are lacking, especially in low-income populations. METHOD:: We evaluated the association of dietary patterns and food groups with longitudinal change of BP in 10 389 participants in the Health Effects of Arsenic Longitudinal Study, with a median of 6.7 years of follow-up. Dietary information was obtained through a previously validated food-frequency questionnaire. BP was measured at baseline and at each biennial follow-up using the same method. RESULT:: Each standard deviation (SD) increase for the 'gourd vegetable' dietary pattern score was related to a slower annual change of 0.08, 0.04, and 0.05 mmHg in SBP, DBP, or pulse pressure, respectively. Each SD increase in the 'balanced' dietary pattern score was related to a decreasing annual change of 0.06 mmHg (P = 0.012) and 0.08 mmHg in SBP and pulse pressure (P < 0.001). On the contrary, one SD increase in 'western' dietary pattern score was related to a greater annual increase of 0.07 (P = 0.005) and 0.05 mmHg in SBP and pulse pressure (P = 0.013). Higher intake of fruits and vegetables was associated with a slower rate of change in annual SBP and pulse pressure, whereas higher meat intake was related to a more rapid increase in annual pulse pressure. CONCLUSION:: The findings suggest that dietary patterns play a significant role in the rate of BP change over time in a low-income population.

BACKGROUND: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited. OBJECTIVE: We investigated whether the association between well-water arsenic and cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. METHOD: We conducted a prospective case-cohort study nested in the Health Effects of Arsenic Longitudinal Study, with a random subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD. Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke cases, and 44 deaths due to other CVD identified during follow-up from 2000 to 2012. RESULTS: Of the 170 SNPs tested, multiplicative interactions between well-water arsenic and two SNPs, rs281432 in ICAM1 (Padj = 0.0002) and rs3176867 in VCAM1 (Padj = 0.035), were significant for CVD after adjustment for multiple testing. Compared with those with GC or CC genotype in rs281432 and lower well-water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31, 2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype, which was greater than expected given aHRs of 1.08 and 0.96 for separate effects of arsenic and the genotype alone, respectively. Similarly, the joint aHR for arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than expected given aHRs for their separate effects of 1.02 and 0.84, respectively. CONCLUSIONS: Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.

BACKGROUND: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. METHODS: We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. RESULTS: Greater waist circumference (per 5 cm: HR = 1.04, 95% CI 1.03-1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05-1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m2: HR = 1.15, 95% CI 1.06-1.24, P-value for trend = 0.0006), but not in former smokers (per 5 kg/m2: HR = 0.99, 95% CI 0.93-1.06, P-value for trend = 0.79) or current smokers (per 5 kg/m2: HR = 0.76, 95% CI 0.71-0.82, P-value for trend = <0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5 cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. CONCLUSIONS: Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers.

BACKGROUND:Herpes simplex virus type 1 (HSV-1) commonly causes orolabial ulcers, while HSV-2 commonly causes genital ulcers. However, HSV-1 is an increasing cause of genital infection. Previously, the World Health Organization estimated the global burden of HSV-2 for 2003 and for 2012. The global burden of HSV-1 has not been estimated. METHODS:We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital. FINDINGS/RESULTS:We estimated that 3709 million people (range: 3440-3878 million) aged 0-49 years had prevalent HSV-1 infection in 2012 (67%), with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67-212 million) people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific. CONCLUSIONS:The global burden of HSV-1 infection is huge. Genital HSV-1 burden can be substantial but varies widely by region. Future control efforts, including development of HSV vaccines, should consider the epidemiology of HSV-1 in addition to HSV-2, and especially the relative contribution of HSV-1 to genital infection.