Faculty Bibliography

PURPOSE: Experimental studies demonstrate that omega-3 polyunsaturated fatty acids (PUFAs) inhibit inflammatory eicosanoids generated by omega-6 PUFAs. Epidemiologic studies on dietary omega-3 PUFA intake show consistent inverse associations with breast cancer incidence among Asian populations, where omega-3, relative to omega-6, intake is high. In contrast, associations are inconsistent among Western populations, where intake of omega-3, relative to omega-6, is low. We hypothesized that examining interactions between omega-3 and omega-6 would help elucidate the PUFA-breast cancer association in the United States. METHODS: In a Long Island, New York, population-based study of 1463 breast cancer cases and 1500 controls, we estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression to examine interactions between omega-3 and omega-6 intake. RESULTS: We observed a super-additive interaction (relative excess risk due to interaction = 0.41; 95% confidence interval = 0.06-0.76) between omega-3 and omega-6 intake in association with breast cancer incidence, although the CIs for the joint exposure of low omega-3/high omega-6 compared to high omega-3/low omega-6 intake were wide (odds ratio = 1.20; 95% confidence interval = 0.85-1.69). CONCLUSIONS: Breast cancer risk reduction may be possible for U.S. women with dietary consumption of higher omega-3, which has anti-inflammatory properties, in concert with lower omega-6, which induces inflammation. Replication from future U.S.-based investigations is needed.

The case cohort (CCH) design is a cost-effective design for assessing genetic susceptibility with time-to-event data especially when the event rate is low. In this work, we propose a powerful pseudo-score test for assessing the association between a single nucleotide polymorphism (SNP) and the event time under the CCH design. The pseudo-score is derived from a pseudo-likelihood which is an estimated retrospective likelihood that treats the SNP genotype as the dependent variable and time-to-event outcome and other covariates as independent variables. It exploits the fact that the genetic variable is often distributed independent of covariates or only related to a low-dimensional subset. Estimates of hazard ratio parameters for association can be obtained by maximizing the pseudo-likelihood. A unique advantage of our method is that it allows the censoring distribution to depend on covariates that are only measured for the CCH sample while not requiring the knowledge of follow-up or covariate information on subjects not selected into the CCH sample. In addition to these flexibilities, the proposed method has high relative efficiency compared with commonly used alternative approaches. We study large sample properties of this method and assess its finite sample performance using both simulated and real data examples.

OBJECTIVES: Epidemiological and molecular studies have shown that sleep duration is associated with metabolic syndrome (MtS), a disease that is on the rise in the Kingdom of Saudi Arabia. We aim to investigate the association between sleep duration and selected cardiometabolic risk factors of MtS in a Saudi Arabian population. SETTING: Secondary care was given to the participants. There were 2 participating centres, shopping malls in North and South Jeddah, Saudi Arabia. PARTICIPANTS: We recruited 2686 participants over a 1-year study period. Participants were selected based on their willingness. The only criterion for exclusion was living in the area (North or South Jeddah) for less than 15 years. PLANNED AND PRIMARY OUTCOME MEASURES: Participants were measured for blood sugar levels, blood pressure and body mass index. All participants were asked to fill out a questionnaire. RESULTS: There was a positive association between longer sleep duration and obesity, hypertension and hyperglycaemia. The adjusted ORs for obesity, hypertension and hyperglycaemia were 1.54 (95% CI 1.20 to 1.98), 1.89 (95% CI 1.45 to 2.48) and 1.59 (95% CI 1.19 to 2.13), respectively, in participants sleeping >8 h/night, as compared with those sleeping 7 h. The positive associations between longer sleep duration, defined as sleeping >7 h, and the disease status, did not differ from other risk factors such as physical activity and nutrition. CONCLUSIONS: This is the first epidemiological study reporting on the association between sleep duration and cardiometabolic risk factors of MtS in a Saudi Arabian population. Sleep durations of 8 h or greater were found to be associated with all 3 cardiometabolic risk factors: obesity, hypertension and hyperglycaemia, and this relationship was not confounded by quality of nutrition or physical activity levels.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP are lacking. In this study, we used mixed effects models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time.

Publisher: Abstract available from the publisher. OABL- RUS

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.