Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years

Objective: To examine whether dietary intake of specific flavonoid sub-classes is associated with weight change over time, including flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and flavonoid polymers. Design: Three prospective cohort studies. Setting: Health professionals in the United States. Participants: 124,086 men and women participating in the Health Professionals Follow-up Study (HPFS), Nurses’ Health Study (NHS), and Nurses’ Health Study II (NHS II). Main outcome measure: Self-reported change in weight over multiple 4-year time intervals between 1986 and 2011. Results: Increased consumption of most flavonoid sub-classes, including flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers was inversely associated with weight change over 4-year time intervals, after adjustment for simultaneous changes in other lifestyle factors including other aspects of diet, smoking status, and physical activity. In the pooled results, the greatest magnitude of association was observed for anthocyanins (-0.22 lbs, 95% CI -0.30 to -0.15 lbs per additional SD/day, 10 mg), flavonoid polymers (-0.18 lbs, 95% CI -0.28 to -0.08 lbs per additional SD/day, 138 mg), and flavonols (-0.16 lbs, 95% CI -0.26 to -0.06 lbs per additional SD/day, 7 mg). After additional adjustment for fiber intake associations remained significant for anthocyanins, proanthocyanidins, and total flavonoid polymers but were attenuated and no longer statistically significant for other sub-classes. Conclusions: Higher intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, may contribute to weight maintenance in adulthood, and may help to refine dietary recommendations for the prevention of obesity and its potential sequelae

Changes in Alcohol Consumption and Subsequent Risk of Type 2 Diabetes in Men

Objective -The objective of this study was to investigate the association of four-year changes in alcohol consumption with subsequent risk of type 2 diabetes. Research Design and Methods - We prospectively examined 38,031 men from the Health Professionals Follow-up Study free of diagnosed diabetes or cancer in 1990. Alcohol consumption was reported on food frequency questionnaires and updated every four years. Results - A total of 1905 cases of type 2 diabetes occurred during 428,497 person-years of follow-up. A 7.5 g/day (~half a glass) increase in alcohol consumption over four years was associated with lower diabetes risk among initial nondrinkers (multivariable hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.60-1.00) and drinkers initially consumin

Use of Systems Biology Approaches to Analysis of Genome-Wide Association Studies of Myocardial Infarction and Blood Cholesterol in the Nurses' Health Study and Health Professionals’ Follow-Up Study

With the advance of genome-wide association studies and newly identified SNP (single-nucleotide polymorphism) associations with complex disease, important discoveries have emerged focusing not only on individual genes but on disease-associated pathways and gene sets. The authors used prospective myocardial infarction case-control studies nested in the Nurses’ Health and Health Professionals Follow-Up Studies to investigate genetic variants associated with myocardial infarction or LDL, HDL, triglycerides, adiponectin and apolipoprotein B (apoB). Using these case-control studies to illustrate an integrative systems biology approach, the authors applied SNP set enrichment analysis to identify gene sets where expression SNPs representing genes from these sets show enrichment in their association with endpoints of interest. The authors also explored an aggregate score approach. While power limited one’s ability to detect significance for association of individual loci with myocardial infarction, the authors found significance for loci associated with LDL, HDL, apoB and triglycerides, replicating previous observations. Applying SNP set enrichment analysis and risk score methods, the authors also found significance for three gene sets and for aggregate scores associated with myocardial infarction as well as for loci-related to cardiovascular risk factors, supporting the use of these methods in practice

Alcohol Consumption, Mediating Biomarkers, and Risk of Type 2 Diabetes Among Middle-Aged Women

OBJECTIVE—The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes. RESEARCH DESIGN AND METHODS—In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for markers of inflammation/endothelial dysfunction (C-reactive protein, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, tumor necrosis factor-α receptor 2, and interleukin-6), fasting insulin, and adiponectin concentrations. RESULTS—Alcohol consumption was associated with a decreased risk of diabetes (odds ratio per 12.5 g/day increment in alcohol use 0.58; 95% CI 0.49–0.69; P 2% of the observed relationship. Without adjustment for BMI, these biomarkers individually explained slightly more of the association, but <10% in all cases. Adiponectin accounted for 25% in a fully adjusted model and for 29% without adjustment for BMI. CONCLUSIONS—In this population of women, alcohol consumption was inversely associated with risk of type 2 diabetes. Adiponectin appeared to be a mediator of this association, but circulating biomarkers of inflammation, endothelial dysfunction, and fasting insulin did not explain this association. These results suggest that further research is needed into the potentially mediating roles of other biomarkers affected by alcohol consumption

Sero-prevalence of herpes simplex type 2 virus (HSV-2) and HIV infection in Kampala, Uganda

Background:Prevalence of herpes simplex type 2 virus (HSV-2) is high worldwide. Previous studies in Uganda were rural or in women. We estimated age and sex-specific sero- prevalence of HSV-2 in Kampala, Uganda.Methods: Using two-stage random sampling stratified on population density, a survey of persons 15-65 years was conducted. Type-specific serological tests for HSV-2, HSV-1(HerpeSelect2 and 1 ELISA), HIV (Rapid tests and ELISA), syphilis (RPR and TPHA) were done. Additional prevalence analysis included post-stratification weighting on the Uganda 2002 Census gender distribution.Results: Among 1124 persons, HSV-2 prevalence was 58% (95% CI: 55, 60), HSV-1; 98% (95% CI: 97.6, 99.1), HIV; 17.7% (95% CI: 14.8, 19.2) and syphilis; 1.7% (95% CI: 1.4, 1.9). Weighted HSV-2 prevalence was 53.8% (Women; 63.8%, men; 43.2%), similar to unweighted data. Weighted HIV prevalence was 20.7% in women, 8.6% in men. Of 165 HIV infected persons, 85.4% had HSV-2. Risk factors for HSV-2 were being a woman (OR 2.0; 95% CI: 1.42, 2.78), age (OR 3.3; 95% CI: 2.43, 4.53), education (OR 1.70; 95% CI: 1.34, 2.34) and HIV (OR 4.5; 95% CI: 2.70, 7.50).Conclusion: Prevalence of HSV-2 and HIV was high especially in women. Syphilis was rare. Awareness of herpes was low. Interventions in young people are needed.Keywords: HSV-2, HIV, Kampala Ugand

Changes in Alcohol Consumption and Subsequent Risk of Type 2 Diabetes in Men

OBJECTIVE: The objective of this study was to investigate the association of 4-year changes in alcohol consumption with a subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively examined 38,031 men from the Health Professionals Follow-Up Study who were free of diagnosed diabetes or cancer in 1990. Alcohol consumption was reported on food frequency questionnaires and updated every 4 years. RESULTS: A total of 1,905 cases of type 2 diabetes occurred during 428,497 person-years of follow-up. A 7.5 g/day (approximately half a glass) increase in alcohol consumption over 4 years was associated with lower diabetes risk among initial nondrinkers (multivariable hazard ratio [HR] 0.78; 95% CI: 0.60–1.00) and drinkers initially consuming <15 g/day (HR 0.89; 95% CI: 0.83–0.96), but not among men initially drinking ≥15 g/day (HR 0.99; 95% CI: 0.95–1.02; Pinteraction < 0.01). A similar pattern was observed for levels of total adiponectin and hemoglobin A1c, with a better metabolic profile among abstainers and light drinkers who modestly increased their alcohol intake, compared with men who either drank less or among men who were already moderate drinkers and increased their intake. Likewise, compared with stable light drinkers (0–4.9 g/day), light drinkers who increased their intake to moderate levels (5.0–29.9 g/day) had a significantly lower risk of type 2 diabetes (HR 0.75; 95% CI: 0.62–0.90). CONCLUSIONS: Increases in alcohol consumption over time were associated with lower risk of type 2 diabetes among initially rare and light drinkers. This lower risk was evident within a 4-year period following increased alcohol intake

Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women

Generalized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized.Using the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses' Health Study. We examined ~700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and 878 matched controls and 435 women with incident CHD with 931 matched controls. We examined the relationship of genome-wide heterozygosity with risk of incident of CHD and with baseline levels of cardiovascular risk factors.In both cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of heterozygous SNPs was not related to risk of CHD in either men or women (adjusted odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13] in women and 0.94 [0.84-1.06] in men). We also found no consistent associations of genome-wide heterozygosity with levels of lipids, inflammatory markers, adhesion molecules, homocysteine, adiponectin, or body-mass index.In these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity

Healthy Lifestyle in the Primordial Prevention of Cardiovascular Disease Among Young Women

AbstractBackgroundOverall mortality rates from coronary heart disease (CHD) in the United States have declined in recent decades, but the rate has plateaued among younger women. The potential for further reductions in mortality rates among young women through changes in lifestyle is unknown.ObjectivesThe aim of this study was to estimate the proportion of CHD cases and clinical cardiovascular disease (CVD) risk factors among young women that might be attributable to poor adherence to a healthy lifestyle.MethodsA prospective analysis was conducted among 88,940 women ages 27 to 44 years at baseline in the Nurses’ Health Study II who were followed from 1991 to 2011. Lifestyle factors were updated repeatedly by questionnaire. A healthy lifestyle was defined as not smoking, a normal body mass index, physical activity ≥ 2.5 h/week, television viewing ≤ 7 h/week, diet in the top 40% of the Alternative Healthy Eating Index–2010, and 0.1 to 14.9 g/day of alcohol. To estimate the proportion of CHD and clinical CVD risk factors (diabetes, hypertension, and hypercholesterolemia) that could be attributed to poor adherence to a healthy lifestyle, we calculated the population-attributable risk percent.ResultsDuring 20 years of follow-up, we documented 456 incident CHD cases. In multivariable-adjusted models, nonsmoking, a healthy body mass index, exercise, and a healthy diet were independently and significantly associated with lower CHD risk. Compared with women with no healthy lifestyle factors, the hazard ratio for CHD for women with 6 lifestyle factors was 0.08 (95% confidence interval: 0.03 to 0.22). Approximately 73% (95% confidence interval: 39% to 89%) of CHD cases were attributable to poor adherence to a healthy lifestyle. Similarly, 46% (95% confidence interval: 43% to 49%) of clinical CVD risk factor cases were attributable to a poor lifestyle.ConclusionsPrimordial prevention through maintenance of a healthy lifestyle among young women may substantially lower the burden of CVD

Habitual intake of flavonoid subclasses and risk of colorectal cancer in two large prospective cohorts

Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one sub-class, flavonols, was significantly associated with reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid sub-classes and intake ranges, yielding inconsistent results.  Objective: To examine whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols and anthocyanins) are associated with lower risk of colorectal cancer.  Design: Using data from validated food frequency questionnaires administered every four years and an updated flavonoid food composition database flavonoid intakes were calculated for 42,478 male participants from the Health Professionals Follow-up Study and for 76,364 female participants from the Nurses’ Health Study.  Results: During up to 26 years of follow-up, 2,519 colorectal cancer cases (1,061 in men, 1,458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted relative risks (95% confidence interval) comparing the highest with the lowest quintile were 1.04 (0.91, 1.18) for flavonols; 1.01 (0.89, 1.15) for flavones; 0.96 (0.84, 1.10) for flavanones; 1.07 (0.95, 1.21) for flavan-3-ols; and 0.98 (0.81, 1.19) for anthocyanins (all p-values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk.  Conclusion: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid sub-class decreases the risk of colorectal cancer

Intakes of fruits, vegetables and carbohydrate and the risk of CVD

BACKGROUND: Low-carbohydrate diets could lead to reduced fruit and vegetable intake, which may be protective against CVD. The role of carbohydrate intake in modifying the association between fruits and vegetables and CVD has not been evaluated. OBJECTIVE: To evaluate whether carbohydrate intake affects the association between fruits and vegetables and CVD. DESIGN: We included participants from two large prospective studies, the Nurses' Health Study (NHS) and the Health Professionals' Follow-Up Study (HPFS). We followed 70870 eligible NHS females for 16 years and 38918 eligible HPFS males for 14 years. Diet was assessed from an FFQ updated every 4 years. Our primary outcome was ischaemic CVD (fatal and non-fatal myocardial infarction and ischaemic stroke). We used Cox proportional hazards models to evaluate the relationship between fruits and vegetables and ischaemic CVD within groups with low, moderate or high carbohydrate intake. RESULTS: Fruit intake was strongly related with carbohydrate intake, but vegetables showed a very small correlation. Vegetable intake showed stronger associations with ischaemic CVD among the low carbohydrate group (multivariate risk ratio (RR) = 0.82 for an increment of 3 servings/d; 95% CI 0.68, 0.99); green leafy vegetables and carotene-rich fruits and vegetables followed a similar pattern. Total fruit intake was associated with a lower risk of ischaemic CVD only among participants with moderate carbohydrate intake (RR = 0.81 comparing extreme quintiles; 95% CI 0.70, 0.94). CONCLUSIONS: Total vegetables, green leafy vegetables and carotene-rich fruits and vegetables showed stronger associations with ischaemic CVD among the low carbohydrate group. No consistent trends were observed for fruit intake