A Prospective Study of Nut Consumption and Risk of Primary Hepatocellular Carcinoma in the U.S. Women and Men.

Although increasing evidence suggests a potential beneficial effect of nut consumption on various diseases, no epidemiologic study has yet examined the association between nut consumption and risk of hepatocellular carcinoma (HCC). We prospectively examined this association in 88,783 women from the Nurses' Health Study and 51,492 men from the Health Professionals Follow-up Study. Nut consumption was assessed every 4 years using validated food frequency questionnaires. Multivariable HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression models after adjusting for HCC risk factors. After an average of 27.9 years of follow-up, we identified a total of 162 incident HCC cases. Higher total nut consumption was not significantly associated with HCC risk (the highest vs. lowest tertile intake, HR, 0.84; 95% CI, 0.56-1.26). For the same comparison, higher tree nut consumption was associated with a lower HCC risk (HR, 0.64; 95% CI, 0.43-0.95). We found nonsignificant inverse associations with consumption of walnuts, peanuts, and peanut butter. Overall, nut consumption was not strongly associated with HCC risk. There was a suggestive inverse association with tree nut consumption. Future studies should carefully consider hepatitis B or C virus infections and examine these associations in other racial/ethnic groups.

Trends in the diagnosis and clinical features of melanoma in situ (MIS) in US men and women: A prospective, observational study.

BACKGROUND: The incidence of melanoma in situ (MIS) is increasing, but little is known about its clinical and epidemiologic features. OBJECTIVE: We sought to determine trends in diagnosis and clinical features of MIS. METHODS: Incident cases of melanoma were collected prospectively from the Nurses' Health Study (1976-2010) and Health Professionals Follow-up Study (1986-2010). RESULTS: MIS incidence increased from 2 to 42 per 100,000 person-year among women, and from 11 to 73 per 100,000 person-year among men, exceeding the rate of increase of invasive melanomas. Melanoma mortality initially increased during the follow-up period then plateaued. Men were more likely than women to develop in situ melanomas on the upper half of the body (P < .001). Invasive melanomas were diagnosed at a younger age than MIS (P < .001), and were more likely to be found on the lower extremities than MIS (P < .001). LIMITATIONS: This is a strictly descriptive study without examination into mechanisms. CONCLUSION: We found epidemiologic and clinical differences for in situ and invasive melanomas, which support further examination into the variations in etiologic pathways. The lack of improvement in mortality despite the increase in detection of in situ relative to invasive lesions further highlights the need to improve invasive melanoma-specific clinical screening features.

Sleep disordered breathing and the risk of psoriasis among US women.

Sleep disordered breathing [snoring and obstructive sleep apnea-hypopnea syndrome (OSAHS)] is common in the US and has been associated with negative health outcomes. There has been no long-term prospective study on the association between sleep disordered breathing and psoriasis risk. We prospectively evaluated the association between OSAHS and snoring and incident psoriasis and psoriatic arthritis (PsA) in 71,598 women over an 11-year period (1997-2008) in the Nurses' Health Study. Participants received follow-up questionnaires every 2 years and were asked about snoring, diagnosis of OSAHS, and diagnosis of psoriasis and PsA. We studied individuals who reported data on snoring and OSAHS prior to the diagnosis of psoriasis or PsA. We used Cox proportional hazards to calculate age-adjusted and multivariate risk ratios. Over the follow-up period, there were 524 cases of psoriasis. Women with OSAHS were more likely to have a higher BMI, be hypertensive, have cardiovascular disease, and have type 2 diabetes (p < 0.001 for all). The age-adjusted relative risk (RR) of psoriasis among women with OSAHS was 2.19 (95% CI 1.39-3.45), the multivariate RR was 1.93 (95% CI 1.21-3.08). Further adjusting for night shift work, hypertension, cardiovascular disease, and type 2 diabetes, the multivariate RR was 1.91 (95% CI 1.20-3.05). There was no effect modification by BMI (p = 0.52), hypertension (p = 0.34), or snoring (p = 0.91). OSAHS was not associated with an increased risk of PsA. Although women with OSAHS were more likely to be snorers, we did not find a statistically significant relationship between snoring and the risk of confirmed psoriasis. In this study, we found that women with OSAHS had a significantly increased risk of psoriasis.

The Mediterranean-style dietary pattern and mortality among men and women with cardiovascular disease.

BACKGROUND: The role of the Mediterranean diet among individuals with previous cardiovascular disease (CVD) is uncertain. OBJECTIVE: The aim of this study was to assess the association between the Alternate Mediterranean Diet (aMED) score and all-cause, cardiovascular, and cancer mortality in men and women with CVD from the Health Professionals Follow-Up Study and the Nurses' Health Study. DESIGN: This study included 6137 men and 11,278 women with myocardial infarction, stroke, angina pectoris, coronary bypass, and coronary angioplasty. Diet was first assessed in 1986 for men and in 1980 for women with a food-frequency questionnaire (FFQ) and then repeatedly every 2-4 y. Cumulative consumption was calculated with all available FFQs from the diagnosis of CVD to the end of the follow-up in 2008. RESULTS: During a median follow-up of 7.7 y (IQR: 4.2-11.8) for men and 5.8 y (IQR: 3.8-8.0) for women, we documented 1982 deaths (1142 from CVD and 344 from cancer) among men and 1468 deaths (666 from CVD and 197 from cancer) among women. In multivariable Cox regression models, the pooled RR of all-cause mortality from a comparison of the top with the bottom quintiles of the aMED score was 0.81 (95% CI: 0.72, 0.91; P-trend < 0.001). The corresponding pooled RR for CVD mortality was 0.85 (95% CI: 0.67, 1.09; P-trend = 0.30), for cancer mortality was 0.85 (95% CI: 0.65, 1.11; P-trend = 0.10), and for other causes was 0.79 (95% CI: 0.65, 0.97; P-trend = 0.01). A 2-point increase in adherence to the aMED score was associated with a 7% (95% CI: 3%, 11%) reduction in the risk of total mortality. CONCLUSION: Adherence to a Mediterranean-style dietary pattern was associated with lower all-cause mortality in individuals with CVD.

The liver toxicity biomarker study phase I: markers for the effects of tolcapone or entacapone.

The Liver Toxicity Biomarker Study is a systems toxicology approach to discover biomarkers that are indicative of a drug's potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a "toxic" drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a "clean" drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug-vehicle or drug-drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the study are detecting substantial "off-target" markers for the two drugs. An additional interesting finding was the modest overlap of the marker data sets for 3-day exposure and 28-day exposure, indicating that the molecular changes in liver and plasma caused by short- and long-term drug treatments do not share common characteristics.

Coffee consumption and mortality in women with cardiovascular disease.

BACKGROUND: Coffee is commonly consumed among populations of all ages and conditions. The few studies that have examined the association between coffee consumption and mortality in patients with cardiovascular disease (CVD) have obtained conflicting results. OBJECTIVE: The objective was to assess the association between filtered caffeinated coffee consumption and all-cause and CVD mortality during up to 24 y of follow-up in women with CVD from the Nurses' Health Study. DESIGN: The Nurses' Health Study included 11,697 women. Coffee consumption was first assessed in 1980 with a food-frequency questionnaire (FFQ) and then repeatedly every 2-4 y. Cumulative consumption was calculated with all available FFQs from the diagnosis of CVD to the end of the follow-up in 2004 to assess long-term effects. In addition, the most recent coffee measurement was related to mortality in the subsequent 2 y to assess shorter-term effects. Analyses were performed by using Cox regression models. RESULTS: We documented 1159 deaths, of which 579 were due to CVD. The relative risks [RRs (95% CI)] of all-cause mortality across categories of cumulative coffee consumption [<1 cup (240 mL or 8 oz)/mo, 1 cup/mo to 4 cups/wk, 5-7 cups/wk, 2-3 cups/d, and ≥4 cups/d] were 1, 1.04 (0.86, 1.27), 1.13 (0.95, 1.36), 1.01 (0.86, 1.18), and 1.18 (0.89, 1.56), respectively (P for trend = 0.91). The RRs of CVD mortality across the same categories of coffee intake were 1, 0.99 (0.75, 1.31), 1.03 (0.80, 1.35), 0.97 (0.78, 1.21), and 1.25 (0.85, 1.84), respectively (P for trend = 0.76). Similarly, caffeine intake was not associated with total or CVD mortality. Finally, we observed no association of the most recent coffee and caffeine intakes with total and CVD mortality in the subsequent 2 y. CONCLUSION: Consumption of filtered caffeinated coffee was not associated with CVD or all-cause mortality in women with CVD.

Rotating night shifts and risk of skin cancer in the nurses' health study.

Night shift work is associated with increased risk of several cancers, but the risk of skin cancer among night shift workers is unknown. We documented 10,799 incident skin cancers in 68,336 women in the Nurses' Health Study from June 1988 to June 2006 and examined the relationship between rotating night shifts and skin cancer. We used Cox proportional hazard models, adjusted for confounding variables (phenotypic and established risk factors of skin cancer), and performed stratified analysis to explore the modifying effect of hair color. Working 10 years or more on rotating night shifts was associated with a 14% decreased risk of skin cancer compared with never working night shifts (age-standardized incidence rate: 976 per 100,000 person-years (PY) vs 1070 per 100,000 PY, respectively; adjusted hazard ratios = 0.86, 95% confidence interval = 0.81 to 0.92, P(trend) < .001). This association was strongest for cutaneous melanoma; working 10 years or more of rotating night shifts was associated with 44% decreased risk of melanoma, after adjustment for melanoma risk factors (age-standardized incidence rate: 20 per 100,000 PY vs 35 per 100,000 PY, respectively; adjusted hazard ratios = 0.56, 95% confidence interval = 0.36 to 0.87, P(trend) = .005). Hair color, a surrogate for an individual's susceptibility to skin cancer, was a statistically significant effect modifier for the observed associations; darker-haired women had the lowest risk (P(interaction) = .02).

Separating the mechanism-based and off-target actions of cholesteryl ester transfer protein inhibitors with CETP gene polymorphisms.

BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. METHODS AND RESULTS: We compared the effect of CETP single-nucleotide polymorphisms and torcetrapib treatment on lipid fractions, blood pressure, and electrolytes in up to 67 687 individuals from genetic studies and 17 911 from randomized trials. CETP single-nucleotide polymorphisms and torcetrapib treatment reduced CETP activity and had a directionally concordant effect on 8 lipid and lipoprotein traits (total, low-density lipoprotein, and HDL cholesterol; HDL2; HDL3; apolipoproteins A-I and B; and triglycerides), with the genetic effect on HDL cholesterol (0.13 mmol/L, 95% confidence interval [CI] 0.11 to 0.14 mmol/L) being consistent with that expected of a 10-mg dose of torcetrapib (0.13 mmol/L, 95% CI 0.10 to 0.15). In trials, 60 mg of torcetrapib elevated systolic and diastolic blood pressure by 4.47 mm Hg (95% CI 4.10 to 4.84 mm Hg) and 2.08 mm Hg (95% CI 1.84 to 2.31 mm Hg), respectively. However, the effect of CETP single-nucleotide polymorphisms on systolic blood pressure (0.16 mm Hg, 95% CI -0.28 to 0.60 mm Hg) and diastolic blood pressure (-0.04 mm Hg, 95% CI -0.36 to 0.28 mm Hg) was null and significantly different from that expected of 10 mg of torcetrapib. CONCLUSIONS: Discordance in the effects of CETP single-nucleotide polymorphisms and torcetrapib treatment on blood pressure despite the concordant effects on lipids indicates the hypertensive action of torcetrapib is unlikely to be due to CETP inhibition or shared by chemically dissimilar CETP inhibitors. Genetic studies could find a place in drug-development programs as a new source of randomized evidence for drug-target validation in humans.

Prospective study of nut consumption, long-term weight change, and obesity risk in women.

BACKGROUND: Data concerning the long-term association between nut consumption and weight change in a free-living population are sparse. OBJECTIVE: The objective was to determine the relation between nut consumption and long-term weight change. DESIGN: The participants were 51,188 women in the Nurses' Health Study II aged 20-45 y, who had no cardiovascular disease, diabetes, or cancer. We prospectively evaluated the dietary intake of nuts and subsequent weight changes from 1991 to 1999. RESULTS: Women who reported eating nuts > or =2 times/wk had slightly less mean (+/- SE) weight gain (5.04 +/- 0.12 kg) than did women who rarely ate nuts (5.55 +/- 0.04 kg) (P for trend < 0.001). For the same comparison, when total nut consumption was subdivided into peanuts and tree nuts, the results were similar (ie, less weight gain in women eating either peanuts or tree nuts > or =2 times/wk). The results were similar in normal-weight, overweight, and obese participants. In multivariate analyses in which lifestyle and other dietary factors were controlled for, we found that greater nut consumption (> or =2 times/wk compared with never/almost never) was associated with a slightly lower risk of obesity (hazard ratio: 0.77; 95% CI: 0.57, 1.02; P for trend = 0.003). CONCLUSIONS: Higher nut consumption was not associated with greater body weight gain during 8 y of follow-up in healthy middle-aged women. Instead, it was associated with a slightly lower risk of weight gain and obesity. The results of this study suggest that incorporating nuts into diets does not lead to greater weight gain and may help weight control.

Regular consumption of nuts is associated with a lower risk of cardiovascular disease in women with type 2 diabetes.

Higher nut consumption has been associated with lower risk of coronary heart disease (CHD) events in several epidemiologic studies. The study examined the association between intake of nuts and incident cardiovascular disease (CVD) in a cohort of women with type 2 diabetes. For the primary analysis, there were 6309 women with type 2 diabetes who completed a validated FFQ every 2-4 y between 1980 and 2002 and were without CVD or cancer at study entry. Major CVD events included incident myocardial infarction (MI), revascularization, and stroke. During 54,656 person-years of follow-up, there were 452 CHD events (including MI and revascularization) and 182 incident stroke cases. Frequent nut and peanut butter consumption was inversely associated with total CVD risk in age-adjusted analyses. After adjustment for conventional CVD risk factors, consumption of at least 5 servings/wk of nuts or peanut butter [serving size, 28 g (1 ounce) for nuts and 16 g (1 tablespoon) for peanut butter] was significantly associated with a lower risk of CVD (relative risk = 0.56; 95% CI: 0.36-0.89). Furthermore, when we evaluated plasma lipid and inflammatory biomarkers, we observed that increasing nut consumption was significantly associated with a more favorable plasma lipid profile, including lower LDL cholesterol, non-HDL cholesterol, total cholesterol, and apolipoprotein-B-100 concentrations. However, we did not observe significant associations for HDL cholesterol or inflammatory markers. These data suggest that frequent nut and peanut butter consumption is associated with a significantly lower CVD risk in women with type 2 diabetes.

Coffee consumption and risk of cardiovascular diseases and all-cause mortality among men with type 2 diabetes.

OBJECTIVE: Coffee consumption has been linked to detrimental acute metabolic and hemodynamic effects. We investigated coffee consumption in relation to risk of CVDs and mortality in diabetic men. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study including 3,497 diabetic men without CVD at baseline. RESULTS: After adjustment for age, smoking, and other cardiovascular risk factors, relative risks (RRs) were 0.88 (95% CI 0.50-1.57) for CVDs (P for trend = 0.29) and 0.80 (0.41-1.54) for all-cause mortality (P for trend = 0.45) for the consumption of >or=4 cups/day of caffeinated coffee compared with those for non-coffee drinkers. Stratification by smoking and duration of diabetes yielded similar results. RRs for caffeine intake for the highest compared with the lowest quintile were 1.02 (0.70-1.47; P for trend = 0.96) for CVDs and 0.96 (0.64-1.44; P for trend = 0.69) for mortality. CONCLUSIONS: These data indicate that regular coffee consumption is not associated with increased risk for CVDs or mortality in diabetic men.

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 70 870 eligible NHS females for 16 years and 38 918 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.

Prospective study of dietary energy density and weight gain in women.

BACKGROUND: Little is known about the long-term effects of dietary energy density (ED) on weight gain. OBJECTIVE: The objective was to assess the long-term relation between changes in dietary ED and age-related weight gain. DESIGN: We conducted a prospective study of 50 026 women (x +/- SD age: 36.5 +/- 4.6 y) in the Nurses' Health Study II followed from 1991 to 1999. Dietary ED and body weight were ascertained in 1991, 1995, and 1999. Total dietary ED was calculated by dividing each subject's daily energy intake (kcal) by the reported weight (g) of all foods consumed. RESULTS: Dietary ED was positively correlated with saturated fat (r = 0.16), trans fat (r = 0.15), and the glycemic index (r = 0.16), but was inversely correlated with vegetable protein (r = -0.30), vegetables (r = -0.27), and fruit (r = -0.17). ED was not significantly correlated with total fat intake as a percentage of energy (r = 0.08). Women who increased their dietary ED during follow-up the most (5th quintile) had a significantly greater multivariate-adjusted weight gain than did those who decreased their dietary ED (1st quintile) (8-y time period: 6.42 kg compared with 4.57 kg; P for trend < 0.001). However, the amount of weight change over time varied considerably according to the ED values of individual foods and beverages. CONCLUSION: A high dietary ED reflects a dietary pattern higher in saturated and trans fats and refined carbohydrates. Increases in dietary ED were associated with greater weight gain among middle-aged women during 8 y of follow-up. However, public health recommendations cannot be made simply on the basis of ED values of individual foods and beverages.

The relationship of coffee consumption with mortality.

BACKGROUND: Coffee consumption has been linked to various beneficial and detrimental health effects, but data on its relation with mortality are sparse. OBJECTIVE: To assess the association between coffee consumption and mortality from cardiovascular disease (CVD), cancer, and all causes during 18 years of follow-up in men and 24 years of follow-up in women. DESIGN: Sex-specific Cox proportional hazard models were used to investigate the association between coffee consumption and incidence of all-cause and disease-specific mortality in a prospective cohort study. SETTING: Health Professionals Follow-up Study and Nurses' Health Study. PARTICIPANTS: 41,736 men and 86,214 women with no history of CVD or cancer at baseline. MEASUREMENTS: Coffee consumption was assessed first in 1986 for men and in 1980 for women and then every 2 to 4 years through 2004. Investigators documented 6888 deaths (2049 due to CVD and 2491 due to cancer) among men and 11,095 deaths (2368 due to CVD and 5011 due to cancer) among women. RESULTS: After adjustment for age, smoking, and other CVD and cancer risk factors, the relative risks for all-cause mortality in men across categories of coffee consumption (<1 cup per month, 1 cup per month to 4 cups per week, 5 to 7 cups per week, 2 to 3 cups per day, 4 to 5 cups per day, and >or=6 cups per day) were 1.0, 1.07 (95% CI, 0.99 to 1.16), 1.02 (CI, 0.95 to 1.11), 0.97 (CI, 0.89 to 1.05), 0.93 (CI, 0.81 to 1.07), and 0.80 (CI, 0.62 to 1.04), respectively (P for trend = 0.008). For women, the relative risks were 1.0, 0.98 (CI, 0.91 to 1.05), 0.93 (CI, 0.87 to 0.98), 0.82 (CI, 0.77 to 0.87), 0.74 (CI, 0.68 to 0.81), and 0.83 (CI, 0.73 to 0.95), respectively (P for trend < 0.001). This inverse association was mainly due to a moderately reduced risk for CVD mortality and was independent of caffeine intake. By contrast, coffee consumption was not statistically significantly associated with risk for cancer death after adjustment for potential confounders. Decaffeinated coffee consumption was associated with a small reduction in all-cause and CVD mortality. LIMITATION: Coffee consumption was estimated from self-report; thus, some measurement error is inevitable. CONCLUSION: Regular coffee consumption was not associated with an increased mortality rate in either men or women. The possibility of a modest benefit of coffee consumption on all-cause and CVD mortality needs to be further investigated.

Intake of fruit, vegetables, and fruit juices and risk of diabetes in women.

OBJECTIVE: The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 71,346 female nurses aged 38-63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported. RESULTS: During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94-1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72-0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84-0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10-1.26]). CONCLUSIONS: Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.

Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women.

BACKGROUND: Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. METHODS AND RESULTS: In a prospective cohort study of 44,636 women in the Nurses' Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P<0.001 for trend). Among normal-weight women (body mass index, 18.5 to < 25 kg/m(2)), abdominal obesity was significantly associated with elevated CVD mortality: Relative risk associated with waist circumference > or = 88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio > 0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality. CONCLUSIONS: Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.

Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up.

The relation between consumption of coffee, tea and caffeine and risk of breast cancer remains unsettled. We examined data from a large, long-term cohort study to evaluate whether high intake of coffee and caffeine is associated with increased risk of breast cancer. This was a prospective cohort study with 85,987 female participants in the Nurses' Health Study. Consumption of coffee, tea and caffeine consumption was assessed in 1980, 1984, 1986, 1990, 1994, 1998 and the follow-up continued through 2002. We documented 5,272 cases of invasive breast cancer during 1,715,230 person-years. The multivariate relative risks (RRs) of breast cancer across categories of caffeinated coffee consumption were: 1.0 for <1 cup/month (reference category), 1.01 (95% confidence interval: 0.92-1.12) for 1 month to 4.9 week, 0.92 (0.84-1.01) for 5 week to 1.9 days, 0.93 (0.85-1.02) for 2-3.9 days, 0.92 (0.82-1.03) for >or=4 cups per day (p for trend = 0.14). Intakes of tea and decaffeinated coffee were also not significantly associated with risk of breast cancer. RRs (95% CI) for increasing quintiles of caffeine intake were 1.00, 0.98 (0.90-1.07), 0.92 (0.84-1.00), 0.94 (0.87-1.03) and 0.93 (0.85-1.01) (p for trend = 0.06). A significant inverse association of caffeine intake with breast cancers was observed among postmenopausal women; for the highest quintile of intake compared to the lowest RR 0.88 (95% CI = 0.79-0.97, p for trend = 0.03). We observed no substantial association between caffeinated and decaffeinated coffee and tea consumption and risk of breast cancer in the overall cohort. However, our results suggested a weak inverse association between caffeine-containing beverages and risk of postmenopausal breast cancer.

Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men.

BACKGROUND: A low plasma HDL-cholesterol concentration is a major characteristic of diabetic dyslipidemia. HDL concentrations are determined by both environmental factors and genetic factors. Cholesterol ester transfer protein (CETP) plays an important role in the regulation of HDL metabolism, and the TaqIB polymorphism of the CETP gene has been associated with elevated HDL concentrations. OBJECTIVE: We examined the association between the CETP TaqIB polymorphism and plasma HDL concentrations and evaluated whether this association was modified by dietary fat intake. DESIGN: We followed 780 diabetic men aged 40-75 y who participated in the Health Professionals Follow-Up Study since its initiation in 1986. The participants had confirmed type 2 diabetes and were free of cardiovascular disease at the time blood was drawn. RESULTS: After adjustment for age, smoking, alcohol consumption, fasting status, hemoglobin A(1c), physical activity, total energy intake, and body mass index, HDL concentrations were significantly higher in men with the B2B2 or B1B2 genotype than in those with the B1B1 genotype (adjusted x +/- SE: 37.9 +/- 0.02, 40.3 +/- 0.01, and 42.6 +/- 0.02 mg/dL for B1B1, B1B2, and B2B2, respectively; P for trend = 0.0004). This inverse association of the B1 allele with plasma HDL concentrations existed for those with a high consumption of animal fat (P for interaction = 0.02), saturated fat (P for interaction = 0.02), and monounsaturated fat (P for interaction = 0.04). CONCLUSION: These data confirmed a significant effect of the CETP Taq1 gene on HDL concentrations and suggested a potential interaction between the CETP TaqIB polymorphism and intake of dietary fat on plasma HDL concentration.