Hazard Ratios For Quintile Research Articles

A colorectal cancer diet quality index is inversely associated with colorectal cancer in the Malmö diet and cancer study.

The World Cancer Research Fund International has concluded strong evidence for that high intake of dairy products and foods containing dietary fiber and low intake of processed meat are associated with decreased risk of colorectal cancer (CRC). As food items are consumed together, it is important to study dietary patterns. The aim of the present study was to examine the association between an a priori constructed dietary index and incident CRC and between intake of processed meat, fiber, and dairy products and CRC. In the Malmö Diet and Cancer study cohort, 923 cases of CRC were identified, during 502 136 person-years of follow-up. A Colorectal Diet Quality Index (CDQI) was constructed regarding intakes of processed meat, fiber, and dairy products in relation to CRC. Higher index indicated a higher dietary quality. Higher CDQI was associated with lower risk of CRC [hazard ratios (HR): 0.57 for highest compared with lowest quintile; 95% confidence interval (CI): 0.43, 0.75; P<0.001]. Intake of dairy products was inversely associated with risk of CRC [HR for highest vs. lowest quintile was 0.77 (CI: 0.62, 0.96); P = 0.008], as was dietary fiber [HR for highest vs. lowest quintile was 0.77 (CI: 0.61, 0.98); P = 0.043]. High intake of processed meat was associated with CRC [HR for highest vs. lowest quintile was 1.31; CI: 1.05, 1.63; P = 0.012]. High adherence to a predefined CRC-specific diet quality index was inversely associated with the risk of CRC and gave a stronger association with CRC, than when analyzing the components of the CDQI individually.

A Prospective Study of Toenail Trace Element Levels and Risk of Skin Cancer.

Few epidemiologic studies have investigated trace element exposure and skin cancer risk. Toenail levels of mercury, selenium, chromium, iron, and zinc were measured from 6,708 women in the Nurses' Health Study (1984-2012) and 3,730 men in the Health Professionals Follow-up Study (1986-2012) with data from prior nested case-control studies. Participants were free of skin cancer at toenail collection and followed for incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of skin cancer associated with the elements in each study. We calculated pooled multivariable HRs using a fixed-effects model. During 26 to 28 years of follow-up, 2,433 BCC, 334 SCC, and 130 melanoma cases were documented. Higher toenail mercury levels were associated with risk of BCC [pooled HR for top vs. bottom quintiles = 1.34 (95% CI, 1.18-1.52), P trend < 0.0001]. Similar direct associations were found with risks of SCC [pooled HR for top vs. bottom quartiles = 1.41 (95% CI, 1.03-1.94), P trend = 0.04] and melanoma [pooled HR for top vs. bottom quartiles = 1.88 (95% CI, 1.12-3.16), P trend = 0.02]. Chromium was positively associated with BCC in women only. No associations were found between other metals and skin cancer risk. Our prospective data found that increased toenail mercury concentrations were associated with increased skin cancer risk. If our novel findings are confirmed, mercury may play a role in skin carcinogenesis.

Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA wasassociated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Rice intake and risk of type 2 diabetes: the Singapore Chinese Health Study.

The prevalence of type 2 diabetes (T2D) is increasing in Asian populations. White rice is a common staple food in these populations and results from several studies suggest that high white rice consumption increases T2D risk. We assessed whether rice, noodles and bread intake was associated with T2D risk in an ethnic Chinese population. We included data from 45,411 male and female Chinese participants of the Singapore Chinese Health Study cohort aged 45-74years at baseline. Usual diet at baseline was evaluated by a validated 165-item semi-quantitative food frequency questionnaire. Physician-diagnosed T2D was self-reported during two follow-up interviews. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 11 years, 5207 incident cases of T2D were documented. Rice intake was not associated with higher T2D risk [HR for extreme quintiles, 0.98 (95% CI 0.90, 1.08)] despite the large variation in intake levels (median intake for extreme quintiles: 236.5g/day vs. 649.3g/day), although the precise risk estimate depended greatly on the substitute food. Replacing one daily serving of rice with noodles [HR 1.14 (95% CI 1.07, 1.22)], red meat [HR 1.40 (95% CI 1.23, 1.60)] and poultry [HR 1.37 (95% CI 1.18, 1.59)] was associated with higher T2D risk, whereas the replacement of rice with white bread [HR 0.90 (95% CI 0.85, 0.94)] or wholemeal bread [HR 0.82 (95% CI 0.75, 0.90)] was associated with lower T2D risk. Higher rice consumption was not substantially associated with a higher risk of T2D in this Chinese population. Recommendations to reduce high white rice consumption in Asian populations for the prevention of T2D may only be effective if substitute foods are considered carefully. NCT03356340, http://www.clinicaltrials.gov.

Intake of folate and other nutrients related to one-carbon metabolism and risk of cutaneous melanoma among US women and men

BackgroundNutrients involved in one-carbon metabolism - folate, vitamins B6 and B12, methionine, choline, and betaine - have been inversely associated with multiple cancer sites and may be related to skin cancer. However, there is a lack of research on the association between intake of these nutrients and cutaneous melanoma risk. The aim of this study was to examine the associations between intake of one-carbon metabolism nutrients and cutaneous melanoma risk in two large prospective cohorts. MethodsThe cohorts included 75,311 white women and 48,523 white men. Nutrient intake was assessed repeatedly by food frequency questionnaires and self-reported supplement use. We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and then pooled HRs using a random-effects model. ResultsOver 24–26 years of follow-up, we documented 1328 melanoma cases (648 men and 680 women). Higher intake of folate from food only, but not total folate, was associated with increased melanoma risk (pooled HR for top versus bottom quintile: 1.36; 95% CI: 1.13–1.64; P for trend = 0.001). The association was significant in men, but attenuated in women. Higher intake of vitamins B6 and B12, choline, betaine, and methionine were not associated with melanoma risk, although there was modest increasing trend of risk for vitamin B6 from food only (pooled HR for top versus bottom quintile: 1.18; 95% CI: 0.99–1.41; P for trend = 0.03). ConclusionsWe found some evidence that higher intake of folate from food only was associated with a modest increased risk of cutaneous melanoma. However, since other factors related to dietary folate intake may account for the observed association, our findings warrant further investigation.

Green leafy and cruciferous vegetable consumption and risk of type 2 diabetes: results from the Singapore Chinese Health Study and meta-analysis.

Several previous prospective studies suggest that consumption of green leafy and cruciferous vegetables may lower the risk of type 2 diabetes (T2D). We investigated the association between consumption of different types of vegetables in relation to T2D risk in an Asian Population. We included 45 411 participants (age range: 45-74 years) of the Singapore Chinese Health Study (SCHS) free of diabetes, cancer or CVD at baseline (1993-1998). Dietary information was collected using a validated FFQ. Physician-diagnosed incident diabetes was reported at follow-up I (1999-2004) and II (2006-2010) interviews. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95 % CI of T2D risk. An updated meta-analysis was also conducted to summarise results for green leafy and cruciferous vegetables. During 494 741 person-years of follow-up, 5207 incident T2D occurred. After adjustment for potential confounders, neither total vegetables (top v. bottom quintile HR=1·08; 95 % CI 0·98, 1·18, P trend=0·66) nor specific vegetables including dark green leafy vegetables (HR=1·05; 95 % CI 0·96, 1·15, P trend=0·21) and cruciferous vegetables (HR=0·97; 95 % CI 0·88, 1·06, P trend=0·29) were substantially associated with risk of T2D. A meta-analysis (eleven studies with 754 729 participants and 58 297 cases) including the SCHS and all previous prospective studies suggested borderline significant inverse associations between green leafy (summary relative risk (RR)=0·91; 95 % CI 0·84, 1·00) and cruciferous vegetable consumption (RR=0·87; 95 % CI 0·76, 1·00) and T2D risk, with moderate-to-high heterogeneity. In conclusion, green leafy or cruciferous vegetable consumption was not substantially associated with risk of T2D in an Asian population. Meta-analysis of available cohort data indicated that evidence for a beneficial effect of green leafy or cruciferous vegetable consumption on T2D risk is not convincing.

Newer glomerular filtration rate estimating equations for the full age spectrum based on serum creatinine and cystatin C in predicting mortality in patients with ischemic stroke

BackgroundRenal dysfunction is associated with increased risk of mortality. The novel Full Age Spectrum (FAS) equations estimating the glomerular filtration rate (GFR) based on serum creatinine (FAScrea) and cystatin C (FAScysC) are validated across the entire age spectrum and are superior markers of renal function compared to other equations. Possible association of these equations with mortality in patients with ischemic stroke is not known. Patients and methodsWe included 390 patients (207 men, 183 women) in our observational cohort study who had suffered from an ischemic stroke and followed-up on for 3 years. Serum creatinine and cystatin C were measured at admission; GFR was estimated according to the FAScrea, CKD-EPIcrea, FAScysC and CKD-EPIcysC equations. The values of estimated GFRs were divided into quintiles. ResultsDuring the follow-up period, 173 (44.4%) patients died. The association of hazard ratios for FAScrea and CKD-EPIcrea with all-cause mortality was J-shaped and only significantly higher when comparing the fifth quintile hazard ratio for mortality with the first quintile (P < 0.001). For FAScysC and CKD-EPIcysC, hazard ratios increased from the first to the fifth quintile linearly. In an adjusted analysis, FAScrea and CKD-EPIcrea were not associated with all-cause mortality and the hazard ratios of the fifth quintile of FAScysC (P = 0.008) and CKD-EPIcysC (P = 0.042) were significantly associated with mortality compared to the first quintile. ConclusionsIn patients with an ischemic stroke, estimated GFR based on serum cystatin (FAScysC and CKD-EPIcysC) was a better predictor of all-cause and cardiovascular mortality than estimated GFR based on serum creatinine.

Dietary intake of isoflavones and coumestrol and the risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Experimental studies have revealed that phytoestrogens may modulate the risk of certain sites of cancer due to their structural similarity to 17β-estradiol. The present study investigates whether intake of these compounds may influence prostate cancer risk in human populations. During a median follow up of 11.5 years, 2,598 cases of prostate cancer (including 287 advanced cases) have been identified among 27,004 men in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Dietary intake of phytoestrogens (excluding lignans) was assessed with a food frequency questionnaire. Cox proportional hazards regression analysis was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary isoflavones and coumestrol in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer [HR (95% CI) for quintile (Q) 5 vs. Q1] was found for the dietary intake of total isoflavones [1.91 (1.25-2.92)], genistein [1.51 (1.02-2.22), daidzein [1.80 (1.18-2.75) and glycitein [1.67 (1.15-2.43)] (p-trend for all associations ≤0.05). For example, HR (95% CI) for comparing the Q2, Q3, Q4 and Q5 with Q1 of daidzein intake was 1.45 (0.93-2.25), 1.65 (1.07-2.54), 1.73 (1.13-2.66) and 1.80 (1.18-2.75), respectively (p-trend: 0.013). No statistically significant associations were observed between the intake of total isoflavones and individual phytoestrogens and non-advanced and total prostate cancer after adjustment for confounders. This study revealed that dietary intake of isoflavones was associated with an elevated risk of advanced prostate cancer.

Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California.

Background:Ambient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.Objective:We determined the impact of residential traffic on mortality during treatment of active TB.Methods:From 2000–2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in to radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.Results:Participants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio [95% confidence interval (CI): 0.86, 1.25]; third quintile (95% CI: 0.95, 1.37); fourth quintile (95% CI: 0.99, 1.43); fifth quintile (95% CI: 1.07, 1.53), respectively; ].Conclusions:Residential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699

Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor

Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (Ptrend= .02), and varied with degree of peritumoral lymphocytic reaction (Pheterogeneity < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; Ptrend < .001), but not risk of tumors with intermediate or highperitumoral lymphocytic reaction (Ptrend > .80). In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response.

Niacin intake and risk of skin cancer in US women and men.

A recent clinical trial found a protective role of niacinamide, a derivative of niacin, against skin cancer recurrence. However, there is no epidemiologic study to assess the association between niacin intake and risk of skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma]. We prospectively evaluated whether total, dietary and supplemental niacin intake was associated with skin cancer risk based on 72,308 women in the Nurses' Health Study (1984-2010) and 41,808 men in the Health Professionals Follow-up Study (1986-2010). Niacin intake was assessed every 2 to 4 years during follow-up and cumulative averaged intake. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI) and cohort-specific results were pooled using a random-effects model. During the follow-up, we documented 23,256 BCC, 2,530 SCC and 887 melanoma cases. Total niacin intake was inversely associated with SCC risk; the pooled HR for top vs. bottom quintiles was 0.84 (95% CI = 0.74-0.95; ptrend = 0.08). However, there were a marginally positive association between total niacin intake and BCC risk; the pooled HR for top versus bottom quintiles was 1.05 (95% CI = 1.01-1.10; ptrend < 0.01). Higher total niacin intake was also marginally positively associated with melanoma risk in men, but not in women. The results were similar in stratified analyses according to sun exposure related factors and by body location of melanoma and SCC. Our study supports a potential beneficial role of niacin intake in relation to SCC but not of BCC or melanoma.

218 Vitiligo and vitamin D

Vitiligo has been associated with certain polymorphisms in the vitamin D receptor gene and it is hypothesized that low serum 25-hydroxyvitamin D levels may confer an increased risk of vitiligo. However, studies investigating this relationship have yielded conflicting results. Using data from large prospective studies including the Nurses’ Healthy Study (NHS), Nurses’ Health Study II (NHS II) and Health Professionals Follow-up Study (HPFS), we identified 408 incident cases of vitiligo among 662,195 participants and investigated the relationship between risk of incident vitiligo and: (1) dietary vitamin D intake, (2) supplemental vitamin D intake, (3) total vitamin intake (sum of dietary and supplemental intake) and (4) vitamin D score. The vitamin D score, an estimate of plasma levels of 25-hydroxyvitamin D, was calculated using a validated multivariate linear regression model. The vitamin D score is based on known life-style determinants of plasma 25-hydroxyvitamin D, such as age, race, ultraviolet flux at residence, dietary vitamin D and supplemental vitamin D, among others. Cox proportional hazard models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Intakes of total vitamin D, dietary vitamin D, and supplemental vitamin D, as well as vitamin D score, were not associated with risk of incident vitiligo. The multivariate HRs for top versus bottom quintiles of vitamin D score were 1.22 (95% CI 0.75-1.99; Ptrend 0.46) in NHS, 1.09 (95% CI 0.53-2.25; Ptrend 0.75) in NHSII and 1.10 (95% CI 0.64-1.88; Ptrend 0.74) in HPFS. These data suggest no major role of vitamin D intake or circulating vitamin D levels in development of vitiligo.

Associations of Dietary Long-Chain ω-3 Polyunsaturated Fatty Acids and Fish Consumption With Endometrial Cancer Risk in the Black Women's Health Study.

Dietary long-chain (LC) ω-3 polyunsaturated fatty acids (PUFAs), which derive primarily from intakes of fatty fish, are thought to inhibit inflammation and de novo estrogen synthesis. This study prospectively examined the associations of dietary LC ω-3 PUFAs and fish with endometrial cancer risk in 47,602 African-American women living in the United States, aged 21-69 years at baseline in 1995, and followed them until 2013 (n = 282 cases). Multivariable-adjusted Cox regression models estimated hazard ratios and 95% confidence intervals for associations of LC ω-3 PUFA (quintiled) and fish (quartiled) intake with endometrial cancer risk, overall and by body mass index (BMI; weight (kg)/height (m)(2)). The hazard ratio for quintile 5 of total dietary LC ω-3 PUFAs versus quintile 1 was 0.79 (95% confidence interval (CI): 0.51, 1.24); there was no linear trend. Hazard ratios for the association were smaller among normal-weight women (BMI <25: hazard ratio (HR) = 0.53, 95% CI: 0.18, 1.58) than among overweight/obese women (BMI ≥ 25: HR = 0.88, 95% CI: 0.54, 1.43), but these differences were not statistically significant. Fish intake was also not associated with risk (quartile 4 vs. quartile 1: HR = 0.86, 95% CI: 0.56, 1.31). Again hazard ratios were smaller among normal-weight women (HR = 0.65) than among overweight/obese women (HR = 0.94). While compatible with no association, the hazard ratios observed among leaner African-American women are similar to those from recent prospective studies conducted in predominantly white populations.

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine.

Plasma phospholipid trans-fatty acids levels, cardiovascular diseases, and total mortality: the cardiovascular health study.

BackgroundWhile self‐reported trans–fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t‐16:1n9, total t‐18:1, and cis/trans‐(c/t‐), t/c‐ and t/t‐18:2) and cardiovascular disease (CVD) or total mortality are not well established.Methods and ResultsWe evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non‐CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person‐years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t‐18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, P‐trend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, P‐trend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, P‐trend=0.01). t/c‐18:2 was positively related to total mortality (HR=1.19, P‐trend=0.05), total CHD (HR=1.67, P‐trend=0.002), and nonfatal CHD (HR=2.06, P‐trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t‐16:1n9 nor t‐18:1 was significantly associated with total mortality or CVD, nor was c/t‐18:2 if we excluded early cases.ConclusionsAmong circulating TFAs, t/t‐18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c‐18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t‐18:2 isomers.

Dietary fat intake in relation to lethal breast cancer in two large prospective cohort studies.

Whether fat intake influences risk of developing more aggressive, lethal breast tumors is unknown. We evaluated intakes of total fat, specific types of fat, and cholesterol prior to diagnosis in relation to lethal breast cancer risk in 88,759 women in the Nurses' Health Study (NHS; 1980-2010) and 93,912 women in the Nurses' Health Study II (NHSII; 1991-2010). Diet was assessed every 4 years using a semi-quantitative food frequency questionnaire. Breast cancers were confirmed with pathology reports; deaths were confirmed by next of kin or the National Death Index. We defined lethal cases as women with invasive breast cancer who died of breast cancer. We pooled the cohorts and used multivariable Cox proportional hazards models. We identified 1,529 lethal breast cancer cases (1,279 in NHS and 250 in NHSII). Higher total fat intake was associated with a slightly lower lethal breast cancer risk (top vs. bottom quintile hazard ratio [HR] 0.85; 95 % CI 0.72, 1.01; p trend = 0.05). Specific types of fat were generally not associated with lethal breast cancer risk. For example, compared with those in the lowest quintile of saturated fat intake, those in the highest quintile had a HR of 0.98 (95 % CI 0.75, 1.26; p trend = 0.96). Among women diagnosed with breast cancer, pre-diagnosis fat intake was not associated with survival. Higher pre-diagnosis fat intake was not associated with greater risk of lethal breast cancer in these large prospective cohort studies, consistent with the weight of the evidence against a causal role for fat intake and breast cancer incidence.

Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort

ObjectivesUrinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death. MethodsThe association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes. ResultsHigh u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2–5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7–36, P < 0.001, compared to all three biomarkers normal). ConclusionsThis study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

Metabolomics and Incident Hypertension Among Blacks

Development of hypertension is influenced by genes, environmental effects, and their interactions, and the human metabolome is a measurable manifestation of gene–environment interaction. We explored the metabolomic antecedents of developing incident hypertension in a sample of blacks, a population with a high prevalence of hypertension and its comorbidities. We examined 896 black normotensives (565 women; aged, 45–64 years) from the Atherosclerosis Risk in Communities study, whose metabolome was measured in serum collected at the baseline examination and analyzed by high-throughput methods. The analyses presented here focus on 204 stably measured metabolites during a period of 4 to 6 weeks. Weibull parametric models considering interval censored data were used to assess the hazard ratio for incident hypertension. We used a modified Bonferroni correction accounting for the correlations among metabolites to define a threshold for statistical significance ( P &lt;3.9×10 –4 ). During 10 years of follow-up, 38% of baseline normotensives developed hypertension (n=344). With adjustment for traditional risk factors and estimated glomerular filtration rate, each +1SD difference in baseline 4-hydroxyhippurate, a product of gut microbial fermentation, was associated with 17% higher risk of hypertension ( P =2.5×10 –4 ), which remained significant after adjusting for both baseline systolic and diastolic blood pressure ( P =3.8×10 –4 ). After principal component analyses, a sex steroids pattern was significantly associated with risk of incident hypertension (highest versus lowest quintile hazard ratio, 1.72; 95% confidence interval, 1.05–2.82; P for trend, 0.03), and stratified analyses suggested that this association was consistent in both sexes. Metabolomic analyses identify novel pathways in the pathogenesis of hypertension.

Income Inequality and Mortality: Results From a Longitudinal Study of Older Residents of São Paulo, Brazil

We determined whether community-level income inequality was associated with mortality among a cohort of older adults in São Paulo, Brazil. We analyzed the Health, Well-Being, and Aging (SABE) survey, a sample of community-dwelling older adults in São Paulo (2000-2007). We used survival analysis to examine the relationship between income inequality and risk for mortality among older individuals living in 49 districts of São Paulo. Compared with individuals living in the most equal districts (lowest Gini quintile), rates of mortality were higher for those living in the second (adjusted hazard ratio [AHR] = 1.44, 95% confidence interval [CI] = 0.87, 2.41), third (AHR = 1.96, 95% CI = 1.20, 3.20), fourth (AHR = 1.34, 95% CI = 0.81, 2.20), and fifth quintile (AHR = 1.74, 95% CI = 1.10, 2.74). When we imputed missing data and used poststratification weights, the adjusted hazard ratios for quintiles 2 through 5 were 1.72 (95% CI = 1.13, 2.63), 1.41 (95% CI = 0.99, 2.05), 1.13 (95% = 0.75, 1.70) and 1.30 (95% CI = 0.90, 1.89), respectively. We did not find a dose-response relationship between area-level income inequality and mortality. Our findings could be consistent with either a threshold association of income inequality and mortality or little overall association.

Prospective Associations Between Measures of Adiposity and Periodontal Disease

Obesity induced inflammation may promote periodontal tissue destruction and bone resorption inducing tooth loss. We examined the association between measures of adiposity and self-reported periodontal disease, using data from 36,910 healthy male participants of the Health Professionals Follow-Up Study (HPFS) who were free of periodontal disease at baseline and followed for ≤20 years (1986-2006). Self-reported height, weight, and periodontal disease data were collected at baseline, weight and periodontal disease were additionally collected on biennial follow-up questionnaires and waist and hip circumference were self-reported in 1987. These self-reported measures have been previously validated. The multivariable adjusted associations between BMI (kg/m(2)), waist circumference (WC), waist-to-hip ratio (WHR), and first report of periodontal disease diagnosis were evaluated using time-varying Cox models. We observed 2,979 new periodontal disease diagnoses during 596,561 person-years of follow-up. Significant associations and trends were observed between all measures of adiposity and periodontal disease after adjusting for age, smoking, race, dental profession, physical activity, fruit and vegetable intake, alcohol consumption, and diabetes status at baseline. BMI ≥30 kg/m(2) compared to BMI 18.5-24.9 kg/m(2) was significantly associated with greater risk of periodontal disease (hazard ratios (HR) = 1.30; 95% confidence interval (CI): 1.17-1.45). Elevated WC and WHR were significantly associated with a greater risk of periodontal disease (HR for extreme quintiles: WC = 1.27, 95% CI: 1.11-1.46; WHR = 1.34, 95% CI: 1.17-1.54). The associations of BMI and WC were significant even among nondiabetics and never smokers. Given the high prevalence of overweight, obesity, and periodontal disease this association may be of substantial public health importance.