EAT-Lancet Diet Pattern, Genetic Predisposition, Inflammatory Biomarkers, and Risk of Lung Cancer Incidence and Mortality.

SCOPE: The association between a planetary and sustainable EAT-Lancet diet and lung cancer remains inconclusive, with limited exploration of the role of genetic susceptibility and inflammation. METHODS AND RESULTS: The study includes 175 214 cancer-free participants in the UK Biobank. Fourteen food components are collected from a 24-h dietary recall questionnaire. A polygenic risk score is constructed through capturing the overall risk variants for lung cancer. Sixteen inflammatory biomarkers are assayed in blood samples. Participants with the highest EAT-Lancet diet scores (≥12) have a lower risk of lung cancer incidence (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.51-0.80) and mortality (HR = 0.65, 95% CI: 0.48-0.88), compared to those with the lowest EAT-Lancet diet scores (≤8). Interestingly, there is a significantly protective trend against both lung adenocarcinoma and lung squamous cell carcinoma with higher EAT-Lancet diet scores. Despite no significant interactions, a risk reduction trend for lung cancer is observed with increasing EAT-Lancet diet scores and decreasing genetic risk. Ten inflammatory biomarkers partially mediate the association between the EAT-Lancet diet and lung cancer risk. CONCLUSION: The study depicts a lower risk of lung cancer conferred by the EAT-Lancet diet associated with lower inflammation levels among individuals with diverse genetic predispositions.

Dietary flavonoid intake and risk of hormone-related cancers: A population-based prospective cohort study.

BACKGROUND: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms. METHODS: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis. RESULTS: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (Ptrend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (Ptrend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer. CONCLUSIONS: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines.

Life's essential 8, genetic susceptibility, and risk of inflammatory bowel diseases: a population-based cohort study.

BACKGROUND: Evidence has shown that the individual metrics in Life's Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD). We also tested whether genetic susceptibility could modify these associations. METHODS: A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0-49), moderate CVH (50-79), and high CVH (80-100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status. RESULTS: Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20-0.45; CD: 0.33, 95% CI: 0.20-0.57) was observed in participants with both high CVH and low genetic risk. CONCLUSIONS: Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD.

Life's Essential 8 and risks of cardiovascular morbidity and mortality among individuals with type 2 diabetes: A cohort study.

BACKGROUND: The association of cardiovascular health levels, as measured by the Life's Essential 8 score, with cardiovascular disease (CVD) incidence and mortality among individuals with type 2 diabetes (T2D) has not been fully elucidated. METHODS: This cohort study included 15,118 participants with T2D from the UK Biobank who were free of CVD and cancer at baseline. The cardiovascular health of participants was evaluated using the Life's Essential 8 score, categorizing their health levels into low, moderate, and high based on this assessment. RESULTS: During a median follow-up period of 13.0 years, we observed a total of 4421 cases of CVD, comprising 3467 cases of coronary heart disease (CHD), 811 cases of stroke, 1465 cases of heart failure (HF), and 523 cases of CVD mortality. Compared to participants with low cardiovascular health, those with high cardiovascular health had a 52 %, 50 %, 47 %, 67 %, and 51 % lower risk of CVD, CHD, stroke, HF, and CVD mortality, respectively. Among the components of the Life's Essential 8 score, body mass index showed the highest population attributable risk of 12.1 %. Similar findings were observed in joint analyses of cardiovascular health and diabetes severity status. CONCLUSIONS: This study emphasizes the importance of maintaining good cardiovascular health among individuals with T2D to reduce their risk of CVD incidence and mortality.

Physical frailty, genetic predisposition, and incident arrhythmias.

BACKGROUND: Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. METHODS: In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. RESULTS: This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. CONCLUSIONS: Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.

Physical frailty, genetic predisposition, and the risks of severe non-alcoholic fatty liver disease and cirrhosis: a cohort study.

BACKGROUND: Frailty, defined as a phenotype of decreased physiological reserves and diminished ability to respond to stressors, has been linked to the development of chronic diseases. Epidemiological evidence connecting frailty to non-alcoholic fatty liver disease (NAFLD) and cirrhosis risks remain sparse. We aimed to assess the longitudinal associations of frailty with the risks of severe NAFLD and cirrhosis in middle-aged to older adults and further explore the modification role of genetic risk on these associations. METHODS: This study included a total of 398 386 participants from the UK Biobank. Incident cases of severe NAFLD and cirrhosis were ascertained through linked hospital records and death registries. Frailty status was assessed by a modified version of the frailty phenotype, encompassing five key components: weight loss, tiredness, physical activity, gait speed, and grip strength. Participants were classified as pre-frailty if they met one or two of these criteria, and as frailty if they met three or more. Genetic predisposition to NAFLD and cirrhosis was estimated by genetic risk score (GRS) and further categorized into high, intermediate, and low genetic risk levels according to tertiles of GRSs. Cox proportional hazards regression model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for their associations. RESULTS: The mean (standard deviation) age of the study population was 56.6 (8.03) years. 214 408 (53.8%) of the participants was female; 14 924 (3.75%) of participants met the criteria for frailty, 170 498 (42.8%) for pre-frailty, and 212 964 (53.5%) for non-frailty. Over a median follow-up of 12.0 years, we documented 4439 incident severe NAFLD and 3323 incident cirrhosis cases, respectively. Compared with non-frailty, both pre-frailty (HR: 1.50; 95% CI: 1.40-1.60) and frailty (HR: 1.98; 95% CI: 1.77-2.21) were associated with increased risk of NAFLD. Similar associations were observed for cirrhosis, the corresponding HRs (95% CIs) for non-frailty, pre-frailty, and frailty were 1.00 (reference), 1.29 (1.20, 1.38), and 1.90 (1.66, 2.18). Such associations were consistent across all genetic risk levels, with no observed interactions between frailty and GRSs (all P for interactions ≥0.10). Compared with participants with frailty and a low level of genetic risk, the greatest risk increasement in developing severe NAFLD (HR: 3.36; 95% CI: 2.83-3.99) and cirrhosis (HR: 2.81; 95% CI: 2.29-3.44) was both observed in those with frailty and a high level of genetic risk. CONCLUSIONS: Our findings indicate that frailty is a significant predictor of severe NAFLD and cirrhosis, irrespective of genetic predisposition.

Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant health care problem within both developed and developing countries, has been associated with genetic risk factors. An association between physical activity and KSD risk also has been hypothesized, but studies have yielded inconsistent findings. This study investigated the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURE: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOME: Individuals with KSD were identified using the International Classification of Diseases, Tenth Revision (ICD-10), and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential nonlinear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared with those in the lowest quartiles: HR, 0.50 (95% CI, 0.44-0.56), 0.57 (95% CI, 0.51-0.64), and 0.66 (95% CI, 0.59-0.74), respectively. TPA, MVPA, and LPA were associated with a lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSIONS: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations. PLAIN-LANGUAGE SUMMARY: The association between the intensity of physical activity (PA) and the incidence of kidney stone disease (KSD) after accounting for genetic risk is unclear. We conducted a comprehensive prospective cohort study utilizing participants from the UK Biobank to assess the intensity of PA using accelerometers. Our study findings indicated that greater total PA, moderate-to-vigorous-intensity PA, and light-intensity PA were each associated with a lower risk of KSD irrespective of an individual's genetic risk. Our study informs the understanding of risk factors for KSD.

Dietary Macronutrient Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

Associations of Combined Lifestyle Factors with MAFLD and the Specific Subtypes in Middle-Aged and Elderly Adults: The Dongfeng-Tongji Cohort Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the crucial pathogenesis for intra-hepatic and extra-hepatic diseases, especially in elderly adults. Lifestyle management may be a modifiable cost-effective measure for MAFLD prevention, but the evidence is limited. A total of 23,408 middle-aged and elderly individuals were included in a longitudinal study from 2008 to 2018. Combined lifestyle scores (range 0-6) were evaluated by BMI, smoking, drinking, diet, physical activity, and sleep. Logistic regression models were used to calculate ORs for the risks of MAFLD and specific subtypes. The mean age of participants was 61.7 years, and 44.5% were men. Compared with poor lifestyle (scores 0-2), ORs (95% CIs) of the ideal lifestyle (scores 5-6) were 0.62 (0.57-0.68) for MAFLD, 0.31 (0.28-0.34) for MAFLD with excess weight and obesity, 0.97 (0.75-1.26) for MAFLD with diabetes, and 0.56 (0.51-0.62) for MAFLD with metabolic dysregulation. Additionally, lifestyle improvement was associated with lower risks of MAFLD (OR, 0.76; 95% CI, 0.68-0.86), MAFLD with excess weight and obesity (OR, 0.72; 95% CI, 0.63-0.81), MAFLD with diabetes (OR, 0.74; 95% CI, 0.54-1.02) and MAFLD with metabolic dysregulation (OR, 0.49; 95% CI, 0.43-0.55), respectively. Our findings suggest that adherence to a combined healthy lifestyle was associated with lower risks of MAFLD, particularly in excess weight/obese individuals or those with metabolic dysregulation.

The relationships between plasma advanced glycation end products level and cognitive function in middle-aged and elderly Chinese subjects.

OBJECTIVES: To determine the relationships between circulating representative advanced glycation end products (AGEs) and cognitive performance in middle-aged and elderly Chinese adults. METHOD: A cross-sectional study with 1834 participants were included. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE). Plasma free AGEs including Nε-carboxymethyl-L-lysine (CML), Nε-(1-carboxyethyl) lysine (CEL), S-carboxymethyl-L-cysteine (CMC) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Multivariate adjusted linear and logistic regression analysis were used to explore the associations between plasma AGEs and cognitive function. RESULTS: The prevalence of mild cognitive impairment (MCI) was 17.94%. Plasma CMC and MG-H1 level were negatively associated with MMSE score (ß = -0.42, p < 0.001 for all) in the multivariate linear regression analysis. In the multivariate logistic regression analysis, compared to the lowest tertile, participants within the highest tertile of CMC and MG-H1 had increased risk of MCI [ORs (95% CI): 1.62 (1.21-2.17), P trend <0.001, and ORs (95% CI): 1.30 (0.97-1.76), P trend = 0.069, respectively]. In addition, the weighted quantile sum (WQS) index was negatively associated with MMSE (ß = -0.48, P < 0.001) and increased risk of MCI [ORs (95% CI): 1.35 (1.20-1.52), P < 0.001]. CONCLUSION: Combined exposure of plasma free AGEs including CML, CEL, CMC and MG-H1 were associated with increased risk of cognitive impairment. Plasma CMC and MG-H1 might the main contributors for cognitive impairment, while further longitudinal studies are required to verify the associations.

Associations of physical frailty with incidence and mortality of overall and site-specific cancers: A prospective cohort study from UK biobank.

OBJECTIVE: Evidence regarding the role of physical frailty in cancer-related outcomes is limited. We aimed to examine the association of frailty with cancer incidence and mortality risk. METHODS: This prospective study included 348,144 participants free of cancer at baseline from the UK Biobank. Frailty phenotypes (non-frail, pre-frail, and frail) were constructed from 5 components: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The outcome was incidence and mortality of overall and cite-specific cancers. Cox proportional hazard regression was used to estimate the association of frailty phenotypes with cancer incidence and mortality risk. RESULTS: A total of 43,304 incident cancer cases and 10,152 cancer deaths were documented during a median of 12.0 years of follow-up. For overall cancer, compared with non-frailty, the incidence risk increased by 4% for pre-frailty and 11% for frailty, and the mortality risk increased by 11% for pre-frailty and 39% for frailty. Frailty phenotypes were also dose-dependently associated with a higher risk of incidence and mortality of some site-specific cancers (including liver and lung), with significant sex differences. We observed a synergetic association of frailty phenotypes and smoking with overall cancer incidence and mortality risk. CONCLUSIONS: Frailty phenotypes contributed significantly to a higher risk of overall and some site-specific cancers incidence and mortality in a stepwise manner or within individual categories. Future studies are warranted to emphasize the identification, management and prevention of frailty in the whole population and complements of lifestyle-targeted interventions such as quitting smoking.

Diabetes and the risk of cirrhosis and HCC: An analysis of the UK Biobank.

BACKGROUND: Diabetes increases the risk of cirrhosis and HCC. We aimed to assess such associations given different diabetes statuses. METHODS: We included 449,497 participants in the UK Biobank cohort (mean age 56.7±8.0 y; 45.5% male) and assessed the association between preclinical diabetes (prediabetes, having a high risk of diabetes), clinical diabetes (presence, duration, or glycemic control of type 2 diabetes), and incident liver cirrhosis and HCC by the Cox regression. Liver diseases were ascertained through inpatient records and national death registration. Gene-environment interaction was examined using the polygenic risk scores of cirrhosis and HCC. RESULTS: Compared with normoglycemia, having <5 years,≥5 years of diabetes showed adjusted HRs (aHRs) of cirrhosis as 2.85 (2.45-3.32) and 3.43 (2.92-4.02), respectively, which was similarly observed in HCC. In diabetes, a level of hemoglobin A1c ≥ 7.5% showed aHRs of 1.37 (1.07-1.76) and 1.89 (1.10-3.25) for cirrhosis and HCC, respectively, compared with hemoglobin A1c < 6.5%. In non-diabetes, prediabetes presented aHRs of 1.41 (1.14-1.73) and 1.80 (1.06-3.04) of cirrhosis and HCC, respectively. Participants with a high risk of diabetes at baseline showed an aHR of 3.31 (2.65-4.13) for cirrhosis and 2.09 (1.15-3.80) for HCC. In those with a high genetic risk of HCC, having an increased risk of diabetes posed a significantly higher risk of HCC (aHR: 1.93, 1.45-2.58, Pinteraction=0.005), compared with those without a high genetic risk of HCC. CONCLUSIONS: Not only diabetes but preclinical diabetes, longer diabetes duration, and higher baseline hemoglobin A1c were associated with an increased risk of incident cirrhosis and HCC in the general population.

Plant-based dietary patterns, genetic predisposition and risk of colorectal cancer: a prospective study from the UK Biobank.

BACKGROUND: Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk. METHODS: This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model. RESULTS: Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81-0.96) and 0.91 (95% CI, 0.84-0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males. CONCLUSIONS: Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.

Physical frailty, adherence to ideal cardiovascular health and risk of cardiovascular disease: a prospective cohort study.

BACKGROUND: longitudinal evidence concerning frailty phenotype and the risk of cardiovascular disease (CVD) remained insufficient, and whether CVD preventive strategies exert low CVD risk on frail adults is unclear. OBJECTIVES: we aimed to prospectively evaluate the association of frailty phenotype, adherence to ideal cardiovascular health (CVH) and their joint associations with the risk of CVD. METHODS: a total of 314,093 participants from the UK Biobank were included. Frailty phenotype was assessed according to the five criteria of Fried et al.: weight loss, exhaustion, low physical activity, slow gait speed and low grip strength. CVH included four core health behaviours (smoking, physical activity and diet) and three health factors (weight, cholesterol, blood pressure and glycaemic control). The outcome of interest was incident CVD, including coronary heart disease, heart failure and stroke. RESULTS: compared with the non-frail people whose incident rate of overall CVD was 6.54 per 1,000 person-years, the absolute rate difference per 1,000 person-years was 1.67 (95% confidence interval, CI: 1.33, 2.02) for pre-frail and 5.00 (95% CI: 4.03, 5.97) for frail. The ideal CVH was significantly associated with a lower risk of all CVD outcomes. For the joint association of frailty and CVH level with incident CVD, the highest risk was observed among frailty accompanied by poor CVH with an HR of 2.92 (95% CI: 2.68, 3.18). CONCLUSIONS: our findings indicate that physical frailty is associated with CVD incidence. Improving CVH was significantly associated with a considerable decrease in CVD risk, and such cardiovascular benefits remain for the frailty population.

Frequency of adding salt at the table and risk of incident cardiovascular disease and all-cause mortality: a prospective cohort study.

BACKGROUND: Adding salt at the table is a prevalent eating habit, but its long-term relationship with cardiovascular disease (CVD) and all-cause mortality remains unclear. We evaluated the associations of adding salt at the table with the risk of incident CVD and all-cause mortality. METHODS: Among 413,109 middle- and old-aged adults without cancer or CVD, all participants reported the frequency of adding salt at the table at baseline. The associations between adding salt at the table and incident CVD (the composite endpoint of coronary heart disease, stroke, heart failure, and CVD deaths) and all-cause mortality were investigated using Cox proportional hazards models. RESULTS: Of the study population, the mean age was 55.8 years and 45.5% were men; 44.4% reported adding salt at the table; 4.8% reported always adding salt at the table. During a median follow-up of 12 years, there were 37,091 incident CVD cases and 21,293 all-cause deaths. After adjustment for demographic, lifestyle, and cardiometabolic risk factors, the multivariable-adjusted hazard ratios (HRs) for participants who always added salt at the table versus never/rarely added salt at the table were 1.21 (95% confidence interval [CI]: 1.16-1.26) for CVD, 1.19 (95%CI: 1.05-1.35) for CVD mortality, and 1.22 (95%CI: 1.16-1.29) for all-cause mortality, respectively. CONCLUSIONS: In this prospective cohort study, a higher frequency of adding salt at the table was associated with a greater risk of incident CVD and mortality. Our findings support the benefits of restricting the habit of adding salt at the table in promoting cardiovascular health.

Associations of physical activity intensity with incident cardiovascular diseases and mortality among 366,566 UK adults.

BACKGROUND: The associations of the proportion of vigorous physical activity (VPA) to moderate to vigorous physical activity (MVPA) with incident cardiovascular disease (CVD) and all-cause mortality are unclear. METHODS: The present study included 366,566 participants (aged 40-69 years) without baseline CVD from the UK biobank during 2006 to 2010. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of outcomes. RESULTS: During a median 11.8 years of follow-up, among 366,566 participants (mean age [SD]: 56.0 [8.1]), 31,894 incident CVD and 19,823 total deaths were documented. Compared with no VPA, 0%-30% of VPA to MVPA was associated with 12% and 19% lower risks of incident CVD (HR, 0.88 [95% CI, 0.86-0.91]) and all-cause mortality (HR, 0.81 [95% CI, 0.78-0.84]), respectively. Furthermore, we found that the maximum reduction of risks of incident CVD and all-cause mortality occurred at performing approximately 30% of VPA to MVPA (P < 0.001). Compared with participants reporting the lowest levels of MVPA (moderate physical activity [MPA], 0-150 min/week; VPA, 0-75 min/week), those performing 150-300 min/week of MPA and ≥ 150 min/week of VPA experienced the lowest risk of incident CVD (HR, 0.87 [95% CI, 0.79-0.95]) and all-cause mortality (HR, 0.71 [95% CI, 0.63-0.80]). Interestingly, we found that smokers yielded more cardiovascular benefits than non-smokers by performing a higher volume of VPA. CONCLUSIONS: Comparing with UK adults reporting no VPA, engaging in 30% of VPA was associated with the lowest risk of incident CVD and all-cause mortality.

Phthalate acid esters and polycyclic aromatic hydrocarbons concentrations with their determining factors among Chinese pregnant women: A focus on dietary patterns.

BACKGROUND: Pregnant women are susceptible to adverse health effects associated with phthalate acid esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs), and diet is a significant exposure source. Little is known about the contributions of dietary patterns during pregnancy to the exposure variability of these environmental contaminants. OBJECTIVES: To identify dietary patterns in relation to PAEs and PAHs exposure in the Chinese pregnant population. METHODS: Dietary data and urinary concentrations of environmental pollutants were obtained from 1190 pregnant women in the Tongji Birth Cohort (TJBC). PAEs and PAHs were measured in spot urine samples. Food intake was assessed using a food-frequency questionnaire. Dietary patterns were constructed by principal component analysis (PCA). Through PCA, we also extracted three chemical mixture scores that represent different co-exposure patterns of PAEs and PAHs. Multiple linear regression models were adopted to identify predictors of PAEs and PAHs exposure. RESULTS: Four dietary patterns were identified by PCA that explained 44.9 % of the total variance of food intake. We found egg-dairy products pattern, whole grain-tuber crop pattern, and meat-aquatic products pattern were positively associated with specific pollutants exposure. In contrast, fruit-nut-vegetable pattern was negatively correlated with PAEs and PAHs exposure. Every SD increase in this pattern score was associated with 14.36 % reduced mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (95 % CI: -24.50 ~ -2.96, p-trend = 0.01), 10.86 % reduced 2-hydroxynaphthalene (2-OHNap) (95 % CI: -20.07 ~ -0.60, p-trend = 0.04), 19.35 % reduced 9-hydroxyphenanthrene (9-OHPhe) (95 % CI: -34.49 ~ -0.70, p-trend = 0.01), and 8.33 % reduced scores of PAHs group (95 % CI: -15.97 ~ -0.10, p-trend = 0.02). In addition, disposable tableware usage and passive smoking were suggested as potentially modifiable sources of PAEs and PAHs exposure, respectively. CONCLUSION: Adhering to egg-dairy products pattern, whole grain-tuber crop pattern, and meat-aquatic products pattern may be related to increased PAEs and PAHs exposure, while following fruit-nut-vegetable pattern seems to correlate with a lower burden of such exposure.

Associations of Serum Carotenoids With Risk of Cardiovascular Mortality Among Individuals With Type 2 Diabetes: Results From NHANES.

OBJECTIVE: Although carotenoids have been suggested to exhibit antioxidant properties, some experimental studies reported that ß-carotene may show pro-oxidant effects under certain conditions. Current evidence regarding the cardiovascular effects of carotenoids among patients with type 2 diabetes (T2D) is scarce. This study aimed to prospectively examine the associations of individual serum carotenoid concentrations with cardiovascular mortality among adults with T2D. RESEARCH DESIGN AND METHODS: This analysis included 3,107 individuals with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2006. Cardiovascular mortality was ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After multivariate adjustment including lifestyles, dietary factors, glucose control, and other major carotenoids, higher serum ß-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner. When extreme quartiles of ß-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (Ptrend = 0.002); and per one-unit increment in natural log-transformed serum ß-carotene was associated with a 46% higher risk of cardiovascular mortality (P = 0.001). Other individual carotenoids (α-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) were not significantly associated with the risk of cardiovascular mortality. Consistent results were observed when stratifying by age, sex, race, BMI, smoking status, diabetes duration, and glycated hemoglobin A1c levels. CONCLUSIONS: Higher concentrations of serum ß-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D. Our findings, if replicated, underscore the need to estimate the optimal serum ß-carotene concentrations in individuals with T2D.

Association of Sleep Patterns and Lifestyles With Incident Hypertension: Evidence From a Large Population-Based Cohort Study.

Background: Adherence to a healthy lifestyle (no smoking, consuming a healthy diet, engaging in physical activity, and maintaining a healthy weight) is recommended in current guidelines for hypertension prevention. However, evidence regarding the association between sleep behaviors, independently and jointly with traditional lifestyle factors, and the risk of hypertension is limited. Methods: This prospective study included 165,493 participants who are free of hypertension at baseline from the UK Biobank. Sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness were used to construct a healthy sleep score. We also derived a healthy lifestyle score based on smoking status, diet quality, physical activity, and body mass index (BMI). Cox proportional hazards regression models and competing risk analyses were used to estimate the associations of the healthy sleep score and healthy lifestyle score with the risk of hypertension. The population attributable risk percent (PAR%) was estimated for increased cases of hypertension due to poor adherence to a healthy sleep pattern or a healthy lifestyle. Results: A total of 10,941 incident hypertension cases were documented during a median of 11.8 years of follow-up. The multivariable-adjusted hazard ratio (HR) for hypertension was 0.58 [95% confidence interval (CI): 0.52, 0.65] for participants with a sleep score of 5 compared with 0-1, and 0.48 (95% CI: 0.43, 0.54) for participants with a lifestyle score of 4 compared with those who scored 0. For joint association, those with a poor sleep pattern and a poor lifestyle had the highest risk of hypertension [HR: 2.41 (95% CI: 2.12, 2.74)]. PAR% was 14.7% (95% CI: 12.3%, 17.1%), 20.1% (95% CI: 17.6%, 22.6%), and 31.7% (95% CI: 27.6%, 35.6%) for poor adherence to a healthy sleep pattern, a healthy lifestyle, and the combination of a healthy sleep pattern and a healthy lifestyle. Conclusion: Both a healthy sleep pattern and a healthy lifestyle were associated with a lower risk of hypertension, and the benefits of adhering to a healthy sleep pattern complement the well-established lifestyle for the optimal primary prevention of hypertension. These findings support the current perspective that a healthy sleep pattern is an important part of a healthful and productive lifestyle for hypertension prevention.

DHPPA, a major plasma alkylresorcinol metabolite reflecting whole-grain wheat and rye intake, and risk of metabolic syndrome: a case-control study.

PURPOSE: Whole-grain intake assessed through self-reported methods has been suggested to be inversely associated with the metabolic syndrome (MetS) risk in epidemiological studies. However, few studies have evaluated the association between whole-grain intake and MetS risk using objective biomarkers of whole-grain intake. The aim of this study was to examine the association between plasma 3-(3,5-Dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, and MetS risk in a Chinese population. METHODS: A case-control study of 667 MetS cases and 667 matched controls was conducted based on baseline data of the Tongji-Ezhou Cohort study. Plasma DHPPA concentrations were assessed by high-performance liquid chromatography-tandem mass spectrometry. The MetS was defined based on criteria set by the Joint Interim Statement. RESULTS: Plasma DHPPA was inversely associated with MetS risk. After adjustment for age, sex, body mass index, smoking status, alcohol drinking status, physical activity and education level, the odds ratios (ORs) for MetS across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.86 (0.58-1.26), 0.77 (0.52-1.15), and 0.59 (0.39-0.89), respectively. In addition, the cubic spline analysis revealed a potential nonlinear association between plasma DHPPA and MetS, with a steep reduction in the risk at the lower range of plasma DHPPA concentration. CONCLUSION: Our study revealed that individuals with higher DHPPA concentrations in plasma had lower odds of MetS compared to those with lower DHPPA concentrations in plasma. Our findings provided further evidence to support health benefits of whole grain consumption.