Adherence to a healthy lifestyle including sleep and sedentary behaviors and risk of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

OBJECTIVE: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. METHODS: This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. RESULTS: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. CONCLUSION: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

The EAT-Lancet Diet Index, Plasma Proteins, and Risk of Heart Failure in a Population-Based Cohort.

BACKGROUND: The landmark EAT-Lancet Commission proposed that a planetary health diet is comprised mainly of plant-based foods. However, studies examining whether this diet is associated with heart failure (HF) are currently lacking. In addition, the potential proteomics mechanism on the association between diet and HF warrants further elucidation. OBJECTIVES: This study aims to both examine the association between the EAT-Lancet diet index and risk of HF and identify plasma proteins underlying such an association. METHODS: This prospective cohort study included 23,260 participants. HF cases during the follow-up were identified through the Swedish national register. An EAT-Lancet diet index (score range: 0-42) was created to assess adherence to the EAT-Lancet reference diet. In a subcohort (n = 4,742), fasting plasma proteins were quantified. RESULTS: During a median follow-up of 25.0 years, 1,768 incident HF cases were documented. After adjusting for sociodemographic, lifestyle, diabetes, hypertension, use of lipid-lowering drugs, and body mass index, the HR per 3-point increase of the EAT-Lancet diet index was 0.93 (95% CI: 0.88-0.97). This association was robust in several sensitivity analyses. Among the included 136 plasma proteins, a total of 8 proteins (AM, GDF15, IL6, TIM, CTSD, CCL20, FS, and FUR) were both inversely associated with the EAT-Lancet diet index and positively associated with risk of HF; the overall proteomic score mediated 9.4% (95% CI: 2.2%-32.1%) of the association. CONCLUSIONS: Higher adherence to the EAT-Lancet diet was associated with a lower risk of HF. The identified eight plasma proteins provide information on potential pathways mediating such an association.

Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

Low-level exposure to lead and atherosclerosis in the carotid arteries: Results from the Swedish population-based cohort SCAPIS.

BACKGROUND: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. AIM: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. METHODS: We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013-2018. Blood lead (B-Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B-Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. RESULTS: Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2-222). The median B-Pb concentration was 14 µg/L (range: 0.75-203). After adjusting for potential confounders, individuals in the fourth quartile of B-Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 µg/L increase in B-Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). CONCLUSIONS: This study shows an association between B-Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.

High consumption of dairy products and risk of major adverse coronary events and stroke in a Swedish population.

The association between the consumption of dairy products and risk of CVD has been inconsistent. There is a lack of studies in populations with high intakes of dairy products. We aimed to examine the association between intake of dairy products and risk of incident major adverse coronary events and stroke in the Swedish Malmö Diet and Cancer cohort study. We included 26 190 participants without prevalent CVD or diabetes. Dietary habits were obtained from a modified diet history, and endpoint data were extracted from registers. Over an average of 19 years of follow-up, 3633 major adverse coronary events cases and 2643 stroke cases were reported. After adjusting for potential confounders, very high intakes of non-fermented milk (>1000 g/d) compared with low intakes (<200 g/d) were associated with 35 % (95 % CI (8, 69)) higher risk of major adverse coronary events. In contrast, moderate intakes of fermented milk (100-300 g/d) were associated with a lower risk of major adverse coronary events compared with no consumption. Intakes of cheese (only in women) and butter were inversely associated with the risk of major adverse coronary events. We observed no clear associations between any of the dairy products and stroke risk. These results highlight the importance of studying different dairy foods separately. Further studies in populations with high dairy consumption are warranted.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

Background: It is currently unknown whether ultra-processed foods (UPFs) consumption is associated with a higher incidence of multimorbidity. We examined the relationship of total and subgroup consumption of UPFs with the risk of multimorbidity defined as the co-occurrence of at least two chronic diseases in an individual among first cancer at any site, cardiovascular disease, and type 2 diabetes. Methods: This was a prospective cohort study including 266,666 participants (60% women) free of cancer, cardiovascular disease, and type 2 diabetes at recruitment from seven European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Foods and drinks consumed over the previous 12 months were assessed at baseline by food-frequency questionnaires and classified according to their degree of processing using Nova classification. We used multistate modelling based on Cox regression to estimate cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations of total and subgroups of UPFs with the risk of multimorbidity of cancer and cardiometabolic diseases. Findings: After a median of 11.2 years of follow-up, 4461 participants (39% women) developed multimorbidity of cancer and cardiometabolic diseases. Higher UPF consumption (per 1 standard deviation increment, ∼260 g/day without alcoholic drinks) was associated with an increased risk of multimorbidity of cancer and cardiometabolic diseases (HR: 1.09, 95% CI: 1.05, 1.12). Among UPF subgroups, associations were most notable for animal-based products (HR: 1.09, 95% CI: 1.05, 1.12), and artificially and sugar-sweetened beverages (HR: 1.09, 95% CI: 1.06, 1.12). Other subgroups such as ultra-processed breads and cereals (HR: 0.97, 95% CI: 0.94, 1.00) or plant-based alternatives (HR: 0.97, 95% CI: 0.91, 1.02) were not associated with risk. Interpretation: Our findings suggest that higher consumption of UPFs increases the risk of cancer and cardiometabolic multimorbidity. Funding: Austrian Academy of Sciences, Fondation de France, Cancer Research UK, World Cancer Research Fund International, and the Institut National du Cancer.

Clusters of carbohydrate-rich foods and associations with type 2 diabetes incidence: a prospective cohort study.

BACKGROUND: About one in ten adults are living with diabetes worldwide. Intake of carbohydrates and carbohydrate-rich foods are often identified as modifiable risk factors for incident type 2 diabetes. However, strong correlation between food variables can make it difficult to identify true associations. The purpose of this study was to identify clusters of carbohydrate-rich foods and analyse their associations with type 2 diabetes incidence in the Malmö Diet and Cancer Study cohort in southern Sweden. METHODS: Dietary intake of 26 622 participants was assessed using a validated three-part diet history method: a 7-day food diary, a 168-item food frequency questionnaire, and a 60-minute interview. K-means clustering analysis identified five clusters from 21 food variables. The Cox proportional hazard regression model was applied to calculate hazard ratios (HR) and 95% confidence intervals (CI) of the association between clusters and incident type 2 diabetes. RESULTS: The cluster analysis resulted in five clusters; high vegetables/low added sugar, high sugar-sweetened beverages, high juice, high fruit, and high refined carbohydrates/low fruit & vegetables (reference). During mean follow-up of 18 years, 4046 type 2 diabetes cases were identified. After adjustment for potential confounding (including lifestyle, body mass index, and diet), a high fruit cluster (HR 0.86; 95% CI 0.78, 0.94) was inversely associated with type 2 diabetes compared to the reference cluster. No other significant associations were identified. CONCLUSIONS: A dietary pattern defined by a high intake of fruits was associated with a lower incidence of type 2 diabetes. The findings provide additional evidence of a potential protective effect from fruit intake in reducing type 2 diabetes risk. Future studies are needed to explore this association further.

Associations of ultra-processed food consumption, circulating protein biomarkers, and risk of cardiovascular disease.

BACKGROUND: We aim to examine the association between ultra-processed foods (UPF) consumption and cardiovascular disease (CVD) risk and to identify plasma proteins associated with UPF. METHODS: This prospective cohort study included 26,369 participants from the Swedish Malmö Diet and Cancer Study, established in 1991-1996. Dietary intake was assessed using a modified diet history method, and UPF consumption was estimated using the NOVA classification system. A total of 88 selected CVD-related proteins were measured among 4475 subjects. Incident CVD (coronary heart disease and ischemic stroke) was defined as a hospital admission or death through registers. Cox proportional hazards regression models were performed to analyze the associations of UPF intake with risks of CVD. Linear regression models were used to identify the plasma proteins associated with UPF intake. RESULTS: During 24.6 years of median follow-up, 6236 participants developed CVD, of whom 3566 developed coronary heart disease and 3272 developed ischemic stroke. The adjusted hazard ratio (95% confidence interval) in the 4th versus 1st quartile of UPF was 1.18 (1.08, 1.29) for CVD, 1.20 (1.07, 1.35) for coronary heart disease, and 1.17 (1.03, 1.32) for ischemic stroke. Plasma proteins interleukin 18, tumor necrosis factor receptor 2, macrophage colony-stimulating factor 1, thrombomodulin, tumor necrosis factor receptor 1, hepatocyte growth factor, stem cell factor, resistin, C-C motif chemokine 3, and endothelial cell-specific molecule 1 were positively associated with UPF after correcting for multiple testing. CONCLUSIONS: Our study showed that high UPF intake increased the risk of CVD and was associated with several protein biomarkers. Future studies are warranted to validate these findings and assess the potential pathways between UPF intake and CVD.

Dairy intake and risk of type 2 diabetes: results of a large prospective cohort.

Background and aims: Previous studies of primarily Western populations have consistently documented a lower risk of type 2 diabetes (T2D) among people with a higher yogurt intake, but an inconsistent association with milk intake. However, little is known about the association between dairy intake and risk of T2D among Chinese adults who consume considerably less dairy (mainly milk and yogurt) compared with Western populations. The aim is to investigate the associations of dairy intake with the risk of incident T2D in the general adult population in China. Methods: This cohort study consisted of 22 843 participants without prevalent cardiovascular disease, cancer, or diabetes at the baseline. Dietary data were collected using a validated food frequency questionnaire at the baseline (2013-2018); dairy intake was categorized into tertiles after zero consumers were taken as the reference. Incident T2D was ascertained by medical examinations and self-report of physician-diagnosed diabetes during follow-up visits. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In total, 735 incident T2D cases were recorded over a median follow-up of 4.0 years. Relative to zero consumers, the HRs (95% CIs) for incident T2D among participants in the highest tertiles were 0.70 (0.57, 0.87) for total dairy, 0.73 (0.60, 0.90) for milk, and 0.81 (0.66, 1.00) for yogurt. Such associations were slightly attenuated by additional adjustment for the body mass index. In addition, such inverse associations were robust in sensitivity analyses and consistent in most of the subgroups defined by baseline characteristics. Conclusion: Higher intakes of total dairy, milk, and yogurt were all associated with a lower risk of T2D among Chinese adults.

Comparisons of Different Carbohydrate Quality Indices for Risk of Type 2 Diabetes in the Malmö Diet and Cancer Study.

Carbohydrate quality might be more important than quantity to reduce type 2 diabetes (T2D) risk. Various metrics of carbohydrate quality exist; however, their associations with T2D have only been studied to a limited extent. Consequently, the aim was to investigate the association between four different pre-defined carbohydrate quality indices, with various amounts of fiber (≥1 g) and free sugar (<1 or <2 g) per 10 g of carbohydrates, and T2D risk among 26,622 individuals without diabetes from the Malmö Diet and Cancer cohort. Dietary data were collected through a food diary, diet frequency questionnaire, and interview. After a mean follow-up of 18 years, 4046 cases were identified through registers. After adjusting for potential confounders, no statistically significant associations were found for any of the indices. When excluding individuals with past dietary changes and potential misreporting of energy (36% of the population), lower risk was found for the following intake ratios: 10:1:2 carbohydrate:fiber:free sugar (HR = 0.82; 95% CI = 0.70-0.97), and 10:1&1:2 carbohydrate:fiber and fiber:free sugar, respectively (HR = 0.84; 95% CI = 0.72-0.97). Our findings indicate that adherence to a diet with high amounts of fiber and moderate amounts of free sugar in relation to total carbohydrate intake may be associated with a lower risk of T2D.

Association between added sugars and kidney stones in U.S. adults: data from National Health and Nutrition Examination Survey 2007-2018.

Purpose: Added sugar is associated with a variety of adverse health outcomes, but its association with kidney stones is unclear. This study was to determine whether added sugar is associated with kidney stones. Materials and methods: This nationally representative study used National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2018 for analysis. People aged ≥20 years who reported a history of kidney stones and provided dietary recall data on added sugars were included. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were used to evaluate the associations between added sugars and kidney stones by adjusting potential confounders. Results: Totally 28,303 adults were included, with weighted mean age [95% confidence interval (CI)] of 48.03 (47.56, 48.51) years, 47.74% (47.09, 48.40%) males and 52.26% (51.60, 52.91%) females. The overall mean (95% CI) energy intake from added sugars was 272.10 (266.59, 277.60) kilocalories. In the fully-adjusted multivariable model, the percentage of energy intake from added sugars was positively correlated with kidney stones. Compared to the first quartile of added sugar energy intake percentage, the population in the fourth quartile had a higher prevalence of kidney stones (OR = 1.39; 95% CI 1.17 to 1.65). Compared with the less than 5% calories from added sugar population, the more than or equal to 25% calories from added sugar had a higher kidney stone prevalence (OR = 1.88; 95% CI 1.52 to 2.32). Conclusion: A higher percentage of energy intake from added sugars is significantly associated with a higher prevalence of kidney stones. This study provides cross-sectional evidence for the relationship between added sugars and health outcomes.

The EAT-Lancet diet, genetic susceptibility and risk of atrial fibrillation in a population-based cohort.

BACKGROUND: The EAT-Lancet Commission proposed a global reference diet with both human health benefits and environmental sustainability in 2019. However, evidence regarding the association of such a diet with the risk of atrial fibrillation (AF) is lacking. In addition, whether the genetic risk of AF can modify the effect of diet on AF remains unclear. This study aimed to assess the association of the EAT-Lancet diet with the risk of incident AF and examine the interaction between the EAT-Lancet diet and genetic susceptibility of AF. METHODS: This prospective study included 24,713 Swedish adults who were free of AF, coronary events, and stroke at baseline. Dietary habits were estimated with a modified diet history method, and an EAT-Lancet diet index was constructed to measure the EAT-Lancet reference diet. A weighted genetic risk score was constructed using 134 variants associated with AF. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: During a median follow-up of 22.9 years, 4617 (18.7%) participants were diagnosed with AF. The multivariable HR (95% CI) of AF for the highest versus the lowest group for the EAT-Lancet diet index was 0.84 (0.73, 0.98) (P for trend < 0.01). The HR (95% CI) of AF per one SD increment of the EAT-Lancet diet index for high genetic risk was 0.92 (0.87, 0.98) (P for interaction = 0.15). CONCLUSIONS: Greater adherence to the EAT-Lancet diet index was significantly associated with a lower risk of incident AF. Such association tended to be stronger in participants with higher genetic risk, though gene-diet interaction was not significant.

Corrigendum: Characterization of the degree of food processing in the European Prospective Investigation into Cancer and Nutrition: application of the Nova classification and validation using selected biomarkers of food processing.

[This corrects the article DOI: 10.3389/fnut.2022.1035580.].

Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. OBJECTIVE: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. METHODS: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. RESULTS: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. CONCLUSIONS: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

Association of Ultra-Processed Food Intake with Cardiovascular and Respiratory Disease Multimorbidity: A Prospective Cohort Study.

SCOPE: Evidence suggests a positive association between ultra-processed food (UPF) consumption and the incidence of cardiovascular disease (CVD). The study aims to investigate associations between UPF intake and respiratory disease, CVD, and their multimorbidity in a large prospective cohort. METHODS AND RESULTS: Within the UK Biobank, participants who are free from respiratory disease or CVD at baseline and completed at least two times 24-h dietary records are included in this study. After adjusting for socioeconomic status and lifestyle factors, the hazard ratios (95% confidence interval) for each 10% increase in UPF are 1.06 (1.04, 1.09) for CVD, 1.04 (1.02, 1.06) for respiratory disease, 1.15 (1.08, 1.22) for CVD mortality, and 1.06 (1.01, 1.12) for their multimorbidity, respectively. In addition, replacing 20% of UPF weight in diet with an equivalent proportion of unprocessed or minimally processed foods is estimated to be associated with 11% lower risk of CVD, 7% lower risk of respiratory disease, 25% lower risk of CVD mortality, and 11% lower risk of CVD and respiratory disease multimorbidity. CONCLUSION: In this prospective cohort study, higher consumption of UPF is associated with higher risks of CVD and respiratory disease multimorbidity. Further longitudinal studies are needed to confirm these findings.

Genetic Susceptibility to Mood Disorders and Risk of Stroke: A Polygenic Risk Score and Mendelian Randomization Study.

BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders in stroke. METHODS: We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and Cancer cohort (24 631 individuals with a median follow-up of 21.3 (interquartile range: 16.6-23.2) years. We further examined the causal effects for mood disorders on all strokes and ischemic strokes using summary statistics from large genome-wide association studies of mood disorders (up to 609 424 individuals, Psychiatric Genomics Consortium), all strokes and ischemic strokes (up to 446 696 individuals, MEGASTROKE Consortium). RESULTS: Among 24 366 stroke-free participants at baseline, 2632 individuals developed strokes, 2172 of them ischemic, during follow-up. After properly adjusting for well-known risk factors, participants in the highest quintile of polygenic risk scores for mood disorders had 1.45× (95% CI, 1.21-1.74) higher risk of strokes and 1.44× (95% CI, 1.18-1.76) higher risk of ischemic strokes compared with the lowest quintile in women. Mendelian randomization analyses suggested that mood disorders had a causal effect on strokes (odds ratio, 1.07 [95% CI, 1.03-1.11]) and ischemic strokes (odds ratio, 1.09 [95% CI, 1.04-1.13]). CONCLUSIONS: Our results suggest a causal role of mood disorders in the risk of stroke. High-risk women could be identified early in life using polygenic risk scores to ultimately prevent mood disorders and strokes.

Adherence to the EAT-Lancet diet and risk of coronary events in the Malmö Diet and Cancer cohort study.

BACKGROUND: The EAT-Lancet Commission proposed a globally environmentally sustainable dietary pattern featuring mainly plant-based foods in 2019. However, evidence on this dietary pattern in preventing coronary events is minimal. OBJECTIVES: We aimed to examine the association between the EAT-Lancet diet and risk of coronary events. METHODS: The Malmö Diet and Cancer cohort study (recruited between 1991 and 1996) included 23,877 participants aged 44.5-73.6 y (62.5% women) without CVDs and diabetes at baseline. A modified diet history was used to collect the dietary data. An EAT-Lancet diet index (range, 0-42 points) was applied on the basis of 14 food components scored 0 (nonadherence) to 3 (adherence). Coronary events were extracted from the registers. Cox proportional hazards models were used to estimate the HRs and 95% confidential intervals (CIs). RESULTS: Over a median of 24.9 y of follow-up, 3031 coronary events occurred (incidence rate: 5.89/1000 person-years). After adjusting for age, sex, dietary assessment methods, season, total energy intake, leisure-time physical activity, alcohol consumption, smoking status, educational level, and BMI, the multivariable HR (95% CI) for coronary events among participants who had the highest adherence to the EAT-Lancet diet index (≥23 points, 8.1%) was 0.80 (0.67, 0.96) compared with those who had the lowest adherence (≤13 points, 9.7%) (P-trend = 0.01 across 5 groups of the EAT-Lancet diet). The inverse association was consistent in men and women and was robust after excluding those with misreported energy and significant diet changes or excluding coronary events occurred within the first 2 y of follow-up. CONCLUSIONS: Our data indicate that adherence to the EAT-Lancet diet was associated with a lower risk of coronary events.

Consumption of ultraprocessed food and development of chronic kidney disease: the Tianjin Chronic Low-Grade Systemic Inflammation and Health and UK Biobank Cohort Studies.

BACKGROUND: Many ultraprocessed food (UPF)-derived by-products may play a role in the development of chronic kidney disease (CKD). Although several studies have assessed the association of UPFs with kidney function decline or CKD in various countries, no evidence has been shown in China and the United Kingdom. OBJECTIVES: This study aims to evaluate the association between UPF consumption and risk of CKD in 2 large cohort studies from China and the United Kingdom. METHODS: In total, 23,775 and 102,332 participants without baseline CKD were enrolled in the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) and UK Biobank cohort studies, respectively. Information on UPF consumption was obtained from a validated food frequency questionnaire in the TCLSIH and 24-h dietary recalls in the UK Biobank cohort. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2, albumin-to-creatinine ratio ≥30 mg/g, or as having a clinical diagnosis of CKD in both cohorts. Multivariable Cox proportional hazard models were used to examine the association between UPF consumption and the risk of CKD. RESULTS: After a median follow-up of 4.0 and 10.1 y, the incidence rates of CKD were around 1.1% and 1.7% in the TCLSIH and UK Biobank cohorts, respectively. The multivariable hazard ratio [95% confidence interval] of CKD across increasing quartiles (quartiles 1-4) of UPF consumption were 1 (reference), 1.24 (0.89, 1.72), 1.30 (0.91, 1.87), and 1.58 (1.07, 2.34) (P for trend = 0.02) in the TCLSIH cohort and 1 (reference), 1.14 (1.00, 1.31), 1.16 (1.01, 1.33), and 1.25 (1.09, 1.43) (P for trend < 0.01) in the UK Biobank cohort, respectively. CONCLUSIONS: Our finding indicated that higher UPF consumption is associated with a higher risk of CKD. Moreover, restricting UPF consumption may potentially benefit the prevention of CKD. Further clinical trials are required to clarify the causality. This trial was registered at UMIN Clinical Trials Registry as UMIN000027174 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031137).

Starch intake, amylase gene copy number variation, plasma proteins, and risk of cardiovascular disease and mortality.

BACKGROUND: Salivary amylase, encoded by the AMY1 gene, initiate the digestion of starch. Whether starch intake or AMY1 copy number is related to disease risk is currently rather unknown. The aim was to investigate the association between starch intake and AMY1 copy number and risk of cardiovascular disease (CVD) and mortality and whether there is an interaction. In addition, we aim to identify CVD-related plasma proteins associated with starch intake and AMY1 copy number. METHODS: This prospective cohort study used data from 21,268 participants from the Malmö Diet and Cancer Study. Dietary data were collected through a modified diet history method and incident CVD and mortality were ascertained through registers. AMY1 gene copy number was determined by droplet digital polymerase chain reaction, a risk score of 10 genetic variants in AMY1 was measured, and a total of 88 selected CVD-related proteins were measured. Cox proportional hazards regression was used to analyze the associations of starch intake and AMY1 copy number with disease risk. Linear regression was used to identify plasma proteins associated with starch intake and AMY1 copy number. RESULTS: Over a median of 23 years' follow-up, 4443 individuals developed CVD event and 8125 died. After adjusting for potential confounders, a U-shape association between starch intake and risk of CVD (P-nonlinearity = 0.001) and all-cause mortality (P-nonlinearity = 0.03) was observed. No significant association was found between AMY1 copy number and risk of CVD and mortality, and there were no interactions between starch intake and AMY1 copy number (P interaction > 0.23). Among the 88 plasma proteins, adrenomedullin, interleukin-1 receptor antagonist protein, fatty acid-binding protein, leptin, and C-C motif chemokine 20 were associated with starch intake after adjusting for multiple testing. CONCLUSIONS: In this large prospective study among Swedish adults, a U-shaped association between starch intake and risk of CVD and all-cause mortality was found. Several plasma proteins were identified which might provide information on potential pathways for such association. AMY1 copy number was not associated with CVD risk or any of the plasma proteins, and there was no interaction between starch intake and AMY1 copy number on disease risk.