Plant Omega-3 Fatty Acids May Lower Risk of Atrial Fibrillation in Individuals with a Low Intake of Marine Omega-3 Fatty Acids.

BACKGROUND: Omega-3 fatty acids derived from seafood acids may influence cardiac arrhythmogenesis, whereas the role of the major plant-derived omega-3 fatty acid, alpha-linolenic acid (ALA), on atrial fibrillation (AF) is largely unknown. OBJECTIVES: We aimed to investigate the association between ALA intake and risk of incident AF overall and in subjects with a low intake of marine omega-3 fatty acids. METHODS: We followed a total of 54,260 middle-aged men and women enrolled into the Danish Diet, Cancer, and Health cohort for development of AF using nationwide registries. Intake of ALA was assessed using a validated food frequency questionnaire and modeled as a restricted cubic spline. Statistical analyses were conducted using Cox proportional hazards regression. RESULTS: We identified a total of 4902 incident AF events during a median of 16.9 y of follow-up. In multivariable analyses, we observed indications of a statistically nonsignificant inverse association between ALA intake and risk of AF up to an ALA intake of 2.5 g/d, whereas no appreciable association was found for higher intakes of ALA. A statistically significant dose-dependent negative association was found between ALA intake and risk of AF in individuals consuming < 250 mg marine omega-3 fatty acids daily, whereas no association was found in those with a higher intake of marine omega-3 fatty acids. CONCLUSIONS: Intake of ALA was associated with a lower risk of AF in individuals consuming a low intake of marine omega-3 fatty acids. This finding is novel and warrants further investigation.

A systematic evaluation of seven different scores representing the EAT-Lancet reference diet and mortality, stroke, and greenhouse gas emissions in three cohorts.

Different approaches have been used for translation of the EAT-Lancet reference diet into dietary scores that can be used to assess health and environmental impact. Our aim was to compare the different EAT-Lancet diet scores, and to estimate their associations with all-cause mortality, stroke incidence, and greenhouse gas emissions. We did a systematic review (PROSPERO, CRD42021286597) to identify different scores representing adherence to the EAT-Lancet reference diet. We then qualitatively compared the diet adherence scores, including their ability to group individuals according the EAT-Lancet reference diet recommendations, and quantitatively assessed the associations of the diet scores with health and environmental outcome data in three diverse cohorts: the Danish Diet, Cancer and Health Cohort (DCH; n=52 452), the Swedish Malmö Diet and Cancer Cohort (MDC; n=20 973), and the Mexican Teachers' Cohort (MTC; n=30 151). The DCH and MTC used food frequency questionnaires and the MDC used a modified diet history method to assess dietary intake, which we used to compute EAT-Lancet diet scores and evaluate the associations of scores with hazard of all-cause mortality and stroke. In the MDC, dietary greenhouse gas emission values were summarised for every participant, which we used to predict greenhouse gas emissions associated with varying diet adherence scores on each scoring system. In our review, seven diet scores were identified (Knuppel et al, 2019; Trijsburg et al, 2020; Cacau et al, 2021; Hanley-Cook et al, 2021; Kesse-Guyot et al, 2021; Stubbendorff et al, 2022; and Colizzi et al, 2023). Two of the seven scores (Stubbendorff and Colizzi) were among the most consistent in grouping participants according to the EAT-Lancet reference diet recommendations across cohorts, and higher scores (greater diet adherence) were associated with decreased risk of mortality (in the DCH and MDC), decreased risk of incident stroke (in the DCH and MDC for the Stubbendorff score; and in the DCH for the Colizzi score), and decreased predicted greenhouse gas emissions in the MDC. We conclude that the seven different scores representing the EAT-Lancet reference diet had differences in construction, interpretation, and relation to disease and climate-related outcomes. Two scores generally performed well in our evaluation. Future studies should carefully consider which diet score to use and preferably use multiple scores to assess the robustness of estimations, given that public health and environmental policy rely on these estimates.

Corrigendum.

[This corrects the article DOI: 10.29219/fnr.v62.1339.].

Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study.

INTRODUCTION: Nitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality. METHODS: In 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes--calculated using comprehensive food composition and national drinking water quality monitoring databases--and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality over 27 years were examined using restricted cubic splines within Cox proportional hazards models adjusting for demographic, lifestyle, and dietary confounders. Analyses were stratified by factors hypothesised to influence the formation of carcinogenic N-nitroso compounds (namely, smoking and dietary intakes of vitamin C, vitamin E, folate, and polyphenols). RESULTS: Plant-sourced nitrate intake was inversely associated with all-cause mortality [HRQ5vsQ1: 0.83 (0.80, 0.87)] while higher risks of all-cause mortality were seen for higher intakes of naturally occurring animal-sourced nitrate [1.09 (1.04, 1.14)], additive permitted meat-sourced nitrate [1.19 (1.14, 1.25)], and tap water-sourced nitrate [1.19 (1.14, 1.25)]. Similar source-dependent associations were seen for nitrite and for CVD-related and cancer-related mortality except that naturally occurring animal-sourced nitrate and tap water-sourced nitrate were not associated with cancer-related mortality and additive permitted meat-sourced nitrate was not associated with CVD-related mortality. No clear patterns emerged in stratified analyses. CONCLUSION: Nitrate/nitrite from plant sources are inversely associated while those from naturally occurring animal-sources, additive-permitted meat sources, and tap water-sources are positively associated with mortality.

Human antibody signatures towards the Chlamydia trachomatis major outer membrane protein after natural infection and vaccination.

BACKGROUND: Chlamydia trachomatis (CT) Major Outer Membrane Protein (MOMP) holds a neutralising epitope in the Variable Domain 4 (VD4), and this region's immune dominance during infection is well known. This study aimed to assess the antibody response induced after infection and compare it for specificity and functionality to the response following vaccination with the vaccine CTH522, which contains VD4's from serovars D, E, F, and G. METHODS: We assessed the antibody epitopes in MOMP by a high density peptide array. Furthermore, the role of the VD4 epitope in neutralisation was explored by competitive inhibition experiments with a fusion protein holding the neutralising VD4 linear epitope. This was done in two independent groups: 1) MOMP seropositive individuals infected with CT (n = 10, from case-control study) and 2) CTH522/CAF®01-vaccinated females (n = 14) from the CHLM-01 clinical trial. FINDINGS: We identified the major antigenic regions in MOMP as VD4 and the conserved region just before VD3 in individuals infected with CT. The same regions, with the addition of VD1, were identified in vaccine recipients. Overall, the VD4 peptide responses were uniform in vaccinated individuals and led to inhibition of infection in vitro in all tested samples, whereas the VD4 responses were more heterogenous in individuals infected with CT, and only 2 out of 10 samples had VD4-mediated neutralising antibody responses. INTERPRETATION: These data provide insights into the role of antibodies against MOMP VD4 induced after infection and vaccination, and show that their functionality differs. The induction of functional VD4-specific antibodies in vaccine recipients mimics previous results from animal models. FUNDING: This work was supported by the European Commission through contract FP7-HEALTH-2011.1.4-4-280873 (ADITEC) and Fonden til Lægevidenskabens Fremme.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial.

BACKGROUND: There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens. METHODS: CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18-45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A-F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A-E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A-E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 µg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 µg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 µg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 µg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 µg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete. FINDINGS: Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A-E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 µg CTH522-CAF01 than 15 µg, although not significantly (intention-to-treat median IgG titre ratio groups A-C:D=5·6; p=0·062), with no difference after three injections of 85 µg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522. INTERPRETATION: CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 µg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials. FUNDING: The EU Horizon Program TRACVAC.

Inflammation and Gut Barrier Function-Related Genes and Colorectal Cancer Risk in Western European Populations.

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N=1,374; colon=871, rectum=503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set of participants (Ncases=1,001; Ncontrols=667). Forty-two unique SNPs from 19 different genes were associated with serum biomarkers at Punadjusted≤0.05 among controls. Among SNPs associated with a gut permeability score, 24 SNPs were in genes related to LPS sensing and mucin synthesis. Nine out of 12 SNPs associated with CRP were in genes related to inflammation or Crohn's disease. TLR4 was associated with colon cancer at the SNP level (nine SNPs, all Punadjusted≤0.04) and at the gene level (Punadjusted≤0.01). TLR4 rs10759934 was associated with rectal cancer but not colon cancer. Similarly, IL10 was associated with rectal cancer risk at a SNP and gene level (both Punadjusted ≤ 0.01), but not colon cancer. Genes and SNPs were selected a priori therefore we present unadjusted P-values. However, no association was statistically significant after multiple testing correction. This large and comprehensive study has identified gut barrier function and inflammation-related genes possibly contributing to CRC risk in European populations and is consistent with potential etiological links between host genetic background, gut barrier permeability, microbial endotoxemia and CRC development.

Whole-grain intake in mid-life and healthy ageing in the Danish Diet, Cancer and Health cohort.

PURPOSE: Growing elderly populations worldwide have sparked interest in factors promoting healthy aging. Diet and other lifestyle patterns are key factors for healthy ageing; however, evidence is sparse for specific dietary guidelines that are easily implemented in everyday life. Whole grains constitute specific dietary components with unexplored potential in healthy ageing. METHODS: We applied an illness-death multistate model to assess the association between whole-grain intake and life expectancy, both with and without disease, over a 20-year period. Healthy ageing was defined as absence of cancer, ischemic heart disease, stroke, type 2 diabetes, asthma, chronic obstructive pulmonary disease, and dementia during follow-up. RESULTS: Based on information from 22,606 men and 25,468 women in the Danish Diet, Cancer and Health cohort, followed for an average of 13.8 and 17.5 years, respectively, a doubling in whole-grain intake was associated with 0.43 (95% CI: 0.33-0.52) and 0.15 (0.06-0.24) additional years without disease for men and women, respectively. Comparing the highest and lowest quartiles of whole-grain intake, with a special emphasis on men, we found that those with the highest intake lived, on average, one year longer without disease compared to those with the lowest intake. Additionally, although a high intake of whole grains yielded longer life expectancy, the duration of living with disease was shorter. CONCLUSION: Intake of whole grains in mid-life was associated with healthy ageing looking 20 years ahead.

Source-specific nitrate and nitrite intakes and associations with sociodemographic factors in the Danish Diet Cancer and Health cohort.

Background: The dietary source and intake levels of nitrate and nitrite may govern its deleterious versus beneficial effects on human health. Existing evidence on detailed source-specific intake is limited. The objectives of this study were to assess nitrate and nitrite intakes from different dietary sources (plant-based foods, animal-based foods, and water), characterize the background diets of participants with low and high intakes, and investigate how sociodemographic and lifestyle factors associate with intake levels. Methods: In the Danish Diet, Cancer and Health Cohort, sociodemographic and lifestyle information was obtained from participants at enrolment (1993-1997). Source-dependent nitrate and nitrite intakes were calculated using comprehensive food composition databases, with tap water nitrate intakes estimated via the national drinking water quality monitoring database linked with participants' residential addresses from 1978 to 2016. Underlying dietary patterns were examined using radar plots comparing high to low consumers while sociodemographic predictors of source-dependent nitrate intakes were investigated using linear regression models. Results: In a Danish cohort of 55,754 participants aged 50-65 at enrolment, the median [IQR] intakes of dietary nitrate and nitrite were 58.13 [44.27-74.90] mg/d and 1.79 [1.43-2.21] mg/d, respectively. Plant-based foods accounted for ~76% of nitrate intake, animal-based foods ~10%, and water ~5%. Nitrite intake was sourced roughly equally from plants and animals. Higher plant-sourced nitrate intake was associated with healthier lifestyles, better dietary patterns, more physical activity, higher education, lower age and lower BMI. Females and participants who had never smoked also had significantly higher plant-sourced nitrate intakes. Higher water-sourced nitrate intake was linked to sociodemographic risk factors (smoking, obesity, lower education). Patterns for animal-sourced nitrate were less clear. Conclusion: Participants with higher plant-sourced nitrate intakes tend to be healthier while participants with higher water-sourced nitrate intakes tended to be unhealthier than their low consuming counterparts. Future research in this cohort should account for the sociodemographic and dietary predictors of source-specific nitrate intake we have identified.

Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. METHODS: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. INTERPRETATION: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. FUNDING: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Immune signature of Chlamydia vaccine CTH522/CAF®01 translates from mouse-to-human and induces durable protection in mice.

The clinical development of an effective Chlamydia vaccine requires in-depth understanding of how well protective pre-clinical immune signatures translate to humans. Here, we report a comparative immunological characterization of CTH522/CAF®01 in female mice and humans. We find a range of immune signatures that translate from mouse to human, including a Th1/Th17 cytokine profile and antibody functionality. We identify vaccine-induced T cell epitopes, conserved among Chlamydia serovars, and previously found in infected individuals. Using the mouse model, we show that the common immune signature protected against ascending infection in mice, and vaccine induced antibodies could delay bacterial ascension to the oviduct, as well as development of pathology, in a T cell depleted mouse model. Finally, we demonstrate long-lasting immunity and protection of mice one year after vaccination. Based on the results obtained in the present study, we propose to further investigate CTH522/CAF®01 in a phase IIb study.

Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Five-year changes in weight and risk of atrial fibrillation in the Danish Diet, Cancer, and Health Cohort.

AIMS: Obesity is a major risk factor for atrial fibrillation (AF). Compared with stable weight, gaining weight was associated with a higher risk of incident AF in observational studies. The results, however, are conflicting regarding weight loss and risk of AF. This study aimed to assess the association between 5-year weight changes and risk of incident AF. METHODS AND RESULTS: The study was based on participants from the Danish Diet, Cancer, and Health Cohort. Body mass index (BMI) was assessed at a baseline examination and at a second examination 5 years later. Diagnoses of AF and co-morbidities were retrieved from the Danish National Patient Registry. In total, 43 758 participants without prior AF were included. The median age was 61 years and 54% were female. During a median follow-up of 15.7 years, 5312 individuals had incident AF (incidence rate 8.6/1000 person-years). Compared with stable weight, weight gain between 2.5 and 5 BMI units (kg/m2) was associated with a higher risk of AF [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09-1.41]. Weight gain of 5 or more BMI units (kg/m2) was associated with a HR of 1.95 (95% CI 1.48-2.56) of incident AF. However, there was no statistically significant association between weight loss and risk of AF. CONCLUSION: Five-year weight gain was associated with greater risk of AF compared with stable weight in the Danish Diet, Cancer, and Health Cohort. There was no statistically significant association between weight loss and risk of AF.

We sought to understand the association between 5-year changes in weight and the future risk of atrial fibrillation, a common heart rhythm disturbance. Overweight, obesity, and underweight were associated with a higher risk of atrial fibrillation compared with normal weight.Gaining weight over a period of 5 years was associated with a higher risk of atrial fibrillation compared with maintaining a stable weight.

Body mass index in parents and their adult offspring: A systematic review and meta-analysis.

Obesity may track across generations, due to genetics and shared family environmental factors, or possibly intrauterine programming. However, many studies only assess associations between maternal body mass index (BMI) and offspring BMI in childhood. To determine whether maternal and paternal associations with offspring BMI differ and whether associations persist into adulthood, a systematic review and meta-analysis was done. PubMed, Embase, Web of Science, and Google Scholar (to October 2022) were searched. Observational studies reporting associations between maternal or paternal BMI and adult offspring BMI were included. Offspring BMIs were reported as continuous or categorical measures. Forty-six studies were included in the systematic review. Meta-analyses were conducted using random-effects models. Parental BMI was positively associated with offspring BMI in adulthood. The pooled mother-offspring standardized mean difference (SMD) was 0.23 (95% confidence interval [CI]: 0.20, 0.26), and father-offspring SMD was similar: 0.22 (95% CI: 0.19, 0.25) in adjusted models. Offspring of mothers with overweight or obesity had the same risk of higher BMI as offspring of fathers with overweight or obesity. If these associations are causal, they support interventions targeting all family members, rather than focusing solely on mothers, to obtain a healthy weight development among offspring.

Interaction of genetic risk and lifestyle on the incidence of atrial fibrillation.

BACKGROUND: The relationship between combined genetic predisposition and lifestyle and the risk of incident atrial fibrillation (AF) is unclear. Therefore, we aimed to assess a possible interaction between lifestyle and genetics on AF risk. METHODS: We included AF cases and a randomly drawn subcohort of 4040 participants from the Danish Diet, Cancer and Health cohort. Lifestyle risk factors were assessed, a score was calculated, and participants were categorised as having a poor, intermediate, or ideal lifestyle. We calculated a genetic risk score comprising 142 variants, and categorised participants into low (quintile 1), intermediate (quintiles 2-4) or high (quintile 5) genetic risk of AF. RESULTS: 3094 AF cases occurred during a median follow-up of 12.9 years. Regardless of genetic risk, incidence rates per 1000 person-years were gradually higher with worse lifestyle. For participants with high genetic risk, the incidence rates of AF per 1000 person-years were 5.0 (95% CI 3.4 to 7.3) among individuals with ideal lifestyle, 6.6 (95% CI 5.4 to 8.1) among those with intermediate lifestyle and 10.4 (95% CI 9.2 to 11.8) among participants with poor lifestyle. On an additive scale, there was a positive statistically significant interaction between genetic risk and lifestyle (relative excess risk due to interaction=0.86, 95% CI 0.68 to 1.03, p<0.001). CONCLUSIONS: The rates of AF increased gradually with worse lifestyle within each category of genetic risk. We found a positive interaction on an additive scale between genetic risk and lifestyle, suggesting that risk factor modification is especially important in individuals with a high genetic risk of AF.

Dietary intakes of dioxins and polychlorobiphenyls (PCBs) and mortality: EPIC cohort study in 9 European countries.

Dioxins and polychlorinated biphenyls (PCBs) are toxic, endocrine disruptors and persistent chemicals for which the main exposure source is diet due to their bioaccumulation and biomagnification in food chains. Cohort studies in the general populations have reported inconsistent associations between these chemicals in serum/plasma and mortality. Our objective was to study the association between dietary intake of 17 dioxins and 35 PCBs and all-cause, cancer-specific and cardiovascular-specific mortalities were assessed in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with European food contamination data provided by the European Food Safety Authority. We applied multivariable Cox regressions. The analysis included 451,390 adults (mean ± SD age:51.1 ± 9.7 years) with 46,627 deaths and a median follow-up of 17.4 years (IQR = 15.2-19.1). A U-shaped non-linear association with all-cause mortality for dietary intake of dioxins (Pnon-linearity<0.0001), DL-PCB (Pnon-linearity = 0.0001), and NDL-PCBs (Pnon-linearity<0.01) was observed. For example, the hazard ratios (95%Confidance interval) for all-cause mortality obtained with the spline model was equal to 1.03 (1.02-1.05) for low levels of intake to dioxins (7 pg TEQ/day), 0.93 (0.90-0.96) for moderate levels of intake (25 pg TEQ/day), while for high levels of intake (55 pg TEQ/day) it was 1.03 (0.97-1.09). Intake of dioxins, DL-PCBs and NDL-PCBs was not associated with cardiovascular mortality. There was no association between intakes of dioxins and cancer mortality, but a U-shaped association was observed for intake of DL-PCBs and intakes of NDL-PCBs and cancer mortality. The PCBs and dioxins are known to have endocrine disrupting properties which can lead to non-monotonic dose responses. These results need to be interpreted with caution and further studies are needed to better clarify the association between dietary intake of dioxins and PCB and mortality in the general population.

Parental cardiovascular disease and cardiovascular disease risk factors in the offspring: The Diet, Cancer and Health cohorts.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) aggregates in families and offspring with parental CVD may have adverse risk factor levels long time before the potential onset of CVD. We compared risk factor levels in offspring of parents with atherosclerotic CVD (ASCVD) and parents with no ASCVD at different parental ages at onset. METHODS: The study included 5751 participants (median age: 50 years) of the Diet, Cancer and Health - Next Generations study. Measurements included blood pressure, body composition and lipid fractions. Information on parental ASCVD and age at disease onset was obtained through register linkage. Parental ASCVD was defined as myocardial infarction, ischemic stroke or peripheral artery disease occurring <70 years, prematurely (mothers: <65 years fathers: <55 years), divided into age categories or using a broader classification of CVD. Linear regression models using Generalized Estimating Equations were used for analysis. Analyses were adjusted for age, sex, education, smoking, alcohol intake, physical activity and some additionally for BMI. RESULTS: Offspring with parental ASCVD had a higher blood pressure, waist circumference, BMI, visceral adipose tissue, percentage of body fat and non-HDL cholesterol levels, but not other lipid levels, compared to offspring with no parental ASCVD (all p < 0.01). Overall, the same patterns were observed for parental ASCVD occurring prematurely and using a broader CVD classification. CONCLUSIONS: Offspring with parental ASCVD had a higher blood pressure, higher body composition measures and higher non-HDL cholesterol levels compared to offspring with no parental ASCVD. Findings were overall consistent across different classifications of parental ASCVD.