von Falkenhausen AS, Wenner FN, Freyer L
… +9 more, Sams LE, Heier M, Peters A, Linkohr B, Massberg S, Bauer A, Kääb S, Rizas KD, Sinner MF
Eur J Epidemiol
· 2025 Jul · PMID 40569484
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AIMS: Heart-rate variability (HRV) measures are surrogates of autonomic function at the level of the sinus node and have evolved as markers of cardiovascular mortality in patients after myocardial infarction (MI). Tradit...AIMS: Heart-rate variability (HRV) measures are surrogates of autonomic function at the level of the sinus node and have evolved as markers of cardiovascular mortality in patients after myocardial infarction (MI). Traditionally, HRV is assessed in time-domain and frequency domain. Advanced measures of autonomic function include deceleration capacity (DC) and periodic repolarization dynamics (PRD). DC predominantly quantifies the influence of parasympathetic tone. PRD captures low-frequency oscillations of repolarization instability and is considered to reflect sympathetic activity at the level of the left ventricular myocardium. However, population-based reference values are missing. METHODS AND RESULTS: In 505 participants of the population-based KORA F3 study (Cooperative Health Research in the Region of Augsburg) with extant digital 24-h Holter electrocardiograms we assessed markers of HRV in time and frequency domains. Additionally, we determined advanced measures of autonomic function including DC and PRD applying previously established technologies. We used standard, pre-defined cut-off values to define high-risk groups. The cohort's mean age was 63.6 ± 5.5 years, and 256 (50.1%) were women. Among HRV measures, exemplarily the median standard deviation of all normal-to-normal intervals (SDNN) was 141 ms [119;165] and the median low frequency to high frequency ratio (LF/HF-ratio) was 3.92 [2.69;6.18]. Regarding autonomic function, median DC was 5.32 ms [2.69;6.18], and median PRD was 2.92 ms [2.06;4.14]. Among these measures LF/HF-ratio was significantly higher among men (5.15 [3.23; 7.20]) than women (3.37 [2.36;4.53], p < 0.001). Measured distribution is also provided in a cohort subset without overt cardiovascular conditions. While DC decreased with age, SDNN, LF/HF-ratio, and PRD were stable across age-groups. For participants with comorbidities including hypertension, intake of betablockers, history of MI, stroke, or diabetes mellitus significantly lower SDNN, LF/HF-ratio, and DC were observed. CONCLUSION: In a large population-based cohort, we systematically present traditional and advanced measures of HRV of cardiac autonomic function. We report reference values in the overall cohort, as well as stratified by sex, age, and concomitant cardiovascular conditions.
Hamaya R, Cook NR, Sesso HD
… +3 more, Mora S, Buring JE, Manson JE
Eur J Epidemiol
· 2025 Jul · PMID 40569483
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Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear...Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals benefit the most from supplementation. We sought to develop an omega-3 effect score to stratify individuals according to their expected benefit from supplementation. Among the 25,871 randomized participants without a history of cardiovascular disease in the VITamin D and OmegA-3 TriaL (VITAL), we applied machine-learning (ML) approaches to predict individual treatment effect of omega-3 FA supplementation on 5-year CHD risk using 11 covariates pre-specified in the VITAL protocol. An omega-3 effect score was developed such that each covariate contributed linearly. ML algorithms effectively stratified participants by their expected benefit according to individual factors; for example, there was 1.21% absolute CHD risk reduction in the top tertile of the expected benefit, compared with the average effect of 0.47% risk reduction. Baseline diabetes, race, hypertension, sex, and fish intake contributed the most to the omega-3 effect score. Five-year CHD risk was 2.5% among those in the omega-3 arm and 3.2% among those in the placebo arm with omega-3 effect score ≥ 4 (upper 70th percentile), and 1.4% among the omega-3 arm and 1.3% among the placebo arm in those with the score < 4, respectively. The transportability of the score to the National Health and Nutrition Examination Survey (NHANES) data was confirmed. Although testing of the score in a new RCT is warranted, the proposed omega-3 effect score holds promise for guiding decision making for omega-3 FA supplementation in the US primary prevention population.
Amadou C, Wei Y, Tuomi T
… +2 more, Feychting M, Carlsson S
Eur J Epidemiol
· 2025 Jul · PMID 40553354
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Incidence of early-onset (< 40 years) type 2 diabetes (T2D) is increasing. While multiple risk factors have been identified, particularly obesity and low socioeconomic status, early-life factors are hypothesised to play...Incidence of early-onset (< 40 years) type 2 diabetes (T2D) is increasing. While multiple risk factors have been identified, particularly obesity and low socioeconomic status, early-life factors are hypothesised to play a role via fetal programming. We investigated sociodemographic and early-life factors in relation to early-onset T2D using a family-based design that accounts for shared genetic and environmental factors. We included 1,814,062 individuals born in Sweden 1983 to 2002 with follow-up data until 2020, and identified early-onset (age 19-39) T2D cases (n = 3505) through National Diabetes, Patient and Prescribed Drug Registers. Perinatal and sociodemographic factors were retrieved from registers. We used a cohort and sibling design, with multivariable-adjusted Cox proportional hazards regression. Sociodemographic factors associated with early-onset T2D included low parental education, single parenthood, younger parental age and non-Swedish origin. The latter association did not remain after mutual adjustment. Regarding perinatal factors, a higher incidence was noted in relation to lower birth weight (hazard ratio 2.38 [95% confidence interval: 1.98-2.87] and 1.43[1.33-1.54] for < 2500 g and 2500-3500 g, respectively, vs 3500-4500 g), small-for-gestational-age (SGA) (2.24[1.96-2.56]), large-for-gestational-age (LGA) (1.19[1.01-1.39]), and maternal obesity (2.34[2.04-2.69]), diabetes (1.59[1.36-1.85]), smoking (1.59[1.48-1.71]), and infection (1.21[1.03-1.41]) during pregnancy. In the sibling analysis, only low birth weight and SGA remained associated with early-onset T2D. Early-onset T2D is associated with sociodemographic and multiple perinatal factors; only growth restriction likely reflects fetal programming, while other perinatal-related associations might involve confounders. This study highlights the need for early-life, targeted strategies to prevent T2D and reduce health inequities.
The Guangzhou Older Longitudinal Dynamic Health (GOLD-Health) Cohort is a prospective population-based cohort study aimed at investigating the risk factors associated with non-communicable diseases (NCDs) among adult ind...The Guangzhou Older Longitudinal Dynamic Health (GOLD-Health) Cohort is a prospective population-based cohort study aimed at investigating the risk factors associated with non-communicable diseases (NCDs) among adult individuals in Guangzhou, one of China's most developed and densely populated cities. From 1 Jan 2018 until 31 Dec 2020, 737,863 participants (mean age = 71.8 years, 58.9% were female) completed baseline data collection, among which approximately 92.1% donated blood samples. Baseline data collection comprises various factors, including general characteristics, socio-economic factors, lifestyle habits, cooking fuel usage and living standards, and medical history of chronic diseases. Additionally, physical and biochemical indicator examinations are conducted by trained medical staff. Two complementary follow-up approaches are utilized to validate and enrich the outcome information on mortality and non-communicable disease outcomes, ensuring its reliability and comprehensiveness. First, routine linkage with the Guangzhou Municipal Health Commission's electronic records provides continuous monitoring of mortality events and participants' inpatient and outpatient hospital visits. Second, periodic follow-up is conducted through telephone interviews and regular face-to-face surveys to collect detailed information on health status, lifestyle changes, newly diagnosed conditions, and self-reported events not captured in hospital records. This combined approach ensures both the completeness and accuracy of the cohort data. This cohort may serve as a decision-making tool for chronic disease management and contributes to the evaluation of scientific findings under real-world conditions.
Sánchez-Sáez F, Sanfélix-Gimeno G, Hurtado I
… +5 more, García-Sempere A, Garcés-Sánchez M, Llopis-Cardona F, Peiró S, Rodríguez-Bernal CL
Eur J Epidemiol
· 2025 Jul · PMID 40549278
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The main aim of the PREGVAL cohort is to evaluate and monitor the in-utero safety of medication administered to pregnant women, as usually this population is excluded from clinical trials assessing drugs. It is a populat...The main aim of the PREGVAL cohort is to evaluate and monitor the in-utero safety of medication administered to pregnant women, as usually this population is excluded from clinical trials assessing drugs. It is a population-based cohort, comprised by pregnant women and their offspring in the Valencia Region (Spain), between July 1st 2009 and December 31st 2021, which will be followed from 6 months pre-conception until death, loss of coverage or end of study, with over 520.000 pregnancies for the study period. The data source will be the Valencia Integrated Database (VID), which links records at the individual level using a unique personal identification code, with exhaustive data on comorbidities (diabetes, hypertension, etc.) and other clinical variables, sociodemographic variables (age, socio-economic status, risk of social exclusion) and other potential confounders (smoking, alcohol intake). It also provides accurate data on timing of exposure for most livebirths and all of the stillbirths occurred in the region, and partially for spontaneous abortions and elective terminations (due to the availability of gestational age by ultrasound or last menstrual period for these outcomes allowing the calculation of the date of conception) and allows the identification of medications prescription and dispensation data with a very high detail, avoiding the problem of potential exposure misclassification present in many of the existent registries/cohorts. Regarding outcomes, there is exhaustive and accurate data on pregnancy complications, spontaneous abortions, terminations (in this case, those occurred within the public health system), birth weight, preterm birth, congenital anomalies, and perinatal mortality; as well as the availability of post-natal long-term follow-up. These features make the PREGVAL study one of the largest and most exhaustive cohorts to assess real-world in-utero safety of medications to date.
Ola I, Cardoso R, Hoffmeister M
… +1 more, Brenner H
Eur J Epidemiol
· 2025 Jul · PMID 40526328
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Despite increasing implementation of colorectal cancer (CRC) screening programs in Europe, utilization of screening tests has varied significantly over the years. We examined recent trends in the utilization of colonosco...Despite increasing implementation of colorectal cancer (CRC) screening programs in Europe, utilization of screening tests has varied significantly over the years. We examined recent trends in the utilization of colonoscopy and fecal occult blood test (FOBT), the primary tests recommended for CRC screening, across European countries with various screening programs. Population-based data from the second and third waves of the European Health Interview Survey (EHIS) were analyzed to determine changes in utilization of fecal occult blood test within the preceding 2 years or colonoscopy within the preceding 10 years among people aged 50-74 years between 2013-2015 and 2018-2020. Absolute percentage changes (APC) in screening test use were calculated in each country and subgroup meta-analyses were conducted using random effects models to estimate the pooled APCs and their 95% confidence intervals across different categories of screening offers. A total of 234,251 respondents across 28 European countries were included in the analysis. The increase in use of either test was highest among countries which fully rolled out nationwide organized screening programs with fecal tests between 2013-2015 and 2018-2020 (increases ranging from 19.1% units in Belgium to 46.3% units in The Netherlands) and was lowest among countries with opportunistic offering of fecal test, colonoscopy or flexible sigmoidoscopy (from - 3% units in Germany to + 12.2% units in Slovakia). Changes in screening programs were strongly associated with higher rates of utilization of colonoscopy and fecal occult blood test across all screening offers. Our findings highlight that well-organized and dynamic population screening strategies can rapidly and sustainably increase utilization of CRC screening tests in Europe.
Darbani B, Brodersen T, Liljensøe A
… +70 more, Sørensen SB, Olsson-Svendsen JB, Buil A, Kamal A, Schork AJ, Poulsen A, Kjerulff BD, Aagaard B, Lund BØ, Rittig CS, Mikkelsen C, Larsen DM, Westergaard D, Rudbeck-Resdal D, Mikkelsen DH, Randers E, Schiødt FV, Hoffmann HJ, Jørgensen IF, Brandslund I, Brodersen JB, von Stemann JH, Bay JT, Nissen J, Sørensen J, Boldsen JK, Dowsett J, Gladov J, Banasik K, Kaspersen KA, Carlsen K, Dinh KM, Kellermann L, Christoffersen LAN, Quinn LJE, Thørner LW, Larsen L, Aamann L, Andersen MR, Didriksen M, Alexandraki MJ, Thomsen MK, Julsgaard M, Nyegaard M, Schwinn M, Topholm-Bruun M, Leite MN, Halling ML, Pedersen N, Bonderup OK, Rohde PD, Ovesen PD, Dessau RB, Saboori S, Holm-Christensen S, Bank S, Mikkelsen S, Hansen TF, Werge T, Qvist N, Sørensen E, Burisch J, Hetland ML, Glintborg B, Erikstrup C, Brunak S, Ullum H, Ostrowski SR, Pedersen OBV, Andersen V
Eur J Epidemiol
· 2025 Jun · PMID 40488802
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The Copenhagen Hospital Biobank-chronic inflammatory disease-inflammatory bowel disease (CHB-CID: IBD) cohort contributes to genetic research in inflammatory bowel disease, including Crohn's disease and ulcerative coliti...The Copenhagen Hospital Biobank-chronic inflammatory disease-inflammatory bowel disease (CHB-CID: IBD) cohort contributes to genetic research in inflammatory bowel disease, including Crohn's disease and ulcerative colitis. Of the 327,084 enrolled and genotyped individuals in the cohort, 10,626 have been diagnosed with IBD as of May 2023. The CHB-CID: IBD cohort includes both patients without IBD and healthy blood donors as control groups. Clinical data is collected from Danish registries and patient records, including details on hospital contacts, co-morbidities, medication, surgical procedures, and laboratory investigations. The cohort features a wide age range (> 18 years), extensive population coverage representative of Danish adults, and validated IBD diagnoses. Finally, the cohort benefits from continuous recruitment and regular updates of clinical information. The aim is to enhance IBD management and ultimately improve patients' quality of life.
Jiesisibieke ZL, Cronjé HT, Schooling CM
… +1 more, Burgess S
Eur J Epidemiol
· 2025 Jun · PMID 40488801
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Ketogenic diets are popular among people aiming for weight management. Ketone supplementation has been linked to improved cognitive performance and increased risk of insulin resistance. We aim to identify common genetic...Ketogenic diets are popular among people aiming for weight management. Ketone supplementation has been linked to improved cognitive performance and increased risk of insulin resistance. We aim to identify common genetic variants that allow Mendelian randomization investigations into further potential effects of ketone metabolism. We set four premises that we believe any valid instrument for ketone metabolism should satisfy. These are: (1) location in a gene region relevant to ketone metabolism, (2) association with all three primary ketone bodies (acetone, acetoacetate, and beta-hydroxybutyrate), (3) no pleiotropic associations, (4) associations with positive control variables (cognitive performance, two-hour glucose, and insulin fold change). We considered gene regions containing variants previously associated with acetone. Four of these regions had biological relevance to ketone metabolism. Lead variants for three of these four regions (SLC2A4, HMGCS2, OXCT1) were associated with all three primary ketone bodies. One region (SLC2A4) was associated with two-hour glucose and insulin fold change; however, this region had strong pleiotropic associations with blood pressure. One region (OXCT1) showed an association with cognitive performance, and thus satisfied all our premises to be a valid instrument for ketone metabolism. In a complementary agnostic approach considering all genome-wide significant predictors of the three primary ketone bodies in turn, genetically predicted acetoacetate based on seven variants was associated with improved cognitive performance. However, several variants selected in this approach were not located in biologically relevant gene regions and were pleiotropic. Causal claims from Mendelian randomization will be most reliable when the instrumental variable assumptions are plausibly satisfied. We illustrate a framework to identify candidate instruments based on biological considerations.
Infections in utero and early childhood are associated with an increased epilepsy risk; however, confounding by familial predisposition has not been adequately accounted for in previous studies. We aimed to assess the ep...Infections in utero and early childhood are associated with an increased epilepsy risk; however, confounding by familial predisposition has not been adequately accounted for in previous studies. We aimed to assess the epilepsy risk attributable to infections in utero and early childhood by performing population-based and sibling-comparison analyses to account for residual and unmeasured familial confounding factors. This nationwide birth cohort study included 2,609,289 individuals born 2001-2016 in Taiwan. Maternal infection during pregnancy and early childhood infection during the first year of life were defined. Maternal pre-pregnancy infection was used as negative control. In the population analyses, offspring exposed to any maternal infection during pregnancy had an increased epilepsy risk (hazard ratio (HR) = 1.36, 95% confidence interval (CI):1.27-1.45). However, the association with maternal infection was attenuated to the null (HR = 1.11, 95% CI:0.98-1.27), except for maternal infection in sepsis (HR = 2.54, 95% CI:1.74-3.70) and central nervous system (HR = 24.59, 95% CI:3.28-184.23), in the sibling analyses. The association of maternal pre-pregnancy infection with offspring epilepsy was observed in the population analyses, but not in the sibling analyses. Individuals exposed to childhood infection had an increased epilepsy risk (HR = 1.49, 95% CI:1.45-1.54) in the population analyses; the association was still observed in the sibling analyses (HR = 1.31, 95% CI:1.23-1.40). The association between maternal infection during pregnancy and epilepsy risk in the offspring appears largely because of familial confounding factors. Infections during early childhood may play a causal role in the subsequent epilepsy risk.
Ke Y, Zhao Y, Sun D
… +12 more, Pei P, Du H, Chen Y, Yang L, Yang X, Chen Y, Chen J, Chen Z, Lv J, Li L, Yu C, China Kadoorie Biobank Collaborative Group
The prevalence of chronic obstructive pulmonary disease (COPD) is rising in China, yet population-based evidence on COPD-related mortality risk remains limited. This study examined the association between prevalent COPD...The prevalence of chronic obstructive pulmonary disease (COPD) is rising in China, yet population-based evidence on COPD-related mortality risk remains limited. This study examined the association between prevalent COPD and all-cause and cause-specific mortality in a large Chinese cohort. 484,301 adults aged 30 to 79 years who received spirometry at the baseline of the China Kadoorie Biobank Study (2004-2008) were included. COPD was defined as FEV/ FVC < 0.7. Mortality data were tracked via local death registries and national health insurance systems over a median follow-up period of 16.0 years. Cox proportional hazard models and competing risk regression were used to estimate hazard ratios (HRs) and subdistribution HRs (SHRs), respectively. The COPD group had higher all-cause and cause-specific mortality, with adjusted HR (95%CI) for all-cause mortality of 1.44 (1.41-1.47), and adjusted SHR (95%CI) of 1.09 (1.05-1.13), 1.06 (1.01-1.11), 3.30 (3.12-3.49), 1.45 (1.16-1.81), for circulatory disease, neoplasms, respiratory disease, and infectious disease mortality, respectively. Specifically, young COPD (aged < 50 years) showed a stronger mortality association than those aged ≥ 50 years. Moreover, individuals with preserved ratio impaired spirometry (PRISm) had a 1.4-fold higher risk of all-cause mortality compared with non-COPD participants. COPD is associated with a significantly elevated risk of mortality from all causes, circulatory disease, neoplasms, respiratory disease, and infectious disease in the Chinese population. Additionally, young COPD and those with PRISm faced significant mortality burdens.
Hamilton FW, Hughes DA, Lu T
… +5 more, Kutalik Z, Gkatzionis A, Tilling K, Hartwig FP, Davey Smith G
Eur J Epidemiol
· 2025 Jun · PMID 40455395
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Non-linear Mendelian randomisation (NLMR) is a relatively recently developed approach to estimate the causal effect of an exposure on an outcome where this is expected to be non-linear. Two commonly used techniques-based...Non-linear Mendelian randomisation (NLMR) is a relatively recently developed approach to estimate the causal effect of an exposure on an outcome where this is expected to be non-linear. Two commonly used techniques-based on stratifying the exposure and performing Mendelian randomisation (MR) within each strata-are the residual and doubly-ranked methods. The residual method is known to be biased in the presence of genetic effect heterogeneity-where the effect of the genotype on the exposure varies between individuals. The doubly-ranked method is considered to be less sensitive to genetic effect heterogeneity. In this paper, we simulate genetic effect heterogeneity and confounding of the exposure and outcome and identify that both methods are susceptible to likely unpredictable bias in this setting. Using UK Biobank, we identify empirical evidence of genetic effect heterogeneity and show via simulated outcomes that this leads to biased MR estimates within strata, whilst conventional MR across the full sample remains unbiased. We suggest that these biases are highly likely to be present in other empirical NLMR analyses using these methods and urge caution in current usage. Simulated outcome analyses may represent a useful test to identify if genetic effect heterogeneity is likely to bias NLMR estimates in future analyses.
Zazueta-Borboa JD, van Wissen L, Sizer A
… +1 more, Janssen F
Eur J Epidemiol
· 2025 May · PMID 40455394
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The increase in life expectancy at birth (e0) has stagnated since 2011 in England & Wales (E&W). Prior research hypothesized that the stagnation is related to increasing austerity measures and widening socio-economic ine...The increase in life expectancy at birth (e0) has stagnated since 2011 in England & Wales (E&W). Prior research hypothesized that the stagnation is related to increasing austerity measures and widening socio-economic inequalities. We formally assessed the contribution of education-specific mortality trends and increasing educational inequalities to the stagnation. We used individually-linked mortality data by sex, educational attainment (low, middle, high), and age (30+) from the ONS Longitudinal Study. We compared, by sex, the observed with the expected (= projected) increase in remaining life expectancy at age 30 (e30) in 2011-2017 for the national and education-specific populations. We assessed the education-specific mortality contributions using stepwise decomposition, and the contribution of increasing educational inequalities using a scenario analysis that assumes constant inequalities. In E&W in 2011-2017, e30 increased by 1.32 years (males) and 1.14 years (females) less than expected, which translates into 2.3 and 1.9 months annually. Stagnation of the increase in e30 occurred across all educational groups, with declines in e30 after 2011 for middle-educated males and low-educated females. Mortality trends among low-educated males (41.4%), middle-educated males (53.5%), and low-educated females (86.1%) contributed the most to the sex-specific stagnation. The observed increases in educational inequalities between 2011 and 2017 contributed approximately 27% to the national e30 stagnation.Widening educational inequalities, and particularly the unfavourable mortality trends observed for middle educated males and low educated females since 2011, contributed substantially to the e30 stagnation since 2011 in England & Wales.
OBJECTIVES: Gout is the most common inflammatory arthritis and affects quality of life. Dietary polyunsaturated fatty acids (PUFAs) have protective effects against various diseases, but its role in gout remains uncertain...OBJECTIVES: Gout is the most common inflammatory arthritis and affects quality of life. Dietary polyunsaturated fatty acids (PUFAs) have protective effects against various diseases, but its role in gout remains uncertain. Our study aims to assess the association between PUFAs intake and gout risk, the role of genetic factors, and the possible impact of metabolites. METHODS: This study included 198,033 participants who were free of gout at baseline and completed at least one reliable dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between PUFAs intake and gout risk, and the modified effects of genetic predisposition. Mediation analysis also explored the mediating role of metabolic signature in associations between specific PUFAs intake and gout. RESULTS: Over a median follow-up of 9.47 years, 1,708 incident cases of gout were recorded. Gout risk was significantly associated with the second quartile of linoleic acid (LA) (0.86 [0.75, 1.00]) intake and the highest quartiles of alpha-linolenic acid (ALA) (0.72 [0.62, 0.84]), total PUFA (HR: 0.84 [95% CI:0.71, 0.99]), n-6 PUFA (0.84 [0.71, 0.99]), n-3 PUFA (0.83 [0.71, 0.98]), and eicosapentaenoic acid (EPA) (0.79 [0.68, 0.91]), compared to the lowest quartiles. We observed joint effects of PUFAs intake and genetic susceptibility on gout risk. Mediation analysis showed that high-density lipoprotein (HDL) and triglycerides mediated the associations of ALA and LA with gout risk. CONCLUSION: Our findings suggested the potential benefits of PUFAs in reducing gout risk, particularly vegetable sources, with HDL and triglycerides as key mediators.
Inflammation and insulin resistance are associated with increased mortality in the general population. However, it remains unclear how physical activity and proinflammatory/hyperinsulinemic diets influence overall surviv...Inflammation and insulin resistance are associated with increased mortality in the general population. However, it remains unclear how physical activity and proinflammatory/hyperinsulinemic diets influence overall survival in prostate cancer patients. We analyzed 4779 men with nonmetastatic prostate cancer from the Health Professionals Follow-up Study. Postdiagnosis physical activity and diet were assessed using validated self-reported questionnaires. We used the validated dietary scores to empirically assess the anti-inflammatory (rEDIP) and anti-insulinemic (rEDIH) potential of dietary patterns based upon specific combinations of food groups. Cox regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median of 15 years of follow-up, we identified 2282 deaths. Compared to men with < 3 MET-h/week of postdiagnosis physical activity, multivariable-adjusted HRs (95% CI) were 0.80 (0.68-0.95) for 9-< 24 MET-h/week, 0.63 (0.53-0.75) for 24-< 48 MET-hours/week and 0.61 (0.51-0.73) for ≥ 48 MET-hours/week in relation to all-cause mortality (P-trend < 0.001). Both vigorous and non-vigorous activities after diagnosis were associated with lower all-cause mortality (P-trend < 0.001). Moreover, post-diagnosis rEDIP and rEDIH scores were inversely associated with all-cause mortality (HR per 1-SD increase: 0.93 (0.89-0.99) for rEDIP; 0.91 (0.86-0.96) for rEDIH). In joint analyses, men with high physical activity and high rEDIP (or rEDIH) score showed approximately 30-36% lower risks of all-cause mortality, compared to those with low physical activity and low diet scores. In conclusion, high physical activity and low proinflammatory and hyperinsulinemic diets were independently associated with decreased risk of all-cause mortality in men with prostate cancer. Men with both high physical activity and low proinflammatory and hyperinsulinemic diets after diagnosis have the lowest mortality rate.
In utero exposure to diethylstilbestrol (DES) is associated with increased risk of clear cell adenocarcinoma (CCAC) of the vagina or cervix. It is not clear whether these risks remain increased at older ages, and if the...In utero exposure to diethylstilbestrol (DES) is associated with increased risk of clear cell adenocarcinoma (CCAC) of the vagina or cervix. It is not clear whether these risks remain increased at older ages, and if the risks of other cancer sites, including breast cancer, are increased. This nationwide cohort study included 12,249 DES-exposed women and 2,070 unexposed sisters. Hormone-related risk factors and medical history were assessed through questionnaires, and cancer incidence through linkages with nationwide registries. Comparison with general population rates showed no difference in overall cancer risk (SIR = 0.98, 95%CI 0.93-1.04) or breast cancer risk (SIR = 1.03, 95%CI 0.96-1.11) for DES-exposed women. The rate of vaginal cancer was strongly increased for DES-exposed women (SIR = 10.5, 95%CI 5.72-17.6) and was increased in all age categories, including age 60-69 years (SIR = 8.3, 95%CI 1.00-29.9). Risks of both CCAC (SIR = 49.1, 95%CI 21.2-96.8) and squamous cell carcinoma (SCC; SIR = 5.86, 95%CI 2.15-12.8) of the vagina were significantly elevated. When comparing DES-exposed women with DES-unexposed sisters, overall cancer risk and risk of breast cancer were similar (HR = 0.93, 95%CI 0.78-1.11 and HR = 0.97, 95%CI 0.76-1.23, respectively). Apart from the established increased risk of vaginal cancer, women exposed to DES in utero do not seem to be at increased risk of cancer, including breast cancer. The risk of vaginal cancer remains increased also for women in their fifties/sixties. Moreover, the increased risk of vaginal cancer was seen for both subtypes CCAC and SCC. Screening for vaginal cancer up to higher ages than currently recommended (< 60 years) should be considered.