Large Population-based Cohort Research Articles

Propofol sedation does not improve measures of colonoscopy quality but increase cost – findings from a large population-based cohort study

Propofol is often used for sedation during colonoscopy. We assessed the impact of propofol sedation on colonoscopy related quality metrics and cost in a population-based cohort study. All colonoscopies performed at 21 hospitals in the province of Ontario, Canada, during an 18-month period, from April 1, 2017 to October 31, 2018, using either propofol or conscious sedation were evaluated. The primary outcome was adenoma detection rate (ADR) and secondary outcomes were sessile serrated polyp detection rate (ssPDR), polyp detection rate (PDR), cecal intubation rate (CIR), and perforation rate. Binary outcomes were assessed using a modified Poisson regression model adjusted for clustering and potential confounders based on patient, procedure, and physician characteristics. A total of 46,634 colonoscopies were performed, of which 16,408 (35.2%) received propofol and 30,226 (64.8%) received conscious sedation. Compared to conscious sedation, the use of propofol was associated with a lower ADR (24.6% vs. 27.0%, p<0.0001) but not ssPDR (5.0% vs. 4.7%, p=0.26), PDR (40.5% vs 40.4%, p=0.79), CIR (97.1% vs. 96.8%, p=0.15) or perforation rate (0.04% vs. 0.06%, p=0.45). On multi-variable analysis, propofol sedation was not associated with any differences in ADR (RR=0.90, 95% CI 0.74-1.10, p=0.30), ssPDR (RR=1.20, 95% CI 0.90-1.60, p=0.22), PDR (RR=1.00, 95% CI 0.90-1.11, p=0.99), or CIR (RR=1.00, 95% CI 0.80-1.26, p=0.99). The additional cost associated with propofol sedation was $12,730,496 for every 100,000 cases. The use of propofol sedation was not associated with improved colonoscopy related quality metrics but increased costs. The routine use of propofol for colonoscopy should be reevaluated. None.

Birth by caesarean section and semen quality in adulthood: a Danish population-based cohort study

BackgroundThe caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons’ semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality.MethodsThis study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs).ResultsAmong included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): − 7.5% (− 14.1% to − 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally.ConclusionsThis large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.

Association of Combined Healthy Lifestyle Factors With Incident Dementia in Participants With and Without Multimorbidity: A Large Population-Based Prospective Cohort Study.

The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. Over a median follow-up period of 12.5 years, 5852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.

Noise annoyance and cardiovascular disease risk: results from a 10-year follow-up study

The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35–74 years, baseline investigation period 2007–2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13–1.27, p < 0.0001). While in the 10-year follow-up, mostly positive associations (although not significant) between noise annoyance and incident CVD were observed, no indication of increased CVD risk was observed after 5 years of follow-up. Noise annoyance due to different sources was associated with prevalent CVD, whereas only weak associations with incident CVD were found. Further large-scale studies are needed to establish the relationship between noise annoyance and risk of CVD.

Plasma proteomic signature of human longevity.

The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age. Plasma proteomics was measured using a SOMAscan assay in 3067 participants from the Cardiovascular Health Study (discovery cohort) and 4690 participants from the Age Gene/Environment Susceptibility-Reykjavik Study (replication cohort). Logistic regression identified 211 significant proteins in the CHS cohort using a Bonferroni-adjusted threshold, of which 168 were available in the replication cohort and 105 were replicated (corrected p value <0.05). The most significant proteins were GDF-15 and N-terminal pro-BNP in both cohorts. A parsimonious protein-based prediction model was built using 33 proteins selected by LASSO with 10-fold cross-validation and validated using 27 available proteins in the validation cohort. This protein model outperformed a basic model using traditional factors (demographics, height, weight, and smoking) by improving the AUC from 0.658 to 0.748 in the discovery cohort and from 0.755 to 0.802 in the validation cohort. We also found that the associations of 169 out of 211 proteins were partially mediated by physical and/or cognitive function. These findings could contribute to the identification of biomarkers and pathways of aging and potential therapeutic targets to delay aging and age-related diseases.

The Association between Psychosocial Stressors and Gestational Weight Gain: Analysis of the National Pregnancy Risk Assessment Monitoring System (PRAMS) Results from 2012 to 2015.

Both psychosocial stress and gestational weight gain are independently associated with adverse maternal and fetal outcomes. Studies of the association between psychosocial stress and gestational weight gain (GWG) have yielded mixed results. The objective of this study was to evaluate the association between psychosocial stress and GWG in a large population-based cohort. Data from the nationally representative Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 7 questionnaire 2012-2015 was utilized. Maternal psychosocial stress was assessed through response to questions designed to examine four domains of psychosocial stress (i.e., traumatic, financial, emotional, partner-related) three months prior to or during pregnancy. GWG was categorized using pre-pregnancy BMI and total GWG into inadequate, adequate, or excessive according to the Institute of Medicine's GWG guidelines. Multinomial logistic regression was used to evaluate the association between psychosocial stressors and adequacy of GWG. Analyses took into account complex survey design. All respondents who delivered ≥ 37 weeks gestation with GWG information available were included in the analysis (n = 119,183). After adjusting for confounders, patients who reported financial stress were more likely to experience excessive versus adequate GWG (RRR 1.09 [95%CI: 1.02-1.17]). Exposure to any of the stressor groups did not significantly increase the risk of inadequate GWG. This large, population-based study revealed that among pregnant people in the US, exposure to financial stress is associated with higher risk of excessive GWG. Understanding the role stress plays in GWG will help to inform initiatives targeting this important aspect of prenatal care.

Long-term air pollution exposure and risk of SARS-CoV-2 infection: A UK-wide cohort study

BackgroundThe association between air quality and risk of SARS-CoV-2 infection is poorly understood. We investigated this association using serological individual-level data adjusting for a wide range of confounders, in a large population-based cohort (COVIDENCE UK). MethodsWe assessed the associations between long-term (2015–19) nitrogen dioxide (NO2) and fine particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5), exposures with SARS-CoV-2 infection, level of antibody response among those infected, and COVID-19 disease severity. We used serological data from 10,489 participants in the COVIDENCE UK cohort, and estimated annual average air pollution exposure at each participant's home postcode. ResultsAfter controlling for potential confounders, we found a positive association between 5-year NO2 and PM2.5 exposures and the risk of seropositivity: 10 unit increase in NO2 (μg/m3) was associated with an increasing risk of seropositivity by 1.092 (95% CI 1.02 to 1.17; p-for-trend 0.012). For PM2.5, 10 unit increase (μg/m3) was associated with an increasing risk of seropositivity by 1.65 (95% CI 1.015–2.68; p-for-trend 0·049). In addition, we found that NO2 was positively associated with higher antibody titres (p-for-trend 0·013) among seropositive participants, with no evidence of an association for PM2.5. ConclusionOur findings suggest that the long-term burden of air pollution increased the risks of SARS-CoV-2 infection and has important implications for future pandemic preparedness. This evidence strengthens the case for reducing long-term air pollution exposures to reduce the vulnerability of individuals to respiratory viruses.

Association of serum five heavy metals level with all-cause and cause-specific mortality: a large population-based cohort study

The study aimed to explore the association between five heavy metals exposure (Cadmium, Lead, Mercury, Manganese, and Selenium) and mortality [all-cause, cardiovascular disease (CVD), and cancer-related]. We integrated the data into the National Health and Nutrition Examination Survey from 2011 to 2018 years. A total of 16,092 participants were recruited. The link between heavy metals exposure and mortality was analyzed by constructing a restricted cubic spline (RCS) curve, Cox proportional hazard regression model, and subgroup analysis. The RCS curve was used to show a positive linear relationship between Cadmium, Lead, and all-cause mortality. In contrast, there was a negative linear correlation between Mercury and all-cause mortality. Additionally, Manganese and Selenium also had a J-shaped and L-shaped link with all-cause mortality. The positive linear, positive linear, negative liner, J-shaped, and L-shaped relationships were observed for Cadmium, Lead, Mercury, Manganese, and Selenium and CVD mortality, respectively. Cadmium, Lead, Mercury, and Selenium were observed to exhibit positive linear, U-shaped, negative linear, and L-shaped relationships with cancer-related mortality, respectively. There was an increase and then a decrease in the link between Manganese and cancer-related morality. This study revealed the correlation between the content of different elements and different types of mortality in the U.S. general population.

How do men and women differ in their depressive symptomatology? A gendered network analysis of depressive symptoms in a French population-based cohort

BackgroundThe experience of depressive manifestations and the presentation of symptoms in clinical settings may differ in men and women. Despite the extensive literature, it remains unclear how depressive manifestations interact at symptom levels in men and women. First, we aimed to describe and compare depressive networks by sex. Second, we examined symptom connections to Clinical depression and Functional Limitations as a proxy of self-recognition of a depressive episode. MethodsWe estimated networks from the 20 CES-D items in men and women from a large population-based French cohort. We computed centrality measures and ran comparisons. Then, we re-estimated two networks in men and women separately, adding, on the one hand, Clinical Depression and, on the other hand, Limitations due to a depressive episode. ResultsOver 200,000 participants were included in this study. Women were twice as likely to have a previous diagnosis of depression. Sex-ratio was less pronounced (1,7:1) for Limitations due to depression. Centrality measures revealed similar symptom patterns. However, network structures differed between men and women. We found some symptom connections to Clinical depression and Limitations to be non-invariant according to sex. LimitationsCross-sectional data does not capture the direction of the connections between symptoms and an eventual diagnosis. We lacked data about the diagnosis's context and could not account for other factors influencing depressive symptomatology. ConclusionsNetwork structures differed, suggesting gender-specific mechanisms in activating symptoms and depressive states. Addressing central symptoms evoking depressed moods with tailored interventions may serve to tackle depressive states in men and women.

Risk of premature mortality due to smoking, alcohol use, obesity and physical activity varies by income: A population-based cohort study

BackgroundPremature deaths are a strong population health indicator. There is a persistent and widening pattern of income inequities for premature mortality. We sought to understand the combined effect of health behaviours and income on premature mortality in a large population-based cohort. MethodsWe analyzed a cohort of 121,197 adults in the 2005–2014 Canadian Community Health Surveys, linked to vital statistics data to ascertain deaths for up to 5 years following baseline. Information on household income quintile and mortality-relevant risk factors (smoking status, alcohol use, body mass index (BMI), and physical activity) was captured from the survey. Hazard ratios (HR) for combined income-risk factor groups were estimated using Cox proportional hazards models. Stratified Cox models were used to identify quintile-specific HR for each risk factor. ResultsFor each risk factor, HR of premature mortality was highest in the lowest-income, highest-risk group. Additionally, an income gradient was seen for premature mortality HR for every exposure level of each risk factor. In the stratified models, risk factor HRs did not vary meaningfully between income groups. All findings were consistent in the unadjusted and adjusted models. ConclusionThese findings highlight the need for targeted strategies to reduce health inequities and more careful attention to how policies and interventions are distributed at the population level. This includes targeting and tailoring resources to those in lower income groups who disproportionately experience premature mortality risk to prevent further widening health inequities.

A new surgical technique: robotic intracorporeal Kono-S anastomosis in Crohn's - a safety and feasibility case series on short-term outcomes.

The Kono-S anastomosis was introduced as a possible solution to the high surgical recurrence rates in Crohn's disease. However, this technique is known to be challenging, which is why it was originally performed in an extracorporeal setting. The aim of this case series was to assess safety, in terms of intra-/postoperative complications, and feasibility, in terms of successful performance of anastomosis, of a robot-assisted intracorporeal Kono-S anastomosis. This is a prospective single-centre consecutive case series. Patients were considered eligible if they were diagnosed with refractory Crohn's disease with significant bowel stenosis of the terminal ileum. All patients underwent robot-assisted intracorporeal Kono-S anastomosis. Perioperative care was provided according to the Enhanced Recovery After Surgery® protocol. Follow-up for postoperative complications was 30 days. Twenty patients were included, of whom 11 (55%) were men. The median age was 30 years [interquartile range (IQR) 22-51 years] and the median BMI was 25 kg/m2 (IQR 19-28 kg/m2). Intracorporeal Kono-S anastomosis was successfully performed in all cases. The median operating time was 155 min (IQR 144-176 min) and the median length of stay was 3 days (IQR 1-5 days). No conversions or 30-day mortality were observed. One patient experienced anastomotic leakage, which was treated with radiologically guided drainage. A total of three patients experienced postoperative complications in the first 30 days. Performance of intracorporeal robot-assisted Kono-S anastomosis seems safe and feasible in this case series for Crohn's disease. Since this is a first case series, further research is required to confirm results in a larger population-based cohort.

Short-term exposure to air pollution and hospital admission after COVID-19 in Catalonia: the COVAIR-CAT study.

A growing body of evidence has reported positive associations between long-term exposure to air pollution and poor COVID-19 outcomes. Inconsistent findings have been reported for short-term air pollution, mostly from ecological study designs. Using individual-level data, we studied the association between short-term variation in air pollutants [nitrogen dioxide (NO2), particulate matter with a diameter of <2.5 µm (PM2.5) and a diameter of <10 µm (PM10) and ozone (O3)] and hospital admission among individuals diagnosed with COVID-19. The COVAIR-CAT (Air pollution in relation to COVID-19 morbidity and mortality: a large population-based cohort study in Catalonia, Spain) cohort is a large population-based cohort in Catalonia, Spain including 240902 individuals diagnosed with COVID-19 in the primary care system from 1 March until 31 December 2020. Our outcome was hospitalization within 30 days of COVID-19 diagnosis. We used individual residential address to assign daily air-pollution exposure, estimated using machine-learning methods for spatiotemporal prediction. For each pandemic wave, we fitted Cox proportional-hazards models accounting for non-linear-distributed lagged exposure over the previous 7days. Results differed considerably by pandemic wave. During the second wave, an interquartile-range increase in cumulative weekly exposure to air pollution (lag0_7) was associated with a 12% increase (95% CI: 4% to 20%) in COVID-19 hospitalizations for NO2, 8% (95% CI: 1% to 16%) for PM2.5 and 9% (95% CI: 3% to 15%) for PM10. We observed consistent positive associations for same-day (lag0) exposure, whereas lag-specific associations beyond lag0 were generally not statistically significant. Our study suggests positive associations between NO2, PM2.5 and PM10 and hospitalization risk among individuals diagnosed with COVID-19 during the second wave. Cumulative hazard ratios were largely driven by exposure on the same day as hospitalization.

Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. ClinicalTrials.gov NCT03335644.

Extrahepatic Malignancies Are the Leading Cause of Death in Patients with Chronic Hepatitis B without Cirrhosis: A Large Population-Based Cohort Study.

(1) Background: Accurate statistics on the causes of death in patients with chronic hepatitis B (CHB) are lacking. We investigated mortality rates and causes of death over time. (2) Methods: Data on patients newly diagnosed with CHB from 2007 to 2010 (cohort 1, n = 223,424) and 2012 to 2015 (cohort 2, n = 177,966) were retrieved from the Korean National Health Insurance Service. Mortality data were obtained from Statistics Korea. The causes of death were classified as liver-related (hepatic decompensation or hepatocellular carcinoma [HCC]) or extrahepatic (cardiovascular-related, cerebrovascular-related, or extrahepatic malignancy-related). (3) Results: Over a 10-year follow-up period of 223,424 patients (cohort 1) with CHB, the overall mortality was 1.54 per 100 person-years. The mortality associated with HCC was the highest (0.65 per 100 person-years), followed by mortality related to extrahepatic malignancies (0.26 per 100 person-years), and cardio/cerebrovascular diseases (0.18 per 100 person-years). In the non-cirrhotic CHB (87.4%), 70% (11,198/15,996) of patients died due to non-liver-related causes over ten years. The 10-year overall mortality was 0.86 per 100 person-years. Among these, mortality due to extrahepatic malignancies had the highest rate (0.23 per 100 person-years), followed by mortality related to HCC (0.20 per 100 person-years), and cardio/cerebrovascular diseases (0.16 per 100 person-years). The 5-year mortality associated with extrahepatic malignancies increased from 0.36 per 100 person-years (cohort 1) to 0.40 per 100 person-years (cohort 2). (4) Conclusions: Mortality related to HCC decreased, whereas mortality related to extrahepatic malignancies increased in the antiviral era. Extrahepatic malignancies were the leading cause of death among patients with CHB without cirrhosis.

Smoking is associated with increased eryptosis, suicidal erythrocyte death, in a large population-based cohort

Smoking has multiple detrimental effects on health, and is a major preventable cause of premature death and chronic disease. Despite the well-described effect of inhaled substances from tobacco smoke on cell toxicity, the association between smoking and suicidal erythrocyte death, termed eryptosis, is virtually unknown. Therefore, the blood samples of 2023 participants of the German National Cohort Study (NAKO) were analyzed using flow cytometry analysis to determine eryptosis from fluorescent annexin V-FITC-binding to phosphatidylserine-exposing erythrocytes. Blood analyses were complemented by the measurement of hematologic parameters including red blood cell count, hematocrit, hemoglobin, mean corpuscular cell volume (MCV) and mean corpuscular hemoglobin (MCH). Eryptosis was higher in smokers than in non- and ex-smokers, and positively associated with the number of cigarettes smoked daily (r = 0.08, 95% CI [0.03, 0.12]). Interestingly, despite increased eryptosis, smokers had higher red blood cell indices than non-smokers. To conclude, smokers were characterized by higher eryptosis than non-smokers, without showing any obvious detrimental effect on classic hematological parameters.

Mitochondrial genetic variation and risk of chronic kidney disease and acute kidney injury in UK Biobank participants

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFRCr-CysC, N = 362,802), prevalent (N = 416 cases) and incident (N = 405 cases) end-stage kidney disease (ESKD), AKI defined by diagnostic codes (N = 14,170 cases), and urine albumin/creatinine ratio (ACR, N = 114,662). The mean age was 57 ± 8 years and the mean eGFR was 90 ± 14 ml/min/1.73 m2. MtDNA haplotype was significantly associated with eGFR (p = 2.8E−12), but not with prevalent ESKD (p = 5.9E−2), incident ESKD (p = 0.93), AKI (p = 0.26), or urine ACR (p = 0.54). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p = 1.2E−10). When compared to the reference haplotype, mtDNA haplotypes I (β = 0.402, standard error (SE) = 0.111; p = 2.7E−4), IV (β = 0.430, SE = 0.073; p = 4.2E−9), and V (β = 0.233, SE = 0.050; p = 2.7E−6) were each associated with higher eGFR. Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with ESKD, AKI or albuminuria.

P1173 Higher total antioxidant capacity of diet is associated with reduced surgery risk in individuals with Inflammatory Bowel Disease in a prospective cohort study

Abstract Background Oxidative stress exacerbates inflammatory Bowel Disease (IBD), and dietary antioxidants are proposed as a promising manner to counteract this imbalance. However, the role of individual antioxidants in the complex milieu of the human body may exhibit synergistic or interactive effects. The research has yet to comprehensively examine the impact of dietary total antioxidant capacity (TAC) on IBD prognosis. To fill this knowledge gap, this study aimed to investigate the assocaitions between dietary TAC and risk of related surgery among individuals with IBD in a prospectively recruited cohort. Methods We included 2439 individuals with IBD at baseline from UK Biobank. All participants have completed a web-based validated 24-h dietary recall up to five rounds in 2009-2012, reporting their consumption of more than 200 foods and beverages. We calculated the TAC of the diet using the oxygen radical absorbance capacity method and were grouped by quintiles. The outcomes of interest were IBD-related surgery (bowel resection, perianal-related surgery, Strictureplasty, and ileoanal pouch formation), ascertained via linkage to national inpatient data. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a mean follow-up of 10.4 years, we identified 261 incident surgical cases related to IBD. The mean age of the participants was 56.9 years, and 51% were females. When comparing extreme quintiles of dietary TAC, individuals with higher dietary TAC were associated with a lower risk of related surgery (HR 0.57, 95% CI 0.38-0.86, P=0.007). The inverse associations between dietary TAC and related surgery were consistent among individuals with ulcerative colitis (HR comparing extreme quintiles 0.59, 95% CI 0.36-0.96, P=0.036). For individuals with Crohn’s disease, the associations were not significant when comparing extreme quintiles of dietary TAC (HR 0.51, 95% CI 0.25-1.03, P=0.060), while we observed a significant 9% risk reduction (HR 0.81, 95% CI 0.65-1.00, P=0.048) of related surgery by per 1-SD increment in dietary TAC among individuals with Crohn’s disease.(Table 1) Conclusion In this large large-scale population-based cohort study, we observed that higher dietary TAC was associated with reduced risk of related surgery in individuals with IBD. Our findings provide insights that could inform dietary recommendations and potentially improve IBD management strategies.

DOP20 Changes in systemic antibody epitope repertoires from preclinical to established Inflammatory Bowel Disease

Abstract Background Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), exhibit unique immunological changes early in development. Although &amp;gt;300 IBD-specific antibody responses have been identified1, systemic antibody epitope repertoires of preclinical IBD remain elusive. This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers. Methods This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up. Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021). Individuals who reported IBD during follow-up and with available serum samples were included. Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq). Results A total of 178 individuals with new-onset IBD were identified (Fig. 1). Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3) years. Most individuals reported newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%). A total of 5,174 antibody responses were observed in 5-95% of participants. Fifty-nine antibodies were differentially abundant (FDR&amp;lt;0.05) pre-diagnosis vs. post-diagnosis (Fig. 2), 14 of which (24%) were previously reported as IBD-specific1. Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis. Those developing UC exhibited 33 differentially abundant antibody responses, while those with CD exhibiting only four (FDR&amp;lt;0.05). Individuals developing IBD exhibited lower frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g. Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and varicella-zoster virus, alongside higher antibody responses against bacterial flagellins. Individuals developing UC showed elevated antibody responses mainly against viruses (e.g. human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g. pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis. Conclusion Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development. Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis. 1. Bourgonje et al. Immunity. 2023.

Reconstructing individual-level exposures in cohort analyses of environmental risks: an example with the UK Biobank.

Recent developments in linkage procedures and exposure modelling offer great prospects for cohort analyses on the health risks of environmental factors. However, assigning individual-level exposures to large population-based cohorts poses methodological and practical problems. In this contribution, we illustrate a linkage framework to reconstruct environmental exposures for individual-level epidemiological analyses, discussing methodological and practical issues such as residential mobility and privacy concerns. The framework outlined here requires the availability of individual residential histories with related time periods, as well as high-resolution spatio-temporal maps of environmental exposures. The linkage process is carried out in three steps: (1) spatial alignment of the exposure maps and residential locations to extract address-specific exposure series; (2) reconstruction of individual-level exposure histories accounting for residential changes during the follow-up; (3) flexible definition of exposure summaries consistent with alternative research questions and epidemiological designs. The procedure is exemplified by the linkage and processing of daily averages of air pollution for the UK Biobank cohort using gridded spatio-temporal maps across Great Britain. This results in the extraction of exposure summaries suitable for epidemiological analyses of both short and long-term risk associations and, in general, for the investigation of temporal dependencies. The linkage framework presented here is generally applicable to multiple environmental stressors and can be extended beyond the reconstruction of residential exposures. IMPACT: This contribution describes a linkage framework to assign individual-level environmental exposures to population-based cohorts using high-resolution spatio-temporal exposure. The framework can be used to address current limitations of exposure assessment for the analysis of health risks associated with environmental stressors. The linkage of detailed exposure information at the individual level offers the opportunity to define flexible exposure summaries tailored to specific study designs and research questions. The application of the framework is exemplified by the linkage of fine particulate matter (PM2.5) exposures to the UK Biobank cohort.

The impact of prediabetes and diabetes on endothelial function in a large population-based cohort

Background Diabetes and prediabetes are well-recognized risk factors for cardiovascular disease (CVD) and are marked by vascular endothelial dysfunction (ED). However, there is a scarcity of thorough population-based studies examining ED in individuals with diabetes/prediabetes free from manifest CVD. Here, we examined the association between ED assessed by reactive hyperaemia index (RHI) in the finger and diabetes/prediabetes in a large middle-aged population cohort. Methods Within the Malmö Offspring Study, following the exclusion of participants <30 years and participants with prevalent CVD, 1384 participants had complete data on all covariates. The RHI was calculated using pulse amplitude tonometry. ED was defined as RHI < 1.67. Multivariable logistic and linear regression models were conducted to investigate associations between ED and RHI with diabetes and prediabetes. Results The study population had a mean age of 53.6 ± 7.6 years (53% women). In study participants with manifest diabetes (n = 121) and prediabetes (n = 514), ED was present in 42% and 25% respectively, compared to 23% in those with normal glucometabolic status. In multivariable logistic regression analyses, prevalent diabetes was significantly associated with ED (OR 1.95; 95%CI 1.57-3.39; p = 0.002), as well as with lower RHI (β-coeff. -0.087; p = 0.002). However, prediabetes showed no association with neither ED nor RHI. Conclusion In a population free from CVD, vascular endothelial dysfunction was primarily associated with manifest diabetes, but not with prediabetes, implying that finger ED may develop when diabetes is established, rather than being an early sign of glucose intolerance. Further research is needed to explore whether addressing glucose intolerance could potentially delay or prevent vascular ED onset.