European Prospective Investigation Of Cancer Research Articles

Comparison of dietary patterns and daily food intake across kidney disease stages in England: a-posteriori cluster analysis

ObjectiveDietary patterns are rapidly becoming a major focus of medical nutrition therapy in CKD and the analysis of dietary patterns has emerged as a practical approach to evaluate qualitative as well as quantitative aspects of overall diet. In an a-posteriori data-driven approach, dietary patterns are based on the actual food intake of the population evaluated. Investigation of dietary patterns in CKD are not well described, and, to our knowledge, have not been conducted in a UK-based cohort. MethodsAdult participants with a diagnosed kidney condition (CKD 1-5 not requiring dialysis) were recruited into a multi-centre observational cross-sectional study. Dietary intake was assessed using the European Prospective Investigation of Cancer in Norfolk Food Frequency Questionnaire. Logistic Principal Components Analysis was used to identify food group clusters. Differences between groups were assessed using univariate general linear modelling. ResultsIn total, 696 patients were included. The mean age was 64.7 (±14.0) years, 61% of the cohort were male. Most participants were White British (89%). The mean eGFR was 36.6 (±20.9) ml/min/1.732. We found differences in food group intake across stages (e.g., greater intake of nuts and seeds intake in CKD 1-2 versus CKD 4) and across sex (e.g., females had a higher intake of fruit and vegetables versus males). Comparison with the reference cohort revealed that, overall, the CKD cohort had reduced intakes of food stuffs such as cereals and cereal products, but higher intakes of groups such as meat and meat products. There were limited differences in micronutrients, although Vitamin B2 and calcium were higher in earlier stages. ConclusionOverall, the findings from a novel a-posteriori approach underline the complex diversity of food patterns in CKD. The findings from our study may inform dieticians and other healthcare providers about the need to consider treatment modalities and stages when giving dietary recommendations.

Validation of Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons in the EPIC-Norfolk prospective population cohort.

The European Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models are recommended to identify individuals at high 10-year risk for cardiovascular disease (CVD). Independent validation and assessment of clinical utility is needed. This study aims to assess discrimination, calibration, and clinical utility of low-risk SCORE2 and SCORE2-OP. Validation in individuals aged 40-69 years (SCORE2) and 70-79 years (SCORE2-OP) without baseline CVD or diabetes from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population study. We compared 10-year CVD risk estimates with observed outcomes (cardiovascular mortality, non-fatal myocardial infarction, and stroke). For SCORE2, 19 560 individuals (57% women) had 10-year CVD risk estimates of 3.7% [95% confidence interval (CI) 3.6-3.7] vs. observed 3.8% (95% CI 3.6-4.1) [observed (O)/expected (E) ratio 1.0 (95% CI 1.0-1.1)]. The area under the curve (AUC) was 0.75 (95% CI 0.74-0.77), with underestimation of risk in men [O/E 1.4 (95% CI 1.3-1.6)] and overestimation in women [O/E 0.7 (95% CI 0.6-0.8)]. Decision curve analysis (DCA) showed clinical benefit. Systematic Coronary Risk Evaluation 2-Older Persons in 3113 individuals (58% women) predicted 10-year CVD events in 10.2% (95% CI 10.1-10.3) vs. observed 15.3% (95% CI 14.0-16.5) [O/E ratio 1.6 (95% CI 1.5-1.7)]. The AUC was 0.63 (95% CI 0.60-0.65) with underestimation of risk across sex and risk ranges. Decision curve analysis showed limited clinical benefit. In a UK population cohort, the SCORE2 low-risk model showed fair discrimination and calibration, with clinical benefit for preventive treatment initiation decisions. In contrast, in individuals aged 70-79 years, SCORE2-OP demonstrated poor discrimination, underestimated risk in both sexes, and limited clinical utility.

Regional Differences in Thyroid Function Parameters: A Comparison of European Cohort Studies

The aim of the project was to investigate regional differences in thyroid stimulating hormone (TSH), and free thyroxine (fT4) concentrations and iodine status in comparable German and European cohort studies. Sex- and age-stratified TSH, fT4, and urine iodine concentrations of thyroid-healthy participants (age group 45-75 years) of the HNR (Heinz Nixdorf Recall) Study in the Ruhr region of Germany, the southern German KORA (Cooperative Health Research in the Augsburg Region) and northeastern German SHIP (Study of Health in Pomerania) studies, as well as the Norwegian HUNT (Nord-Trøndelag Health) study (age group 40-79 years), the English EPIC (European Prospective Investigation of Cancer)-Norfolk study, and the Dutch Rotterdam study were compared. The TSH reference range for the HNR study population was calculated and compared to the KORA and SHIP studies. Regional differences showed a stronger influence on TSH and fT4 concentrations than sex and age of the subjects in the 45- to 75-year age group. The estimated difference in medians, as measured by the HNR study, was lowest in the SHIP study, -0.47 (95% CI: -0.53; -0.41) for men and -0.41 (-0.53; -0.41) for women. The Rotterdam study had the highest difference in medians for both men and women (men: 0.56 with 0.44; 0.68 and women: 0.62 with 0.46; 0.78). The lowest median TSH concentrations, across all age categories considered, were seen in the German cohorts. Comparison of thyroid function parameters and iodine in elderly subjects between six comparable cohort studies from Germany and Europe showed a significant influence of region, which exceeded the sex and age dependence of the parameters.

Alcohol Consumption and Incident Cataract Surgery in Two Large UK Cohorts

PurposeTo examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.DesignLongitudinal, observational study.ParticipantsWe included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.MethodsSelf-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.Main Outcome MeasuresIncident cataract surgery.ResultsThere were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85–0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84–0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P < 0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.ConclusionsOur findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.

Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis

The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40–79 years were followed up for a median of 20.36 years (20.32–20.38). Compared to the first quintile of calcium intake (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074–1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83–0.99) and 0.85 (0.77–0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87–1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72–0.97), 0.83 (0.71–0.97), 0.78 (0.66–0.92) and 0.95 (0.78–1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women.

Epigenetic Changes in Islets of Langerhans Preceding the Onset of Diabetes.

The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.

Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study.

Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke). Based on the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort (n = 27,548), we constructed case-cohorts including a random subsample of 2,500 participants and all physician-verified incident cases of type 2 diabetes (n = 820; median follow-up time 6.5 years) and CVD (n = 508; median follow-up time 8.2 years). Information on the relative abundance of 39 N-glycan groups in baseline plasma samples was generated by chromatographic profiling. We selected predictive N-glycans for type 2 diabetes and CVD separately, based on cross-validated machine learning, nonlinear model building, and construction of weighted prediction scores. This workflow for CVD was applied separately in men and women. The N-glycan-based type 2 diabetes score was strongly predictive for diabetes risk in an internal validation cohort (weighted C-index 0.83, 95% CI 0.78-0.88), and this finding was externally validated in the Finland Cardiovascular Risk Study (FINRISK) cohort. N-glycans were moderately predictive for CVD incidence (weighted C-indices 0.66, 95% CI 0.60-0.72, for men; 0.64, 95% CI 0.55-0.73, for women). Information on the selected N-glycans improved the accuracy of established and clinically applied risk prediction scores for type 2 diabetes and CVD. Selected N-glycans improve type 2 diabetes and CVD prediction beyond established risk markers. Plasma protein N-glycan profiling may thus be useful for risk stratification in the context of precisely targeted primary prevention of cardiometabolic diseases.

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification

Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. Case-control studies. Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006). In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS.

The effect of long-term low lipoproteins on neurocognitive function

Aim: It has been hypothesized that treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors could result in cognitive impairment. Recently, the EBBINGHAUS trial showed that treatment with evolocumab did not result in cognitive decline over a median follow-up of 19 months. Although these results are reassuring, the relatively short-term follow-up of this trial hampers a definitive answer as to whether PCSK9 inhibitors can be considered safe for neurocognition following long-term treatment. To address this, we performed an analysis using three differently defined high versus low LDL-C categories in the European Prospective Investigation of Cancer (EPIC)-Norfolk prospective population study.

PO-052 Selenium status and survival from colorectal cancer in the european prospective investigation of cancer and nutrition

IntroductionSuboptimal levels of selenium (Se) or selenoprotein P (SELENOP), which is an antioxidant protein that also distributes Se from the liver to target tissues, may contribute to risk of colorectal cancer (CRC) development, as we previously showed using serum samples taken pre-diagnostically in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohortHughes et al, 2015 Int J Cancer 136: 1149–61). However, the relationship between Se and survival outcomes following cancer diagnosis is more uncertain. Here, we examined the association of Se status with mortality from CRC and overall mortality in the same study group.Material and methodsSe was measured by reflection X-ray fluorescence spectrometry and SELENOP by immunoluminometric sandwich assay. Multivariable adjusted Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of the association between Se and SELENOP and CRC-death and all-cause mortality.Results and discussionsHigher levels of Se showed non-significant inverse associations with reduction in both CRC and overall mortality: Respective multivariable adjusted HRs for the fifth quintile versus the first quintile (HRQ5 vs. Q1) were 0.76 (95% CI: 0.52–1.11, Ptrend=0.10), and 0.82 (95% CI: 0.56–1.16, Ptrend=0.14). Higher levels of SELENOP were also not associated with a statistically significant reduction in CRC mortality (HRQ5 vs. Q1 = 0.83, 95% CI: 0.57–1.19, Ptrend=0.33). However, higher SELENOP concentrations were associated with a significant reduction in overall mortality (HRQ5 vs. Q1 = 0.70, 95% CI: 0.50–0.98, Ptrend=0.05). Similar results were also obtained by tumour site and sex. Possible interactions of potential effect modifiers and sensitivity analyses showed no considerable change in these estimates, although CRC stage data sensitivity analyses were significant for the association between Se and overall mortality (HRQ5 vs. Q1 = 0.89, 95% CI: 0.80–0.99, Ptrend=0.03).ConclusionWe found no major association of Se status markers with survival after CRC diagnosis, but an association of SELENOP with overall mortality. Detailed investigation of Se metabolism is needed to further explore relevance for CRC prognosis especially for individuals of suboptimal SELENOP status.

Selenium status and survival from colorectal cancer in the European prospective investigation of cancer and nutrition

Introduction Suboptimal levels of selenium (Se) or selenoprotein P (SELENOP), which is an antioxidant protein that also distributes Se from the liver to target tissues, may contribute to risk of colorectal cancer (CRC) development, as we previously showed using serum samples taken pre-diagnostically in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort [1] . However, the relationship between Se and survival outcomes following cancer diagnosis is more uncertain. Here, we examined the association of Se status with mortality from CRC and overall mortality in the same study group. Methods Se was measured by total reflection X-ray fluorescence and SELENOP by immunoluminometric sandwich assay. Multivariable-adjusted Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of the association between Se and SELENOP and CRC death and all-cause mortality. Results Higher levels of Se showed non-significant inverse associations with reduction in both CRC and overall mortality: respective multivariable-adjusted HRs for the fifth quintile versus the first quintile (HRQ5 vs. Q1) were 0.76 (95% CI: 0.52–1.11, Ptrend = 0.10), and 0.82 (95% CI: 0.56–1.16, Ptrend = 0.14). Higher levels of SELENOP were also not associated with a statistically significant reduction in CRC mortality (HRQ5 vs. Q1 = 0.83, 95% CI: 0.57–1.19, Ptrend = 0.33). However, higher SELENOP concentrations were associated with a significant reduction in overall mortality (HRQ5 vs. Q1 = 0.70, 95% CI: 0.50–0.98, Ptrend = 0.05). Similar results were also obtained by tumour site and sex. Possible interactions of potential effect modifiers and sensitivity analyses showed no considerable change in these estimates, although CRC stage data sensitivity analyses were significant for the association between Se and overall mortality (HRQ5 vs. Q1 = 0.89, 95% CI: 0.80–0.99, Ptrend = 0.03). Conclusions We found no major association of Se status markers with survival after CRC diagnosis, but an association of SELENOP with overall mortality. Detailed investigation of Se metabolism is needed to further explore relevance for CRC prognosis especially for individuals of suboptimal SELENOP status.

Association between intake of less-healthy foods defined by the United Kingdom's nutrient profile model and cardiovascular disease: A population-based cohort study.

BackgroundIn the United Kingdom, the Food Standards Agency-Ofcom nutrient profiling model (FSA-Ofcom model) is used to define less-healthy foods that cannot be advertised to children. However, there has been limited investigation of whether less-healthy foods defined by this model are associated with prospective health outcomes. The objective of this study was to test whether consumption of less-healthy food as defined by the FSA-Ofcom model is associated with cardiovascular disease (CVD).Methods and findingsWe used data from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort study in adults (n = 25,639) aged 40–79 years who completed a 7-day diet diary between 1993 and 1997. Incident CVD (primary outcome), cardiovascular mortality, and all-cause mortality (secondary outcomes) were identified using record linkage to hospital admissions data and death certificates up to 31 March 2015. Each food and beverage item reported was coded and given a continuous score, using the FSA-Ofcom model, based on the consumption of energy; saturated fat; total sugar; sodium; nonsoluble fibre; protein; and fruits, vegetables, and nuts. Items were classified as less-healthy using Ofcom regulation thresholds. We used Cox proportional hazards regression to test for an association between consumption of less-healthy food and incident CVD. Sensitivity analyses explored whether the results differed based on the definition of the exposure. Analyses were adjusted for age, sex, behavioural risk factors, clinical risk factors, and socioeconomic status. Participants were followed up for a mean of 16.4 years. During follow-up, there were 4,965 incident cases of CVD (1,524 fatal within 30 days). In the unadjusted analyses, we observed an association between consumption of less-healthy food and incident CVD (test for linear trend over quintile groups, p < 0.01). After adjustment for covariates (sociodemographic, behavioural, and indices of cardiovascular risk), we found no association between consumption of less-healthy food and incident CVD (p = 0.84) or cardiovascular mortality (p = 0.90), but there was an association between consumption of less-healthy food and all-cause mortality (test for linear trend, p = 0.006; quintile group 5, highest consumption of less-healthy food, versus quintile group 1, HR = 1.11, 95% CI 1.02–1.20). Sensitivity analyses produced similar results. The study is observational and relies on self-report of dietary consumption. Despite adjustment for known and reported confounders, residual confounding is possible.ConclusionsAfter adjustment for potential confounding factors, no significant association between consumption of less-healthy food (as classified by the FSA-Ofcom model) and CVD was observed in this study. This suggests, in the UK setting, that the FSA-Ofcom model is not consistently discriminating among foods with respect to their association with CVD. More studies are needed to understand better the relationship between consumption of less-healthy food, defined by the FSA-Ofcom model, and indices of health.

Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study.

Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, (r=0.39), particle numbers of very-low-density lipoprotein (r=0.25), intermediate-density lipoprotein (r=0.23), small dense low-density lipoprotein (r=0.26), and high-sensitivity C-reactive protein (r=0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number (r=-0.11), P<0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein. ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association.

Change in plasma phospholipid fatty acids over 13 years and determinants of change: EPIC‐Norfolk Study

We aimed to investigate the changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and examine potential determinants of these changes. In the European Prospective Investigation of Cancer (EPIC)‐Norfolk study, plasma phospholipid fatty acids (%mol) were profiled in 722 participants at three time‐points (1993–1997, 1998–2000, 2004–2011) over approximately 13 years. Linear mixed‐effects models were used to estimate 1) the annual change in individual plasma fatty acids and fatty acid groups, adjusting for potential confounders and 2) associations of change in dietary or lifestyle factors with change in 8 pre‐specified plasma fatty acid groups, with mutual adjustment for dietary/lifestyle factors and other confounders. The pre‐specified fatty acid groups were odd‐chain saturated fatty acids (SFA, C15:0+C17:0), even‐chain SFAs (C14:0+C16:0+C18:0), very‐long‐chain SFAs (C20:0+C22:0+C23:0+C24:0), marine n‐3 polyunsaturated fatty acids (PUFA, C20:5n3+C22:5n3+C22:6n3), plant n‐3 PUFA (C18:3n3), n‐6 PUFAs, monounsaturated fatty acids (MUFAs) and trans fatty acids. There were significant annual decreases in levels of odd‐chain SFAs (−0.63%, 95%CI: −0.73%, −0.52%), even‐chain SFAs (−0.05%, 95%CI: −0.06%, −0.03%), n‐6 PUFAs (−0.25%, 95%CI: −0.29%, −0.20%) and trans fatty acids (−7.84%, 95%CI: −8.07%, −7.61%), significant annual increases in marine n‐3 PUFAs (1.28%, 95%CI: 1.11%, 1.44%) and MUFAs (0.45%, 95%CI: 0.37%, 0.54%), and no significant changes in very‐long‐chain SFAs or plant n‐3 PUFA. Change in each plasma fatty acid group was associated with change in intake of various food groups; for example, 100g/day increase of change in fatty fish intake was associated with a 5.26% (95% CI: 1.26%, 9.42%) annual increase in plasma marine n‐3 PUFAs. Change in BMI or physical activity was not associated with change in any fatty acid group. The annual changes observed cannot be explained by diet alone and therefore suggest that aging processes have a discernible effect on fatty acids of the plasma phospholipid fraction. In conclusion, most individual plasma fatty acids and fatty acid groups changed over time. These changes were partially explained by changes in aspects of diet.Support or Funding InformationMedical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5; Medical Research Council Human Nutrition Research MC_UP_A090_1006; Cambridge Lipidomics Biomarker Research Initiative G0800783; Cambridge Initiative‐Nutrition (RG71466, SJAH/004), Marie Skłodowska‐Curie Fellowships (701708, RG82205, SJAI/051),

Dietary Assessment in the MetaCardis Study: Development and Relative Validity of an Online Food Frequency Questionnaire

BackgroundThe European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term diet–disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study. ObjectiveThe objectives of this study were to describe the development of three semiquantitative online FFQs used in the MetaCardis study—one FFQ per country—and to assess the relative validity of the French MetaCardis FFQ. DesignThe layout and format of the MetaCardis FFQ was based on the European Prospective Investigation of Cancer (EPIC)-Norfolk FFQ and the content was based on relevant European FFQs. Portion size and nutrient composition were derived from national food consumption surveys and food composition databases. To assess the validity of the French MetaCardis FFQ, a cross-sectional study design was utilized. Participants/settingThe validation study included 324 adults recruited between September 2013 and June 2015 from different hospitals in Paris, France. Main outcome measuresFood intakes were measured with both the French MetaCardis FFQ and 3 consecutive self-administered web-based 24-hour dietary recalls (DRs). Statistical analyses performedSeveral measures of validity of the French MetaCardis FFQ were evaluated: estimations of food groups, energy, and nutrient intakes from the DRs and the FFQ, Spearman and Pearson correlations, cross-classification, and Bland-Altman analyses. ResultsThe French MetaCardis FFQ tended to report higher food, energy, and nutrient intakes compared with the DRs. Mean correlation coefficient was 0.429 for food, 0.460 for energy, 0.544 for macronutrients, 0.640 for alcohol, and 0.503 for micronutrient intakes. Almost half of participants (44.4%) were correctly classified within tertiles of consumption, whereas 12.9% were misclassified in the opposite tertile. Performance of the FFQ was relatively similar after stratification by sex. ConclusionsThe French MetaCardis FFQ was found to have an acceptable level of validity and may be a useful instrument to rank individuals based on their food and nutrient intakes.

Mediterranean diet in UK shows positive effects in study.

Following a Mediterranean-type diet in the United Kingdom is linked to a lower incidence of cardiovascular disease and mortality, a study has found. The European Prospective Investigation of Cancer (EPIC) Norfolk study is an ongoing UK prospective cohort and part of the Europe-wide EPIC study. The research, published in the journal BMC Medicine , included 23 902 initially healthy people who were assessed at baseline from 1993 to 1997 and followed up for an average of 12-17 …

179 Duration of Physical Activity Following Total Hip or Knee Replacement: An Analysis of the Epic-Norfolk Cohort

Background: It has been suggested that following total hip (THR) and knee replacement (TKR) people increase their levels of physical activity as a result of reduced pain and increased range of motion. Engagement in physical activity is important for promoting physical and mental health and reducing the burden of non-communicable diseases on primary and secondary care services. Therefore, joint replacement is hypothesized to have wider health benefits in addition to improvement of joint pain and disability. However, the degree to which physical activity increases following THR and TKR is unknown. This study answered this question with a UK population cohort, the European Prospective Investigation of Cancer (EPIC)-Norfolk. We determined whether there was a change in the duration of physical activity following THR or TKR; if the duration of physical activity changes following THR or TKR, which specific forms of physical activity are altered and by how much; and which characteristics or variables predicted an absolute change in duration of physical activity following THR or TKR. Methods: In total, 653 people from the EPIC-Norfolk community cohort were identified who had undergone primary THR or TKR between EPIC Health Check 2 (1998–2001) and 3 (2006–2011). Paired t-test and multivariable regression analyses were conducted to determine whether there was a change in pre- vs post-arthroplasty duration of physical activity [assessed through duration of waking hours, stair climbing, activities of extended daily living (in and around the home), time spent undertaking physically active recreational pursuits]. Paired t-test analyses were undertaken to assess the change in physical activity over time, while a multivariable regression analysis modelled the absolute change in physical activity measures against potential explanatory factors such as age, gender and co-morbidities. Results: There was a statistically significant reduction from pre- to post-arthroplasty duration of daily stair climbing at home [THR: mean difference 6.19 (95% CI 2.88, 9.50), P < 0.01; TKR: mean difference 9.42 (95% CI 3.00, 15.43), P < 0.01] and time spent participating in recreational activities [THR: mean difference 1.10 (95% CI 0.26, 1.95), P = 0.03]. There was no statistical difference in pre- to post-arthroplasty change in physical activity duration for the other activities. Only age was consistently associated with the duration of physical activity change, whereby older people pre-arthroplasty demonstrated the least change in duration of physical activity. Conclusion: The duration of physical activity does not increase and may actually decrease following THR and TKR for some domains, most notably stair climbing. This is contrary to previous understanding. Accordingly, greater education by primary and secondary care services at pre- and post-operative stages should be provided to patients on their expected change and/or their potential change in physical activity post-arthroplasty. This is warranted given the benefits physical activity confers on physical and mental health.

Retinal Nerve Fiber Layer Measures and Cognitive Function in the EPIC-Norfolk Cohort Study.

PurposeWe examined the relationship between retinal nerve fiber layer (RNFL) thickness and cognitive function in a population of older British adults.MethodsParticipants of the European Prospective Investigation of Cancer (EPIC) Norfolk cohort study underwent ophthalmic and cognitive assessment. Measurements of RNFL thickness were made using the Heidelberg Retina Tomograph (HRT). Cognitive testing included a short form of the Mini-Mental State Examination (SF-MMSE), an animal naming task, a letter cancellation task, the Hopkins Verbal Learning Test (HVLT), the National Adult Reading Test (NART), and the Paired Associates Learning Test. Multivariable linear regression models were used to assess associations of RNFL thickness with cognitive test scores, adjusted for age, sex, education level, social class, visual acuity, axial length, and history of cataract surgery.ResultsData were available from 5563 participants with a mean age of 67 years. A thicker HRT-derived RNFL thickness was associated with better scores for the SF-MMSE (0.06; 95% confidence interval [CI], [0.02, 0.10], P = 0.005), HVLT (0.16, 95% CI [0.03, 0.29]; P = 0.014), and NART (−0.24, 95% CI [−0.46, −0.02], P = 0.035). The associations of RNFL thickness with SF-MMSE and HVLT remained significant following further adjustment for NART.ConclusionsWe found a significant association between HRT-derived RNFL thickness and scores from cognitive tests assessing global function, recognition, learning, episodic memory, and premorbid intelligence. However, the associations were weak and not currently of predictive value. Further research is required to confirm and clarify the nature of these associations, and identify biological mechanisms.

Investigating Physical Activity in the Etiology of Pancreatic Cancer: The Age at Which This Is Measured Is Important and Is Independent of Body Mass Index.

There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although findings from epidemiological studies are inconsistent. We investigated whether the risk is dependent on the age at which PA is measured and if independent of body mass index (BMI). A total of 23,639 participants, aged 40 to 74 years, were recruited into the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study between 1993 and 1997 and completed validated questionnaires on PA. The cohort was monitored for pancreatic cancer development, and hazard ratios (HRs) were estimated and adjusted for covariates. Within 17 years, 88 participants developed pancreatic cancer (55% female). There was no association between PA and risk in the cohort (HR trend, 1.06; 95% confidence interval [CI], 0.86-1.29). However, in participants younger than 60 years, higher PA was associated with decreased risk (highest vs lowest category HR, 0.27; 95% CI, 0.07-0.99). Higher PA was not inversely associated when older than 60 years (HR trend, 1.23; 95% CI, 0.96-1.57). Including BMI in all models produced similar estimates. The reasons why PA in younger, but not older, people may prevent pancreatic cancer need to be investigated. Physical activity may operate through mechanisms independent of BMI. If this association is causal, 1 in 6 cases might be prevented by encouraging more PA.

Thyroid dysfunction and anaemia in a large population-based study.

Anaemia and thyroid dysfunction are common and often co-occur. Current guidelines recommend the assessment of thyroid function in the work-up of anaemia, although evidence on this association is scarce. In the 'European Prospective Investigation of Cancer' (EPIC)-Norfolk population-based cohort, we aimed to examine the prevalence and type of anaemia (defined as haemoglobin <13 g/dl for men and <12 g/dl for women) according to different thyroid function groups. The mean age of the 8791 participants was 59·4 (SD 9·1) years and 55·2% were women. Thyroid dysfunction was present in 437 (5·0%) and anaemia in 517 (5·9%) participants. After excluding 121 participants with three most common causes of anaemia (chronic kidney disease, inflammation, iron deficiency), anaemia was found in 4·7% of euthyroid participants. Compared with the euthyroid group, the prevalence of anaemia was significantly higher in overt hyperthyroidism (14·6%, P < 0·01), higher with borderline significance in overt hypothyroidism (7·7%, P = 0·05) and not increased in subclinical thyroid dysfunction (5·0% in subclinical hypothyroidism, 3·3% in subclinical hyperthyroidism). Anaemia associated with thyroid dysfunction was mainly normocytic (94·0%), and rarely macrocytic (6·0%). The prevalence of anaemia was higher in overt hyperthyroidism, but not increased in subclinical thyroid dysfunction. Systematic measurement of thyroid-stimulating hormone in anaemic patients is likely to be useful only after excluding common causes of anaemia.