| 1. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 2. |
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| 3. |
- Asselbergs, Folkert W., et al.
(författare)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 4. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 6. |
- Campanella, Gianluca, et al.
(författare)
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Epigenome-wide association study of adiposity and future risk of obesity-related diseases
- 2018
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 42:12, s. 2022-2035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waistheight ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P=9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P=6.00×10−7), higher triglyceride levels (P=5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P=1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P<1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P<1.25×10−3), independently of obesity and established risk factors.Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.
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| 7. |
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| 8. |
- Chen, Jie, et al.
(författare)
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Long-term exposure to ambient air pollution and bladder cancer incidence in a pooled European cohort : the ELAPSE project
- 2022
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 126:10, s. 1499-1507
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence linking ambient air pollution to bladder cancer is limited and mixed.Methods: We assessed the associations of bladder cancer incidence with residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight PM2.5 elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in a pooled cohort (N = 302,493). Exposures were primarily assessed based on 2010 measurements and back-extrapolated to the baseline years. We applied Cox proportional hazard models adjusting for individual- and area-level potential confounders.Results: During an average of 18.2 years follow-up, 967 bladder cancer cases occurred. We observed a positive though statistically non-significant association between PM2.5 and bladder cancer incidence. Hazard Ratios (HR) were 1.09 (95% confidence interval (CI): 0.93–1.27) per 5 µg/m3 for 2010 exposure and 1.06 (95% CI: 0.99–1.14) for baseline exposure. Effect estimates for NO2, BC and O3 were close to unity. A positive association was observed with PM2.5 zinc (HR 1.08; 95% CI: 1.00–1.16 per 10 ng/m3).Conclusions: We found suggestive evidence of an association between long-term PM2.5 mass exposure and bladder cancer, strengthening the evidence from the few previous studies. The association with zinc in PM2.5 suggests the importance of industrial emissions.
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| 9. |
- Chen, Jie, et al.
(författare)
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Long-Term Exposure to Source-Specific Fine Particles and Mortality-A Pooled Analysis of 14 European Cohorts within the ELAPSE Project
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:13, s. 9277-9290
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Tidskriftsartikel (refereegranskat)abstract
- We assessed mortality risks associated with sourcespecific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5 identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5 components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 mu g/m(3) increase) across five identified sources. On a 1 mu g/m(3) basis, the residual oil-related PM2.5 had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5 mass, suggesting that past estimates using the generic PM2.5 exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.
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| 10. |
- Cordova, Reynalda, et al.
(författare)
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Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases : a multinational cohort study
- 2023
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Ingår i: The Lancet Regional Health - Europe. - 2666-7762. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is currently unknown whether ultra-processed foods (UPFs) consumption is associated with a higher incidence of multimorbidity. We examined the relationship of total and subgroup consumption of UPFs with the risk of multimorbidity defined as the co-occurrence of at least two chronic diseases in an individual among first cancer at any site, cardiovascular disease, and type 2 diabetes. Methods: This was a prospective cohort study including 266,666 participants (60% women) free of cancer, cardiovascular disease, and type 2 diabetes at recruitment from seven European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Foods and drinks consumed over the previous 12 months were assessed at baseline by food-frequency questionnaires and classified according to their degree of processing using Nova classification. We used multistate modelling based on Cox regression to estimate cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations of total and subgroups of UPFs with the risk of multimorbidity of cancer and cardiometabolic diseases. Findings: After a median of 11.2 years of follow-up, 4461 participants (39% women) developed multimorbidity of cancer and cardiometabolic diseases. Higher UPF consumption (per 1 standard deviation increment, ∼260 g/day without alcoholic drinks) was associated with an increased risk of multimorbidity of cancer and cardiometabolic diseases (HR: 1.09, 95% CI: 1.05, 1.12). Among UPF subgroups, associations were most notable for animal-based products (HR: 1.09, 95% CI: 1.05, 1.12), and artificially and sugar-sweetened beverages (HR: 1.09, 95% CI: 1.06, 1.12). Other subgroups such as ultra-processed breads and cereals (HR: 0.97, 95% CI: 0.94, 1.00) or plant-based alternatives (HR: 0.97, 95% CI: 0.91, 1.02) were not associated with risk. Interpretation: Our findings suggest that higher consumption of UPFs increases the risk of cancer and cardiometabolic multimorbidity. Funding: Austrian Academy of Sciences, Fondation de France, Cancer Research UK, World Cancer Research Fund International, and the Institut National du Cancer.
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| 11. |
- Dam, Veerle, et al.
(författare)
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Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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| 12. |
- Dam, Veerle, et al.
(författare)
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Genetically Determined Reproductive Aging and Coronary Heart Disease : A Bidirectional 2-sample Mendelian Randomization
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:7, s. E2952-E2961
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures: CHD, CHD risk factors, and ANM. Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.
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| 13. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 14. |
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| 15. |
- Deschasaux, Melanie, et al.
(författare)
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Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality : EPIC cohort study in 10 European countries
- 2020
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 370
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN Population based cohort study. SETTING European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P(0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P(0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P(0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.
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| 16. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 17. |
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| 18. |
- Ganesh, Santhi K., et al.
(författare)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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| 19. |
- Gasull, Magda, et al.
(författare)
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Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
- 2019
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 169, s. 417-433
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
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| 20. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 21. |
- Giampaoli, Simona, et al.
(författare)
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Foreword.
- 2007
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Ingår i: Eur J Cardiovasc Prev Rehabil. - 1741-8267. ; 14 Suppl 3, s. S1-
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Tidskriftsartikel (refereegranskat)
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| 22. |
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| 23. |
- Holmes, Michael V., et al.
(författare)
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Mendelian randomization of blood lipids for coronary heart disease
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 36:9, s. 539-539
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a priormeta-analysis (threshold P < 2 x 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P <= 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestrictedallele score (48SNPs) was associated with CHD(OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
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| 24. |
- Huybrechts, Inge, et al.
(författare)
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Characterization of the degree of food processing in the European prospective investigation into cancer and nutrition : application of the nova classification and validation using selected biomarkers of food processing
- 2022
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.Methods: After grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort (71.5% women; mean age 51 [standard deviation (SD) 9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples (N between 417 and 9,460) within the EPIC cohort via (partial) correlation analyses (unadjusted and adjusted by sex, age, BMI and country). These biomarkers included an industrial transfatty acid (ITFA) isomer (elaidic acid; exogenous fatty acid generated during oil hydrogenation and heating) and urinary 4-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke used in UPF).Results: Contributions of UPF intake to the overall diet in % grams/day varied across countries from 7% (France) to 23% (Norway) and their contributions to overall % energy intake from 16% (Spain and Italy) to >45% (in the UK and Norway). Differences were also found between sociodemographic groups; participants in the highest fourth of UPF consumption tended to be younger, taller, less educated, current smokers, more physically active, have a higher reported intake of energy and lower reported intake of alcohol. The UPF pattern as defined based on the Nova classification (group 4;% kcal/day) was positively associated with blood levels of industrial elaidic acid (r = 0.54) and 4-methyl syringol sulfate (r = 0.43). Associations for the other 3 Nova groups with these food processing biomarkers were either inverse or non-significant (e.g., for unprocessed and minimally processed foods these correlations were –0.07 and –0.37 for elaidic acid and 4-methyl syringol sulfate, respectively).Conclusion: These results, based on a large pan-European cohort, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, these results suggest that the Nova classification can accurately capture consumption of UPF, reflected by stronger correlations with circulating levels of industrial elaidic acid and a syringol metabolite compared to diets high in minimally processed foods.
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| 25. |
- Key, Timothy J., et al.
(författare)
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Consumption of Meat, Fish, Dairy Products, Eggs and Risk of Ischemic Heart Disease : A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort
- 2019
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 139:25, s. 2835-2845
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort.METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates.RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol.CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-HDL cholesterol, and for red and processed meat with systolic blood pressure, which could mediate such effects.
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