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1. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author

Nita G. Forouhi, Kim Overvad, Ivonne Sluijs, Tammy Y.N. Tong, Christina C. Dahm, Kay-Tee Khaw, Thomas E. Gundersen, José María Huerta, Peter M. Nilsson, Miguel Rodríguez-Barranco, Nasser Laouali, Adam S. Butterworth, Giovanna Masala, Sara Grioni, Rosario Tumino, Anja Olsen, Stephen J. Sharp, Salvatore Panico, J. Ramón Quirós, Yvonne T. van der Schouw, Eleanor Wheeler, Rudolf Kaaks, Alicia K Heath, Eva Ardanaz, Felix R. Day, Eleni Sofianopoulou, Konstantinos K. Tsilidis, Luca A. Lotta, Nicholas J. Wareham, Douae El-Fatouhi, Claudia Langenberg, Heiner Boeing, Guy Fagherazzi, Paula Jakszyn, Olov Rolandsson, Rupal L. Shah, Mazda Jenab, Miren Dorronsoro, Ju-Sheng Zheng, Fumiaki Imamura, Isobel D. Stewart, Elio Riboli, Paul W. Franks, Louise Hansen, John Danesh, Carlotta Sacerdote, Jian'an Luan, Niki Dimou, Annemieke M.W. Spijkerman, Tilman Kühn, Zheng, Ju-Sheng [0000-0001-6560-4890], Sharp, Stephen J [0000-0003-2375-1440], Day, Felix R [0000-0003-3789-7651], Sluijs, Ivonne [0000-0001-7758-4911], Shah, Rupal L [0000-0001-8789-8869], van der Schouw, Yvonne T [0000-0002-4605-435X], Dahm, Christina C [0000-0003-0481-2893], Dimou, Niki [0000-0003-1678-9328], Franks, Paul W [0000-0002-0520-7604], Fagherazzi, Guy [0000-0001-5033-5966], Huerta, José María [0000-0002-9637-3869], Heath, Alicia K [0000-0001-6517-1300], Hansen, Louise [0000-0002-7109-8864], Jenab, Mazda [0000-0002-0573-1852], Kühn, Tilman [0000-0001-7702-317X], Laouali, Nasser [0000-0002-8532-456X], Masala, Giovanna [0000-0002-5758-9069], Olsen, Anja [0000-0003-4788-503X], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Sacerdote, Carlotta [0000-0002-8008-5096], Tong, Tammy YN [0000-0002-0284-8959], Tumino, Rosario [0000-0003-2666-414X], Tsilidis, Konstantinos K [0000-0002-8452-8472], Riboli, Elio [0000-0001-6795-6080], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita G [0000-0002-5041-248X], Wareham, Nicholas J [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Sharp, Stephen J. [0000-0003-2375-1440], Day, Felix R. [0000-0003-3789-7651], Shah, Rupal L. [0000-0001-8789-8869], van der Schouw, Yvonne T. [0000-0002-4605-435X], Dahm, Christina C. [0000-0003-0481-2893], Franks, Paul W. [0000-0002-0520-7604], Heath, Alicia K. [0000-0001-6517-1300], Tong, Tammy Y. N. [0000-0002-0284-8959], Tsilidis, Konstantinos K. [0000-0002-8452-8472], Forouhi, Nita G. [0000-0002-5041-248X], and Wareham, Nicholas J. [0000-0003-1422-2993]

Subjects
Male, Single Nucleotide Polymorphisms, Organic chemistry, Genome-wide association study, Type 2 diabetes, VARIANTS, 030204 cardiovascular system & hematology, Biochemistry, Endocrinology, Medical Conditions, Mathematical and Statistical Techniques, 0302 clinical medicine, DESIGN, Risk Factors, Medicine and Health Sciences, Metabolites, VITAMIN-D SUPPLEMENTATION, 030212 general & internal medicine, Prospective Studies, Vitamin D, 11 Medical and Health Sciences, RISK, Diabetis, Statistics, Diabetes, Genomics, Vitamins, General Medicine, Metaanalysis, Middle Aged, Type 2 Diabetes, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Physical sciences, Chemistry, OBESITY, Endokrinologi och diabetes, Medicine, LIFE-STYLE, Female, Life Sciences & Biomedicine, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, DATABASE, Vitamina D, European Continental Ancestry Group, Single-nucleotide polymorphism, Endocrinology and Diabetes, Research and Analysis Methods, Lower risk, White People, Chemical compounds, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Internal medicine, Organic compounds, Diabetes Mellitus, Genome-Wide Association Studies, medicine, Vitamin D and neurology, Genetics, Humans, Statistical Methods, Science & Technology, business.industry, Biology and Life Sciences, Computational Biology, Human Genetics, Odds ratio, Mendelian Randomization Analysis, Genome Analysis, medicine.disease, Metabolism, Diabetes Mellitus, Type 2, Genetic Loci, Metabolic Disorders, Relative risk, Dietary Supplements, GENETIC-DETERMINANTS, business, Mathematics, Genètica, Genome-Wide Association Study
Abstract

Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals., Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.

Published
2020
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2. Dietary Intake of 91 Individual Polyphenols and 5-Year Body Weight Change in the EPIC-PANACEA Cohort

Author

Mercedes Gil-Lespinard, Jazmín Castañeda, Enrique Almanza-Aguilera, Jesús Humberto Gómez, Anne Tjønneland, Cecilie Kyrø, Kim Overvad, Verena Katzke, Matthias B. Schulze, Giovanna Masala, Claudia Agnoli, Maria Santucci de Magistris, Rosario Tumino, Carlotta Sacerdote, Guri Skeie, Cristina Lasheras, Esther Molina-Montes, José María Huerta, Aurelio Barricarte, Pilar Amiano, Emily Sonestedt, Marisa da Silva, Ingegerd Johansson, Johan Hultdin, Anne M. May, Nita G. Forouhi, Alicia K. Heath, Heinz Freisling, Elisabete Weiderpass, Augustin Scalbert, Raul Zamora-Ros, Almanza-Aguilera, Enrique [0000-0002-4805-0774], Kyrø, Cecilie [0000-0002-9083-8960], Masala, Giovanna [0000-0002-5758-9069], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Skeie, Guri [0000-0003-2476-4251], Molina-Montes, Esther [0000-0002-0428-2426], Huerta, José María [0000-0002-9637-3869], Sonestedt, Emily [0000-0002-0747-4562], da Silva, Marisa [0000-0003-1215-8625], Johansson, Ingegerd [0000-0002-9227-8434], Hultdin, Johan [0000-0002-9599-0961], Heath, Alicia K [0000-0001-6517-1300], Freisling, Heinz [0000-0001-8648-4998], Weiderpass, Elisabete [0000-0003-2237-0128], Zamora-Ros, Raul [0000-0002-6236-6804], and Apollo - University of Cambridge Repository

Subjects
obesity, Nutrition and Dietetics, polyphenol, intake, body weight, cohort, EPIC, Physiology, Estrès oxidatiu, Clinical Biochemistry, Pes corporal, Polyphenols, Cell Biology, Biochemistry, Article, Näringslära, Oxidative stress, Polifenols, Obesitat, Molecular Biology
Abstract

Peer reviewed: True, Funder: International Agency for Research on Cancer (IARC), Funder: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Funder: NIHR Imperial Biomedical Research Centre (BRC), Funder: Danish Cancer Society (Denmark), Funder: Ligue Contre le Cancer, Funder: Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Funder: Institut National de la Santé et de la Recherche Médicale (INSERM), Funder: German Cancer Aid, Funder: German Cancer Research Center (DKFZ), Funder: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Funder: Federal Ministry of Education and Research (BMBF), Funder: Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Funder: Compagnia di San Paolo, Funder: National Research Council, Funder: Dutch Ministry of Public Health, Welfare and Sports (VWS), Funder: Netherlands Cancer Registry (NKR), Funder: LK Research Funds, Funder: Dutch Prevention Funds, Funder: Dutch ZON (Zorg Onderzoek Nederland), Funder: World Cancer Research Fund (WCRF), Funder: Statistics Netherlands, Funder: Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Funder: Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Funder: Catalan Institute of Oncology—ICO, Funder: Swedish Cancer Society, Funder: Swedish Research Council, Funder: County Councils of Skåne and Västerbotten, Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 349,165 adult participants from nine European countries. Polyphenol intake was estimated through country-specific validated dietary questionnaires and the Phenol-Explorer database. Body weight was obtained at recruitment and after a mean follow-up time of 5 years. Associations were estimated using multilevel mixed linear regression models. From 91 polyphenols included, the majority (n = 67) were inversely associated with 5-year body weight change after FDR-correction (q < 0.05). The greatest inverse associations were observed for quercetin 3-O-rhamnoside (change in weight for doubling in intake: -0.071 (95% CI: -0.085; -0.056) kg/5 years). Only 13 polyphenols showed positive associations with body weight gain, mainly from the subclass hydroxycinnamic acids (HCAs) with coffee as the main dietary source, such as 4-caffeoylquinic acid (0.029 (95% CI: 0.021; 0.038) kg/5 years). Individual polyphenols with fruit, tea, cocoa and whole grain cereals as the main dietary sources may contribute to body weight maintenance in adults. Individual HCAs may have different roles in body weight change depending on their dietary source.

Published
2023
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3. Association between classes and subclasses of polyphenol intake and 5‐year body weight changes in the EPIC‐PANACEA study

Author

Jazmin Castañeda, Mercedes Gil‐Lespinard, Enrique Almanza‐Aguilera, Fjorida Llaha, Jesús‐Humberto Gómez, Nicola Bondonno, Anne Tjønneland, Kim Overvad, Verena Katzke, Matthias B. Schulze, Giovanna Masala, Claudia Agnoli, Maria Santucci de Magistris, Rosario Tumino, Carlotta Sacerdote, Guri Skeie, Magritt Brustad, Cristina Lasheras, Esther Molina‐Montes, María‐Dolores Chirlaque, Aurelio Barricarte, Emily Sonestedt, Marisa da Silva, Ingegerd Johansson, Johan Hultdin, Anne M. May, Nita G. Forouhi, Alicia K. Heath, Heinz Freisling, Elisabete Weiderpass, Augustin Scalbert, Raul Zamora‐Ros, Castañeda, Jazmin [0000-0002-8521-9946], Gil-Lespinard, Mercedes [0000-0002-7387-2139], Almanza-Aguilera, Enrique [0000-0002-4805-0774], Llaha, Fjorida [0000-0003-0534-6484], Gómez, Jesús-Humberto [0000-0001-8442-8327], Bondonno, Nicola [0000-0001-5905-444X], Tjønneland, Anne [0000-0003-4385-2097], Overvad, Kim [0000-0001-6429-7921], Katzke, Verena [0000-0002-6509-6555], Schulze, Matthias B [0000-0002-0830-5277], Masala, Giovanna [0000-0002-5758-9069], Agnoli, Claudia [0000-0003-4472-1179], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Skeie, Guri [0000-0003-2476-4251], Brustad, Magritt [0000-0003-0114-5271], Lasheras, Cristina [0000-0003-0482-4229], Molina-Montes, Esther [0000-0002-0428-2426], Chirlaque, María-Dolores [0000-0001-9242-3040], Barricarte, Aurelio [0000-0001-6750-1270], Sonestedt, Emily [0000-0002-0747-4562], da Silva, Marisa [0000-0003-1215-8625], Johansson, Ingegerd [0000-0002-9227-8434], Hultdin, Johan [0000-0002-9599-0961], Forouhi, Nita G [0000-0002-5041-248X], Heath, Alicia K [0000-0001-6517-1300], Freisling, Heinz [0000-0001-8648-4998], Weiderpass, Elisabete [0000-0003-2237-0128], Scalbert, Augustin [0000-0001-6651-6710], Zamora-Ros, Raul [0000-0002-6236-6804], and Apollo - University of Cambridge Repository

Subjects
Male, Flavonoids, Nutrition and Dietetics, Coumaric Acids, Endocrinology, Diabetes and Metabolism, Body Weight, Medicine (miscellaneous), Polyphenols, Weight Gain, Coffee, Diet, Näringslära, Endocrinology, Neoplasms, Humans, Female, Prospective Studies
Abstract

Objective: The aim of this study was to evaluate the associations among the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and body weight change over 5years. Methods: A total of 349,165 men and women aged 25 to 70years were recruited in the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (PANACEA) project of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries. Body weight was measured at baseline and at follow-up after a median time of 5years. Polyphenol intake, including four main polyphenol classes and eighteen subclasses, was estimated using validated dietary questionnaires and Phenol-Explorer. Multilevel mixed linear regression models were used to estimate the associations. Results: Participants gained, on average, 2.6 kg (5.0 kg) over 5years. Total flavonoids intake was inversely associated with body weight change (-0.195kg/5 years, 95% CI: -0.262 to -0.128). However, the intake of total polyphenols (0.205kg/5 years, 95% CI: 0.138 to 0.272) and intake of hydroxycinnamic acids (0.324kg/5 years, 95% CI: 0.267 to 0.381) were positively associated with body weight gain. In analyses stratified by coffee consumption, hydroxycinnamic acid intake was positively associated with body weight gain in coffee consumers (0.379kg/5 years, 95% CI: 0.319 to 0.440), but not in coffee nonconsumers (-0.179kg/5 years, 95% CI: -0.490 to 0.133). Conclusions: Higher intakes of flavonoids and their subclasses are inversely associated with a modest body weight change. Results regarding hydroxycinnamic acids in coffee consumers require further investigation., Consejo Nacional de Ciencia y Tecnologia (CONACyT) 693636, Instituto de Salud Carlos III CD20/ 00071 CPII20/00009 FI19/00185 PI18/ 00191

Published
2022
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4. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Author

Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel C. Posner, Katja Mosconi, Cassianne Robinson-Cohen, Amy M. Mason, Thomas R. Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R. Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth L.M. Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustín Gómez de la Cámara, Vilmundur Gudnason, Graeme J. Hankey, Per-Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K. Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Koenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, Charlotte Onland-Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Tong, Rosario Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W.M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raul Zamora-Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nick Wareham, Elio Riboli, J.Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela M. Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Shaw, Robert Atkins, Paul Zimmet, Peter Whincup, Johann Willeit, Christoph Leitner, Anne Tybjaerg-Hansen, Peter Schnohr, Shoaib Afzal, David Lora Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, E. M. van Zutphen, N. M. van Schoor, Cinzia Lo Noce, Richard Kronmal, Georg Lappas, Peter M. Nilsson, Bo Hedblad, Jonathan Shaffer, Joseph Schwartz, Daichi Shimbo, Shinichi Sato, Mina Hayama-Terada, Simerjot Jassal, Thor Aspelund, Bolli Thorsson, Gunnar Sigurdsson, Layal Chaker, Kamran M. Ikram, Maryam Kavousi, Hugh Tunstall-Pedoe, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Edith Feskens, Johanna M Geleijnse, Daan Kromhout, Internal Medicine, Neurology, Epidemiology, Bell, Steven [0000-0001-6774-3149], Posner, Daniel C [0000-0002-3056-6924], Mason, Amy M [0000-0002-8019-0777], Allara, Elias [0000-0002-1634-8330], Staplin, Natalie [0000-0003-4482-4418], Arndt, Volker [0000-0001-9320-8684], Ärnlöv, Johan [0000-0002-6933-4637], Barr, Elizabeth LM [0000-0003-4284-1716], Boer, Jolanda MA [0000-0002-9714-4304], Brenner, Hermann [0000-0002-6129-1572], Casiglia, Edoardo [0000-0002-0003-3289], Chiodini, Paolo [0000-0003-0139-2264], Coresh, Josef [0000-0002-4598-0669], Cushman, Mary [0000-0002-7871-6143], Davidson, Karina W [0000-0002-9162-477X], de Jongh, Renate T [0000-0001-8414-3938], Engström, Gunnar [0000-0002-8618-9152], de la Cámara, Agustín Gómez [0000-0001-6827-6319], Gudnason, Vilmundur [0000-0001-5696-0084], Hankey, Graeme J [0000-0002-6044-7328], Hansson, Per-Olof [0000-0001-6323-0506], Heath, Alicia K [0000-0001-6517-1300], Hoorn, Ewout J [0000-0002-8738-3571], Imano, Hironori [0000-0002-6661-4254], Katzke, Verena [0000-0002-6509-6555], Kiechl, Stefan [0000-0002-9836-2514], Koenig, Wolfgang [0000-0002-2064-9603], Kronmal, Richard A [0000-0002-9897-7076], Kyrø, Cecilie [0000-0002-9083-8960], Ljungberg, Börje [0000-0002-4121-3753], MacDonald, Conor [0000-0002-4989-803X], Masala, Giovanna [0000-0002-5758-9069], Ninomiya, Toshiharu [0000-0003-1345-9032], Nordestgaard, Børge G [0000-0002-1954-7220], Onland-Moret, Charlotte [0000-0002-2360-913X], Palmieri, Luigi [0000-0002-4298-2642], Rosengren, Annika [0000-0002-5409-6605], Schulze, Matthias B [0000-0002-0830-5277], Sieri, Sabina [0000-0001-5201-172X], Sundström, Johan [0000-0003-2247-8454], Tikhonoff, Valérie [0000-0001-7846-0101], Tong, Tammy [0000-0002-0284-8959], Tzoulaki, Ioanna [0000-0002-4275-9328], van der Schouw, Yvonne T [0000-0002-4605-435X], Wannamethee, S Goya [0000-0001-9484-9977], Weiderpass, Elisabete [0000-0003-2237-0128], Willeit, Peter [0000-0002-1866-7159], Woodward, Mark [0000-0001-9800-5296], Yamagishi, Kazumasa [0000-0003-3301-5519], Zamora-Ros, Raul [0000-0002-6236-6804], Gagnon, David R [0000-0002-6367-3179], Tsao, Philip S [0000-0001-7274-9318], Edwards, Todd L [0000-0003-4318-6119], Damrauer, Scott M [0000-0001-8009-1632], Joseph, Jacob [0000-0002-7279-4896], Pennells, Lisa [0000-0002-8594-3061], Gaziano, Thomas A [0000-0002-5985-345X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nick [0000-0003-1422-2993], Hung, Adriana M [0000-0002-3203-1608], Butterworth, Adam S [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Gaziano, Liam, Sun, Luanluan, Arnold, Matthew, Bell, Steven, Cho, Kelly, Kaptoge, Stephen K, Song, Rebecca J, Burgess, Stephen, Posner, Daniel C, Mosconi, Katja, Robinson-Cohen, Cassianne, Mason, Amy M, Bolton, Thomas R, Tao, Ran, Allara, Elia, Schubert, Petra, Chen, Lingyan, Staley, James R, Staplin, Natalie, Altay, Servet, Amiano, Pilar, Arndt, Volker, Ärnlöv, Johan, Barr, Elizabeth L M, Björkelund, Cecilia, Boer, Jolanda M A, Brenner, Hermann, Casiglia, Edoardo, Chiodini, Paolo, Cooper, Jackie A, Coresh, Josef, Cushman, Mary, Dankner, Rachel, Davidson, Karina W, de Jongh, Renate T, Donfrancesco, Chiara, Engström, Gunnar, Freisling, Heinz, de la Cámara, Agustín Gómez, Gudnason, Vilmundur, Hankey, Graeme J, Hansson, Per-Olof, Heath, Alicia K, Hoorn, Ewout J, Imano, Hironori, Jassal, Simerjot K, Kaaks, Rudolf, Katzke, Verena, Kauhanen, Jussi, Kiechl, Stefan, Koenig, Wolfgang, Kronmal, Richard A, Kyrø, Cecilie, Lawlor, Deborah A, Ljungberg, Börje, Macdonald, Conor, Masala, Giovanna, Meisinger, Christa, Melander, Olle, Moreno Iribas, Conchi, Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Børge G, Onland-Moret, Charlotte, Palmieri, Luigi, Petrova, Dafina, Garcia, Jose Ramón Quiró, Rosengren, Annika, Sacerdote, Carlotta, Sakurai, Masaru, Santiuste, Carmen, Schulze, Matthias B, Sieri, Sabina, Sundström, Johan, Tikhonoff, Valérie, Tjønneland, Anne, Tong, Tammy, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Monique Verschuren, W M, Völzke, Henry, Wallace, Robert B, Wannamethee, S Goya, Weiderpass, Elisabete, Willeit, Peter, Woodward, Mark, Yamagishi, Kazumasa, Zamora-Ros, Raul, Akwo, Elvis A, Pyarajan, Saiju, Gagnon, David R, Tsao, Philip S, Muralidhar, Sumitra, Edwards, Todd L, Damrauer, Scott M, Joseph, Jacob, Pennells, Lisa, Wilson, Peter W F, Harrison, Seamu, Gaziano, Thomas A, Inouye, Michael, Baigent, Colin, Casas, Juan P, Langenberg, Claudia, Wareham, Nick, Riboli, Elio, Gaziano, J Michael, Danesh, John, Hung, Adriana M, Butterworth, Adam S, Wood, Angela M, Di Angelantonio, Emanuele, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology and Data Science, APH - Aging & Later Life, and APH - Personalized Medicine

Subjects
kidney disease, General Practice, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program, Coronary Disease, coronary disease, Kidney, Malalties coronàries, 1117 Public Health and Health Services, Coronary diseases, SDG 3 - Good Health and Well-being, cardiovascular disease, Risk Factors, Physiology (medical), Diabetes Mellitus, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Kardiologi, Kidney diseases, Malalties cardiovasculars, Cardiovascular Diseases, Kidney Diseases, Stroke, 1103 Clinical Sciences, Mendelian Randomization Analysis, kidney diseases, stroke, Allmänmedicin, Cardiovascular diseases, Cardiovascular System & Hematology, Malalties del ronyó, Cardiology and Cardiovascular Medicine, cardiovascular diseases
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 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 –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.

Published
2022
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5. Dietary fatty acids, macronutrient substitutions, food sources and incidence of coronary heart disease: Findings from the EPIC-CVD case-cohort study across nine european countries

Author

Matthias B. Schulze, Vittorio Krogh, Rosario Tumino, Nita G. Forouhi, Christina C. Dahm, Kim Overvad, Marie-Christine Boutron-Ruault, Angela M. Wood, Yvonne T. van der Schouw, Guri Skeie, Laura Johnson, Fumiaki Imamura, Ivonne Sluijs, José R Quirós, Elisabete Weiderpass, Nicholas J. Wareham, Timothy J. Key, Adam S. Butterworth, Giovanna Masala, Alicia K Heath, Albert Koulman, Conchi Moreno-Iribas, Inge Huybrechts, John Danesh, Stephen J. Sharp, Salvatore Panico, Carlotta Sacerdote, Aurora Perez-Cornago, Olle Melander, Rudolf Kaaks, Elio Riboli, Tammy Y.N. Tong, María José Sánchez, Rajiv Chowdhury, Ju-Sheng Zheng, Miguel Rodríguez-Barranco, W M Monique Verschuren, Marinka Steur, Ingegerd Johansson, Heiner Boeing, Anne Tjønneland, Carmen Santiuste, Antonia Trichopoulou, Maria Wennberg, Jolanda M. A. Boer, Marcela Guevara, Cecilie Kyrø, Raul Zamora-Ros, Liher Imaz, Tilman Kühn, Marianne Uhre Jakobsen, Ulrika Ericson, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G0800270, MR/L003120/1, Pfizer, AstraZeneca, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, Merck Sharp and Dohme, MSD, Seventh Framework Programme, FP7: HEALTH-F2-2012-279233, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MC_UU_00006/1, National Institute for Health Research, NIHR, British Heart Foundation, BHF: RG/18/13/33946, RG13/13/30194, SP/09/002, Cancer Research UK, CRUK: C8221/A29017, MR/M012190/1, World Cancer Research Fund, WCRF, Imperial College London, European Research Council, ERC: 268834, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, European Social Fund, ESF, Sixth Framework Programme, FP6: LSHM_CT_2006_037197, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Akademi Sains Malaysia, ASM: MR/P013880/1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, UCLH Biomedical Research Centre, NIHR BRC: BRC-1215-20014, NIHR Imperial Biomedical Research Centre, BRC, Hellenic Health Foundation, HHF: CP15/00100, IS-BRC-1215-20014, MC_UU_00006/3, Dr Danesh reports grants, personal fees and non-financial support from Merck Sharp & Dohme, grants, personal fees, and nonfinancial support from Novartis, grants from Pfizer, and grants from AstraZeneca outside the submitted work. He is member of the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the Steering Committee of UK Biobank (since 2011), the MRC International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science ‘Omics Panel Member, London (since 2013), the Scientific Advisory Committee for Sanofi (since 2013), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, and the Astra Zeneca Genomics Advisory Board (2018). Dr Butterworth reports grants outside of this work from AstraZeneca, Biogen, BioMarin, Bioverativ, Merck, Novartis, Pfizer, and Sanofi and personal fees from Novartis. The remaining authors have no disclosures to report., EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270, MR/L003120/1), British Heart Foundation (BHF) (SP/09/002, RG13/13/30194, RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Health Research Fund– Instituto de Salud Carlos III, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R.Z.-R. thanks the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund–European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart). R.C. was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award., Steur, Marinka [0000-0002-9028-0290], Imamura, Fumiaki [0000-0002-6841-8396], Key, Timothy J [0000-0003-2294-307X], Chowdhury, Rajiv [0000-0003-4881-5690], Guevara, Marcela [0000-0001-9242-6364], Jakobsen, Marianne U [0000-0001-6518-4136], Johansson, Ingegerd [0000-0002-9227-8434], Weiderpass, Elisabete [0000-0003-2237-0128], Boer, Jolanda MA [0000-0002-9714-4304], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Heath, Alicia K [0000-0001-6517-1300], Huybrechts, Inge [0000-0003-3838-855X], Imaz, Liher [0000-0002-3777-4953], Masala, Giovanna [0000-0002-5758-9069], Zamora-Ros, Raul [0000-0002-6236-6804], Perez-Cornago, Aurora [0000-0002-5652-356X], Tong, Tammy YN [0000-0002-0284-8959], Wareham, Nicholas J [0000-0003-1422-2993], Forouhi, Nita G [0000-0002-5041-248X], and Apollo - University of Cambridge Repository

Subjects
Saturated fat, Physiology, Coronary Disease, 030204 cardiovascular system & hematology, EPIC, Cohort Studies, 0302 clinical medicine, Medicine, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, Kardiologi, Primary prevention, Incidence, Incidence (epidemiology), Fatty Acids, Fatty acids in human nutrition, 3. Good health, Europe, Näringslära, Coronary heart disease, Dietary guidelines, Cardiology and Cardiovascular Medicine, Polyunsaturated fatty acid, Cohort study, Malalties coronàries, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Àcids grassos en la nutrició, Diseases of the circulatory (Cardiovascular) system, Humans, Nutritional epidemiology, business.industry, Nutrients, Dietary Fats, chemistry, Food, RC666-701, SPS Exercise, Nutrition and Health Sciences, business
Abstract

EPIC-CVD was supported by the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the European Research Council (268834). The coordinating center was supported by core funding from the: United Kingdom MRC (G0800270; MR/L003120/1), British Heart Foundation (BHF) (SP/09/002; RG13/13/30194; RG/18/13/33946), and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014).* The establishment of the study subcohort was supported by the European Union Sixth Framework Programme (grant LSHM_CT_ 2006_037197 to the InterAct project) and the MRC Epidemiology Unit (grant MC_UU_00006/1). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by NIHR Imperial BRC. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro--AIRC--Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands); Health Research Fund-Instituto de Salud Carlos III, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), MRC (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). EPIC-Greece was supported by the Hellenic Health Foundation (Greece). M.S., N.J.W., N.G.F., and F.I. acknowledge support from MRC Epidemiology Unit (MC_UU_ 00006/1 and MC_UU_00006/3). N.J.W. and N.G.F. acknowledge support from NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215--20014) and NGF is a NIHR Senior Investigator Award holder. M.S. was also supported by BHF for part of this work while working in the BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. R. Z.-R. thanks the "Miguel Servet" program (CP15/00100) from the Institute of Health Carlos III (co-funded by the European Social Fund--European Social Fund Investing in Your Future). A.W. was supported by a BHF-Turing Cardiovascular Data Science Award and by the European Commission-Innovative Medicines Initiative (BigData@Heart).R.C.was funded by a MRC-Newton project grant to study genetic risk factors of cardiovascular disease among Southeast Asian people and the Academy of Sciences Malaysia (grant no. MR/P013880/1) and a United Kingdom Research and Innovation-Global Challenges Research Fund Project Grant to study risk factors of noncommunicable diseases in Bangladesh. J.D. holds a BHF Professorship and a NIHR Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization. The funders of the study had no role in study design, data collection, analysis, data interpretation, or writing of the article, or in the decision to submit for publication. M.S. had full access to all the data in the study, and M.S. and N.G.F. had final responsibility for the decision to submit for publication., BACKGROUND: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. METHODS AND RESULTS: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). CONCLUSIONS: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix., European Commission Framework Programme 7 HEALTH-F2-2012-279233, European Research Council (ERC), European Commission 268834, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) G0800270 MR/L003120/1, British Heart Foundation SP/09/002 RG13/13/30194 RG/18/13/33946, National Institute for Health Research (NIHR) BRC-1215-20014, European Commission LSHM_CT_ 2006_037197, Medical Research Council UK (MRC) MC_UU_ 00006/1 MC_UU_00006/3, International Agency for Research on Cancer, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (France), German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam, Rehbruecke, Federal Ministry of Education and Research (Germany), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund International (WCRF), Netherlands Government, Instituto de Salud Carlos III, Junta de Andalucia, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of Oncology (Spain), Swedish Cancer Society, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, Medical Research Council UK (MRC) 1000143 MR/M012190/1, Hellenic Health Foundation (Greece), NIHR* Cambridge BRC: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, British Heart Foundation, Institute of Health Carlos III (European Social Fund-European Social Fund Investing in Your Future) CP15/00100, BHF-Turing Cardiovascular Data Science Award, European Commission-Innovative Medicines Initiative (BigData@Heart), MRC-Newton project grant MR/P013880/1, United Kingdom Research and Innovation-Global Challenges Research Fund, NIHR Senior Investigator Award

Published
2021
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