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1. 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

2. Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study

Author

Amy M. Mason, Dipender Gill, Bowen Liu, Luanluan Sun, Stephen Burgess, Emanuele Di Angelantonio, Gill, Dipender [0000-0001-7312-7078], and Apollo - University of Cambridge Repository

Subjects
Male, medicine.medical_specialty, endocrine system diseases, type 2 diabetes mellitus, Population, Coronary Artery Disease, QH426-470, Coronary artery disease, chemistry.chemical_compound, Internal medicine, Diabetes mellitus, Mendelian randomization, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Stroke, hemoglobin A1c, Genetics (clinical), Genetic Association Studies, average blood glucose, Ischemic Stroke, Genetics & Heredity, Glycated Hemoglobin, Heart Failure, Peripheral Vascular Diseases, 0604 Genetics, education.field_of_study, Science & Technology, business.industry, Vascular disease, Communication, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Genetic Variation, Aortic Valve Stenosis, Mendelian Randomization Analysis, Middle Aged, medicine.disease, cardiovascular diseases, chemistry, Diabetes Mellitus, Type 2, mendelian randomization, Female, Glycated hemoglobin, business, Life Sciences & Biomedicine
Abstract

(1) Aim: To investigate the causal effects of T2DM liability and glycated haemoglobin (HbA1c) levels on various cardiovascular disease outcomes, both in the general population and in non-diabetic individuals specifically. (2) Methods: We selected 243 variants as genetic instruments for T2DM liability and 536 variants for HbA1c. Linear Mendelian randomization analyses were performed to estimate the associations of genetically-predicted T2DM liability and HbA1c with 12 cardiovascular disease outcomes in 367,703 unrelated UK Biobank participants of European ancestries. We performed secondary analyses in participants without diabetes (HbA1c < 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c < 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p < 0.004, 0.05/12) with peripheral vascular disease, aortic valve stenosis, coronary artery disease, heart failure, ischaemic stroke, and any stroke. Genetically-predicted HbA1c was positively associated with coronary artery disease and any stroke. Mendelian randomization estimates generally shifted towards the null when excluding diabetic and pre-diabetic participants from analyses. (4) Conclusions: This genetic evidence supports causal effects of T2DM liability and HbA1c on a range of cardiovascular diseases, suggesting that improving glycaemic control could reduce cardiovascular risk in a general population, with greatest benefit in individuals with diabetes.

Published
2021

3. Association of beta-2-microglobulin and cardiovascular events and mortality: A systematic review and meta-analysis

Author

Fanchao Shi, Luanluan Sun, Stephen Kaptoge, Shi, Fanchao [0000-0003-2361-5799], Kaptoge, Stephen [0000-0002-1155-4872], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, medicine.medical_specialty, Coronary Disease, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Beta-2-microglobulin, 0302 clinical medicine, Internal medicine, Medicine, Humans, cardiovascular diseases, Mortality, Stroke, business.industry, Beta-2 microglobulin, Incidence (epidemiology), medicine.disease, Meta-analysis, 030104 developmental biology, Cardiovascular diseases, Relative risk, Dietary Supplements, Biomarker (medicine), Observational study, Cardiology and Cardiovascular Medicine, business, beta 2-Microglobulin
Abstract

Background and aims Beta-2-microglobulin (B2M) has been suggested as an emerging biomarker for cardiovascular diseases (CVD), including coronary heart disease (CHD) and stroke, and mortality. Methods Three databases were searched from inception to January 2, 2020, supplemented by scanning reference lists of identified studies. We identified studies that reported associations of baseline serum or plasma B2M and CVD incidence, CVD mortality, or CHD and stroke separately, in either general populations or patients with renal disease. Relative risks (RR) were extracted and harmonized to a comparison of the highest versus lowest third of the distribution of B2M, and the results were aggregated. Results Sixteen studies (5 in general populations, and 11 in renal disease populations) were included, involving 30,988 participants and 5391 CVD events. Based on random-effects meta-analysis, the pooled adjusted RRs comparing the highest versus lowest third of the distribution of B2M were 1.71 (95%CI: 1.37–2.13) for CVD, 2.29 (1.51–3.49) for CVD mortality, 1.64 (1.14–2.34) for CHD, and 1.51 (1.28–1.78) for stroke, with little to high heterogeneity between studies (0.0% ≤ I2 ≤ 80.0%). The positive associations between B2M and risks of CVD outcomes remained broadly significant across subgroup analyses. Moreover, the pooled adjusted RRs were 2.51 (1.94–3.26; I2 = 83.7%) for all-cause mortality and 2.64 (1.34–5.23; I2 = 83.1%) for infectious mortality. Conclusions Available observational data show that there are moderate positive associations between B2M levels and CVD events and mortality, although few studies have been conducted in general populations., Graphical abstract Image 1, Highlights • Available epidemiological evidence shows that circulating B2M levels are moderately associated with CVD events and mortality. • Future large-scale general population-based prospective studies and genetic studies are needed to assess the causality.

Published
2021

4. Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

Author

Adam S. Butterworth, Scott C. Ritchie, Nilesh J. Samani, Steven Bell, Stephen Kaptoge, Matthew Arnold, Michael Inouye, Qi Guo, Frank Dudbridge, Christopher P. Nelson, Lisa Pennells, Emanuele Di Angelantonio, John R. Thompson, Angela M. Wood, Eleni Sofianopoulou, John Danesh, David Stevens, Stephen Burgess, Gad Abraham, Luanluan Sun, Thomas A. W. Bolton, Pennells, Lisa [0000-0002-8594-3061], Nelson, Christopher P. [0000-0001-8025-2897], Ritchie, Scott C. [0000-0002-8454-9548], Arnold, Matthew [0000-0001-6339-1115], Bell, Steven [0000-0001-6774-3149], Burgess, Stephen [0000-0001-5365-8760], Dudbridge, Frank [0000-0002-8817-8908], Stevens, David [0000-0001-8874-7122], Thompson, John R. [0000-0003-4819-1611], Wood, Angela [0000-0002-7937-304X], Samani, Nilesh J. [0000-0002-3286-8133], Inouye, Michael [0000-0001-9413-6520], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Nelson, Christopher P [0000-0001-8025-2897], Ritchie, Scott C [0000-0002-8454-9548], Thompson, John R [0000-0003-4819-1611], and Samani, Nilesh J [0000-0002-3286-8133]

Subjects
Male, Epidemiology, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Biochemistry, Vascular Medicine, Cohort Studies, Welsh, 0302 clinical medicine, Medical Conditions, Endocrinology, Agency (sociology), Coronary Heart Disease, 030212 general & internal medicine, Incidence, General Medicine, Middle Aged, Medical research, C-Reactive Proteins, Lipids, Social research, Stroke, Cholesterol, Neurology, Cardiovascular Diseases, language, Medicine, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, Cerebrovascular Diseases, Cardiology, Library science, Risk Assessment, 03 medical and health sciences, Political science, medicine, Diabetes Mellitus, Humans, Ischemic Stroke, Aged, Medicine and health sciences, Government, Biology and life sciences, Public health, Proteins, Cardiovascular Disease Risk, language.human_language, United Kingdom, Heart Disease Risk Factors, Medical Risk Factors, Metabolic Disorders, Polygenic risk score, Biomarkers
Abstract

Background Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. Methods and findings Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to, Luanluan Sun and colleagues investigate whether adding polygenic risk scores to conventional risk factors of cardiovascular disease helps predict disease risk., Author summary Why was this study done? Application of polygenic risk scores (PRSs) has opened opportunities to enhance risk stratification and prevention for common diseases. The clinical utility of PRSs in cardiovascular disease (CVD) risk prediction is, however, uncertain. Previous analyses have generally focused only on coronary heart disease (CHD) rather than the composite outcome of CHD and stroke, and have often lacked modelling of clinical implications of initiating guideline-recommended interventions (e.g., statin therapy). What did the researchers do and find? We quantified the incremental predictive gain with PRSs on top of conventional risk factors using data on 306,654 individuals from UK Biobank. We modelled the population health implications of initiating statin therapy as recommended by current guidelines using data from 2.1 million individuals from the Clinical Practice Research Datalink. Addition of information on PRSs to a conventional risk prediction model increased the C-index (a measure of risk discrimination) and improved risk classification of cases and non-cases. We estimated that targeted assessment of PRSs among people at intermediate (i.e., 5% to

Published
2021

5. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality : observational and Mendelian randomisation analyses

Author

Eleni Sofianopoulou, Stephen K Kaptoge, Shoaib Afzal, Tao Jiang, Dipender Gill, Thomas E Gundersen, Thomas R Bolton, Elias Allara, Matthew G Arnold, Amy M Mason, Ryan Chung, Lisa A M Pennells, Fanchao Shi, Luanluan Sun, Peter Willeit, Nita G Forouhi, Claudia Langenberg, Stephen J Sharp, Salvatore Panico, Gunnar Engström, Olle Melander, Tammy Y N Tong, Aurora Perez-Cornago, Margareta Norberg, Ingegerd Johansson, Verena Katzke, Bernard Srour, María José Sánchez, Daniel Redondo-Sánchez, Anja Olsen, Christina C Dahm, Kim Overvad, Magritt Brustad, Guri Skeie, Conchi Moreno-Iribas, N Charlotte Onland-Moret, Yvonne T van der Schouw, Konstantinos K Tsilidis, Alicia K Heath, Claudia Agnoli, Vittorio Krogh, Ian H de Boer, Camilla Jannie Kobylecki, Yunus Çolak, Armin Zittermann, Johan Sundström, Paul Welsh, Elisabete Weiderpass, Elom K Aglago, Pietro Ferrari, Robert Clarke, Marie-Christine Boutron, Gianluca Severi, Conor MacDonald, Rui Providencia, Giovanna Masala, Raul Zamora Ros, Jolanda Boer, WM Monique Verschuren, Peggy Cawthon, Louise L Schierbeck, Cyrus Cooper, Matthias B Schulze, Manuela M Bergmann, Anke Hannemann, Stefan Kiechl, Hermann Brenner, Natasja M van Schoor, Juan R Albertorio, Carlotta Sacerdote, Allan Linneberg, Line L Kårhus, José María Huerta, Liher Imaz, Christel Joergensen, Yoav Ben-Shlomo, Annamari Lundqvist, John Gallacher, Naveed Sattar, Angela M Wood, Nicholas J Wareham, Børge G Nordestgaard, Emanuele Di Angelantonio, John Danesh, Adam S Butterworth, Stephen Burgess, Epidemiology and Data Science, APH - Aging & Later Life, APH - Personalized Medicine, and Collaboration, Emerging Risk Factors Collaboration/EPIC-CVD/Vitamin D Studies

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Myocardial Infarction, Coronary Disease, Disease, Endocrinology and Diabetes, vitamin D deficiency, 1117 Public Health and Health Services, Endocrinology, Risk Factors, Internal medicine, Internal Medicine, Vitamin D and neurology, Medicine, Humans, Cardiac and Cardiovascular Systems, Myocardial infarction, Prospective Studies, Vitamin D, Prospective cohort study, education, Stroke, education.field_of_study, Kardiologi, Nutrition and Dietetics, business.industry, 1103 Clinical Sciences, Articles, Vitamins, Mendelian Randomization Analysis, Middle Aged, medicine.disease, Vitamin D Deficiency, Näringslära, 1101 Medical Biochemistry and Metabolomics, Dietary Supplements, Endokrinologi och diabetes, business, Cohort study
Abstract

Background Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration Interpretation Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies. Funding British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

Published
2021

6. Causal associations of blood lipids with risk of ischemic stroke and intracerebral hemorrhage in Chinese adults

Author

Luanluan, Sun, Robert, Clarke, Derrick, Bennett, Yu, Guo, Robin G, Walters, Michael, Hill, Sarah, Parish, Iona Y, Millwood, Zheng, Bian, Yiping, Chen, Canqing, Yu, Jun, Lv, Rory, Collins, Junshi, Chen, Richard, Peto, Liming, Li, Zhengming, Chen, and Zhe, Qiu

Subjects
Adult, Male, China, Middle Aged, Lipids, Brain Ischemia, Stroke, Asian People, Risk Factors, Case-Control Studies, Odds Ratio, Humans, Female, Triglycerides, Aged, Cerebral Hemorrhage, Proportional Hazards Models
Abstract

Stroke is the second leading cause of death worldwide and accounts for 2 million deaths annually in China

Published
2018

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