Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

Vimaleswaran KS, Cavadino A, Berry DJ, LifeLines Cohort Study investigators, Jorde R, Dieffenbach AK, Lu C, Alves AC, Heerspink HJ, Tikkanen E, Eriksson J, Wong A, Mangino M, Jablonski KA, Nolte IM, Houston DK, Ahluwalia TS, van der Most PJ, Pasko D, Zgaga L, Thiering E, Vitart V, Fraser RM, Huffman JE, de Boer RA, Schöttker B, Saum KU, McCarthy MI, Dupuis J, Herzig KH, Sebert S, Pouta A, Laitinen J, Kleber ME, Navis G, Lorentzon M, Jameson K, Arden N, Cooper JA, Acharya J, Hardy R, Raitakari O, Ripatti S, Billings LK, Lahti J, Osmond C, Penninx BW, Rejnmark L, Lohman KK, Paternoster L, Stolk RP, Hernandez DG, Byberg L, Hagström E, Melhus H, Ingelsson E, Mellström D, Ljunggren O, Tzoulaki I, McLachlan S, Theodoratou E, Tiesler CM, Jula A, Navarro P, Wright AF, Polasek O, International Consortium for Blood Pressure (ICBP), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, Global Blood Pressure Genetics (Global BPGen) consortium, Caroline Hayward, Wilson JF, Rudan I, Salomaa V, Heinrich J, Campbell H, Price JF, Karlsson M, Lind L, Michaëlsson K, Bandinelli S, Frayling TM, Hartman CA, Sørensen TI, Kritchevsky SB, Langdahl BL, Eriksson JG, Florez JC, Spector TD, Lehtimäki T, Kuh D, Humphries SE, Cooper C, Ohlsson C, März W, de Borst MH, Kumari M, Kivimaki M, Wang TJ, Power C, Brenner H, Grimnes G, van der Harst P, Snieder H, Hingorani AD, Pilz S, Whittaker JC, Järvelin MR, Hyppönen E

The lancet. Diabetes & endocrinology · 288 citas

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Cómo se estudió

Diseño: Metaanálisis (indexado por PubMed)
Estudiado en: Personas
Resultado principal: Eventos clínicos como enfermedad o muerte

Quién lo pagó

Financiación: Financiado por la industria
Empresa: Bristol-Myers Squibb
Universidad u hospital: George Washington University
Organización sin fines de lucro: Wellcome Trust
Gobierno: National Institute for Health and Care Research
Organización sin fines de lucro: British Heart Foundation
Universidad u hospital: University College London
Universidad u hospital: University of South Australia
Gobierno: Academy of Finland
Empresa: Novo Nordisk
Empresa: Novo Nordisk Fonden
Gobierno: National Institutes of Health
Gobierno: Medical Research Council
Gobierno: Economic and Social Research Council
Gobierno: National Institute of Diabetes and Digestive and Kidney Diseases
Gobierno: Chief Scientist Office
Gobierno: National Institute for Health Research (NIHR)
Gobierno: Intramural NIH HHS
Gobierno: NIDDK NIH HHS
Subvenciones: Novo Nordisk Fonden (NNF14OC0010513); Economic and Social Research Council (ES/K005146/1); Medical Research Council (MR/K013351/1); Economic and Social Research Council (ES/K005774/1); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072041); Medical Research Council (MR/K006584/1); Wellcome Trust (098381); Economic and Social Research Council (ES/J023299/1); Medical Research Council (G0601653); Medical Research Council (MC_UU_12011/4); Novo Nordisk Fonden (NNF13OC0005785); British Heart Foundation (RG/08/008/25291); Economic and Social Research Council (ES/K005774/1); Medical Research Council (MR/J012165/1); British Heart Foundation (RG/10/12/28456); National Institute for Health and Care Research (NF-SI-0508-10082); Economic and Social Research Council (ES/H029745/1); British Heart Foundation (PG/09/023/26806); British Heart Foundation (PG/09/023); Medical Research Council (MC_UU_12011/1); National Institute for Health and Care Research (NF-SI-0513-10085); Economic and Social Research Council (ES/J023299/1); Economic and Social Research Council (ES/K005146/1); Economic and Social Research Council (ES/H029745/1)

Según 18 financiadores declarados.

Publicación

Publicado: 2014-06-25 · Lancet Diabetes Endocrinol · vol. 2 · número 9 · págs. 719–729
Editorial: Elsevier BV
Citado: 370 citas · más que el 100% de estudios similares · 27.9× el promedio de su campo
Impacto: Entre el 10 % más citado de su campo
Referencias: 38 trabajos
Acceso: Acceso abierto (revista híbrida) · CC-BY-NC-ND
Áreas de investigación: Vitamin D Research Studies · Genetic Associations and Epidemiology · Blood Pressure and Hypertension Studies
Palabras clave: vitamin D status, 25-hydroxyvitamin D, arterial blood pressure, hypertension risk, systolic blood pressure, diastolic blood pressure, CYP2R1, DHCR7, vitamin D synthesis, causal relationship, genetic variants, charge
MeSH: humans, hypertension, vitamin d deficiency, genetic predisposition to disease, oxidoreductases acting on ch-ch group donors, vitamin d, body mass index, phenotype, polymorphism, single nucleotide, adult, middle aged, female, male, randomized controlled trials as topic, mendelian randomization analysis, cholestanetriol 26-monooxygenase, cytochrome p450 family 2

DOI ↗PubMed Central ↗OpenAlex ↗

100 autores

Karani Santhanakrishnan Vimaleswaran🇬🇧University College London; University of Reading
Alana Cavadino🇬🇧University College London
Diane J. Berry🇬🇧University College London
Rolf Jorde🇳🇴UiT The Arctic University of Norway
Aida Karina Dieffenbach🇩🇪German Cancer Research Center
Chen Lu🇺🇸Boston University
Alexessander Couto Alves🇬🇧🇫🇮Imperial College London; University of Oulu
Hiddo J.L. Heerspink🇳🇱University Medical Center Groningen; University of Groningen
Emmi Tikkanen🇫🇮University of Helsinki; Institute for Molecular Medicine Finland
Joel Eriksson🇫🇮🇸🇪University of Helsinki; Helsinki University Hospital; Sahlgrenska University Hospital
Andrew Wong🇬🇧MRC Unit for Lifelong Health and Ageing; University College London
Massimo Mangino🇬🇧King's College London
Kathleen A. Jablonski🇺🇸George Washington University
Ilja Maria Nolte🇳🇱University Medical Center Groningen; University of Groningen
Denise K. Houston🇺🇸Wake Forest University Health Sciences; Wake Forest University
Tarunveer S. Ahluwalia🇩🇰University of Copenhagen; Novo Nordisk Foundation; Gentofte Hospital; Copenhagen Prospective Studies on Asthma in Childhood; Novo Nordisk Foundation Center for Basic Metabolic Research
Peter J. van der Most🇳🇱University Medical Center Groningen; University of Groningen
Dorota Pasko🇬🇧University of Exeter
Lina Zgaga🇮🇪🇬🇧Trinity College Dublin; University of Edinburgh
Elisabeth Thiering🇩🇪Helmholtz Munich; Ludwig-Maximilians-Universität München
Véronique Vitart🇬🇧Institute of Genetics and Cancer; MRC Human Genetics Unit; University of Edinburgh
Ross M. Fraser🇬🇧University of Edinburgh
Jennifer E. Huffman🇬🇧Institute of Genetics and Cancer; MRC Human Genetics Unit; University of Edinburgh
Rudolf A. de Boer🇳🇱University Medical Center Groningen; University of Groningen
Ben Schöttker🇩🇪German Cancer Research Center
Kai-Uwe Saum🇩🇪German Cancer Research Center
Mark I. McCarthy🇬🇧Centre for Human Genetics; University of Oxford; NIHR Oxford Biomedical Research Centre; Oxford Centre for Diabetes, Endocrinology and Metabolism
Josée Dupuis🇺🇸Boston University; Framingham Heart Study
Karl‐Heinz Herzig🇫🇮Oulu University Hospital; University of Oulu
Sylvain P Sebert🇫🇮University of Oulu
Anneli Pouta🇫🇮Oulu University Hospital; Finnish Institute for Health and Welfare
Jaana H. Laitinen🇫🇮Finnish Institute of Occupational Health
Marcus Edi Kleber🇩🇪Heidelberg University; Medizinische Fakultät Mannheim
Gerjan J Navis🇳🇱University Medical Center Groningen; University of Groningen
Mattias Lorentzon🇸🇪Sahlgrenska University Hospital
Karen Jameson🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton
Nigel Arden🇬🇧University of Oxford; MRC Lifecourse Epidemiology Unit; University of Southampton
Jackie A. Cooper🇬🇧University College London
Jayshree Acharya🇬🇧University College London
Rebecca Hardy🇬🇧MRC Unit for Lifelong Health and Ageing; University College London
Olli Tuomas Raitakari🇫🇮University of Turku; Turku University Hospital
Samuli Ripatti🇫🇮University of Helsinki; Institute for Molecular Medicine Finland
Liana K. Billings🇺🇸Broad Institute; Endeavor Health; Harvard University; Massachusetts General Hospital
Jari M. T. Lahti🇫🇮University of Helsinki
Clive Osmond🇬🇧MRC Lifecourse Epidemiology Unit; University of Southampton
Brenda W.J.H. Penninx🇳🇱Amsterdam Public Health; Amsterdam UMC Location Vrije Universiteit Amsterdam
Lars Rejnmark🇩🇰Aarhus University Hospital
Kurt K. Lohman🇺🇸Wake Forest University Health Sciences; Wake Forest University
Lavinia Paternoster🇬🇧University of Bristol; MRC Integrative Epidemiology Unit
Ronald P. Stolk🇳🇱University Medical Center Groningen; University of Groningen
Dena G. Hernandez🇺🇸National Institutes of Health; National Institute on Aging
Liisa Byberg🇸🇪Uppsala University
Emil Hagström🇸🇪Uppsala University
Håkan Melhus🇸🇪Uppsala University
Erik Ingelsson🇸🇪🇬🇧Uppsala University; Centre for Human Genetics; Science for Life Laboratory; University of Oxford
Dan Mellström🇸🇪Sahlgrenska University Hospital
Östen Ljunggren🇸🇪Uppsala University
Ioanna Tzoulaki🇬🇧Imperial College London
Stela McLachlan🇬🇧University of Edinburgh
Evropi Τheodoratou🇬🇧University of Edinburgh
Carla M. T. Tiesler🇩🇪Helmholtz Munich; Ludwig-Maximilians-Universität München
Antti M. Jula🇫🇮Finnish Institute for Health and Welfare
Pau Navarro🇬🇧Institute of Genetics and Cancer; MRC Human Genetics Unit; University of Edinburgh
Alan F. Wright🇬🇧Institute of Genetics and Cancer; MRC Human Genetics Unit; University of Edinburgh
Ozren Polašek🇭🇷University of Split
James F. Wilson🇬🇧University of Edinburgh
Igor Rudan🇬🇧University of Edinburgh
Veikko V Salomaa🇫🇮Finnish Institute for Health and Welfare
Joachim Heinrich🇩🇪Helmholtz Munich
Harry Campbell🇬🇧University of Edinburgh
Jacqueline F Price🇬🇧University of Edinburgh
Magnus K. Karlsson🇸🇪Lund University; Skåne University Hospital
Lars Lind🇸🇪Uppsala University
Karl Michaëlsson🇸🇪Uppsala University
Stefania Bandinelli🇮🇹Azienda Sanitaria di Firenze
Timothy M. Frayling🇬🇧University of Exeter
Catharina Annette Hartman🇳🇱University Medical Center Groningen; University of Groningen
Thorkild I. A. Sørensen🇩🇰University of Copenhagen; Novo Nordisk Foundation; Frederiksberg Hospital; Bispebjerg Hospital; Novo Nordisk Foundation Center for Basic Metabolic Research
Stephen B. Kritchevsky🇺🇸Wake Forest University Health Sciences; Wake Forest University
Bente Lomholt Langdahl🇩🇰Aarhus University Hospital
Johan Gunnar Eriksson🇫🇮🇸🇪University of Helsinki; Helsinki University Hospital; Sahlgrenska University Hospital; Vaasa Central Hospital; Folkhälsans Forskningscentrum
José C. Florez🇺🇸Massachusetts General Hospital
Tim D. Spector🇬🇧King's College London
Terho J. Lehtimäki🇫🇮Fimlab (Finland); University of Tampere
Diana J. Kuh🇬🇧MRC Unit for Lifelong Health and Ageing; University College London
Steve Eric Humphries🇬🇧University College London
Cyrus C. Cooper🇬🇧University of Oxford; MRC Lifecourse Epidemiology Unit; University of Southampton
Claes Ohlsson🇸🇪Sahlgrenska University Hospital
Winfried März🇦🇹🇩🇪Medical University of Graz; Heidelberg University; Synlab (Germany); Medizinische Fakultät Mannheim
Martin H. de Borst🇳🇱University Medical Center Groningen; University of Groningen
Meena Kumari🇬🇧University College London
Mika Kivimaki B🇬🇧University College London
Thomas J. Wang🇺🇸Vanderbilt University
Chris Power🇬🇧University College London
Hermann Brenner🇩🇪German Cancer Research Center
Guri Grimnes🇳🇴UiT The Arctic University of Norway
Pim van der Harst🇳🇱University Medical Center Groningen; University of Groningen
Harold Snieder🇳🇱University Medical Center Groningen; University of Groningen
Aroon Dinesh Hingorani🇬🇧University College London
Stefan Pilz🇦🇹Medical University of Graz

Resumen

El texto original del estudio, en el idioma en que se publicó.

Background

Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

Methods

In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

Findings

In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

Interpretation

Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Funding

British Heart Foundation, UK Medical Research Council, and Academy of Finland.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

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