Homocysteine, B vitamins, and cardiovascular disease: a Mendelian randomization study.

Cardiovascular Diseases / epidemiology Folic Acid Homocysteine Humans Mendelian Randomization Analysis Risk Factors Vitamin B 12 Vitamin B Complex
B vitamins Cardiovascular disease Homocysteine Mendelian randomization

Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
23 04 2021
Historique:
received: 10 02 2021
accepted: 29 03 2021
entrez: 23 4 2021
pubmed: 24 4 2021
medline: 16 10 2021
Statut: epublish

Résumé

Whether a modestly elevated homocysteine level is causally associated with an increased risk of cardiovascular disease remains unestablished. We conducted a Mendelian randomization study to assess the associations of circulating total homocysteine (tHcy) and B vitamin levels with cardiovascular diseases in the general population. Independent single nucleotide polymorphisms associated with tHcy (n = 14), folate (n = 2), vitamin B6 (n = 1), and vitamin B12 (n = 14) at the genome-wide significance level were selected as instrumental variables. Summary-level data for 12 cardiovascular endpoints were obtained from genetic consortia, the UK Biobank study, and the FinnGen consortium. Higher genetically predicted circulating tHcy levels were associated with an increased risk of stroke. For each one standard deviation (SD) increase in genetically predicted tHcy levels, the odds ratio (OR) was 1.11 (95% confidence interval (CI), 1.03, 1.21; p = 0.008) for any stroke, 1.26 (95% CI, 1.05, 1.51; p = 0.013) for subarachnoid hemorrhage, and 1.11 (95% CI, 1.03, 1.21; p = 0.011) for ischemic stroke. Higher genetically predicted folate levels were associated with decreased risk of coronary artery disease (OR This study reveals suggestive evidence that B vitamin therapy and lowering of tHcy may reduce the risk of stroke, particularly subarachnoid hemorrhage and ischemic stroke.

Sections du résumé

BACKGROUND
Whether a modestly elevated homocysteine level is causally associated with an increased risk of cardiovascular disease remains unestablished. We conducted a Mendelian randomization study to assess the associations of circulating total homocysteine (tHcy) and B vitamin levels with cardiovascular diseases in the general population.
METHODS
Independent single nucleotide polymorphisms associated with tHcy (n = 14), folate (n = 2), vitamin B6 (n = 1), and vitamin B12 (n = 14) at the genome-wide significance level were selected as instrumental variables. Summary-level data for 12 cardiovascular endpoints were obtained from genetic consortia, the UK Biobank study, and the FinnGen consortium.
RESULTS
Higher genetically predicted circulating tHcy levels were associated with an increased risk of stroke. For each one standard deviation (SD) increase in genetically predicted tHcy levels, the odds ratio (OR) was 1.11 (95% confidence interval (CI), 1.03, 1.21; p = 0.008) for any stroke, 1.26 (95% CI, 1.05, 1.51; p = 0.013) for subarachnoid hemorrhage, and 1.11 (95% CI, 1.03, 1.21; p = 0.011) for ischemic stroke. Higher genetically predicted folate levels were associated with decreased risk of coronary artery disease (OR
CONCLUSIONS
This study reveals suggestive evidence that B vitamin therapy and lowering of tHcy may reduce the risk of stroke, particularly subarachnoid hemorrhage and ischemic stroke.

Identifiants

DOI: 10.1186/s12916-021-01977-8 PMID: 33888102 PMC: PMC8063383
pubmed: 33888102
doi: 10.1186/s12916-021-01977-8
pii: 10.1186/s12916-021-01977-8
pmc: PMC8063383
doi:

Substances chimiques

Homocysteine 0LVT1QZ0BA
Vitamin B Complex 12001-76-2
Folic Acid 935E97BOY8
Vitamin B 12 P6YC3EG204

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

97

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/13/13/30194
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204623/Z/16/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/13/33946
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/12/2/29428
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00002/7
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/1996001/9454
Pays : United Kingdom

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Auteurs

Shuai Yuan (S)

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobelsväg 13, 17177, Stockholm, Sweden.

Amy M Mason (AM)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, UK.

Paul Carter (P)

Department of Medicine, University of Cambridge, Cambridge, UK.

Stephen Burgess (S)

MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Susanna C Larsson (SC)

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobelsväg 13, 17177, Stockholm, Sweden. susanna.larsson@ki.se.
Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. susanna.larsson@ki.se.
ORCID: 0000-0003-0118-0341

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Classifications MeSH

questionsmedicales.fr › Maladies cardiovasculaires › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Ptéridines › Acide folique › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Homocystéine › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Composés polycycliques › Composés macrocycliques › Tétrapyrroles › Corrinoïdes › Vitamine B12 › Homocysteine, B vitamins, and cardiovascular...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Complexe vitaminique B › Homocysteine, B vitamins, and cardiovascular...