Thyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study.
Adult
Atrial Fibrillation
/ epidemiology
Body Mass Index
Coronary Artery Disease
/ epidemiology
Datasets as Topic
Female
Graves Disease
/ blood
Hashimoto Disease
/ blood
Humans
Male
Mendelian Randomization Analysis
Middle Aged
Polymorphism, Single Nucleotide
Reference Values
Risk Factors
Stroke
/ epidemiology
Thyroid Function Tests
Thyroid Gland
/ physiopathology
Thyrotropin
/ blood
Thyroxine
/ blood
Mendelian randomization
TSH
coronary artery disease
mediation
stroke
thyroid function
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
22
11
2019
accepted:
01
05
2020
pubmed:
7
5
2020
medline:
9
2
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
Observational studies suggest that variations in normal range thyroid function are associated with cardiovascular diseases. However, it remains to be determined whether these associations are causal or not. To test whether genetically determined variation in normal range thyroid function is causally associated with the risk of stroke and coronary artery disease (CAD) and investigate via which pathways these relations may be mediated. Mendelian randomization analyses for stroke and CAD using genetic instruments associated with normal range thyrotropin (TSH) and free thyroxine levels or Hashimoto's thyroiditis and Graves' disease. The potential mediating role of known stroke and CAD risk factors was examined. Publicly available summary statistics data were used. Stroke or CAD risk per genetically predicted increase in TSH or FT4 levels. A 1 standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91-0.99; P = 0.008). Multivariable MR analyses indicated that this effect is mainly mediated via atrial fibrillation. MR analyses did not show a causal association between normal range thyroid function and CAD. Secondary analyses showed a causal relationship between Hashimoto's thyroiditis and a 7% increased risk of CAD (OR, 1.07; 95% CI, 1.01-1.13; P = 0.026), which was mainly mediated via body mass index. These results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke, and CAD. We identify variation in normal range thyroid function and Hashimoto's thyroiditis as risk factors for stroke and CAD, respectively.
Identifiants
pubmed: 32374820
pii: 5831244
doi: 10.1210/clinem/dgaa239
pmc: PMC7316221
pii:
doi:
Substances chimiques
Thyrotropin
9002-71-5
Thyroxine
Q51BO43MG4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : British Heart Foundation
ID : RG/14/5/30893
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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