Evidence map›Paper›PMID 34727949›Full record

ArticleBMC medicine2021

Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling.

Nicolien A van Vliet, Maxime M Bos, Carisha S Thesing, Layal Chaker, Maik Pietzner, Evelyn Houtman, Matt J Neville, Ruifang Li-Gao, Stella Trompet, Rima Mustafa and 35 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Thyroid and cardiovascular diseases.Turkish journal of medical sciences · 2024
    Review
  13. Review
  14. Article
  15. Article
  16. Hypothyroidism.Nature reviews. Disease primers · 2022
    Review
  17. Article
  18. Review
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors at 11 institutions in 3 countries.

Nicolien A van VlietDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Maxime M BosDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Carisha S ThesingAmsterdam UMC, Vrije Universiteit, Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam, The Netherlands.
Layal ChakerDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Maik PietznerComputational Medicine, Berlin Institute of Health (BIH), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Evelyn HoutmanDepartment of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Matt J NevilleNIHR Oxford Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Stella TrompetDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Rima MustafaMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Fariba AhmadizarDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Marian BeekmanDepartment of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Mariska BotAmsterdam UMC, Vrije Universiteit, Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam, The Netherlands.
Kathrin BuddeInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Constantinos ChristodoulidesNIHR Oxford Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK.
Abbas DehghanMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Christian DellesInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Paul ElliottMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Marina EvangelouDepartment of Mathematics, Faculty of Natural Sciences, Imperial College London, London, UK.
He GaoMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Mohsen GhanbariDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Antonius E van HerwaardenDepartment of Laboratory Medicine, Radboud Laboratory for Diagnostics (RLD), Radboud University Medical Center, Nijmegen, The Netherlands.
M Arfan IkramDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Martin JaegerDepartment of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Ibrahim KaramanMRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Fredrik KarpeNIHR Oxford Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK.
Margreet KloppenburgDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Jennifer M T A MeessenDepartment of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Ingrid MeulenbeltDepartment of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Yuri MilaneschiAmsterdam UMC, Vrije Universiteit, Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam, The Netherlands.
Simon P MooijaartDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Mihai G NeteaDepartment of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
Romana T Netea-MaierDepartment of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
Robin P PeetersAcademic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands.
Brenda W J H PenninxAmsterdam UMC, Vrije Universiteit, Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam, The Netherlands.
Naveed SattarBHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, UK.
P Eline SlagboomDepartment of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
H Eka D SuchimanDepartment of Biomedical Data Sciences, section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Ko Willems van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. r.noordam@lumc.nl.ORCID 0000-0001-7801-809X
Diana van HeemstDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. d.van_heemst@lumc.nl.
BBMRI Metabolomics Consortium
Leiden University Medical Center · NLErasmus MC · NLAmsterdam University Medical Centers · NLRadboud University Nijmegen · NLImperial College London · GBUniversity of Oxford · GBUK Dementia Research Institute · GBUniversitätsmedizin Greifswald · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DENIHR Imperial Biomedical Research Centre · GBUniversity of Glasgow · GB

Funding

British Heart Foundation FS/16/45/32359Medical Research Council MC_UU_00006/1Medical Research Council MR/L01341X/1Medical Research Council MR/R023484/1Medical Research Council MR/S019669/1
6 · The paper itself

Abstract

backgroundObservational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status.

methodsMulti-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction.

resultsCirculating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59).

conclusionsLower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk.

Indexed as

Cardiovascular DiseasesThyrotropinAdultAgedFemaleHumansLipidsMaleMendelian Randomization AnalysisMiddle AgedThyroxineYoung AdultLipidsThyrotropinThyroxineCoronary artery diseaseMendelian randomizationMetabolomicsThyroid hormones

Identifiers

PMID34727949
PMCPMC8565073
OpenAlexW3210593913

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.