Circulating Metabolome and White Matter Hyperintensities in Women and Men.
brain
glucuronic acid
hydroxyphenylpyruvate
lipid ratios
lipidomics
lipids
lysophosphatidylcholines
metabolomics
sphingomyelins
white matter
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
05 04 2022
05 04 2022
Historique:
pubmed:
21
1
2022
medline:
7
4
2022
entrez:
20
1
2022
Statut:
ppublish
Résumé
White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites. We studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted In the meta-analysis of results from the basic models, we identified 30 metabolomic measures associated with WMH ( Circulating metabolomic measures, including multiple lipid measures (eg, lysophosphatidylcholines, hydroxysphingomyelins, low-density lipoprotein size and composition) and nonlipid metabolites (eg, hydroxyphenylpyruvate, glucuronate), associate with WMH in a general population of middle-aged and older adults. Some metabolomic measures show marked sex specificities and explain a sizable proportion of WMH variance.
Sections du résumé
BACKGROUND
White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.
METHODS
We studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted
RESULTS
In the meta-analysis of results from the basic models, we identified 30 metabolomic measures associated with WMH (
CONCLUSIONS
Circulating metabolomic measures, including multiple lipid measures (eg, lysophosphatidylcholines, hydroxysphingomyelins, low-density lipoprotein size and composition) and nonlipid metabolites (eg, hydroxyphenylpyruvate, glucuronate), associate with WMH in a general population of middle-aged and older adults. Some metabolomic measures show marked sex specificities and explain a sizable proportion of WMH variance.
Identifiants
pubmed: 35050683
doi: 10.1161/CIRCULATIONAHA.121.056892
pmc: PMC9645366
mid: NIHMS1783705
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1040-1052Subventions
Organisme : Medical Research Council
ID : MC_PC_12025
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R024065/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M013111/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001245
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00019/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701120
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG056726
Pays : United States
Commentaires et corrections
Type : CommentIn
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