Imperial College London
Alternate

Dr Matthew R. Lewis

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Senior Research Officer
 
 
 
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Contact

 

matthew.lewis

 
 
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Location

 

660Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sliz:2022:10.1161/CIRCULATIONAHA.121.056892,
author = {Sliz, E and Shin, J and Ahmad, S and Williams, DM and Frenzel, S and Gauss, F and Harris, SE and Henning, A-K and Hernandez, MV and Hu, Y-H and Jimenez, B and Sargurupremraj, M and Sudre, C and Wang, R and Wittfeld, K and Yang, Q and Wardlaw, JM and Volzke, H and Vernooij, MW and Schott, JM and Richards, M and Proitsi, P and Nauck, M and Lewis, MR and Launer, L and Hosten, N and Grabe, HJ and Ghanbari, M and Deary, IJ and Cox, SR and Chaturvedi, N and Barnes, J and Rotter, J and Debette, S and Ikram, MA and Fornage, M and Paus, T and Seshadri, S and Pausova, Z},
doi = {10.1161/CIRCULATIONAHA.121.056892},
journal = {Circulation},
pages = {1040--1052},
title = {Circulating metabolome and white matter hyperintensities in women and men},
url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.121.056892},
volume = {145},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 P values (PFDR)<0.05 were considered significant.Results:In the meta-analysis of results from the basic models, we identified 30 metabolomic measures associated with WMH (PFDR<0.05), 7 of which remained significant in the fully adjusted models. The most significant association was with higher level of hydroxyphenylpyruvate in men (PFDR.full.adj=1.40×10−7) and in both the pooled sample (PFDR.full.adj=1.66×10−4) and statin-untreated (PFDR.full.adj=1.65×10−6) subsample. In men, hydroxyphenylpyruvate explained 3% to 14% of variance in WMH. In men and the pooled sample, WMH were also associated with lower levels of lysophosphatidylcholines and hydroxysphingo
AU  - Sliz,E
AU  - Shin,J
AU  - Ahmad,S
AU  - Williams,DM
AU  - Frenzel,S
AU  - Gauss,F
AU  - Harris,SE
AU  - Henning,A-K
AU  - Hernandez,MV
AU  - Hu,Y-H
AU  - Jimenez,B
AU  - Sargurupremraj,M
AU  - Sudre,C
AU  - Wang,R
AU  - Wittfeld,K
AU  - Yang,Q
AU  - Wardlaw,JM
AU  - Volzke,H
AU  - Vernooij,MW
AU  - Schott,JM
AU  - Richards,M
AU  - Proitsi,P
AU  - Nauck,M
AU  - Lewis,MR
AU  - Launer,L
AU  - Hosten,N
AU  - Grabe,HJ
AU  - Ghanbari,M
AU  - Deary,IJ
AU  - Cox,SR
AU  - Chaturvedi,N
AU  - Barnes,J
AU  - Rotter,J
AU  - Debette,S
AU  - Ikram,MA
AU  - Fornage,M
AU  - Paus,T
AU  - Seshadri,S
AU  - Pausova,Z
DO  - 10.1161/CIRCULATIONAHA.121.056892
EP  - 1052
PY  - 2022///
SN  - 0009-7322
SP  - 1040
TI  - Circulating metabolome and white matter hyperintensities in women and men
T2  - Circulation
UR  - http://dx.doi.org/10.1161/CIRCULATIONAHA.121.056892
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000775188200005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056892
VL  - 145
ER  -
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