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Metabolomic Profiles Associated With Incident Ischemic Stroke.
Raji Balasubramanian1, Jie Hu2, Marta Guasch-Ferre2
1From the Department of Biostatistics and Epidemiology (R.B., Y.Z., K.H.S.), University of Massachusetts-Amherst; Division of Women's Health (J.H., K.M.R.) and Channing Division of Network Medicine, Department of Medicine (M.G.-F., F.H.), Brigham and Women's Hospital, Harvard Medical School; Departments of Nutrition (M.G.-F., J.L., F.H.) and Epidemiology (J.L., F.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Davee Department of Neurology, Division of Stroke and Neurocritical Care (F.S.), Northwestern Feinberg School of Medicine, Chicago, IL; Departament de Bioquímica i Biotecnologia, Unitat de Nutrició (J.S.S.), Universitat Rovira i Virgili, Reus; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN) (J.S.-S.), Institute of Health Carlos III, Madrid; Nutrition Unit, Pere Virgili Research Institute (IISPV) (J.S.-S.), University Hospital of Sant Joan de Reus, Spain; and Broad Institute of the Massachusetts Institute of Technology and Harvard University (C.B.C.), Cambridge. rbalasub@umass.edu.
Metabolomic profiles, including specific metabolites like methionine sulfoxide and sucrose, can predict incident stroke risk in women. A novel stroke metabolite score (SMS) improved risk prediction beyond traditional factors.
Area of Science:
- Biochemistry
- Epidemiology
- Metabolomics
Background:
- Women face a higher lifetime risk of stroke compared to men.
- Metabolic factors are more strongly linked to stroke in women, yet few studies explore metabolomic profiles and stroke risk.
Purpose of the Study:
- To investigate the association between plasma metabolites and incident ischemic stroke in women.
- To develop and validate a metabolomic score for stroke risk prediction.
Main Methods:
- Liquid chromatography-tandem mass spectrometry was used to analyze 519 plasma metabolites.
- Discovery in the Nurses' Health Study (NHS) with validation in PREDIMED and NHS2 cohorts.
- Logistic regression models adjusted for traditional risk factors; false discovery rate controlled using q-values.
Main Results:
- Twenty-three metabolites associated with stroke in NHS; 4 validated across cohorts: methionine sulfoxide, N6-acetyllysine, glucuronate, and sucrose.
- A stroke metabolite score (SMS) combining these metabolites significantly predicted incident ischemic stroke.
- SMS improved stroke risk prediction by 5% compared to traditional risk factors alone (AUC 0.70 vs 0.65).
Conclusions:
- Specific plasma metabolites are associated with incident ischemic stroke risk in women.
- A composite stroke metabolite score (SMS) enhances stroke risk prediction beyond established factors.
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