Metabolomics Predicts Stroke Recurrence After Transient Ischemic Attack

Overview

Journal Neurology

Specialty Neurology

Date 2014 Dec 5

PMID 25471397

Citations 46

Authors

Mariona Jove

Gerard Mauri-Capdevila

Idalmis Suarez

Serafi Cambray

Jordi Sanahuja

Alejandro Quilez

Joan Farre

Ikram Benabdelhak

Reinald Pamplona

Manuel Portero-Otin

Francisco Purroy

Affiliations

Soon will be listed here.

Abstract

Objective: To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones.

Methods: Metabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort.

Results: Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described.

Conclusions: The use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases.

Citing Articles

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Turpin J, Wadolowski S, Tambo W, Kim D, Abed Y, Sciubba D Int J Mol Sci. 2024; 25(19).

PMID: 39408978 PMC: 11477326. DOI: 10.3390/ijms251910649.

Body fluid multiomics in 3PM-guided ischemic stroke management: health risk assessment, targeted protection against health-to-disease transition, and cost-effective personalized approach are envisaged.

Chen R, Wang X, Li N, Golubnitschaja O, Zhan X EPMA J. 2024; 15(3):415-452.

PMID: 39239108 PMC: 11371995. DOI: 10.1007/s13167-024-00376-2.

Plasma NOTCH3 and the risk of cardiovascular recurrence in patients with ischemic stroke.

Seet R, Seet R, Quek A, Quek A, Teng O, Teng O QJM. 2024; 117(12):846-857.

PMID: 39012624 PMC: 11760494. DOI: 10.1093/qjmed/hcae136.

Ischemic Brain Injury: Involvement of Lipids in the Pathophysiology of Stroke and Therapeutic Strategies.

Bernoud-Hubac N, Lo Van A, Lazar A, Lagarde M Antioxidants (Basel). 2024; 13(6).

PMID: 38929073 PMC: 11200865. DOI: 10.3390/antiox13060634.

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Golubnitschaja O, Polivka Jr J, Potuznik P, Pesta M, Stetkarova I, Mazurakova A EPMA J. 2024; 15(1):1-23.

PMID: 38463624 PMC: 10923756. DOI: 10.1007/s13167-024-00356-6.

References

Cucchiara B, Messe S, Sansing L, Mackenzie L, Taylor R, Pacelli J . Lipoprotein-associated phospholipase A2 and C-reactive protein for risk-stratification of patients with TIA. Stroke. 2009; 40(7):2332-6. DOI: 10.1161/STROKEAHA.109.553545. View

Whiteley W, Tian Y, Jickling G . Blood biomarkers in stroke: research and clinical practice. Int J Stroke. 2012; 7(5):435-9. DOI: 10.1111/j.1747-4949.2012.00784.x. View

Purroy F, Montaner J, Molina C, Delgado P, Arenillas J, Chacon P . C-reactive protein predicts further ischemic events in transient ischemic attack patients. Acta Neurol Scand. 2006; 115(1):60-6. DOI: 10.1111/j.1600-0404.2006.00715.x. View

Pinto F, Brenner T, Dan P, Krimsky M, Yedgar S . Extracellular phospholipase A2 inhibitors suppress central nervous system inflammation. Glia. 2003; 44(3):275-82. DOI: 10.1002/glia.10296. View

Zhang Z, Lee Y, Kim S, Choi M, Tsai P, Saha A . Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration. Hum Mol Genet. 2007; 16(7):837-47. DOI: 10.1093/hmg/ddm029. View

Patti G, Yanes O, Siuzdak G . Innovation: Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol. 2012; 13(4):263-9. PMC: 3682684. DOI: 10.1038/nrm3314. View

Delgado P, Chacon P, Penalba A, Pelegri D, Garcia-Berrocoso T, Giralt D . Lipoprotein-associated phospholipase A(2) activity is associated with large-artery atherosclerotic etiology and recurrent stroke in TIA patients. Cerebrovasc Dis. 2011; 33(2):150-8. DOI: 10.1159/000334193. View

Purroy F, Suarez-Luis I, Mauri-Capdevila G, Cambray S, Farre J, Sanahuja J . N-terminal pro-brain natriuretic peptide level determined at different times identifies transient ischaemic attack patients with atrial fibrillation. Eur J Neurol. 2013; 21(4):679-83. DOI: 10.1111/ene.12222. View

Ois A, Gomis M, Rodriguez-Campello A, Cuadrado-Godia E, Jimenez-Conde J, Pont-Sunyer C . Factors associated with a high risk of recurrence in patients with transient ischemic attack or minor stroke. Stroke. 2008; 39(6):1717-21. DOI: 10.1161/STROKEAHA.107.505438. View

10.

Purroy F, Begue R, Gil M, Quilez A, Sanahuja J, Brieva L . Patterns of diffusion-weighted magnetic resonance imaging associated with etiology improve the accuracy of prognosis after transient ischaemic attack. Eur J Neurol. 2010; 18(1):121-8. DOI: 10.1111/j.1468-1331.2010.03080.x. View

11.

Purroy F, Montaner J, Molina C, Delgado P, Ribo M, Alvarez-Sabin J . Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke. 2007; 38(12):3225-9. DOI: 10.1161/STROKEAHA.107.488833. View

12.

Katan M, Nigro N, Fluri F, Schuetz P, Morgenthaler N, Jax F . Stress hormones predict cerebrovascular re-events after transient ischemic attacks. Neurology. 2011; 76(6):563-6. DOI: 10.1212/WNL.0b013e31820b75e6. View

13.

Arboix A, Cabeza N, Garcia-Eroles L, Massons J, Oliveres M, Targa C . Relevance of transient ischemic attack to early neurological recovery after nonlacunar ischemic stroke. Cerebrovasc Dis. 2004; 18(4):304-11. DOI: 10.1159/000080356. View

14.

Shanta S, Choi C, Lee J, Shin C, Kim Y, Kim K . Global changes in phospholipids identified by MALDI MS in rats with focal cerebral ischemia. J Lipid Res. 2012; 53(9):1823-31. PMC: 3413223. DOI: 10.1194/jlr.M022558. View

15.

Hung N, Kim M, Sok D . Anti-inflammatory action of arachidonoyl lysophosphatidylcholine or 15-hydroperoxy derivative in zymosan A-induced peritonitis. Prostaglandins Other Lipid Mediat. 2009; 90(3-4):105-11. DOI: 10.1016/j.prostaglandins.2009.10.001. View

16.

Farooqui A, Horrocks L . Phospholipase A2-generated lipid mediators in the brain: the good, the bad, and the ugly. Neuroscientist. 2006; 12(3):245-60. DOI: 10.1177/1073858405285923. View

17.

Jung J, Lee H, Kang D, Kim N, Cha M, Bang O . 1H-NMR-based metabolomics study of cerebral infarction. Stroke. 2011; 42(5):1282-8. DOI: 10.1161/STROKEAHA.110.598789. View

18.

Jiang Z, Sun J, Liang Q, Cai Y, Li S, Huang Y . A metabonomic approach applied to predict patients with cerebral infarction. Talanta. 2011; 84(2):298-304. DOI: 10.1016/j.talanta.2011.01.015. View

19.

Enea C, Seguin F, Petitpas-Mulliez J, Boildieu N, Boisseau N, Delpech N . (1)H NMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise. Anal Bioanal Chem. 2009; 396(3):1167-76. DOI: 10.1007/s00216-009-3289-4. View

20.

Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M . TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J. 2004; 23(13):2684-95. PMC: 449762. DOI: 10.1038/sj.emboj.7600234. View