A stroke metabolite score comprising 4 validated metabolites is associated with incident stroke and improves ischemic stroke risk prediction beyond traditional risk factors, according to a study published in Neurology.Women have a higher lifetime risk for stroke than men, and metabolic factors appear to be more strongly associated with stroke risk among women. Although key stroke risk factors in women are well established, a gap remains between identified risk factors and the biological processes that mediate this risk.

To discover and validate metabolomic profiles associated with incident ischemic stroke risk after adjustment for traditional stroke risk factors, researchers applied liquid chromatography-tandem mass spectrometry (LC-MS) to measure 519 plasma metabolites in a discovery set of women from the Nurses’ Health Study, including 454 women who developed incident ischemic stroke and 454 control individuals. Validation was performed in 2 independent prospective cohorts: Prevención con Dieta Mediterránea (PREDIMED), which included 118 participants who developed stroke and 791 participants who did not, and Nurses’ Health Study 2, which included 49 women who developed incident ischemic stroke and 49 control individuals.

 

Further research to identify the mechanisms responsible for these findings, as well as to replicate other metabolites, is needed.

In the Nurses’ Health Study, 23 metabolites were significantly associated with incident ischemic stroke after adjustment for traditional risk factors (q<0.05). Of these, 14 metabolites were available in PREDIMED, and 3 were significantly associated with incident stroke: methionine sulfoxide, N6-acetyllysine, and sucrose/lactose/trehalose (q<0.05). In Nurses’ Health Study 2, glucuronate was significantly associated with incident ischemic stroke (q<0.05).

Higher levels of all 4 metabolites were associated with increased risk, and the metabolites were used to create a stroke metabolite score. Per 1-standard deviation increase in the stroke metabolite score, the odds ratio for incident stroke was 4.12 (95% CI 2.26-7.51) in PREDIMED after adjustment for traditional risk factors.

In PREDIMED, the area under the receiver operating characteristic curve increased from 0.65 to 0.70 when the stroke metabolite score was added to traditional risk factors, corresponding to a 5% improvement in risk prediction (P <.005).

Study limitations include that metabolomics profiling was obtained at a single point in time, imaging was available for only 69% of participants who developed stroke in Nurses’ Health Study 2, and the discovery dataset in the Nurses’ Health Study was predominantly composed of postmenopausal White women.“We identified 23 metabolites associated with incident ischemic stroke in women, and validated 4 of these in independent cohorts. A score comprising the 4 validated metabolites resulted in significant improvement in stroke risk prediction,” noted the authors. “Further research to identify the mechanisms responsible for these findings, as well as to replicate other metabolites, is needed.”