A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke.

Lind L, Salihovic S, Ganna A, Sundström J, Broeckling CD, Magnusson PK, Pedersen NL, Siegbahn A, Prenni J, Fall T, Ingelsson E, Ärnlöv J

J Stroke Cerebrovasc Dis 29 (2) 104476 [2020-02-00; online 2019-12-02]

To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach. We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites. In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR .69 per SD change, 95% CI .57-0.83, P value = .00014; FDR <5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P < .0069 and .0026, respectively). An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies.

PubMed 31806450

DOI 10.1016/j.jstrokecerebrovasdis.2019.104476

Crossref 10.1016/j.jstrokecerebrovasdis.2019.104476

pii: S1052-3057(19)30559-2