Abstract
African Americans endure a nearly two-fold greater risk of suffering a stroke and are 2-3 times more likely to die from stroke compared to those of European ancestry. African Americans also have a greater risk of recurrent stroke and vascular events, which are deadlier and more disabling than incident stroke. Stroke is a multifactorial disease with both heritable and environmental risk factors. We conducted an integrative, multi-omic study on 922 plasma metabolites, 473,864 DNA methylation loci, and 556 variants from 50 African American participants of the Vitamin Intervention for Stroke Prevention clinical trial to help elucidate biomarkers contributing to recurrent stroke rates in this high risk population. Sixteen metabolites, including cotinine, N-delta-acetylornithine, and sphingomyelin (d17:1/24:1) were identified in t-tests of recurrent stroke outcome or baseline smoking status. Serum tricosanoyl sphingomyelin (d18:1/23:0) levels were significantly associated with recurrent stroke after adjusting for covariates in Cox Proportional Hazards models. Weighted Gene Co-expression Network Analysis identified moderate correlations between sphingolipid markers and clinical traits including days to recurrent stroke. Integrative analyses between genetic variants in sphingolipid pathway genes identified 29 nominal associations with metabolite levels in a one-way analysis of variance, while epigenomic analyses identified xenobiotics, predominately smoking-associated metabolites and pharmaceutical drugs, associated with methylation profiles. Taken together, our results suggest that metabolites, specifically those associated with sphingolipid metabolism, are potential plasma biomarkers for stroke recurrence in African Americans. Furthermore, genetic variation and DNA methylation may play a role in the regulation of these metabolites.
Highlights
Stroke is a leading cause of death and disability globally, resulting in more than 6 million deaths per year [1]
The Vitamin Intervention for Stroke Prevention (VISP) clinical trial was a multi-centered, double-blinded, randomized and controlled clinical trial designed to determine whether a combination pyridoxine, cyanocobalamin, and folic acid supplementation reduced recurrent cerebral infarction, myocardial infarction (MI), or fatal coronary heart disease [8]
Identification of metabolites associated with VISP stroke recurrence
Summary
Stroke is a leading cause of death and disability globally, resulting in more than 6 million deaths per year [1]. For reasons yet to be elucidated, individuals of African descent are more likely to suffer a stroke, have an earlier age of occurrence, and experience poorer outcomes compared to individuals of other ancestry [2]. While overall stroke mortality rates have declined since 1990, the rates have remained higher among African Americans (AAs) than any other racial group in the United States. Stroke mortality rates are approximately 50% higher in AAs than their white counterparts with this mortality increasing with age (e.g. at age 55 the risk is up to three times greater) [3]. The management of stroke risk factors, including hypertension and diabetes, remains an important strategy to decrease the stroke burden
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
