Abstract
Despite contribution of dyslipidemia to ischemic stroke, plasma lipidomic correlates of stroke in CKD is not studied. This study is aimed to identify plasma lipid alterations associated with stroke. Cross sectional. 214 participants of Clinical Phenotyping and Resource Biobank Core (CPROBE). Clinical data and plasma samples at the time of recruitment were obtained and used to generate lipidomic data by liquid chromatography/mass-spectrometry-based untargeted platform. Various levels of free fatty acids, acylcarnitines and complex lipids. Stroke. includes compound by compound comparison of lipids using t-test adjusted by false discovery rate in patients with and without stroke, and application of logistic regression analysis to identify independent lipid predictors of stroke and to estimate the odds associated with their various levels. Overall, we identified 330 compounds. Enrichment analysis revealed overrepresentation of differentially regulated phosphatidylcholines (PC)s and phosphatidylethanolamines (PE)s were overrepresented in stroke (P<0.001). Abundance of PC38:4, PE36:4, PC34:0, and palmitate were significantly higher, but those of plasmenyl-PE (pPE)38:2, and PE 32:2 was significantly lower in patients with stroke (p≤0.0014). After adjusting, each 1-SD increase in palmitate and PC38:4 was independently associated with 1.84 fold (95% CI: 1.06-3.20, p=0.031) and 1.84 fold (1.11-3.05, p=0.018) higher risk of stroke, respectively. We observed a significant trend toward higher abundance of PCs, PEs, pPEs, and sphingomyelins in stroke (p≤0.046). Small sample size; unclear, if similar changes in the same or opposite direction preceded stroke, as the cross-sectional nature of the observation does not allow determining the effect of time course on lipid alterations. Differential regulation of palmitate, PCs, and PEs in patients with CKD and a history of stroke may represent a previously unrecognized risk factor and might be a target of risk stratification and modification.
Highlights
Cerebrovascular Accident is a major cause of death and disability in the United States and around the world [1]
We have shown significant alterations of plasma lipidomics in chronic kidney disease (CKD) characterized by increased abundance of palmitate and longer polyunsaturated complex lipids as well as decreased abundance of long chain acylcarnitines by worsening CKD stage [10]. which is explained in part by upregulation of de novo lipogenesis, and mitochondrial β-oxidation of fatty acids [10,11]
We found that PC and PE, as a class, underwent differential regulation in patients with CKD who had experienced a stroke as compared with patients without stroke
Summary
Cerebrovascular Accident is a major cause of death and disability in the United States and around the world [1]. The Framingham study was pivotal in establishing risk factors for stroke and identified the presence of cardiovascular disease as a major predictor of incident stroke as well as age, systolic blood pressure, use of antihypertensive medications, diabetes mellitus, atrial fibrillation, left ventricular hypertrophy and smoking [4]. Lee and colleagues, identified CKD as independently associated with incident stroke in a meta-analysis [6]. This increased risk is not completely explained by traditional
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