Systemic Metabolic Alterations after Aneurysmal Subarachnoid Hemorrhage: A Plasma Metabolomics Approach

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Aneurysmal subarachnoid hemorrhage (aSAH) causes systemic changes that contribute to delayed cerebral ischemia (DCI) and morbidity. Circulating metabolites reflecting underlying pathophysiological mechanisms warrant investigation as biomarker candidates. Blood samples, prospectively collected within 24 hours (T1) of admission 7-days (T2) post ictus, from patients with acute aSAH two tertiary care centers were retrospectively analyzed. Samples healthy subjects non-neurologic critical illness served controls. A validated external analysis platform was used perform untargeted metabolomics. Bioinformatics analyses conducted identify metabolomic profiles defining each group delineate metabolic pathways altered in group. Machine learning (ML) models developed incorporating key improve DCI prediction. Among 70 aSAH, 30 control, 17 sick control subjects, a total 1,117 detected. Groups matched among clinical variables. occurred 36% poor functional outcome observed 70% at discharge. Metabolomic readily discriminated the groups. demonstrated robust mobilization lipid metabolites, increased levels free fatty acids (FFAs), mono- diacylglycerols (MAG, DAG) compared both also had decreased circulating amino acid derived consistent catabolism. associated sphingolipids (sphingosine sphinganine) acylcarnitines S- adenosylhomocysteine T1. Decreased lysophospholipids outcomes. Incorporating into ML improved prediction variables alone. Profound shifts occur after characteristic increases decreases metabolites. Key outcomes (sphingolipids, lysophospholipids, acylcarnitines) provide insight driving secondary complications. These may prove be useful biomarkers prognostication personalize care.

Language: Английский

Atherogenic index of plasma and triglyceride-glucose index mediate the association between stroke and all-cause mortality: insights from the lipid paradox

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: May 10, 2025

The "lipid paradox" describes the counterintuitive observation that traditionally unfavorable lipid profiles may be associated with improved outcomes in stroke patients. Non-traditional markers such as atherogenic index of plasma (AIP) and triglyceride-glucose (TyG) have been proposed to better reflect complex metabolic disturbances following stroke. This study aims investigate mediating role AIP TyG association between all-cause mortality elucidate potential mechanisms underlying paradox. cohort used data from China Health Retirement Longitudinal Study (CHARLS), including 10,220 participants enrolled 2011 2020, a maximum follow-up 10 years. were calculated baseline serum measurements. U-test, chi-square test, restricted cubic spline analysis (RCS), cox proportional hazards regression mediation model analyze relationship AIP, index, mortality. A total 1,421 deaths (13.90%) occurred during an average 9.21 Compared survivors, non-survivors older, had higher prevalence stroke, lower levels (P < 0.05), while showed no significant group difference. RCS revealed nonlinear mortality, but nonlinearity for AIP. Cox identified age, gender, marital status, smoking history, hypertension, diabetes, lung disease, highest quartile (Q4) independent predictors (all P 0.05). Notably, negative (HR = 0.87, 95% CI: 0.77-0.98),demonstrating paradox phenomenon. Furthermore, chain model, both (β=-0.03, 95%CI: -0.072 -0.002) (β=-0.016, -0.036 independently mediated manner. However, positive effect through (β 0.028, 0.003-0.066) offset this mediation, rendering overall insignificant. or jointly influence risk after demonstrates Moreover, significantly increases post-stroke risk. These findings highlight interplay glucose metabolism prognosis offer novel perspective management.

Language: Английский