Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

Background: Heart failure (HF) is a potential cause of ischemic stroke (IS), and previous studies have reported an association between HF and IS. This study aimed to analyze the causal link between HF and IS using bidirectional and multivariable Mendelian randomization (MR) studies. Methods: Genetic variants significantly associated with HF and IS were selected in the MR analysis from two large genome-wide association studies. Bidirectional and multivariable MR analyses were performed to evaluate the effect of HF on IS or the effect of IS on HF. Results: Two-sample MR analysis showed causal effects of HF on IS of all causes [odds ratio (OR) = 1.555, 95% confidence interval (CI): 1.343-1.799, p = 3.35 × 10-9] and large artery atherosclerosis stroke (LAS) (OR = 1.678, 95% CI: 1.044-2.696, p = 3.03 × 10-5), while there was a suggestive effect of HF on cardioembolic stroke (CES) (OR = 3.355, 95% CI: 1.031-10.919, p = 0.044). Genetically predicted HF was not associated with small artery occlusion stroke. Bidirectional MR analysis showed causal effects of IS of all causes (OR = 1.211, 95% CI: 1.040-1.410, p = 0.014) and CES (OR = 1.277, 95% CI: 1.213-1.344, p = 6.73 × 10-21) on HF, while there were no causal effects of LAS on HF. Conclusion: This MR analysis provided evidence of the causal links between genetically predicted HF and IS. Subgroup analysis highlighted the causal or suggestive relationship between genetically predicted HF and LAS or CES. The potential causal links need further investigation with genetic information about other ancestries or etiologies of HF.

Dual antiplatelet therapy reduced stroke risk in transient ischemic attack with positive diffusion weighted imaging.

Dual antiplatelet therapy (DAPT) reduced stroke risk in high-risk transient ischemic attack (TIA) patients assessed by ABCD2 score. Patients with positive diffusion-weighted imaging (DWI) were identified as imaging-based high-risk. The present study aims to investigate whether DAPT could reduce stroke risk in TIA with DWI positive. The study enrolled TIA patients within 72 h of onset from the prospective TIA database of the First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischemic stroke at 90-day. The relationship between DAPT and stroke was analyzed in a cox proportional hazards model. The Kaplan-Meier curves of TIA patients with DAPT and monotherapy were plotted. Total of 661 TIA patients were enrolled, 279 of whom were DWI positive and 281 used DAPT. The 90-day stroke risk was higher in patients used monotherapy than those used DAPT in TIA with positive DWI (23.7% vs. 13.4%, p = 0.029). DAPT was associated with reduced stroke risk in TIA patients with positive DWI (hazard ratio [HR] = 0.54; 95% confidence interval [CI], 0.30-0.97; p = 0.037). However, the benefit didn't exist in TIA patients with negative DWI (HR = 0.43; 95% CI, 0.14-1.33; p = 0.142). Early use of DAPT reduced stroke risk in TIA patients with positive DWI.

The Association Between Serum Apelin-13 and the Prognosis of Acute Ischemic Stroke.

While a number of studies have reported an association between apelin-13 and ischemic stroke, few have verified its clinical effect. We investigated the prognostic value of serum apelin-13 levels in patients with acute ischemic stroke (AIS). We prospectively recruited 244 AIS patients within 24 h after stroke onset, and 167 healthy controls. We assessed the serum apelin-13 levels using ELISA, and the severity of AIS using the National Institutes of Health Stroke Scale (NIHSS). The primary outcomes included death or major disability (modified Rankin Scale score, 3-6) and major disability (modified Rankin Scale score, 3-5). Secondary outcomes included recurrent stroke and combined events (all-cause death, or cardiovascular and cerebrovascular events). We found that the serum apelin-13 levels in the patients (38.63 ng/mL (interquartile range [IQR], 29.86-50.99)) were lower than those in the healthy controls (42.50 ng/mL [IQR, 31.25-59.17]) (P = 0.017). Patients with a NIHSS score ≤ 3 had higher apelin-13 levels than those with a NIHSS score > 3 (P = 0.048). At the 3-month follow-up, multivariate logistic regression analysis indicated an association between apelin-13 and death or major disability (OR 0.31; 95% CI 0.11-0.86; P = 0.024) and major disability (OR 0.32; 95% CI 0.11-0.90; P = 0.030). At the 1-year follow-up, the patients with high apelin-13 levels showed a lower incidence of stroke and combined events (Log-rank test P < 0.05). Our findings indicate that serum apelin-13 may be a potential prognostic biomarker for AIS.

Changes of Metabolites in Acute Ischemic Stroke and Its Subtypes.

Existing techniques have many limitations in the diagnosis and classification of ischemic stroke (IS). Considering this, we used metabolomics to screen for potential biomarkers of IS and its subtypes and to explore the underlying related pathophysiological mechanisms. Serum samples from 99 patients with acute ischemic stroke (AIS) [the AIS subtypes included 49 patients with large artery atherosclerosis (LAA) and 50 patients with small artery occlusion (SAO)] and 50 matched healthy controls (HCs) were analyzed by non-targeted metabolomics based on liquid chromatography-mass spectrometry. A multivariate statistical analysis was performed to identify potential biomarkers. There were 18 significantly different metabolites, such as oleic acid, linoleic acid, arachidonic acid, L-glutamine, L-arginine, and L-proline, between patients with AIS and HCs. These different metabolites are closely related to many metabolic pathways, such as fatty acid metabolism and amino acid metabolism. There were also differences in metabolic profiling between the LAA and SAO groups. There were eight different metabolites, including L-pipecolic acid, 1-Methylhistidine, PE, LysoPE, and LysoPC, which affected glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, histidine metabolism, and lysine degradation. Our study effectively identified the metabolic profiles of IS and its subtypes. The different metabolites between LAA and SAO may be potential biomarkers in the context of clinical diagnosis. These results highlight the potential of metabolomics to reveal new pathways for IS subtypes and provide a new avenue to explore the pathophysiological mechanisms underlying IS and its subtypes.

The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score Is Associated With Poor Outcome of Acute Ischemic Stroke.

Background: The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP) is considered a novel score to reflect systemic inflammation and nutritional status. This study aimed to investigate the association between HALP score and poor outcome in patients with acute ischemic stroke (AIS). Methods: Consecutive AIS patients within 24 h after onset were prospectively enrolled. Poor outcome was a combination of a new stroke event (ischemic and hemorrhagic) and all-cause death within 90 days and 1 year. The association between HALP score and poor outcome was analyzed using Cox proportional hazards. Results: A total of 1,337 patients were included. Overall, 60 (4.5%) and 118 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Patients in the highest tertile of HALP score had a lower risk of poor outcome within 90 days and 1 year (hazard ratio: 0.25 and 0.42; 95% confidence intervals: 0.11-0.57 and 0.25-0.69, P for trend <0.01 for all) compared with those in the lowest tertile after adjusting relevant confounding factors. Adding HALP score to the conventional risk factors improved prediction of poor outcome in patients with AIS within 90 days and 1 year (net reclassification index, 48.38 and 28.95%; integrated discrimination improvement, 1.51 and 1.51%; P < 0.05 for all). Conclusions: Increased HALP score was associated with a decreased risk of recurrent stroke and death within 90 days and 1 year after stroke onset, suggesting that HALP score may serve as a powerful indicator for AIS.