Evaluating the Causal Effects of Low Density Lipoprotein Cholesterol Levels on Ischemic Stroke: A Mendelian Randomization Study.

Background: Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic stroke. However, higher LDL-C levels were closely related to IS. Based on two antagonistic viewpoints, a Mendelian randomization (MR) study was designed to evaluate the causal effects of LDL-C levels on IS. Methods: Datasets of LDL-C levels and ischemic stroke were acquired from genome-wide association studies (GWAS). Weighted median method was conducted for main analysis, and MR-Egger and inverse-variance weighted (IVW) methods were performed for auxiliary analyses. Heterogeneity and pleiotropic tests were utilized to confirm the reliability of this study. Results: A total of 359 single nucleotide polymorphisms (SNPs) were associated with LDL-C levels (P < 5 × 10-8) and 337 SNPs were available in ischemic stroke with eliminating outliers. LDL-C levels were significantly associated with ischemic stroke (OR = 1.104, 95%CI = 1.019 - 1.195, P = 1.52 × 10-2). MR-Egger and IVW showed directionally similar estimates (MR-Egger: OR = 1.120, 95%CI = 1.040 - 1.207, P = 3.12 × 10-3; IVW: OR = 1.120, 95%CI = 1.064 - 1.178, P = 1.17 × 10-5). Conclusion: LDL-C levels had causal effects on IS, providing insights into the design of future interventions to reduce the burden of ischemic stroke.

Uric acid levels and heart failure: A mendelian randomization study.

BACKGROUND AND AIMS: Uric acid, the end-product of purine metabolism within the human body, has been the subject of studies exploring its potential association with cardiovascular and cerebrovascular diseases. However, the precise relationship between uric acid levels and heart failure remains elusive. METHODS AND RESULTS: In this particular study, aggregated data from genome-wide association studies on uric acid and heart failure were utilized to perform a two-sample Mendelian randomization (MR) analysis utilizing R software. The aim was to uncover any causal link between these variables. The primary outcome was assessed using inverse variance weighted (IVW) methodology, while sensitivity analyses employed MR-Egger, weighted median (WME), and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) techniques. IVW results revealed a possible causal relationship between elevated uric acid levels and an increased risk of heart failure (OR: 1.09, 95 % CI: 1.01-1.17, P < 0.05). Encouragingly, the directions provided by MR-Egger and WME aligned with IVW findings, and no anomalies were detected in the remaining sensitivity analyses. CONCLUSION: These outcomes indicate the stability of the results of the study, thereby suggesting that heightened uric acid levels may contribute to an augmented risk of heart failure.

Uric acid levels and their association with vascular dementia and Parkinson's disease dementia: a meta-analysis.

OBJECTIVES: To explore the association between uric acid (UA) levels and vascular dementia (VaD) and Parkinson's disease dementia (PDD), a meta-analysis was conducted. METHODS: The relevant studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Collaboration Database up to May 2022. Pooled analysis, sensitivity analysis, and publication bias examination were all conducted. All analyses were performed by using STATA 16. RESULTS: Twelve studies with a total of 2097 subjects were included. The pooled analysis showed that UA levels were not associated with VaD (WMD = - 10.99 µmol/L, 95% CI (- 48.05, 26.07), P = 0.561) but were associated with PDD (WMD = - 25.22 µmol/L, 95% CI (- 43.47, - 6.97), P = 0.007). The statistical stability and reliability were evaluated using sensitivity analysis and publication bias outcomes. CONCLUSION: UA levels are associated with PDD but not with VaD. This study will help to strengthen our knowledge of the pathophysiologies of VaD and PDD, and promote the development of prevention and treatment strategies.

Antiplatelet therapy for secondary prevention of lacunar stroke: a systematic review and network meta-analysis.

PURPOSE: To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS). METHODS: The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0. RESULTS: Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study. CONCLUSIONS: This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.