Background/Aim: The putative association between serum 25 hydroxyvitamin D concentration 25(OH)D and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. Method: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Results: Our results unveiled 99 SNPs contributing a causal relationship between 25(OH)D and CES using IVW [OR□=□0.82, 95% CI: 0.67-0.98, p□=□0.037]. Horizontal pleiotropy was not seen by the MR-Egger intercept-based test [MR-Egger intercept□=□0.001; p□=□0.792], suggesting an absence of horizontal pleiotropy. Cochrane’s Q value [Q=78.71, p-value□=□0.924], Rucker’s Q [Q=78.64, p-value=0.913], and I ² =0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity in the connection between 25(OH)D and CES. This result remained consistent using different MR method and sensitivity analyses, including Maximum likelihood [OR=0.82, 95%CI: 0.67-0.98, p-value=0.036], Constrained maximum likelihood method [OR=0.76, 95%CI: 0.64-0.90, p-value=0.002], Debiased inverse-variance weighted method [OR=0.82, 95%CI: 0.68-0.99, p-value=0.002], MR-PRESSO [OR=0.82, 95%CI 0.77-0.87, p-value=0.022], RAPS [OR=0.82, 95%CI 0.67-0.98, p-value=0.038], MR-Lasso [OR=0.82, 95%CI 0.68-0.99, p-value=0.037]. Conclusion: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a causally protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Background: Obesity, a major global health issue, heightens the risk of cardiovascular diseases, including major adverse cardiovascular events (MACE), heart failure (HF) and myocardial infarction (MI). This study provides the first network meta‐analysis (NMA) integrating direct and indirect evidence to compare the cardiovascular efficacy of bariatric surgery (BS) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in individuals with obesity. Methods: A systematic review and NMA were performed in adherence to PRISMA guidelines. PubMed, Embase, Cochrane Library and Google Scholar were searched for studies published from January 2000 to September 2024. Eligible studies reported cardiovascular outcomes, specifically MACEs, HF and MI, in patients with obesity receiving BS, GLP‐1RAs or control treatment. Fixed‐ and random‐effects models were used to analyse hazard ratios (HRs) and risk ratios (RRs), with heterogeneity assessed with I ² and consistency through node‐splitting analysis. Results: Forty‐three studies involving 932,380 patients were included BS was associated with significantly greater reductions in MACEs (HR 0.66; 95% CI 0.60–0.74), HF (HR 0.45; 95% CI 0.38–0.53) and MI (HR 0.53; 95% CI 0.45–0.63) compared with controls in random‐effects models. GLP‐1RAs reduced MACEs (HR 0.85; 95% CI 0.77–0.94) but showed non‐significant effects on HF and MI. Despite high heterogeneity ( I ² : 66%–93%), directional consistency was observed across studies. Conclusions: BS demonstrated more consistent and statistically significant reductions in all cardiovascular outcomes compared to GLP‐1RAs, which showed more variable efficacy, particularly for HF and MI. Nevertheless, GLP‐1RAs remain effective evidence‐based alternatives for cardiovascular risk reduction in patients who are not candidates for surgery, but future studies on newer GLP‐1RAs are required. The high heterogeneity across studies highlights the need for cautious interpretation. These results may inform individualized treatment selection in patients with obesity at high cardiovascular risk.