Abstract
BACKGROUND: Vitamin D (VitD) may protect arterial health, but its link to cerebral aneurysm rupture remains unclear. This study aims to investigate the correlation between serum VitD levels and the risk of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This retrospective study included patients with ruptured or unruptured aneurysms treated between 2018 and 2021. Univariate and multivariate analyses were conducted. Propensity score matching (PSM) analysis was conducted to balance confounding factors. Furthermore, the causal relationship between VitD and aSAH was investigated using a two-sample Mendelian randomization (MR) analysis. Summary-level data for the exposure (VitD) and outcome (aSAH) were obtained from public genome-wide association study datasets. Multiple MR methods, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode, were utilized to assess causality. Sensitivity analyses were conducted to evaluate the robustness and reliability of the causal estimates. RESULTS: A total of 499 patients with 619 intracranial aneurysms were included. Among them, 337 (68%) were female, 184 cases (36.9%) had ruptured aneurysms, and 105 (21.0%) had multiple aneurysms. VitD levels and VitD deficiency showed no association with aSAH in univariate or multivariate analysis before PSM (p > 0.05). After PSM (112 matched aSAH patients), VitD levels and VitD deficiency remained unassociated with the risk of aSAH (p = 0.947). MR analysis, including inverse variance weighted methods, found no causal link between VitD levels and aSAH (OR: 1.00; 95% CI: 0.82-1.23; p = 0.966). CONCLUSION: This study found that serum VitD levels are neither associated with nor causally linked to aSAH. The inverse associations observed in previous studies may be attributed to confounding factors or reverse causation. A prospective, large-scale study with long-term follow-up is warranted to validate these findings.