Kuo-Chuan Hung, Ting-Sian Yu, Yi-Chen Lai, I-Wen Chen
Chronic low serum magnesium levels were associated with an increased risk of intracranial hemorrhage in this observational study. These findings warrant confirmation through prospective studies to clarify whether this association reflects a modifiable risk marker or the underlying illness severity.
BACKGROUND: Magnesium is involved in vascular tone, endothelial function, and coagulation pathways, yet evidence directly linking magnesium status to hemorrhagic cerebrovascular events remains limited. We examined whether chronic low serum magnesium levels are associated with incident nontraumatic intracranial hemorrhage in a large adult population.
METHODS: This retrospective cohort study used the TriNetX Global Collaborative Network (2010-2024). Low magnesium status was defined as two serum magnesium measurements <1.7 mg/dL within 1 year, and the comparator cohort had two normal values (1.70-2.20 mg/dL). A 3-month landmark design was applied, and 1:1 propensity score matching was performed for demographics, comorbidities, medications, and laboratory markers. The primary outcome was incident nontraumatic intracranial hemorrhage over 5 years. Secondary outcomes included intracerebral hemorrhage, subarachnoid hemorrhage, all-cause mortality, and systolic blood pressure >180 mmHg. Sensitivity, subgroup, and exposure gradient analyses were conducted.
RESULTS: After matching, 266,133 patients remained in each group. Low magnesium status was associated with a higher intracranial hemorrhage risk (HR, 1.74; 95% CI, 1.59-1.89; p < 0.001), as well as intracerebral hemorrhage (HR, 1.79; p < 0.001), subarachnoid hemorrhage (HR, 1.64; p < 0.001), all-cause mortality (HR, 1.49; p < 0.001), and systolic blood pressure >180 mmHg (HR, 1.07; p < 0.001). This association remained consistent across the sensitivity and subgroup analyses. Severe low magnesium levels (<1.5 mg/dL) showed a stronger association with intracranial hemorrhage (HR, 2.00; p < 0.001), suggesting an exposure-gradient relationship.
CONCLUSION: Chronic low serum magnesium levels were associated with an increased risk of intracranial hemorrhage in this observational study. These findings warrant confirmation through prospective studies to clarify whether this association reflects a modifiable risk marker or the underlying illness severity.