Higher serum magnesium levels appear to reduce the risk for intracranial aneurysm and aneurysmal subarachnoid hemorrhage. The effects may be partially mediated by magnesium’s influence on systolic blood pressure, new research suggests.
“The modifiable risk factors for intracranial aneurysm are largely unknown. Our findings provided evidence of a causal association between increased serum magnesium levels and reduced risk of intracranial aneurysm,” Susanna Larsson, PhD, Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.
These results suggest that raising serum magnesium levels ― through a magnesium-rich diet or magnesium supplementation ― “may play a role in the primary prevention of intracranial aneurysm and associated hemorrhage,” Larsson added.
The study was published online June 22 in Neurology.
Lower Risk for Rupture
The researchers leveraged randomly allocated genetic variants related to serum magnesium concentrations in a two-sample Mendelian randomization (MR) study to assess whether higher genetically predicted serum magnesium correlates with reduced risk for intracranial aneurysm. They also performed a multivariable MR analysis to assess the role blood pressure might play in this association.
Source data came from a genome-wide association study (GWAS) involving 23,829 individuals that previously identified five single-nucleotide polymorphisms associated with serum magnesium. Genetic association estimates for intracranial aneurysm were derived from a GWAS in 79,429 people (7495 case patients and 71,934 control patients), and genetic association estimates for systolic blood pressure were derived from a GWAS of 757,601 individuals.
The researchers found that higher genetically predicted serum magnesium concentrations were associated with lower risk for intracranial aneurysm.
The odds ratios per 0.1 mmol/L increment in genetically predicted serum magnesium concentrations were 0.66 (95% CI: 0.49 – 0.91) for intracranial aneurysm (unruptured and ruptured combined), 0.57 (95% CI: 0.30 – 1.06) for unruptured intracranial aneurysm, and 0.67 (95% CI: 0.48 – 0.92) for aneurysmal subarachnoid hemorrhage.
Adjustment for genetically predicted systolic blood pressure partially attenuated the associations of genetically predicted serum magnesium with all three outcomes, suggesting that magnesium’s influence was at least partially mediated by systolic blood pressure.
“In addition to a blood pressure lowering effect, increased magnesium concentrations may reduce the risk of intracranial aneurysm rupture by improving endothelial function and reducing oxidative stress,” the investigators note.
They caution that the data were derived from people of European ancestry, which limits the generalizability to other populations.
“Caution should be taken when extrapolating findings from MR to infer the effect of a clinical intervention, and clinical trials are warranted to guide optimal practice,” they add.
Critical Role in Vascular Health
In an accompanying editorial, Joanna Pera, MD, PhD, of Jagiellonian University Medical College, in Krakow, Poland, and Christopher Anderson, MD, of Brigham and Women’s Hospital, in Boston, Massachusetts, note that the study “adds to our understanding of the importance of magnesium in vascular health particularly related to cerebral aneurysms.”
There is a need for “both mechanistic and potentially therapeutic investigation into the role that magnesium plays in subarachnoid hemorrhage,” they add.
Further, they write, the results “raise interesting new questions about the links between circulating magnesium, intracranial aneurysms, and blood pressure. Arterial hypertension is a well-recognized risk factor for intracranial aneurysm development and rupture. Magnesium supplementation may lower blood pressure values.
“Could this mineral prove useful in developing interventions that could prevent intracranial aneurysm development and/or rupture over and above a simple lowering of blood pressure, perhaps through pleiotropic effects on endothelial function or other mechanisms? With these results in hand, work is clearly needed to learn more about the biology of magnesium in the vascular system and in intracranial aneurysm biology in particular,” Pera and Anderson conclude.
This study was supported by the Swedish Research Council for Health, Working Life and Welfare, the British Heart Foundation Research Center of Excellence at Imperial College London, and a National Institute for Health Research Clinical Lectureship at St. George’s, University of London. Larsson has disclosed no relevant financial relationships. Gill is employed part time by Novo Nordisk. Pera has disclosed no relevant financial relationships. Anderson has received research support from the Bayer AG and has consulted for ApoPharma and Invitae.
Neurology. Published online June 22, 2021. Abstract, Editorial
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