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. 2019 Feb 26;92(9):e944-e950.
doi: 10.1212/WNL.0000000000007001. Epub 2019 Jan 25.

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

Susanna C Larsson  1 , Matthew Traylor  2 , Stephen Burgess  2 , Giorgio B Boncoraglio  2 , Christina Jern  2 , Karl Michaëlsson  2 , Hugh S Markus  2 ; MEGASTROKE project of the International Stroke Genetics Consortium
Collaborators, Affiliations

Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

Susanna C Larsson et al. Neurology. .

Abstract

Objective: To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.

Methods: Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).

Results: In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.

Conclusions: This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.

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Figures

Figure 1
Figure 1. Association between genetically predicted serum magnesium concentrations and ischemic stroke and its subtypes
ORs are per genetically predicted 0.1 mmol/L (about 1 SD) increase in serum magnesium concentrations. CI = confidence interval; HetPen = heterogeneity-penalized model-averaging; IVW = inverse variance weighted (standard mendelian randomization method); OR = odds ratio; WM = weighted median.
Figure 2
Figure 2. Association between genetically predicted serum calcium concentrations and ischemic stroke and its subtypes
ORs are per genetically predicted 0.5 mg/dL (about 1 SD) increase in serum calcium concentrations. CI = confidence interval; HetPen = heterogeneity-penalized model-averaging; IVW = inverse variance weighted (standard mendelian randomization method); OR = odds ratio; WM = weighted median.
See this image and copyright information in PMC

Comment in

References

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