Serum Magnesium Levels and Risk of Coronary Artery Disease: Mendelian Randomisation Study

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2018 May 18

PMID 29769070

Citations 26

Authors

Susanna C Larsson

Stephen Burgess

Karl Michaelsson

Affiliations

Soon will be listed here.

Abstract

Background: Observational studies have shown that serum magnesium levels are inversely associated with risk of cardiovascular disease, but whether this association is causal is unknown. We conducted a Mendelian randomisation study to investigate whether serum magnesium levels may be causally associated with coronary artery disease (CAD).

Methods: This Mendelian randomisation analysis is based on summary-level data from the CARDIoGRAMplusC4D consortium's 1000 Genomes-based genome-wide association meta-analysis of 48 studies with a total of 60,801 CAD cases and 123,504 non-cases. Six single-nucleotide polymorphisms associated with serum magnesium levels at genome-wide significance were used as instrumental variables.

Results: A genetic predisposition to higher serum magnesium levels was inversely associated with CAD. In conventional Mendelian randomisation analysis, the odds ratio of CAD was 0.88 (95% confidence interval [CI] 0.78 to 0.99; P = 0.03) per 0.1-mmol/L (about 1 standard deviation) increase in genetically predicted serum magnesium levels. Results were consistent in sensitivity analyses using the weighted median and heterogeneity-penalised model averaging methods, with odds ratios of 0.84 (95% CI 0.72 to 0.98; P = 0.03) and 0.83 (95% CI 0.71 to 0.96; P = 0.02), respectively.

Conclusions: This study based on genetics provides evidence that serum magnesium levels are inversely associated with risk of CAD. Randomised controlled trials elucidating whether magnesium supplementation lowers the risk of CAD, preferably in a setting at higher risk of hypomagnesaemia, are warranted.

Citing Articles

Association of magnesium depletion score with increased stroke incidence and mortality risks in a comprehensive analysis.

Yuan Z, Wang P, Xie Y, Chen J, Zhu S, Wang S Sci Rep. 2025; 15(1):6790.

PMID: 40000741 PMC: 11862158. DOI: 10.1038/s41598-025-91227-1.

Serum magnesium, not calcium, is inversely associated with abnormal HbA1c concentrations in adults with coronary artery disease.

Dong H, Lu N, Wang J, Hu P Asia Pac J Clin Nutr. 2025; 34(1):104-111.

PMID: 39828263 PMC: 11742607. DOI: 10.6133/apjcn.202502_34(1).0010.

The Hypothesis of Trace Elements Involvement in the Coronary Arteries Atherosclerotic Plaques' Location.

Urbanowicz T, Hanc A, Frackowiak J, Piecek J, Spasenenko I, Olasinska-Wisniewska A J Clin Med. 2024; 13(22).

PMID: 39598076 PMC: 11595170. DOI: 10.3390/jcm13226933.

What Can We Learn from the Scalp Hair's Trace Element Content? The Relationship with the Advancement of Coronary Artery Disease.

Urbanowicz T, Hanc A, Frackowiak J, Bialasik-Misiorny M, Radek Z, Krama M J Clin Med. 2024; 13(17).

PMID: 39274472 PMC: 11395935. DOI: 10.3390/jcm13175260.

The role of serum magnesium in the prediction of acute kidney injury after total aortic arch replacement: A prospective observational study.

Jiang X, Li Z, Pan C, Fang H, Xu W, Chen Z J Med Biochem. 2024; 43(4):574-586.

PMID: 39139155 PMC: 11318877. DOI: 10.5937/jomb0-48779.

References

ISERI L, FRENCH J . Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984; 108(1):188-93. DOI: 10.1016/0002-8703(84)90572-6. View

Shungin D, Winkler T, Croteau-Chonka D, Ferreira T, Locke A, Magi R . New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015; 518(7538):187-196. PMC: 4338562. DOI: 10.1038/nature14132. View

Burgess S, Thompson S . Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017; 32(5):377-389. PMC: 5506233. DOI: 10.1007/s10654-017-0255-x. View

Dibaba D, Xun P, Song Y, Rosanoff A, Shechter M, He K . The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2017; 106(3):921-929. PMC: 5573024. DOI: 10.3945/ajcn.117.155291. View

Burgess S, Bowden J, Fall T, Ingelsson E, Thompson S . Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants. Epidemiology. 2016; 28(1):30-42. PMC: 5133381. DOI: 10.1097/EDE.0000000000000559. View

Zhang X, Li Y, Del Gobbo L, Rosanoff A, Wang J, Zhang W . Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016; 68(2):324-33. DOI: 10.1161/HYPERTENSIONAHA.116.07664. View

Reid I, Gamble G, Bolland M . Circulating calcium concentrations, vascular disease and mortality: a systematic review. J Intern Med. 2016; 279(6):524-40. DOI: 10.1111/joim.12464. View

Zheltova A, Kharitonova M, Iezhitsa I, Spasov A . Magnesium deficiency and oxidative stress: an update. Biomedicine (Taipei). 2016; 6(4):20. PMC: 5112180. DOI: 10.7603/s40681-016-0020-6. View

. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010; 42(5):441-7. PMC: 2914600. DOI: 10.1038/ng.571. View

10.

Charoen P, Nitsch D, Engmann J, Shah T, White J, Zabaneh D . Mendelian Randomisation study of the influence of eGFR on coronary heart disease. Sci Rep. 2016; 6:28514. PMC: 4919785. DOI: 10.1038/srep28514. View

11.

Cosaro E, Bonafini S, Montagnana M, Danese E, Trettene M, Minuz P . Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2014; 24(11):1213-20. DOI: 10.1016/j.numecd.2014.05.010. View

12.

Meyer T, Verwoert G, Hwang S, Glazer N, Smith A, van Rooij F . Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels. PLoS Genet. 2010; 6(8). PMC: 2916845. DOI: 10.1371/journal.pgen.1001045. View

13.

Ehret G, Munroe P, Rice K, Bochud M, Johnson A, Chasman D . Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011; 478(7367):103-9. PMC: 3340926. DOI: 10.1038/nature10405. View

14.

Morais J, Severo J, Dos Santos L, de Sousa Melo S, de Oliveira Santos R, de Oliveira A . Role of Magnesium in Oxidative Stress in Individuals with Obesity. Biol Trace Elem Res. 2016; 176(1):20-26. DOI: 10.1007/s12011-016-0793-1. View

15.

Lainez S, Schlingmann K, van der Wijst J, Dworniczak B, van Zeeland F, Konrad M . New TRPM6 missense mutations linked to hypomagnesemia with secondary hypocalcemia. Eur J Hum Genet. 2013; 22(4):497-504. PMC: 3953905. DOI: 10.1038/ejhg.2013.178. View

16.

Holmes M, Asselbergs F, Palmer T, Drenos F, Lanktree M, Nelson C . Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2014; 36(9):539-50. PMC: 4344957. DOI: 10.1093/eurheartj/eht571. View

17.

Simental-Mendia L, Sahebkar A, Rodriguez-Moran M, Guerrero-Romero F . A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res. 2016; 111:272-282. DOI: 10.1016/j.phrs.2016.06.019. View

18.

Joris P, Plat J, Bakker S, Mensink R . Long-term magnesium supplementation improves arterial stiffness in overweight and obese adults: results of a randomized, double-blind, placebo-controlled intervention trial. Am J Clin Nutr. 2016; 103(5):1260-6. DOI: 10.3945/ajcn.116.131466. View

19.

Schlingmann K, Weber S, Peters M, Nejsum L, Vitzthum H, Klingel K . Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet. 2002; 31(2):166-70. DOI: 10.1038/ng889. View

20.

Shiga T, Wajima Z, Inoue T, Ogawa R . Magnesium prophylaxis for arrhythmias after cardiac surgery: a meta-analysis of randomized controlled trials. Am J Med. 2004; 117(5):325-33. DOI: 10.1016/j.amjmed.2004.03.030. View