Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies

Abstract

Background: Clinical hypomagnesemia and experimental restriction of dietary magnesium increase cardiac arrhythmias. However, whether or not circulating or dietary magnesium at usual concentrations or intakes influences the risk of cardiovascular disease (CVD), including fatal ischemic heart disease (IHD), is unclear.

Objective: We performed a systematic review and meta-analysis to investigate prospective associations of circulating and dietary magnesium with incidence of CVD, IHD, and fatal IHD.

Design: Multiple literature databases were systematically searched without language restriction through May 2012. Inclusion decisions and data extraction were performed in duplicate. Linear dose-response associations were assessed by using random-effects meta-regression. Potential nonlinear associations were evaluated by using restricted cubic splines.

Results: Of 2303 articles, 16 studies met the eligibility criteria; these studies comprised 313,041 individuals and 11,995 CVD, 7534 IHD, and 2686 fatal IHD events. Circulating magnesium (per 0.2 mmol/L increment) was associated with a 30% lower risk of CVD (RR: 0.70; 95% CI: 0.56, 0.88 per 0.2 mmol/L) and trends toward lower risks of IHD (RR: 0.83; 95% CI: 0.75, 1.05) and fatal IHD (RR: 0.61; 95% CI: 0.37, 1.00). Dietary magnesium (per 200-mg/d increment) was not significantly associated with CVD (RR: 0.89; 95% CI: 0.75, 1.05) but was associated with a 22% lower risk of IHD (RR: 0.78; 95% CI: 0.67, 0.92). The association of dietary magnesium with fatal IHD was nonlinear (P < 0.001), with an inverse association observed up to a threshold of ∼250 mg/d (RR: 0.73; 95% CI: 0.62, 0.86), compared with lower intakes.

Conclusion: Circulating and dietary magnesium are inversely associated with CVD risk, which supports the need for clinical trials to evaluate the potential role of magnesium in the prevention of CVD and IHD.

FIGURE 1.

Screening and selection of articles on circulating and dietary magnesium and risk of cardiovascular diseases. Records were identified by electronic searches of PubMed (http://www.ncbi.nlm.nih.gov/pubmed), Web of Knowledge (http://wokinfo.com), Ovid (http://gateway.ovid.com), Cochrane library (http://www.thecochranelibrary.com/view/0/index.html), Commonwealth Agricultural Bureau abstracts (http://www.cabdirect.org), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (http://www.ebscohost.com/academic/cinahl-plus-with-full-text/), and Faculty of 1000 (http://f1000.com). Gray literature sources searched included Scirus (http://www.scirus.com/), the System for Information on Grey Literature in Europe (SIGLE) (http://www.opengrey.eu/), and Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism (EPI/NPAM) conference abstracts (http://my.americanheart.org/professional/Sessions/EPINPAM/EPINPAM_UCM_316904_SubHomePage.jsp).

FIGURE 2.

RR of CVD, IHD, and fatal IHD associated with a 0.2-mmol/L higher circulating magnesium concentration quantified by using generalized least-squares trend estimation and pooled by using a random-effects meta-analysis (n = 53,212). Circulating magnesium (per 0.2-mmol/L increment) was associated with a 30% lower risk of CVD (RR: 0.70; 95% CI: 0.56, 0.88 per 0.2 mmol/L) and a trend toward lower risks of IHD (RR: 0.83; 95% CI: 0.75, 1.05) and fatal IHD (RR: 0.61; 95% CI: 0.37, 1.00). CVD, cardiovascular disease; IHD, ischemic heart disease; ref, reference; SCD, sudden cardiac death.

FIGURE 3.

RR of CVD, IHD, and fatal IHD associated with a 200-mg/d higher dietary magnesium intake quantified by using generalized least-squares trend estimation and pooled by using a random-effects meta-analysis (n = 273,963). Dietary magnesium (per 200-mg/d increment) was not significantly associated with CVD (RR: 0.89; 95% CI: 0.75, 1.05) but was associated with a 22% lower risk of IHD (RR: 0.78; 95% CI: 0.67, 0.92). Dietary magnesium intake was not significantly associated with fatal IHD (RR: 0.73; 95% CI: 0.52, 1.03) with linear modeling; however, a significant nonlinear association was observed (Figure 4). CVD, cardiovascular disease; IHD, ischemic heart disease; ref, reference; SCD, sudden cardiac death.

FIGURE 4.

Prospective associations between circulating and dietary magnesium and RR of CVD, IHD, and fatal IHD estimated by random-effects meta-analysis with the use of restricted cubic splines (n = 313,041). Each reference value represents the lowest median value of included studies. P values for nonlinear associations are presented. The association between dietary magnesium and fatal IHD was nonlinear (P-nonlinear < 0.001). In comparison with lower intakes, a 27% lower risk of fatal IHD was observed up to a threshold of ∼250 mg/d (RR: 0.73; 95% CI: 0.62, 0.86). CVD, cardiovascular disease; IHD, ischemic heart disease.