Abstract
Background: Clinical hypomagnesemia and experimental dietary magnesium (Mg) restriction diets are associated with cardiac arrhythmias. Relationships between circulating or dietary Mg at usual concentrations or intakes and risk of cardiovascular disease (CVD), including fatal coronary heart disease (CHD), are not well established. Objective: We performed a systematic review and meta-analysis to summarize all available evidence from prospective studies on the associations between circulating and dietary Mg intake with incidence of total CVD, total CHD, and fatal CHD. Methods: Multiple literature databases and grey literature were systematically searched without language restriction from the earliest online index date to May 2012 for all prospective cohort or nested case-control studies examining the association of circulating or dietary Mg intake with incident total CVD, total CHD and fatal CHD. Two investigators evaluated full text articles for inclusion/exclusion and extracted data, independently and in duplicate. Linear dose-response relationships were assessed using generalized least-squares trend estimation, with pooled RR’s determined using fixed-effects or random-effects in the presence of heterogeneity (I2>30%). Potential non-linear associations were assessed using restricted cubic splines. Prespecified sources of heterogeneity were explored using meta-regression. Publication bias was assessed using formal statistical testing and visual inspection of funnel plots. Results: Of 2,303 abstracts reviewed, 16 studies met eligibility criteria, comprising 761,742 individuals and 11,995 total CVD, 7,534 total CHD, and 2,686 fatal CHD events. In pooled analyses, circulating Mg (per 0.2mmol/L increment) was associated with a 30% lower risk of total CVD (RR=0.70, 95% CI=0.56-0.88; I2=50%) and trends towards lower risk of total CHD (RR=0.83, 95% CI=0.75-1.05; I2=47%) and fatal CHD (RR=0.61, 95% CI=0.37-1.00; I2=80%). Dietary Mg (per 200mg/day increment) was not significantly associated with total CVD (RR=0.89, 95% CI=0.75-1.05; I2=67%), but was associated with a 22% lower risk of total CHD (RR=0.78, 95% CI=0.67-0.92; I2=44%). The association between dietary Mg and fatal CHD was non-linear (p<0.0001), with an inverse association observed up to a threshold of ~250 mg/day (compared to lower intakes, RR=0.73, 95% CI=0.62-0.86). Funnel plot asymmetry was evident for the association between circulating Mg and total CVD, explained by heterogeneity due to stronger associations (p=0.02) in studies including participants with prevalent CVD at baseline and evaluating fatal CHD. Conclusions: Circulating Mg and dietary Mg intake are associated with lower risk of CVD, in particular fatal CHD. These findings support the need for randomized clinical trials and experimental studies to evaluate the possible role of Mg in the prevention of CVD and CHD death.
Published Version
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