Circulating magnesium and cardiovascular events

In their systematic review and meta-analysis of prospective studies, Del Gobbo et al (1) showed an inverse association of magnesium concentrations with the incidence of cardiovascular disease, including fatal and nonfatal ischemic heart disease (IHD). Yet, another recent meta-analysis (2) has reported a beneficial effect of dietary magnesium on cardiovascular disease mortality among women but not among men. However, the meta-analysis by Del Gobbo et al (1) went one step further by analyzing circulating magnesium, which may suggest the key mechanism of the whole issue. All of the studies included in the meta-analysis by Del Gobbo et al (1) that investigated magnesium in women, either by dietary intake or by circulating concentrations, showed a significant protective effect against IHD incidents (3–5). Among studies that reported strictly on circulating magnesium in women, Chiuve et al (4) showed an inverse association with sudden cardiac death, whereas Liao et al (3) reported a trend toward the decreased risk of IHD. Circulating magnesium is directly regulated by renal function (6). On the contrary, dietary magnesium is mostly associated with individual nutrition and dietary habits. Importantly, there is a low correlation between dietary intake and circulating magnesium concentrations. There are reasons why we should distinguish between circulating magnesium concentrations and dietary magnesium and also separate men from women. Prolonged corrected QT (QTc) interval is associated with an increased risk of potentially fatal ventricular tachyarrhythmias (7–13). Intravenous magnesium has been used for treatment and prevention of ventricular tachycardia (8, 11), ventricular fibrillation (10, 13), and polymorphic ventricular tachycardia (7, 12). Because QTc prolongation is more often present in women, we suggested that the beneficial effect of magnesium could be more pronounced in female patients (14). Pathophysiologic mechanisms may include antagonism at the Land T-type calcium channels (15), membrane stabilization (16), reduced frequency of ventricular ectopic beats (17, 18), and conversion to sinus rhythm (7, 8, 10, 19, 20). Accordingly, there is a compelling evidence of benefit from intravenous magnesium application, and so the effect of the circulating magnesium concentration could be substantial for its cardiovascular effects. The facts that intravenous magnesium is effective against ventricular tachyarrhythmias through mechanisms which include prolongation of the QT interval, and that QTc interval is more often prolonged in women could underlie a better antiarrhythmic protection in women than in men. Perhaps Del Gobbo et al could separate the effect of circulating magnesium in men and women and provide the pooled results. The problem of a low correlation between dietary and circulating magnesium must be accounted for in future research. Neither of the authors declared a conflict of interest.