Role of magnesium in events of physiologic stress.
Being the most common bivalent cation in the intra-cellular domain, Magnesium has dominant roles in many, essential, physiologic processes (1). Previous publications focused on the bilateral relationship between low magnesium blood levels and physiologic stress (2). Low magnesium levels were shown to be a pro-inflammatory agent: acting on both innate and acquired immunity cells, hypomagnesemia ignite the oxidative surge on behalf of phagocytic cells and increase the cytokines production by the cellular elements of the adaptive immunity (3, 4). In their extensive and thorough review, Veronse et al. found out that explicit beneficial effects of magnesium supplementation (versus placebo or no intervention) were found in the following scenarios: hospitalization prevention of pregnant women and reduction of the risk for Migraine attacks (5).
Deranged magnesium metabolism in septic patients.
Hypomagnesemia is known to be both common in patients hospitalized in Intensive Care Units (ICUs) and to have a negative effect on significant clinical outcomes, including survival, respiratory insufficiency and increased length of ICU stay (6). Wang et al. suggested a mechanism which may render patients with hypomagnesemia to be in a greater risk for sepsis, septic shock and death during their ICU stay. They describe a pathophysiologic mechanism that associates hypomagnesemia with lower monocyte counts and increased tendency for septic shock evolution in terms of gram-negative bacteremia (7). Alongside its direct effects on immunity and inflammation, magnesium deficiency also accelerates coagulation in favor over fibrinolysis. Tonai et al. found out, in their observational study, that septic patients with low blood magnesium levels were at increased risk of events of disseminated intravascular coagulation (DIC) (8).
Hypomagnesemia also has deleterious effects on the structure and physiology of vascular walls. A previous study showed evidence that magnesium regulates elastin and collagen turnover in the vessel walls. This contributes to the protective effect against atherosclerosis by maintaining the elasticity of the endothelium and decreasing calcium deposition in the elastic fibers (9). Maier et al. found a correlation between low magnesium and increased risk of cardiovascular diseases, mediated by the fact that hypomagnesemia might reversibly inhibit endothelial cell proliferation, therefore increasing the risk of thrombosis and atherosclerosis (10). Locatelli et al. suggested that low magnesium can elevate lipid accumulation intracellularly and furthermore disrupt endothelial homeostasis and exacerbate atherosclerosis (11).
Beneficial effects of magnesium administration in critically ill patients.
In their prospective observation, Patil and Aslam showed that hypomagnesemia is indeed associated with worse clinical outcomes (Sequential Organ Failure Assessment score (SOFA), ICU length of hospitalization and mortality) in a statistically significant manner. However, they did not present the relative contribution of hypomagnesemia in a multivariate model (12). In their retrospective analysis of over 6,000 ICU patients, Gu et al. showed that magnesium administration was beneficial, in terms of 28-days mortality rate reduction, even without consideration of the baseline magnesium blood levels of patients. The beneficial effects of magnesium supplementation increased when patients with hypomagnesemia were compared to patients with normal magnesium blood levels (13).
Aim of the current study.
In the current study we aimed to assess the potential association between hypomagnesemia and the relative risk for VTE amongst hospitalized, elderly patients.