The challenge of Cardiovascular Disease: the role of Magnesium

The prevalence of chronic kidney disease (CKD) is estimated to be 10% among the adult population worldwide, with currently approximately 1,7 million people with CKD in the Netherlands. People with CKD are at increased risk of not only progression of CKD, but even more importantly, they face an increased risk of cardiovascular disease (CVD) and mortality, which is 2 to 4 times higher compared to healthy individuals. Among the main causes of this increased cardiovascular risk in people with CKD are disturbed mineral metabolism and accelerated vascular calcification. Therefore, it is of importance to investigate approaches on how to retard or even prevent the process of vascular pathology. Management of known cardiovascular risk factors, such as hypertension, obesity, smoking, an inactive lifestyle etc. only leads to a moderate reduction of the cardiovascular risk. Consequently, identifying and managing other targets that could reduce the risk of CVD is of importance for people with CKD. In an effort to do so, the NIGRAM(2+) consortium focussed on the role of the mineral magnesium. The hypothesis of a role for magnesium is based on several in vitro and animal studies that have demonstrated that higher magnesium intake and high serum magnesium levels can inhibit vascular calcification, improve vascular function and reduce chronic inflammation. Also, an inverse association between magnesium and CVD and mortality has consistently been demonstrated in various cohorts. At present, magnesium intervention trials that investigate the effect of magnesium supplementation on parameters of cardiovascular health are limited and demonstrate inconsistent results. This thesis focuses on serum magnesium concentration and magnesium intake in clinical research, practicing a wide variety of epidemiological approaches. We aim to investigate if the inverse association between magnesium and CVD and mortality is present in different populations, including people with CKD, type 2 diabetes and the general population. Furthermore, we address different modes of magnesium supplementation and investigate if magnesium supplementation can modify the high cardiovascular risk of people with CKD.