Upper normal serum magnesium is associated with a reduction in incident death from fatal heart failure, coronary heart disease and stroke in non-dialysis patients with CKD stages 4 and 5.

Background: Serum magnesium disturbances are common in patients with cardiovascular disease (CVD). However, the well-established link between low serum magnesium and nutritional or inflammatory disorders has limited its consideration as a non-traditional risk factor for mortality. This study aims to elucidate the relationship between serum magnesium concentrations and mortality due to fatal heart failure (HF), coronary heart disease (CHD) and stroke in non-dialysis patients with chronic kidney disease (CKD) stages 4 and 5. Methods: A cohort of 1271 non-dialysis patients with CKD stages 4 and 5 was followed from 2008 to 2018. Patients with prior major adverse cardiovascular events (MACE) were excluded. Serum magnesium levels were stratified into tertiles and the primary outcomes were incidence rates of fatal HF, CHD and stroke. Secondary outcomes included composite MACE and all-cause mortality. Hazard ratios (HRs) were calculated using multivariate Cox regression, adjusting for demographics, comorbidities and biochemical parameters. E-values were used to assess the robustness of the results. Results: Over the 10-year follow-up, 186 patients died. Higher serum magnesium levels were significantly associated with reduced mortality risk from HF [HR 0.49 (95% CI 0.27-0.89) for T2; HR 0.31 (95% CI 0.16-0.60) for T3] compared with the lowest tertile. Similar trends were observed for CHD and stroke mortality. The incidence rate of MACE per 1000 person-years was reduced from 68.2 in tertile 1 to 26.2 in tertile 2 and 16.8 in tertile 3. Secondary endpoints, including all-cause mortality and composite MACE, followed trends similar to the primary outcomes. Conclusions: Higher serum magnesium concentrations were associated with lower risks of death from fatal HF, CHD and stroke in non-dialysis patients with CKD stages 4 and 5.