Ionized and Total Magnesium Levels and Cardiovascular Risk in Patients with CKD

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Background: We sought to determine whether serum ionized (iMg) and total (tMg) Mg levels are associated with major adverse cardiovascular events (MACE) in patients with CKD. Methods: CKD-REIN is a prospective cohort of CKD outpatients (not on dialysis). Baseline iMg and tMg serum concentrations were respectively centrally measured using the NOVA BIOMEDICAL Stat Profile PRIME ES and with Atellica® CH SIEMENS analyzers. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) for first MACE (CV death, myocardial infarction, stroke or hospitalization for heart failure). Results: Of the 2419 included patients (median [IQR] age: 68[60-76]; mean (SD) eGFR 33.5(13.5) mL/min/1.73 m2), 52% had a history of CV disease. Correlation between iMg and tMg was very high (r=0.88; p<0.001). Over a median follow-up of 4.4 years [IQR,2.3-5.0], 351 experienced a first MACE event, leading to an incidence rate [95%CI] of 3.9[3.5;4.3] per 100 person-years (figure). After multiple adjustments, patients in Tertile 3 (T3) of iMg had a higher risk of MACE compared to patients in Tertile 1 (T1), HR [95% CI], 1.39[1.05;1.83]. No difference was noted for patients in Tertile 2 (T2) compared to patients in T1. Regarding tMg, patients in T3 of total Mg had a higher risk of MACE compared to patients in T1 (HR=1.40[1.07;1.83]). A nonsignificant lower risk of MACE was noted for patients in T2 compared to patients in T1, revealing a potential U shape relation between MACE risk and tMg level. Conclusions: This study suggests that high serum iMg and tMg levels are associated to cardiovascular outcomes in patients with moderate to advanced CKD. Further research is needed to explore the shape of the relationships and the mechanisms. Funding: Government Support - Non-U.S.Figure:: Adjusted HRs for major adverse cardiovascular events, according to the baseline serum magnesium levels.

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