Magnesium Depletion, Metabolic Impairment, and Cardiac Alterations: The NAKO-MRI Study with Mendelian Randomization

CONTEXT: Magnesium deficiency may contribute to subclinical cardiac changes, particularly metabolic diastolic cardiomyopathy. OBJECTIVE: To investigate the association between magnesium depletion, metabolic syndrome (MetS), and MRI-derived cardiac alterations in a population-based sample. METHODS: We cross-sectionally analyzed N = 9568 participants from the baseline examination of the German National Cohort (NAKO) who underwent whole-body MRI. Associations of serum magnesium and magnesium depletion score (MDS) with MetS and cardiac alterations were assessed using multivariable logistic and linear regression, respectively. Two-sample Mendelian Randomization was performed to evaluate the potential causal relationship between serum magnesium and MRI-derived cardiac parameters. RESULTS: Our analysis revealed no correlation between serum magnesium and MDS (Spearman’s rho = 0.065; p < 0.001). A 1-SD increase in serum magnesium was associated with lower MetS prevalence (OR 0.93 [95% CI: 0.88, 0.99]) and reduced left and right ventricular systolic and diastolic volumes. Higher MDS, indicating magnesium deficiency, was linked to increased MetS prevalence (OR per 1-unit 1.32 [95% CI: 1.23, 1.41]) and its individual components. Furthermore, higher MDS was associated with increased LVRI (Estimate 0.012 g/mL [95% CI: 0.008, 0.017]) and decreased left ventricular end-diastolic volume (Estimate -1.132 mL/m(2) [95% CI: -1.538, -0.727]), indicating concentric hypertrophy. Two-sample Mendelian Randomization suggested no causal relationship between serum magnesium and MRI-derived cardiac markers. CONCLUSION: Magnesium depletion may serve as an early indicator of cardiac impairment. However, Mendelian Randomization results do not support a causal role of serum magnesium on cardiac structure and morphology.