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

Abstract 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/m2 [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.