Authors: Rayyan Fahad H Altemani , Manaal Shakir , Ahmed Marwan A Alamrani , Naif khaled F alotaibi , Abdulsalam Muteb A Alanazi , Anwar Mohammad B. Alazmi , Khaled Abdulkarem M Alwesabi , Meshal Abdulaziz S Alanazi , Muhanad Alzahrani , Abdullah Altamimi ,

Abstract

Background: The magnesium depletion score (MDS) combines diuretic use, proton pump inhibitor use, heavy alcohol consumption, and reduced kidney function as an indirect indicator of systemic magnesium status. We evaluated the association between MDS and cardiovascular disease (CVD) mortality.

Methods: Following PRISMA 2020, four databases were searched from inception through March 2025. Fully adjusted hazard ratios (HRs) were synthesized with inverse-variance random-effects models. Analyses were stratified according to whether the reference category was MDS = 0 or MDS = 0–1.

Results: Nine observational reports based on U.S. National Health and Nutrition Examination Survey cohorts met the eligibility criteria; eight contributed to quantitative synthesis. Among five reports using MDS = 0 as the reference, pooled HRs were 1.37 (95% CI, 1.11–1.69) for MDS = 1, 1.64 (95% CI, 1.28–2.10) for MDS = 2, and 2.59 (95% CI, 1.97–3.41) for the highest MDS category, with I² = 0% for each analysis. Among three reports using MDS = 0–1 as the reference, pooled HRs were 1.24 (95% CI, 1.01–1.54; I² = 20%) for MDS = 2 and 1.84 (95% CI, 1.52–2.23; I² = 0%) for the highest category.

Conclusions: Higher MDS was associated with greater CVD mortality, but the observational design, overlapping NHANES populations, indirect exposure definition, and residual confounding limit causal and predictive
interpretation. Prospective external validation is required before MDS is adopted for clinical risk stratification.

Keywords: Cardiovascular mortality, magnesium depletion score, meta-analysis, NHANES, systematic review.