From desalination to deficiency: shifting magnesium-related mortality in heart failure patients
K Faierstein, L T Troyner, A K Kaplan, R R Raphael, V C Copeland, D H Hochstein, Y G Gerber, T H Hasin, M S Shechter, E M MaorAbstract
Introduction
Magnesium is essential for myocardial electrophysiology, vascular tone, and neurohormonal regulation, and hypomagnesemia has been linked to adverse outcomes in heart failure (HF). Widespread adoption of seawater desalination has markedly reduced magnesium content in drinking water, raising concerns about population-level magnesium depletion and potential cardiovascular consequences.
Methods
We conducted a retrospective cohort study of adult patients with HF enrolled in our registry between 2007 and 2025 who had available baseline serum magnesium measurements. Hypomagnesemia was defined as serum magnesium <1.7 mg/dL. The primary outcome was all-cause mortality. Cox proportional hazards models were used to assess associations between serum magnesium, analyzed both categorically and continuously, and mortality, with adjustment for demographic and clinical covariates. Pre-specified analyses were stratified by calendar period (before vs. after 2020); this cutoff was selected because national desalination capacity peaked in 2018, and a 2-year lag period was applied to account for potential delayed population-level effects on magnesium status. Interaction terms were used to evaluate temporal changes in risk estimates.
Results
The cohort included 17,161 patients (mean age 71±12.7 years; 62% male), of whom 9.4% had hypomagnesemia. Over follow-up, hypomagnesemia was independently associated with higher mortality (adjusted hazard ratio [HR] 1.22, 95% CI 1.14–1.30). Modeled continuously, each 0.1 mg/dL decrease in serum magnesium was associated with a 3.8% higher adjusted mortality risk. The strength of association increased significantly after 2020: hypomagnesemia conferred a 41% higher mortality risk (adjusted HR 1.41, 95% CI 1.21–1.64), compared with a 19% increase before 2020.
Conclusion
Hypomagnesemia is an independent predictor of mortality in HF, with a markedly stronger prognostic impact in recent years. These findings raise the possibility that environmental magnesium depletion, potentially related to desalinated drinking water, may amplify the clinical consequences of low magnesium. Enhanced surveillance of magnesium status and consideration of preventive strategies in vulnerable populations may therefore be warranted. Prospective studies are needed to confirm causality, elucidate mechanisms, and determine whether magnesium supplementation or water remineralization can mitigate risk, particularly among high-risk HF subgroups and regions reliant on desalinated water supplies.Magnesium trends and desalination rateAll-cause spline