Magnesium plays a critical role in myocardial function and cardiac rhythm regulation. Patients with heart failure (HF) are prone to magnesium deficiency. Although clinical laboratories commonly define normal serum magnesium levels as 1.6-2.6 mg/dL, some experts have proposed narrower optimal ranges. A large cohort analysis published in the American Journal of Medicine evaluated the association between ambulatory serum magnesium concentrations and one-year mortality in patients with HF.

The study included 627,349 United States Veterans with HF who had ambulatory serum magnesium measurements between 2001 and 2023. Participants were categorized into five groups according to ambulatory serum magnesium levels: <1.6 mg/dL (6%), 1.6-1.7 mg/dL (11%), 1.8-2.0 mg/dL (39%), 2.1–2.3 mg/dL (34%), and >2.3 mg/dL (10%). Multivariable Cox regression models estimated hazard ratios (HRs) for one-year mortality, and restricted cubic spline analysis evaluated nonlinear associations. Restricted cubic spline models used the lower limits of the current clinical range (1.6 mg/dL) and the MaGNet-recommended range (2.1 mg/dL) as reference values.

All-cause mortality rates were 15.4%, 13.3%, 11.6%, 11.5%, and 16.2% across the respective magnesium categories. Compared with the reference group of 2.1–2.3 mg/dL, adjusted HRs for mortality were 1.36 (95% CI 1.32-1.41) for <1.6 mg/dL, 1.23 (95% CI 1.20-1.26) for 1.6–1.7 mg/dL, 1.07 (95% CI 1.05-1.09) for 1.8–2.0 mg/dL, and 1.23 (95% CI 1.20–1.26) for >2.3 mg/dL. Restricted cubic spline analysis demonstrated a U-shaped relationship between serum magnesium and mortality risk, with the lowest risk observed between 1.6 and 2.5 mg/dL.

Serum magnesium levels showed a nonlinear association with mortality in patients with HF. Both lower and higher magnesium levels were associated with higher mortality compared with mid-range concentrations, with the lowest risk observed within the current clinical range of normal values.