Serum Magnesium and Outcomes in U.S. Veterans with Heart Failure

Magnesium is essential for myocardial function and rhythm. Although typically well-regulated, patients with heart failure are prone to magnesium deficiency. Most clinical laboratories define normal serum magnesium as 1.6-2.6 mg/dL, but this range may include chronic latent magnesium deficiency. The Magnesium Global Network (MaGNet) recommends 2.1-2.3 as optimal. We examined outcomes in heart failure patients across and outside these ranges.

Using ambulatory serum magnesium levels, we categorized 627,349 Veterans with heart failure (2001-2023) into <1.6 (6%), 1.6-1.7 (11%), 1.8-2.0 (39%), 2.1-2.3 (34%; reference) and >2.3 (10%) mg/dL. Cox models estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year mortality. Restricted cubic spline models assessed nonlinear associations between serum magnesium as a continuous variable, using two reference values: the lower limits of the current clinical reference range (1.6-2.6 mg/dL) and the MaGNet range (2.1-2.3 mg/dL).

All-cause mortality occurred in 15.4%, 13.3%, 11.6%, 11.5%, and 16.2% of the patients with serum magnesium <1.6, 1.6-1.7, 1.8-2.0, 2.1-2.3, and >2.3 respectively. Corresponding adjusted HRs (95% CIs) were 1.36 (1.32-1.41), 1.23 (1.20-1.26), 1.07 (1.05-1.09), 1.00 (reference), and 1.23 (1.20-1.26), respectively. When the lower limit of current clinical reference range (1.6-2.6 mg/dL) was used as the reference, restricted cubic spline analysis revealed a U-shaped association, with the lowest HR between 1.6 and 2.6 mg/dL, with significantly higher risks outside these ranges.

In US Veterans with heart failure, ambulatory serum magnesium levels showed an independent U-shaped association with one-year mortality, with the lowest risk observed between 1.6 and 2.6 mg/dL, consistent with the current clinical reference range, and higher risks at both lower and higher levels.