The American journal of medicine · 2026
Serum Magnesium and Outcomes in U.S. Veterans with Heart Failure.
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Yin Ying, Morgan Charity J, Costello Rebecca B, Fonarow Gregg C, Cheng Yan, Tekle Senait, Faselis Charles, Lam Phillip H, Sheriff Helen M, Rosanoff Andrea, Anker Stefan D, Raman Venkatesh K, Moore Hans J, Vargas Jose D, Patel Samir S, Sen Sabyasachi, Liu Simin, Zullo Andrew, Heidenreich Paul A, Gottlieb Stephen S, Deedwania Prakash, Wu Wen-Chih, Zeng-Treitler Qing, Ahmed Ali
Аннотация
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.