Higher Serum Magnesium Associated with Lower Risk of Cardiovascular Outcomes in Adults with Atrial Fibrillation

by | Apr 17, 2023 | 2023, Cardiovascular Health, Magnesium, Minerals

Written by Taylor Woosley, Staff Writer. Findings of this observational study using data from the ARIC Study of subjects with atrial fibrillation shows that as 1 SD (~0.21 mg/dL) increased in magnesium concentration, the risk of myocardial infarction decreased by 50% (HR 0.50, 95% CI 0.31, 0.80). 

magnesiumAt present, there are 92.1 million adults (>1 in 3) in the United States who have been diagnosed with cardiovascular disease, with a projection that by 2030 at least 44% of the adult population will have this diagnosis1. Atherosclerosis is the main risk factor for cardiovascular disease (CVD) and is initiated by endothelium activation and, followed by a cascade of events, triggers the vessel narrowing and activation of inflammatory pathways2. Multiple risk factors contributing to atherosclerosis include arterial hypertension, hypercholesterolemia, and diabetes3.

Magnesium (Mg) is the fourth most abundant mineral in the body and acts as a cofactor in hundreds of enzymatic reactions4. Magnesium is a natural calcium antagonist, and it potentiates the production of local vasodilator mediators and alters vascular responses to a variety of vasoactive substances5. Furthermore, Mg plays a key role in regulating mitochondrial function and research has found that Mg deficiency can lead to ATP depletion and overproduction of reactive oxygen species6.

Linzi et al. conducted a study using data from the ARIC Study to investigate how serum Mg is related to major adverse cardiac events (MACE), heart failure (HF), and all-cause mortality among patients with atrial fibrillation (AF). The ARIC Study is a community-based prospective cohort with the aim to investigate cardiovascular risk factors. In 1987-1989, approximately 4000 individuals aged 45-64 years in each field center were enrolled. In total, 15,792 participants completed the baseline examination. After the baseline examination (visit 1), subjects attended follow-up visits, occurring in 1990-1992 (visit 2), 1993-1995 (visit 3), 1996-1998 (visit 4), 2011-2013 (visit 5), 2016-2017 (visit 6), and 2018-2019 (visit 7).

During each visit, information on clinical and lifestyle variables was obtained. The current observational study included participants (n=413) with available serum Mg measurements (collected after an overnight fast) and diagnosis of AF at the time of examination in visit 5. Separate endpoints in the study were incident HF, myocardial infarction (MI), stroke, cardiovascular (CV) death, and all-cause mortality during follow-up. At visit 5, the following variables were measured as covariates: age, sex, race, study center, body mass index (BMI), smoking status, alcohol drinking status, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), diabetes history, and CVD history.

Serum Mg concentration was categorized based on approximate tertiles (1.2-1.9, 2.0, 2.1-2.7 mg/dL) and, separately, using the thresholds defining normal range (1.7 and 2.2 mg/dL). Follow-up time was days from visit 5 to any incident outcome, loss to follow-up, or 31 December 2019, whichever happened earlier. Over an average follow-up of 5.7 years, 79 HFs, 31 MIs, 24 strokes, 80 CV deaths, 110 MACEs, and 198 total deaths were identified in the study population. Significant findings of the study are as follows:

  • There tended to be a linear dose-response inverse association of serum Mg tertiles with incident MI, U-shape associations with incident stroke, CV death, MACE, and all-cause mortality, and an L-shape association with HF.
  • In the models adjusted for age, sex, race, and study center, participants in the second tertile of serum Mg had a lower risk of MI, MACE, and all-cause mortality than patients in the first tertile. The HRs (95% CIs) for MI, MACE, and all-cause mortality were 0.36 (0.14, 0.95), 0.48 (0.28, 0.83), and 0.62 (0.42, 0.92), respectively.
  • There was an inverse association comparing participants in the third tertile and the first tertile for incident MI in all models adjusted for covariates [HRs (95% CI): model 1 0.43 (0.10, 0.93), model 2 0.23 (0.08, 0.65), model 3 0.20 (0.07, 0.61)].

Results of the study suggest that higher serum Mg was associated with a lower risk of MI, HF, MACE, CV death, and all-cause mortality in subjects with atrial fibrillation. However, it showed a consistently significant association with incident MI after adjusting for other CV risk factors. Study limitations include the lack of generalizability of results based on the average age of participants being 78 years, the small number of CV events resulting in imprecise confidence intervals, and the limitation of causal inference between serum Mg and CV outcomes based on the observational study design.

Source: Li, Linzi, Pamela L. Lutsey, Lin Yee Chen, Elsayed Z. Soliman, Mary R. Rooney, and Alvaro Alonso. “Circulating Magnesium and Risk of Major Adverse Cardiac Events among Patients with Atrial Fibrillation in the ARIC Cohort.” Nutrients 15, no. 5 (2023): 1211.

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 

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Posted April 17, 2023.

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