Association Between Subclinical Magnesium Deficiency and Major Cardiovascular Events in Adults: A Meta-Analysis

Abstract

Background: Magnesium is a crucial mineral involved in cardiovascular regulation, yet subclinical deficiency remains highly prevalent. Although prior observational studies suggest an association between hypomagnesemia and cardiovascular outcomes, evidence remains inconsistent regarding risk thresholds and mediating pathways. This meta-analysis aimed to evaluate the association between subclinical magnesium deficiency and major cardiovascular events in adults. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception until June 2024 in accordance with PRISMA guidelines. Eligible studies included prospective cohort designs assessing baseline serum magnesium concentrations and subsequent cardiovascular outcomes in adults (≥18 years) with a minimum follow-up of five years. Data extraction and quality assessment were independently performed using the Newcastle–Ottawa Scale. Random-effects models estimated pooled hazard ratios (HRs) with 95% confidence intervals (Cis). Subgroup analyses were conducted by exposure threshold (<0.70 vs. ≤0.80 mmol/L), adjustment for hypertension/diabetes, and follow-up duration. Results: This meta-analysis included three prospective cohorts with 37,733 participants and follow-ups of 8.7–28.6 years. Low serum magnesium consistently correlated with elevated cardiovascular risk. In the Rotterdam Study, magnesium ≤0.80 mmol/L increased coronary heart disease mortality by 36% (HR 1.36, 95% CI 1.09–1.69) and sudden cardiac death by 54% (HR 1.54, 95% CI 1.12–2.11). NHANES I Follow-up showed magnesium <0.70 mmol/L doubled stroke mortality risk (HR 2.55, 95% CI 1.18–5.48). The ARIC study linked higher magnesium to reduced ischemic stroke risk (HR 0.70, 95% CI 0.56–0.88). Conclusion: Subclinical hypomagnesemia independently predicts major cardiovascular events, highlighting its clinical importance.