Magnesium deficiency drives higher mortality in hyperlipidemia

By Dr. Priyom Bose, Ph.D.Reviewed by Lauren HardakerAug 6 2025

Researchers have uncovered a simple magnesium-based score that could help identify which high-cholesterol patients are most likely to face deadly heart problems, years before symptoms appear.

Study: Association of magnesium depletion score with all-cause and cardiovascular mortality in hyperlipidemia adults: a large nationwide population-based study. Image credit: Carey monticello/Shutterstock.com

Scientists have introduced the magnesium depletion score (MgDS) as a potential biomarker to determine mortality risk in patients with hyperlipidemia. A recent study in the Journal of Health, Population, and Nutrition investigated the potential MgDS in predicting the long-term outcomes in hyperlipidemic patients.

Uncontrolled hyperlipidemia and treatments

Hyperlipidemia is a condition where an individual accumulates abnormally high levels of lipids or lipoproteins, such as triglycerides, fats, cholesterol, and phospholipids, in the blood. Multiple studies have indicated that uncontrolled hyperlipidemia increases the risk of heart attacks and strokes.

Approximately 38% of US adults were found to have elevated cholesterol levels, which contributes to the increased prevalence of cardiovascular disease (CVD). Despite the ability of statins to reduce blood lipid levels, early detection of patients at higher risk of hyperlipidemia would help clinicians implement targeted and precise interventions.

Dietary trace metals, such as magnesium, are protective in managing hyperlipidemia. A randomized trial indicated that 300 mg of Magnesium sulfate (MgSO4) supplement daily for six months could significantly reduce oxidized low-density lipoprotein (ox-LDL) and low-density lipoprotein cholesterol (LDL-C) levels in participants diagnosed with moderate coronary artery disease (CAD).  

An increased magnesium intake has been associated with a lower prevalence of hyperlipidemia. Despite the clinical significance, many American adults do not consume enough magnesium. A prolonged insufficient magnesium intake may lead to chronic or subclinical magnesium deficiency.

Magnesium deficiency often goes undetected due to the absence of noticeable symptoms and a lack of standardized tests for accurate assessment. Previous studies have demonstrated the accuracy of MgDS, which is measured considering four key factors: kidney function decline, current diuretic use, proton pump inhibitors (PPIs), and alcohol consumption. To date, there is a lack of research regarding the association between MgDS and prognosis in hyperlipidemic populations.

About the study

The current observational study examined the relationship between MgDS and prognosis in hyperlipidemic populations using data from the National Health and Nutrition Examination Survey (NHANES), from 1999 to 2018, with follow-up until December 2019. NHANES provides comprehensive nationwide data on the health and nutritional status of the U.S. population.

A total of 12,592 adults with hyperlipidemia were selected from the NHANES database. Participants were classified as having hyperlipidemia if they presented with one of the following laboratory-based criteria of total triglyceride (TG) above 150 mg/dL, total cholesterol (TC) over 200 mg/dL, high-density lipoprotein cholesterol (HDL-C) below 40 mg/dL for men or below 50 mg/dL for women, and LDL-C over 130 mg/dL. In addition, individuals using cholesterol-lowering medications were also classified as having hyperlipidemia. The current study categorized MgDS into three groups: Low (0–1), Medium (2), and High (3–5).

Study findings

The study cohort included 51.03% females with a weighted mean age of 50.28 years. Throughout the median follow-up period of 118 months, 2160 deaths occurred, including 593 from CVDs.

A total of 9,331 participants were classified into the Low MgDS, 2,192 in the Medium MgDS group, and 1,069 in the High MgDS group. At baseline, significant differences in participants' characteristics were observed in the three MgDS groups. For instance, the high MgDS group consisted of approximately 59.11% females, most of whom were older (68.24 years), with a high body mass index (BMI), elevated HbA1c levels, lower albumin levels, lower family poverty income ratio (PIR), and increased serum creatinine levels. This group exhibited the highest proportions of CVD incidence, diabetes, use of lipid-lowering drugs, hypertension, and low educational attainment. Participants with low MgDS had the highest proportion of males and non-smokers and the lowest incidence of CVD.

The weighted Cox proportional hazards models determined the relationship between MgDS and all-cause and CVD mortality. The models revealed an increase in the risk of all-cause and CVD deaths by 1.50 and 2.21 times, respectively, in participants with high MgDS compared to those in the low MgDS group. When MgDS was treated as a continuous variable, each one-unit increase in MgDS was associated with a 1.18-fold higher risk of all-cause mortality and a 1.36-fold higher risk of CVD mortality after full adjustment.

Stratified analyses corroborated a consistent and robust link between increased MgDS and higher risk of all-cause and CVD mortality across most subgroups. The current study identified smoking status, pre-diabetes, and alcohol use as significant modifiers of the relationship between MgDS and all-cause mortality. However, only pre-diabetes significantly altered the association between MgDS and CVD mortality.

Interestingly, the hazard ratio (HR) gradually increased with MgDS levels between 0 and 1, following a sharp rise at MgDS  3. However, HR slightly decreased for CVD mortality at MgDS between 0 and 1, which escalated between MgDS levels of 2 and 3. Restricted cubic spline (RCS) analysis indicated that these patterns were consistent with a largely linear association, with no statistically significant non-linearity detected.

Kaplan–Meier curves demonstrated the lowest survival probability for people with high MgDS. Individuals with medium MgDS exhibited an intermediate survival probability, while those with low MgDS had the highest survival probability. Receiver operating characteristic (ROC) analysis showed that MgDS could independently predict 1-, 3-, and 5-year mortality, with area under the curve (AUC) values up to 0.81 for CVD mortality.

Sensitivity analyses, such as excluding early deaths within two years, adjusting for dietary magnesium intake, and treating MgDS as both categorical and continuous, did not materially change the results, supporting the robustness of the findings.

Conclusions

The current study highlighted the potential of MgDS as an independent predictor for mortality risk in patients with hyperlipidemia. In comparison to low MgDS levels, people with higher MgDS levels were found to be at increased risk of all-cause and cardiovascular mortality.

The authors emphasize that MgDS should be viewed as a risk stratification tool rather than a proven intervention target. Whether correcting magnesium deficiency in high-risk hyperlipidemic individuals can reduce mortality beyond established lipid-lowering and lifestyle interventions remains to be determined. If validated in future trials, the authors propose using the MgDS system to manage hyperlipidemia and reduce mortality rates.

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