Magnesium deficiency index predicts mortality in patients with hyperlipidemia

Magnesium is an essential micronutrient involved in over 300 enzymatic reactions, including the regulation of lipid metabolism and vascular function. Magnesium deficiency is associated with the development of hyperlipidemia and an increased risk of cardiovascular disease (CVD). However, there are virtually no tools to assess clinical magnesium status and predict long-term outcomes in patients with elevated blood lipids. The study is published in the Journal of Health, Population and Nutrition.

How Scientists Invented MgDS

The researchers turned to the massive NHANES database, which has been collecting information on American health for decades. They identified more than 12,000 adults with elevated blood lipids and looked at four red flags for magnesium deficiency:

1. Taking medications that deplete magnesium (diuretics and proton pump inhibitors).
2. Impaired renal function (eGFR index).
3. Alcohol abuse.

Each of these factors was given a score, and the total score – the so-called MgDS – could range from 0 to 5.

Research methods

A retrospective cohort analysis was performed using data from 12,592 adult participants in NHANES (1999–2018) with diagnosed hyperlipidemia. The authors proposed and verified a “magnesium deficiency index” (MgDS) including four components: diuretic and proton pump inhibitor use, eGFR reduction, and alcohol abuse. The outcome variables were all-cause and CVD mortality, determined using the National Death Index until the end of 2019. Weighted Cox models, Kaplan–Meier curves, restricted cubic splines (RCS) analysis, and ROC curves were used to assess the predictive ability of MgDS.

Key Results

• MgDS distribution and baseline characteristics: participants were divided into low (0–1), medium (2), and high (3–5) MgDS. The high MgDS group was dominated by older women, with higher BMI and prevalence of diabetes and CVD (36.9%).
• Mortality: During a median follow-up of 118 months, 2,160 deaths (593 CVD) were recorded. After full adjustment, the risk of all-cause mortality in individuals with high MgDS was 1.50 times higher (HR 1.50; 95% CI 1.27–1.77), and the risk of CVD mortality was 2.21 times higher (HR 2.21; 95% CI 1.69–2.88) compared with the low MgDS group (p for trend < 0.001).
• Linear relationship: RCS analysis showed a predominantly linear increase in HR with increasing MgDS, especially at values above 3 points (p nonlinearity > 0.05).
• Subgroup analysis: prediabetes, smoking, and alcohol abuse strengthened the association between MgDS and mortality (p interaction < 0.05).
• Predictive ability: ROC curves demonstrated high AUC for MgDS in predicting 1-, 3-, and 5-year mortality: for 1-year CVD mortality, AUC 0.81 (95% CI 0.74–0.87).

Here are the key findings:

• People with high MgDS scores (3–5 points) were one and a half times more likely to die from any cause and twice as likely to die from heart and vascular problems than those with low MgDS scores (0–1 point).
• The risk increased almost linearly: each new point increased the probability of an unfavorable outcome.
• Those who had prediabetes, smoking or alcohol abuse in addition to magnesium deficiency were especially vulnerable.

Interpretation and clinical conclusions

The findings demonstrate that MgDS, a clinical index that is easy to calculate and implement, reliably reflects magnesium deficiency and is associated with increased mortality risk in patients with hyperlipidemia. Incorporation of MgDS into standardized risk assessment may:

1. To improve the accuracy of patient stratification and the timeliness of secondary prevention of CVD.
2. To help identify individuals requiring correction of magnesium status through dietary recommendations or supplements.
3. Encourage monitoring and control of factors included in MgDS (medication intake, renal function, alcohol consumption) as part of complex therapy of hyperlipidemia.

Why is this important for the doctor and the patient?

MgDS is a “quick test” based on already known data: no new blood or complicated equipment is needed. If a patient has a high MgDS, the doctor should consider:

• additional examination of magnesium status;
• adjusting medications and habits (reduce diuretics, reduce alcohol consumption);
• prescribing magnesium supplements and monitoring kidney function.

This approach allows for timely intervention and, possibly, the prevention of fatal cardiac events.

Authors' comments

• Chengxing Liu: "MgDS combines clinical parameters available to any physician and is superior to individual laboratory magnesium measurements in predictive value."
• Yuntao Feng: “Our index can become a low-cost tool for primary care clinics, allowing them to quickly identify high-risk patients and adapt treatment strategies.”
• Fan Ping: "Subgroup analysis confirmed that MgDS reflects vulnerability to adverse outcomes, especially in individuals with prediabetes and unfavorable lifestyle habits."