Does Ionized Magnesium Offer a Different Perspective Exploring the Association between Magnesemia and Targeted Cardiovascular Risk Factors?

Abstract

Evidence of the association of magnesium (Mg) with arterial stiffness has so far been conflicting. The interplay between hypertension and elevated body mass index (BMI), with hypomagnesemia, instead, has been described in the literature in a more consistent way. Our study aims at revisiting the correlations between blood Mg levels and hemodynamic and body composition parameters in the general population, exploring the sensitivity profile of ionized Mg (Ion-Mg) compared to total Mg (Tot-Mg). We collected data from 755 subjects randomly chosen from a Swiss population previously described and stratified our sample into four equivalent classes according to ionized (whole blood) and total (serum) magnesium. After correcting for age, statistically significant differences emerged between: (i) Tot-Mg ≤ 0.70 and 0.81 ≤ Tot-Mg ≤ 0.90 for cf-PWV (p = 0.039); (ii) Tot-Mg ≤ 0.70 and Tot-Mg ≥ 0.91 for o-PWV (p = 0.046). We also found a statistically significant difference among groups of Ion-Mg values for the 24 h extremes of systolic blood pressure (p = 0.048) and among groups of Tot-Mg for BMI (p = 0.050). Females showed significantly lower levels of total magnesium (p = 0.035) and ionized magnesium (p < 0.001) than males. The overall agreement between magnesium analysis methods was 64% (95%CI: 60.8–67.7%). Our results confirm that Ion-Mg compared with Tot-Mg offers a different profile in detecting both correlations with hemodynamic and body composition parameters and dysmagnesemias. Lower levels of magnesium were associated with worse arterial aging parameters, larger 24 h blood pressure excursions, and higher BMI. Ion-Mg was superior in detecting the correlation with blood pressure only. Considering Ion-Mg as a more specific marker of the magnesium status, and the partially contradictory results of our explorative cross-sectional study, to avoid confounding factors and misinterpretations, ionized magnesium should be used as reference in future studies.

Dysmagnesemia Measured by Ionized and Total Body Concentrations Among Medically Hospitalized Patients: Incidence, Clinical Characteristics, and Health Outcomes - A Prospective Cohort Study

“…Regarding iMg, intervals of 0.53-0.67 mmol/L and 0.44-0.59 mmol/L have predominantly been utilized, while for tMg, ranges of 0.75-0.95 mmol/L, 0.70-1.00 mmol/L, and 0.70-1.10 mmol/L have commonly been used. (19) A strong positive correlation (Pearson's correlation) between iMg and tMg concentrations was found. The iMg samples were analyzed using fresh blood within 1 hour by trained research assistants in the medical ward, which may account for the observed positive correlation.…”

“…This is in concordance with the literature and supports the fact that hypomagnesemia measured by iMg is associated with unfavorable clinical outcomes, including mortality. (19,35) Besides that, the inverse correlation between serum albumin concentrations and iMg/tMg fraction can be explained by positing that individuals with lower albumin concentrations tend to have a higher proportion of their serum Mg in the ionized form. (37) This was described as "pseudohypomagnesemia" of tMg concentration as a result of hypoalbuminemia with normal serum iMg concentrations.…”

Ionized and total magnesium levels in patients with chronic kidney disease: associated factors and outcomes

“…In fact, the fraction of iMg is not usually measured and is difficult to calculate [ 13 , 14 ]. Recent studies of various non-CKD cohorts have evidenced a moderate correlation between tMg and iMg [ 15 , 16 ]. Given the variations and/or impairments in serum binding proteins observed in patients with CKD, one could expect to find the same moderate correlation in this population.…”

“…The association between magnesium levels and CV outcomes has not been frequently evaluated, and the few published data are conflicting [ 22 , 23 , 25 , 28 ]. Furthermore, most studies of the link between magnesium and patient outcomes have focused on tMg concentrations and not iMg, and some studies have reported that tMg and iMg are not related in the same way to the predicted clinical outcomes [ 15 , 16 ].…”

Arterial Stiffness—What Do We Know about It and What Do We Expect from This Biomarker?

“…Literature data suggested a correlation between serum magnesium levels in the upper part of the distribution and lower arterial stiffness parameters [ 5 ]. However, most recent findings suggest that ionized magnesium should be used as a more specific marker of the magnesium status indicating its association with arterial stiffness [ 6 ].…”