We found no association between serum magnesium levels and the subsequent development of hypertension, CVD, or all-cause mortality. The validity of these findings is supported by the use of a large, well-characterized epidemiologic cohort, routine adjudication for incident hypertension and CVD, a large number of events, and standardized assessment of serum magnesium.
Our findings are in contrast to those of prior studies that have related magnesium status to cardiovascular outcomes.22-27, 30, 42-45
Many of these studies were based on dietary measures, which may be influenced by residual confounding or recall bias. Individuals who report reduced magnesium intake may have other comorbidities that predispose them to hypertension and CVD. Also, diets rich in magnesium may contain other nutrients that influence the development of CVD or CVD risk factors, only some of which can be accounted for in observational studies.
Only a few studies have examined the relationship between serum magnesium and CVD events. An analysis from the Atherosclerosis Risk in Communities (ARIC) cohort showed a significant association between serum magnesium and coronary heart disease in women but not men.30
Although the ARIC sample was large, the follow-up period was relatively short (4 to 7 years), raising the possibility that early findings with serum magnesium could be attenuated over time. In the National Health and Nutritional Examination Survey Epidemiologic Follow-up Study (NHEFS), there was no significant association between serum magnesium and incidence of CVD, although serum magnesium was inversely associated with all-cause mortality and mortality from ischemic heart disease.29
Serum magnesium was also found to be associated with cardiovascular and all-cause mortality in a group of middle-aged men in the Paris Prospective Study 2.28
In the NHEFS and Paris Prospective 2 studies, categorization of death was based upon death certificates and ICD-9 codes, with their attendant limitations.41
The lack of association between baseline concentrations of serum magnesium and incident hypertension is consistent with results from ARIC Study.33
Although there are experimental data to support a role for magnesium in the pathogenesis of hypertension,4
our findings indicate that hypomagnesemia does not predict the development of hypertension, at least not at concentrations normally seen in human subjects.
Several limitations of our investigation deserve comment. Magnesium is predominantly an intracellular cation. Thus, serum magnesium levels may not fully reflect total body magnesium stores.37
However, serum magnesium concentration correlates well with intracellular magnesium and is also the laboratory measurement that is most commonly used in clinical practice. Due to the limited number of study participants with very high or low serum magnesium, it is impossible to draw conclusions about the risk associated with a serum magnesium that is far outside the normal range. However, the lack of such individuals in this sample reflects the characteristics of the general population. This study consists of middle-aged, ambulatory individuals. We cannot exclude the possibility that serum magnesium levels may be linked to hypertension or CVD in other populations, including those with a higher prevalence of magnesium deficiency. Dietary information was not available at this examination, so it was not possible to correlate dietary intake with serum magnesium. Single, as opposed to serial or continuous, blood pressure measurements were obtained as part of this study. Lastly, serum magnesium was only measured once, which does not account for natural variation that may occur in magnesium concentration over time.
Magnesium deficiency is now relatively common, especially among certain populations.1-3
Studies of magnesium supplementation in humans have generally been restricted to individuals with known cardiac disease or hypertension, and have shown conflicting results.35, 46-50
Our findings do not support a link between low magnesium concentration and hypertension or CVD in patients with serum magnesium levels that fall close to or within the normal range of laboratory values. Accordingly, there does not appear to be a role for routine assessment of serum magnesium in identifying individuals at elevated risk of hypertension or CVD.