Title: Magnesium metabolism and cardiovascular abnormalities

 

Key words: magnesium, potassium, calcium, cations, neuromuscular, vasomotor, cardiovascular, CVD, deficiency, pathology, acute myocardial infarction, MI, tachycardia, VF, AF, torsades de point, digitalis sensitivity, infusions, cardioprotective, mortality, left ventricular failure, LVF, anti-arrhythmia, arrhythmia, hypertension, stroke, pre-eclampsia, eclampsia, antihypertensive, calcium ion channel blocker, ACE inhibitor, intracellular

 

Date: Oct 2006

 

Category:

 

Nutrimed Module:

 

Type: Article

 

Author: Morgan, G

 

Magnesium metabolism and cardiovascular abnormalities

Magnesium is the second most prevalent cation and with potassium forms the major intracellular ionic component of the body. It is closely associated with ATP, is involved in critical enzymatic reactions and has an important relationship with calcium, ionic balance between these two cations being necessary for normal function of the neuromuscular junction. In view of its neuromuscular effects it is not surprising that much research has been done looking at the effects of abnormal magnesium metabolism on vasomotor control and cardiovascular disease. In particular, it has been questioned whether prevalent suboptimal levels of this mineral might lead to corresponding pathology. Due to the multifactorial nature of cardiovascular disease it has proved difficult to isolate magnesium deficiency as a major factor and much of the evidence adduced has been equivocal (Fleet 2001).

 

Biomarkers of magnesium metabolism have not proved sensitive enough to elicit clear-cut data from controlled trials. The most suggestive and useful information has therefore come from intervention studies. Here three important areas of research will be mentioned.

 

Acute myocardial infarction

It is known that following acute myocardial infarction serum magnesium levels drop and this state is associated with tachycardia, VF, AF, torsades de point, digitalis sensitivity and an increased mortality rate. A direct causal relationship is difficult to establish but, on the understanding that IV magnesium infusions might be cardioprotective in such conditions, several trials have been conducted to assess the efficacy of this type of therapeutic intervention. One trial (LIMIT-2 1992) showed a mortality reduction of 24% at 28 days and 21% at 2.7 years. There was a significant reduction in LVF but no anti-arrhythmic effects were seen. A much larger controlled trial (ISIS-4 1995) was unable to replicate these results but has been criticised methodologically (Seelig 1996) as magnesium was only administered 8-12 hours after infarction rather than after the 3 hours of the LIMIT-2 trial. Absence of an anti-arrhythmic effect was confirmed in the MAGIC trial (1997) and is surprising in view of the known anti-arrhythmic effects of magnesium especially in patients with LVF (Douban 1996). The beneficial effects of some trials in reducing arrhythmias (for example Seelig 1996) may be related to coincidental LVF.

 

Hypertension and stroke

The multifactorial nature of cardiovascular disease is well illustrated in trials to determine the effects of magnesium on hypertension and stroke. Interactions between factors known to lower blood pressure have been shown to be synergistic in several surveys. The DASH trial (1999) for example showed magnesium, potassium and fibre intake to be inversely related to the incidence of hypertension and strokes. In a similar trial (Ascherio 1998) variable analysis showed that, independent of these other factors, low magnesium levels were associated with an increased risk. Obviously long-term prospective intervention trials are called for to determine the causal nature of magnesium in these conditions.

 

Pre-eclampsia and eclampsia

The antihypertensive effects of magnesium have been postulated as the operative mechanism leading to stabilisation of the eclamptic state and a reduction of the associated eclamptic convulsions. The Collaborative Eclampsia Trial (1995) concluded that its use was beneficial in eclampsia. This was in keeping with an earlier trial (Sibai 1990). Using lower doses of IV magnesium sulphate (1G/hr as opposed to 2-3G/hr in Sibaiís study) Coetzee et al (1998) were able to achieve an 11-fold reduction in eclamptic complications compared with controls and was able to treat severe pre-eclamptic patients without the risks associated with high dosage IV magnesium regimes.

 

Current opinion however is that magnesium should be reserved for the treatment of the eclamptic state alone (Redman 1988). Much evidence therefore exists to support the use of magnesium in these areas as a therapeutic agent. Its efficacy is probably related to its ability to act as a calcium ion channel blocker and in this respect it is interesting that certain hypotensive agents such as ACE inhibitors may owe their clinical effect due to their ability to increase intracellular magnesium levels (Seelig 1996).

 

 

References

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