French edition (Le magnesium en pratique cliniques. Published
in 1985 by J. B. Baillière, Editions Médicales
Internationales, 62 rue des Mathurins, 75008 Paris, France
First English language edition published in 1988 by
John Libbey & Company Ltd, 80/84 Bondway, London SW8 1SF, England (01) 582 5266
John Libbey Eurotest Ltd, 6 rue Blanche, 92120 Montrouge, France (1) 47 35 85 52
Excerpt. Pages 103-106.
1. OTHER MANIFESTATIONS OF PRIMARY MAGNESIUM DEFICIT
Idiopathic mitral valve prolapse represents currently the most widespread cardiologic expression of MDI (frequency: 5% of the population). We have already properly described it by including it among the neuromuscular forms of MDI since it appears as a progressive outcome of their tetanic form (frequency: 15% of the population) which it complicates in one out of three cases. Tetany and prolapse share the same prevalence in women and the same nonspecific symptomatology, running from latency to clinical expression with varying degrees of the same neuromuscular hyperexcitability, whether the tetany is accompanied or not by mitral dyskinesia. Thus these factors have been included in previous descriptions of latent tetany: spasmophilia, hyperventilation syndrome and various other nosologic pictures that are today identified with mitral valve prolapse, such as Da Costa’s syndrome or irritable heart, effort syndrome, soldier’s heart, hyperkinetic syndrome and especially neuro-circulatory asthenia (2, 363, 365, 394, 399, 401a, 533, 657, 1135, 1176, 1386).
Five percent of idiopathic mitral valve prolapse cases progress toward severe complications. Some of these are related to the mitral valve dyskinesia itself. They are either mechanical — and these particular forms of LT due to MDI appear thus to be the most frequent cause of an isolated mitral valve insufficiency — or bacterial which gives rise to the added problem of subacute endocarditis. But the other complications, arrhythmias (1136) that are most often ventricular and especially lengthening of the corrected QT interval (782), sudden deaths, ischemic arterial attacks in the eye or the brain cannot reasonably be explained by the functional mitral valve problem. They are consistent, however, with the theories according to which MD is one of the cardiovascular risk factors (28, 29, 32, 33, 323, 324, 346, 359, 401a, 402, 676, 832, 833, 835, 836, 1165, 1311).
Both epidemiologic and experimental studies lead one to attribute a role to primary magnesium deficit among cardiovascular risk factors.
This notion develops first of all out of epidemiologic research on the role of drinking water in protecting the cardiovascular apparatus. Initial epidemiologic research had concluded that there is an inverse correlation between the hardness of drinking water and cardiovascular mortality — whether it is a question of the adult or the infant. Drinking hard water appeared to diminish cardiovascular risk while in contrast drinking soft water seemed to increase it. However, if this rule seems to hold for nearly two thirds of the cases, in the other third consuming hard water shows no inverse correlation with cardiovascular pathology. The two principal elements that determine the hardness of water are the levels of calcium and of magnesium. Ca and Mg levels in water are found in ratios that are quite variable, the levels of Mg participating as a criterion of hardness in proportions that vary from ten to ninety percent. Hard water that has no protective cardiovascular effect is also the kind that has no more Mg than soft water that is harmful to the heart. Of all the constituents in water, Mg is the one that presents the strongest inverse correlation with cardiovascular mortality. This observation is even more significant in that the amounts of magnesium in water and cardiovascular pathology also show an inverse relationship with the levels of Mg in the myocardium (42, 214, 402, 832, 835, 836).2.412 Harmful cardiovascular effects of experimental magnesium deficit
MD is capable of inducing harmful myocardial and vascular effects, of acting on P/Ca and Na/K metabolism, on lipid, protein and carbohydrate equilibrium, on the functions of platelets and erythrocytes, on hemostasis, on immune factors and on vasomotor activity. It can also increase the effects of cardiovasopathogenic pollutants, thus favoring in a number of ways the development of atherosclerosis, vascular spasms and vascular ischemia (29, 33, 323, 324, 336, 346, 359, 397, 402, 676, 832, 833, 835, 836, 1057, 1165).2.413 The contribution of Mg in drinking water to magnesium intake
The contribution of Mg in drinking water to magnesium intake has both quantitative and qualitative significance.
Since dietary intake of magnesium in developed countries is marginal, the quantity of Mg present in water can, depending on its level, represent the “critical factor” that brings the level of dietary intake from deficiency to an adequate level (832, 833, 834, 835). Potable water provides Mg directly when drunk and it also influences magnesium intake through the amounts in water used for cooking. A food loses much less of its magnesium value when cooked in water high in Mg. One should especially avoid using artificially softened hot water to cook foods in order to gain time (272, 391, 402, 560, 848, 849).2.413 2 Qualitative importance
In the diet, Mg in water has a high level of bioavailability. Experimental work in severely deficient mice shows that an intake of 30 mg/L, i.e., a level available in drinking water from various distribution systems, is sufficient to protect against death (1311). In humans, Mg in drinking water is more rapidly and more highly absorbed than the rest of dietary Mg (132, 778). Its presence in the diet thus appears to be of particular importance. It seems to be necessary, even in the absence of magnesium deficiency. An insufficient level of Mg in drinking water leads in the rat and in humans to the observation — all other data being equal — of a significant arterial hypertension with satellite nervous, endocrine and ion disorders (954). These problems could derive from continued changes in the demands made on the neuro-endocrine regulatory mechanisms of magnesium homeostasis due to a deficient intake of highly bioavailable Mg (361, 398, 401).2.414 MD and cardiovascular disease
With the exception of idiopathic mitral valve prolapse, of the form of MDI that causes phlebothrombosis and of the rare forms of cardiomegaly due to magnesium-dependent hypocalcemia, there exists a large gap between the information provided by epidemiology and experimental research and the clinical proof of a common cardiovascular pathology directly due to MDI. One describes for example “idiopathic” problems of cardiac rhythm that can be cured with magnesium, but their magnesium dependence has in general been established only with the positive effects of parenteral magnesium therapy (405, 633, 1287) which may only be pharmacodynamic. In contrast, the verification in a double blind study of preventive effects obtained by oral magnesium therapy for arrhythmias observed during open heart surgery appear much more convincing. The administration of Mg shows its effects in a significant shortening of the corrected QT interval (712). The existence of arrhythmia due to magnesium deficit appears thus to be established, but only during the course of this secondary magnesium deficit.
MD can only be found occasionally in coronary disease (4, 49, 50). It can only be found during advanced forms and thus seems to be a secondary problem with a physiopathology characteristic of forms with hyperaldosteronism due to left heart failure, with urinary magnesium wasting due to salt diuretics (826) or with the release of catecholamines due to the stress of the infarction (404, 463, 464). Moreover, magnesium deficiency in vivo only rarely leads to coronary lesions (29, 784). It appears rather to be a factor that favors spasms in the coronary arteries (29, 200, 1402).
Hypertension is not normally involved in the hemodynamic problems of experimental magnesium deficiency (641, 1090). To cause hypertension, experimental MD must be induced in subjects with a particular background (31, 125). It may be the same with humans. We have seen that two forms of hypertension, labile hypertension and hypercalcemic hypertension with elevated renin levels may both be forms of MDI, although here again the proof is not certain.
Similar reservations, all the more logical in that cerebral ischemic attacks are themselves correlated with hypertension, must also be expressed about the role of MD in ischemic arterial attacks (33, 323, 324, 346, 359, 402). The occurrence of transient cerebral ischemic accidents seems in any case to be favored by the two major forms of MDI, mitral valve prolapse (207 399) and latent tetany (447).
It is to be desired that clinical studies, justified by such remarkable experimental and epidemiologic research, be systematically undertaken to determine the place of MDI among cardiovascular risk factors. It certainly deserves such a place, but new studies are required to establish where it ranks in importance among these factors.
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