1. Effects of Magnesium Supplementation in Hypertensive Patients
2. Effect on Blood Pressure of Potassium, Calcium, and Magnesium in Women With Low Habitual Intake
3. Oral magnesium supplementation in patients with essential hypertension
4. Combinations of Potassium, Calcium, and Magnesium Supplements in Hypertension
5. Glucose and insulin levels during diuretic therapy in hypertensive men
6. Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease
7. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients
8. Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study

1. Effects of Magnesium Supplementation in Hypertensive Patients
Assessment by Office, Home, and Ambulatory Blood Pressures
Yuhei Kawano; Hiroaki Matsuoka; Shuichi Takishita; ; Teruo Omae (Hypertension. 1998;32:260-265.) © 1998 American Heart Association, Inc.

Abstract: An increase in magnesium intake has been suggested to lower blood pressure (BP). However, the results of clinical studies are inconsistent. We studied the effects of magnesium supplementation on office, home, and ambulatory BPs in patients with essential hypertension. Sixty untreated or treated patients (34 men and 26 women, aged 33 to 74 years) with office BP >140/90 mm Hg were assigned to an 8-week magnesium supplementation period or an 8-week control period in a randomized crossover design. The subjects were given 20 mmol/d magnesium in the form of magnesium oxide during the intervention period. In the control period, office, home, and average 24-hour BPS (mean±SE) were 148.6±1.6/90.0±0.9, 136.4±1.3/86.8±0.9, and 133.7±1.3/81.0±0.8 mm Hg, respectively. All of these BPS were significantly lower in the magnesium supplementation period than in the control period, although the differences were small (office, 3.7±1.3/1.7±0.7 mm Hg; home, 2.0±0.8/1.4±0.6 mm Hg; 24-hour, 2.5±1.0/1.4±0.6 mm Hg). Serum concentration and urinary excretion of magnesium increased significantly with magnesium supplementation. Changes in 24-hour systolic and diastolic BPS were correlated negatively with baseline BP or changes in serum magnesium concentration. These results indicate that magnesium supplementation lowers BP in hypertensive subjects and this effect is greater in subjects with higher BP. Our study supports the usefulness of increasing magnesium intake as a lifestyle modification in the management of hypertension, although its antihypertensive effect may be small. [Get Complete Article]

2. Effect on Blood Pressure of Potassium, Calcium, and Magnesium in Women With Low Habitual Intake
Frank M. Sacks; Walter C. Willett; Angela Smith; Lisa E. Brown; Bernard Rosner; ; Thomas J. Moore (Hypertension. 1998;31:131-138.) © 1998 American Heart Association, Inc.

Abstract: In populations, dietary intakes of potassium, calcium, and magnesium each have been inversely associated with blood pressure. However, most clinical trials in normotensive populations have not found that dietary supplements of these minerals lowered blood pressure. We tested the hypothesis that normotensive persons who have low habitual intake of these minerals would be particularly responsive to supplementation. Three hundred normotensive women in the Nurses Health Study II (mean age, 39 years), whose reported intakes of potassium, calcium, and magnesium were between the 10th and 15th percentiles, received for 16 weeks' duration daily supplements of either potassium 40 mmol, calcium 30 mmol (1200 mg), magnesium 14 mmol (336 mg), all three minerals together or placebos. At baseline, mean (±SD) 24-hour ambulatory blood pressures were 116±8 and 73±6 mm Hg systolic and diastolic, respectively, and mean dietary intakes of potassium, calcium, and magnesium were 62±20 mmol/d, 638±265 mg/d, and 239±79 mg/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were significant for potassium, -2.0 (-3.7 to -0.3) and -1.7 (-3.0 to -0.4), but not for calcium, -0.6 (-2.2 to 1.0) and -0.7 (-2.0 to 0.6), or for magnesium, -0.9 (-2.6 to 0.8) and -0.7 (-2.2 to 0.8). The administration of calcium and magnesium with potassium did not enhance the effect of potassium alone; and the changes in blood pressure were not significant -1.3 (-3.0 to 0.4) and -0.9 (-2.2 to 0.4). In conclusion: Potassium, but not calcium or magnesium supplements, has a modest blood pressure–lowering effect in normotensive persons with low dietary intake. This study strengthens evidence for the importance of potassium for blood pressure regulation in the general population. [Get Complete Article]

3. Oral magnesium supplementation in patients with essential hypertension
T Motoyama, H Sano and H Fukuzaki (Hypertension, Vol 13, 227-232.) Copyright © 1989 by American Heart Association

Abstract: To elucidate the effects of magnesium on high blood pressure, a 4-week study of oral magnesium supplementation (MgO 1 g/day) was conducted in 21 outpatients with uncomplicated essential hypertension. During the study, blood pressure and intraerythrocyte sodium concentration decreased significantly, and the erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) and intraerythrocyte magnesium concentration both increased. Serum triglyceride and free fatty acid concentrations were reduced. Furthermore, the elevation in KOs significantly and positively correlated with both the increase in intraerythrocyte magnesium concentration and the decrease in mean blood pressure. There was a significant inverse correlation between the prestudy KOs and the decrease in mean blood pressure. In addition, when patients were divided according to their overall decrease in mean blood pressure, the prestudy intraerythrocyte sodium concentration was significantly higher in patients with a mean blood pressure decrease of more than 7 mm Hg than that of patients whose mean blood pressure decrease was less than 7 mm Hg. These results suggest that oral magnesium supplementation may lower blood pressure through the activation of a cell membrane sodium pump and may reduce serum lipid concentration. It also suggests that the lower the prestudy KOs or the higher the prestudy intraerythrocyte sodium concentration, the more effective the oral magnesium treatment is in lowering blood pressure. Therefore, we concluded that appropriate oral magnesium intake might be effective as a nonpharmacological treatment for essential hypertension. [Get Complete Article]

4. Combinations of Potassium, Calcium, and Magnesium Supplements in Hypertension
Frank M. Sacks; Lisa E. Brown; Lawrence Appel; Nemat O. Borhani; Denis Evans; Paul Whelton
(Hypertension. 1995;26:950-956.) © 1995 American Heart Association, Inc.

Abstract: Dietary intakes of potassium, calcium, and magnesium have each been reported to lower blood pressure, but the extent of blood pressure reduction in epidemiological studies and clinical trials has tended to be small and inconsistent. We hypothesized that combinations of these mineral supplements would lower blood pressure and that the reductions would be greater than that usually reported in studies of each cation alone. One hundred twenty-five patients (82 men and 43 women) with untreated mild or borderline hypertension were randomly assigned to daily treatment with one of the following four regimens: 60 mmol potassium and 25 mmol (1000 mg) calcium, 60 mmol potassium and 15 mmol (360 mg) magnesium, calcium and magnesium, or placebo. Standardized clinic blood pressure measurements were obtained on 3 days at baseline and after 3 and 6 months of treatment. At baseline, systolic and diastolic blood pressures (mean±SD) were 139±12 and 90±4 mm Hg, respectively, and dietary intakes of potassium, calcium, and magnesium were 77±32, 19±13, and 12±52 mmol/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were not significant: -0.7 (-4.3 to +2.9) and -0.4 (-2.9 to +2.1) for potassium and calcium, -1.3 (-4.4 to +1.8) and 0.4 (-2.5 to +3.3) for potassium and magnesium, and +2.1 (-1.8 to +6.0) and +2.2 (-1.0 to +5.4) for calcium and magnesium.
In conclusion: this trial provides little evidence of an important role of combinations of cation supplements in the treatment of mild or borderline hypertension. [Get Complete Article]

5. Glucose and insulin levels during diuretic therapy in hypertensive men
D Siegel, P Saliba and S Haffner (Hypertension, Vol 23, 688-694.) Copyright © 1994 by American Heart Association

Abstract: We investigated serum glucose and insulin levels resulting from thiazide or thiazide-like diuretic administration and determined whether they were associated with serum or intracellular potassium or magnesium values. We also explored the role of obesity both alone and with thiazides on serum insulin and glucose. Hypertensive men were withdrawn from diuretics and repleted with oral potassium and magnesium and then randomized to 2 months of treatment with (1) hydrochlorothiazide, (2) hydrochlorothiazide with oral potassium, (3) hydrochlorothiazide with oral potassium and magnesium (4) hydrochlorothiazide and triamterene, (5) chlorthalidone, or (6) placebo. Serum was available from 202 participants for insulin and glucose determinations. Mean fasting serum glucose and insulin did not change significantly after 2 months of randomized therapy with the exception of participants randomized to chlorthalidone, who had significant increases in both serum insulin and glucose (P < .05 and P < .01, respectively). As body mass index increased, there was a corresponding increase in serum insulin and to a lesser degree in serum glucose. Also, as body mass index increased, participants taking hydrochlorothiazide had a corresponding increase of serum insulin (P < .05). After treatment, intracellular potassium and magnesium were both associated with higher serum insulin (P < .001 for each), and serum potassium was associated with higher and serum magnesium with lower serum glucose (P < .01 for each). In most hypertensive men, treatment with 50 mg chlorthalidone increases glucose and insulin levels, whereas administration of 50 mg hydrochlorothiazide, with or without potassium and/or magnesium conserving strategies, does not. [Get Complete Article]

6. Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease
Michael Shechter, MD, MAa, C. Noel Bairey Merz, MDa, Robert K. Rude, MDc, Maura J. Paul Labrador, MPHa, Simcha R. Meisel, MDb, Prediman K. Shah, MDb, Sanjay Kaul, MDb
(American Heart Journal 2000; 140: 212-8.) Copyright © 2000 by Mosby, Inc.

Background: Although reduced intracellular levels of magnesium have been described in patients with acute myocardial infarction, its significance as a regulator of thrombosis remains unknown.
Methods and Results: To determine whether reduced intracellular levels of magnesium enhance platelet-dependent thrombosis, we evaluated 42 patients with coronary artery disease (CAD) by exposing porcine aortic media to their flowing unanticoagulated venous blood for 5 minutes by using an ex vivo perfusion (Badimon) chamber. Baseline analysis demonstrated significant associations between intracellular levels of magnesium, platelet-dependent thrombosis (P = .02), and platelet P-selectin (CD62P) expression (P < .05). Patients were divided into 2 groups: below (n = 22) and above (n = 20) the median intracellular levels of magnesium (1.12 µg/mg protein). There were no significant differences in age, body mass index, serum lipids, fibrinogen, platelet count, or serum magnesium levels between the two groups. Platelet-dependent thrombosis was significantly higher in patients with intracellular levels of magnesium below compared with above median (150 ± 128 vs 45 ± 28 µm2/mm, P < .004). Neither platelet aggregation nor CD62P expression was significantly different between the two groups.
Conclusions: Platelet-dependent thrombosis was significantly increased in patients with stable CAD with low intracellular levels of magnesium, suggesting a potential role for magnesium supplementation in CAD. [Get Complete Article]

7. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients.
Shechter M, Merz CN, Paul-Labrador M, Meisel SR, Rude RK, Molloy MD, Dwyer JH, Shah PK, Kaul S. (Magnes Res 2000 Dec;13(4):275-84.) Copyright © 2000 by PubMed.)

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. The aim of our study was to determine whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD). In a randomized prospective, double-blind, cross-over and placebo controlled study, 42 patients with stable CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800-1,200 mg/day) or placebo for 3 months (Phase 1) followed by a 4-week washout period, and the cross-over treatment for 3 months (Phase 2). PDT, platelet aggregation, platelet P-selectin flow-cytometry, monocyte tissue factor procoagulant activity (TF-PCA) and adhesion molecules density were assessed before and after each phase. PDT was evaluated by an ex-vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35 percent in patients who received magnesium versus placebo (D change from baseline: -24 vs. 26 microm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA or adhesion molecules. Oral magnesium treatment inhibits PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD. [Get Complete Article]

8. Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study
Fangzi Liao, MD, Aaron R. Folsom, MD, Frederick L. Brancati, MD.
(Am Heart J 1998;136:480-90.) Copyright © 1998 by Mosby, Inc.

Background: Hypomagnesemia has been hypothesized to play a role in coronary heart disease (CHD), but few prospective epidemiologic studies have been conducted.
Methods and Results: We examined the relation of serum and dietary magnesium with CHD incidence in a sample of middle-aged adults (n = 13,922 free of baseline CHD) from 4 US communities. Over 4 to 7 years of follow-up, 223 men and 96 women had CHD develop. After adjustment for sociodemographic characteristics, waist/hip ratio, smoking, alcohol consumption, sports participation, use of diuretics, fibrinogen, total and high-density lipoprotein cholesterol levels, triglyceride levels, and hormone replacement therapy, the relative risk of CHD across quartiles of serum magnesium was 1.00, 0.92, 0.48, and 0.44 (P for trend = 0.009) among women and 1.00, 1.32, 0.95, and 0.73 (P for trend = 0.07) among men. The adjusted relative risk of CHD for the highest versus the lowest quartile of dietary magnesium was 0.69 in men (95% confidence interval 0.45 to 1.05) and 1.32 in women (0.68 to 2.55).
Conclusions: These findings suggest that low magnesium concentration may contribute to the pathogenesis of coronary atherosclerosis or acute thrombosis. [Get Complete Article]

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