Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease

doi:10.1067/mhj.2000.107553

American Heart Journal

Volume 140, Issue 2, August 2000, Pages 212-218

https://doi.org/10.1067/mhj.2000.107553 Get rights and content

Abstract

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. (Am Heart J 2000;140:212-8.)

Section snippets

Study population

Patients were recruited from a supervised cardiac exercise and rehabilitation program at Cedars-Sinai Medical Center. Inclusion criteria included men and women >20 years of age, with CAD documented by prior myocardial infarction, coronary artery bypass grafting operation, or coronary angiography or angioplasty. Exclusion criteria included unstable angina, congestive heart failure New York Heart Association class >IV, chronic diarrhea, kidney failure (serum creatinine >3 mg/dL), acute myocardial

Results

Our study population comprised 42 stable coronary patients (37 men and 5 women), with a mean age of 68 ± 9 years (range 48 to 83 years). All patients had stable CAD as evidenced by a previous myocardial infarction (n = 23), coronary artery bypass grafting (n = 26), or coronary angioplasty (n = 23).

Platelet-dependent thrombosis was significantly correlated inversely with intracellular magnesium level (r = –0.39, P =.01) and positively with resting systolic blood pressure (r = 0.34, P =.03) and

Discussion

Our study demonstrated that platelet-dependent thrombosis is significantly increased in patients with stable CAD with low intracellular levels of magnesium.

Serum magnesium, like serum potassium, is often normal despite depletion of total body magnesium.¹³ Intracellular levels of magnesium are more accurate measures¹⁴; however, there is often poor correlation of intracellular red blood cell and intracellular mononuclear cell magnesium,¹⁵ and these may correlate poorly with the magnesium content

Acknowledgements

We thank Dr Edwin R. Alexander, Mia D. Molloy, Tony Stephen, Aalok Agarwala, and Care Felix for technical assistance.

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Dietary micronutrients are significantly associated with telomere length, as shown in multiple studies. However, no study has investigated the association between magnesium intake and telomere length in adults with hypertension.
Participants were included from the National Health and Nutrition Examination Survey (NHANES) in 1999–2000 and 2001–2002. Dietary magnesium intake was assessed using the 24 - hour recall method and the telomere length of leukocytes was measured using polymerase chain reaction (PCR). A multivariate regression model was then used to assess the association between dietary magnesium intake and telomere length in adults with hypertension.
Our final analysis included 2199 hypertensive adults (46.79% males) with a mean dietary magnesium intake of 254.82±133.47 mg/day. Linear regression, adjusted for race, sex, age, smoking, uric acid, and other variables, showed that every 1 mg increase in dietary magnesium intake was associated with a 0.20 (95% CI: 0.01, 0.39, p = 0.043) longer telomere length in all participants. In the ≥45 years age group, there was a statistically significant association between the telomere length and dietary magnesium (95% CI: 0.16, 0.63, p <0.001).
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Platelet compatibility of magnesium alloys
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Citation Excerpt :
As described earlier, Mg alloys decompose in wet conditions and elute Mg2 + ions. Further, it is known that Mg2 + ions alone suppress conformational changes of GPIIb/IIIa [25,27,28] as well as the degranulation of α-granule (P-selectin) [29,30]. Thus, the effect of Mg2 + ions alone on the activation of platelets was confirmed using the following test: platelet activation levels were estimated when platelets were activated by PET film under the presence of Mg2 + ions at a predetermined concentration in the PRP.
Lately, Mg alloys have been investigated as a new class of biomaterials owing to their excellent biodegradability and biocompatibility. It has previously been reported that the in vitro compatibility of a Mg alloy containing aluminum and zinc (AZ) alloy with the blood coagulation system is excellent due to Mg^2 + ions eluting from the alloy. In this study, the compatibility of the AZ alloy with platelets was evaluated by scanning electron microscopy (SEM) and flow cytometry. In the flow cytometry analysis, the platelets were stained using PAC-1 and P-selectin antibodies. SEM images and PAC-1 analyses showed no negative effects on the platelets, whereas P-selectin analysis showed marked platelet activation. To understand these contradictory results, the amount of β-thromboglobulin (β-TG) released from the platelets was investigated. From that investigation, it was concluded that platelets are markedly activated by the alloys. In addition to clarifying divergent results depending on the analysis method used, the effects of Mg^2 + ions and pH on platelet activation were studied. These results show that platelet activation is caused by an increase in pH at the alloy surface owing to the erosion of the alloy.
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Citation Excerpt :
Thus, it has been supposed that the measurement of circulating Mg might not reflect total body Mg stores. Accordingly, serial measurements or a measure of intracellular Mg, such as that contained in lymphocytes, erythrocytes or myocytes, may provide a more precise assessment of the true Mg status [19,22]. Conversely, other data suggest that Mg circulating concentration may represent an effective index of Mg status given that levels well correlate with ionized Mg and intracellular Mg [7,11].
Although magnesium (Mg) has recognized cardioprotective properties and hypomagnesemia is common in patients with acute myocardial infarction (AMI), data regarding the role of Mg as prognostic factor for adverse events are scarce, as well as there are conflicting results on the use of Mg as adjuvant therapy in AMI.
To evaluate the role of Mg as predictor for hard events (HE, all cause death, and nonfatal myocardial infarction) in AMI patients.
We studied 406 AMI patients (306 males, age: 67 ± 12 years, mean ± SD). Patient data were collected from the Institute electronic databank which saves demographic, clinical, instrumental, therapeutical and follow-up data of all patients admitted to our Coronary Unit.
During a mean follow-up period of 21 ± 18 months, the combined endpoint accounted for 63 HE, 44 (11%) deaths (35 cardiac deaths), 19 (5%) nonfatal MI.
The multiple regression model identified glycemia as the only independent determinant of Mg in AMI pts. (T value = − 2.8, standard coefficient = − 0.15, p < 0.01). The Kaplan–Meier survival estimates failed to show a significantly worst outcome in patients presenting low Mg (< 0.783 mmol/L, 25th percentile). Aging (> 67 years—50th percentile), and ejection fraction (< 40%) remained as prognostic factors for HE in the adjusted Cox multivariate proportional hazard model (HR = 2.8, 95% CI = 1.6–5, p < 0.001; HR = 3.2, 95% CI = 1.9–5.3 p < 0.001, respectively).
The present findings do not support a significant role of low Mg as predictor for HE in AMI.
Nutritional factors in the prevention and management of coronary artery disease and heart failure
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Magnesium ions are necessary for the cooperative binding of potassium ions to the cell membrane [13]. During magnesium deficiency, less potassium is bound, leading to increases in extracellular potassium concentration near the cell membrane, which results in depolarization and vasoconstriction, and enhanced platelet-dependent thrombosis [13,129,130]. Magnesium is also essential for the activity of Δ6desaturase (D6D) [13,131,132], which converts dietary LA to γ-linolenic acid (GLA).
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^☆: Supported by Blaine Pharmaceutics, Inc, Erlanger, Ky, and in part by Nutrition 21, San Diego, Calif, and the American Physicians Fellowship for Israel, New York, NY.

^☆☆: Reprint requests: Sanjay Kaul, MD, Cedars-Sinai Medical Center, Division of Cardiology, 8700 Beverly Blvd, Room 5314, Los Angeles, CA 90048. E-mail: [email protected]

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Acute Ischemic Heart DiseaseLow intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease☆,☆☆

Abstract

Section snippets

Study population

Results

Discussion

Acknowledgements

Am J Cardiol

Am J Cardiol

Am Heart J

J Pharmacol Methods

Am Heart J

Blood

Am J Cardiol

Thromb Res

Am Heart J

Am J Cardiol

Evidence that prostacyclin mediates the vascular action of magnesium in humans

Hypertension

Magnesium and platelet function: in vivo influence on aggregation and alpha-granule release in healthy volunteers

Magnes Bull

Effects of magnesium on platelet aggregation and adhesion: magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo

Thromb Haemost

Influence of arterial damage and wall shear rate on platelet formation: ex vivo study in a swine model

Arteriosclerosis

Cod-liver oil alters platelet-arterial wall response to injury in pigs

Circ Res

Oral verapamil inhibits platelet thrombus formation in humans

Circulation

Acute Ischemic Heart Disease
Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease☆,☆☆