Higher Serum Magnesium Levels Research Articles

The relationship between serum magnesium levels and mortality in non-diabetic hemodialysis patients: A 10-year follow-up study.

Introduction Recently, although there are many reports showing that serum magnesium concentration is a predictor of mortality in dialysis patients, the observation periods of those reports were of short duration, typically around 12 months. Thus, we investigated this relationship over a longer follow-up period. Methods This retrospective, observational study included a total of 83 non-diabetic hemodialysis patients. The follow-up period was 120 months. Patients were divided into two groups, those with serum magnesium ≥2.5 mg/dL (Mg ≥2.5 mg/dL group) and serum magnesium <2.5 mg/dL (Mg <2.5 mg/dL group), and Kaplan-Meier analysis and Cox proportional hazards analysis were conducted. In addition to the above analysis, single and multiple regression analysis were performed at baseline to reveal the relationship between serum magnesium and clinical parameters. Findings During the follow-up period, 31 out of 83 patients died. Kaplan-Meier analysis showed a significantly higher incidence of death in the Mg <2.5 mg/dL group (log-rank test 4.951, P = 0.026). Multivariate Cox proportional hazards analysis showed a 62% decreased risk of mortality in the Mg ≥2.5 mg/dL group compared to the Mg <2.5 mg/dL group after adjustment for several confounding factors. Simple correlation coefficient analysis showed positive correlations of serum magnesium levels with serum creatinine, phosphorus, high-density lipoprotein, ankle-brachial index and KT/V, and a negative correlation with age. Multiple linear regression analysis showed that the ankle-brachial index was the only parameter that had a positive and significant correlation with the serum magnesium level. Conclusion Our study demonstrated that higher serum magnesium levels were associated with improved survival in non-diabetic hemodialysis patients.

Thiazide but not loop diuretics is associated with hypomagnesaemia in the general population.

Hypomagnesaemia has been associated with various adverse outcomes. Loop and thiazide diuretics promote urinary magnesium excretion. However, it is unknown if this links to hypomagnesaemia. We study if loop or thiazide diuretic use affects serum magnesium levels and if it associates with hypomagnesaemia. In addition, we study the effect of combining a potassium-sparing diuretic with a thiazide diuretic on the presence of hypomagnesaemia. The study performed a cross-sectional analysis within 9820 participants from the prospective Rotterdam Study. Hypomagnesaemia was defined as a serum magnesium level ≤0.72mmol/L. Participants were categorized by defined daily dose (DDD), and all analyses were adjusted for age, sex, BMI, eGFR, serum potassium levels, proton pump inhibitor use, and comorbidities. Loop diuretic use was associated with higher serum magnesium levels (<1 DDD: 0.004mmol/L 95% CI: -0.008; 0.017; 1 DDD: 0.023mmol/L 95% CI: 0.013; 0.032; >1 DDD: 0.043mmol/L 95% CI: 0.028; 0.057). Thiazide diuretic use was associated with lower serum magnesium levels (<1 DDD: -0.013mmol/L 95% CI: -0.023; -0.002; ≥1 DDD: -0.018mmol/L 95% CI: -0.028; -0.010), resulting in an increased odds ratio of hypomagnesaemia of 3.14 (95% CI: 1.67; 5.92) and 2.74 (95% CI: 1.57; 4.77), respectively. These effects were predominantly seen in participants using diuretics for more than 390days. Combining thiazide diuretics with a potassium-sparing agent was not associated with lower serum magnesium levels or hypomagnesaemia. Thiazide diuretic use is associated with lower serum magnesium levels and an increased risk of hypomagnesaemia. This increased risk is not seen in participants using a combination of thiazide diuretics with a potassium-sparing agent. The use of loop diuretics is not associated with an increased risk of hypomagnesaemia.

Magnesium in Hemodialysis Patients: A New Understanding of the Old Problem.

Despite the prognostic significance of mineral and bone disorders in patients undergoing hemodialysis, very few studies have focused on magnesium metabolism in this population. Nephrologists have paid much attention to hypermagnesemia, which is sometimes caused by magnesium administration, but the clinical implication of low magnesium has been largely overlooked. Recently, several cohort studies have reported that lower serum magnesium levels are associated with an increased risk of all-cause and cardiovascular mortality among hemodialysis patients. In addition to its beneficial effect on endothelium, magnesium has been shown to inhibit the progression of vascular calcification both in vitro and in vivo. Although the exact underlying mechanism is still uncertain, magnesium can suppress the maturation of calciprotein particles, a candidate culprit for vascular calcification, which is promoted by high phosphate. Thus, magnesium seems to be useful to alleviate the phosphate-induced calcification stress. Consistently, the risk of cardiovascular death associated with hyperphosphatemia is attenuated among hemodialysis patients with high serum magnesium levels, whereas this risk is exacerbated among those with low serum magnesium levels. In the context of the bone-vascular axis, magnesium may also be involved in the risk of fracture. It should be noted that, although total serum magnesium levels of hemodialysis patients are often above the reference range, the concentration of ionized magnesium, a biologically active form of magnesium, is largely normal or even low. A growing number of observational studies have uncovered the relationship between lower serum magnesium levels and poorer survival of hemodialysis patients. Magnesium modulates the pathogenesis of mineral and bone disorders and might provide a novel therapeutic approach for vascular calcification. Key Messages: Future intervention studies should clarify whether magnesium supplementation and/or increasing dialysate magnesium concentration improves the prognosis of hemodialysis patients.

Serum magnesium is associated with the risk of dementia.

To determine if serum magnesium levels are associated with the risk of all-cause dementia and Alzheimer disease. Within the prospective population-based Rotterdam Study, we measured serum magnesium levels in 9,569 participants, free from dementia at baseline (1997-2008). Participants were subsequently followed up for incident dementia, determined according to the DSM-III-R criteria, until January 1, 2015. We used Cox proportional hazard regression models to associate quintiles of serum magnesium with incident all-cause dementia. We used the third quintile as a reference group and adjusted for age, sex, Rotterdam Study cohort, educational level, cardiovascular risk factors, kidney function, comorbidities, other electrolytes, and diuretic use. Our study population had a mean age of 64.9 years and 56.6% were women. During a median follow-up of 7.8 years, 823 participants were diagnosed with all-cause dementia. Both low serum magnesium levels (≤0.79 mmol/L) and high serum magnesium levels (≥0.90 mmol/L) were associated with an increased risk of dementia (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.02-1.69, and HR 1.30, 95% CI 1.02-1.67, respectively). Both low and high serum magnesium levels are associated with an increased risk of all-cause dementia. Our results warrant replication in other population-based studies.

Effects of Magnesium on the Phosphate Toxicity in Chronic Kidney Disease: Time for Intervention Studies.

Magnesium, an essential mineral for human health, plays a pivotal role in the cardiovascular system. Epidemiological studies in the general population have found an association between lower dietary magnesium intake and an elevated risk of cardiovascular events. In addition, magnesium supplementation was shown to improve blood pressure control, insulin sensitivity, and endothelial function. The relationship between magnesium and cardiovascular prognosis among patients with chronic kidney disease (CKD) has been increasingly investigated as it is becoming evident that magnesium can inhibit vascular calcification, a prominent risk of cardiovascular events, which commonly occurs in CKD patients. Cohort studies in patients receiving dialysis have shown a lower serum magnesium level as a significant risk for cardiovascular mortality. Interestingly, the cardiovascular mortality risk associated with hyperphosphatemia is alleviated among those with high serum magnesium levels, consistent with in vitro evidence that magnesium inhibits high-phosphate induced calcification of vascular smooth muscle cells. Furthermore, a harmful effect of high phosphate on the progression of CKD is also attenuated among those with high serum magnesium levels. The potential usefulness of magnesium as a remedy for phosphate toxicity should be further explored by future intervention studies.

Risk factors of cardiac rupture in patients with acute myocardial infarction

Objective: To analyze the risk factors of cardiac rupture in patients with acute myocardial infarction. Methods: Clinical data were analyzed from 10 284 acute myocardial infarction patients admitted to Beijing Anzhen Hospital from January 2012 to March 2015. Cardiac rupture occurred in 81 patients, including 67 patients of acute left ventricular free wall rupture and 14 patients of ventricular septal defect, were retrospectively analyzed. Binary logistics regression analysis was performed to analyze the risk factors of cardiac rupture. Results: Incidence of cardiac rupture was significantly higher in patients with ST-segment elevation myocardial infarction than in patients with non-ST-segment elevation myocardial infarction (1.5%(70/4 724) vs. 0.2%(11/5 560), P<0.01). Binary logistic regression analysis showed that age (OR=0.827, 95%CI 0.726-0.941, P<0.01), recurrent myocardial infarction during hospital(OR=0.001, 95%CI 0.000-0.418, P<0.05), systolic blood pressure(OR=1.114, 95%CI 1.029-1.206, P<0.01), left anterior descending artery lesion (OR=0.003, 95%CI 0.000-0.334, P<0.05), lower hemoglobin(OR=1.129, 95%CI 1.051-1.212, P<0.01), serum total protein (OR=1.453, 95%CI 1.070-1.971, P<0.05), and serum magnesium level (OR=0.000, 95%CI 0.000-0.001, P<0.01) were associated with cardiac rupture. Conclusion: Older age, recurrent myocardial infarction, lower systolic blood pressure, left anterior descending artery lesion, lower serum hemoglobin, lower serum total protein, and higher serum magnesium level are risk factors of cardiac rupture and these factors should be carefully managed to prevent the occurrence of cardiac rupture.

Serum magnesium and risk of new onset heart failure in men: the Kuopio Ischemic Heart Disease Study.

Serum magnesium is an essential intracellular cation involved in processes that regulate cardiovascular function and has been linked to the risk of several cardiovascular disease outcomes. We aimed to investigate the association of serum magnesium concentrations with risk of incident heart failure (HF). We studied 2181 middle-aged men without prevalent HF (aged 42-61years) enrolled in the finnish Kuopio Ischemic Heart Disease prospective cohort study with serum magnesium measurements made at baseline. Hazard ratios (95% confidence intervals [CI]) for HF were assessed. During a median follow-up of 24.8years, 278 HF events occurred. Baseline serum magnesium was weakly and inversely associated with several clinical markers and was continuously associated with risk of HF. The age-adjusted HR (95% CIs) for HF per 1 standard deviation (SD) higher serum magnesium levels was 0.86 (0.76-0.97). The HR (95% CIs) was 0.87 (0.76-0.98) after controlling for measures of adiposity, socio-economic variables, medical history, blood pressure, renal function, alcohol consumption, and lipids. These findings remained consistent in analyses accounting for incident coronary heart disease. The results were comparable across several clinically relevant subgroups and analyses with atrial fibrillation as a competing risk yielded similar results. Serum magnesium was continuously, inversely and independently associated with future risk of HF. Further research is needed to assess any potential relevance of serum magnesium in HF prevention.

Serum Magnesium and Mortality in Hemodialysis Patients in the United States: A Cohort Study

Low serum magnesium levels in patients with kidney disease have been linked to increased mortality. This study investigated whether similar associations existed in maintenance hemodialysis (HD) patients. Cohort study. All Fresenius Medical Care North America in-center HD patients with available serum magnesium measurements were studied. The initial exploratory study in 21,534 HD patients evaluated associations among serum magnesium level, dialysate magnesium concentration, and mortality from April 2007 through June 2008. The follow-up study in 27,544 HD patients evaluated associations between serum magnesium levels and mortality over 1 year (January through December 2008). The primary predictor was serum magnesium level, with adjustment for case-mix (age, sex, race, diabetes, and dialysis vintage and additionally for follow-up study: body surface area and vascular access) and laboratory variables (albumin, hemoglobin, phosphorus, equilibrated Kt/V, potassium, calcium, and intact parathyroid hormone values). Primary outcome variable was 1-year mortality risk, evaluated using Cox proportional hazards models. Among 21,534 HD patients in the exploratory study, there were 3,682 deaths. Higher dialysate magnesium level was associated with higher serum magnesium level (R=0.22; P<0.001). Patients with the lowest serum magnesium levels (<1.30 mEq/L) were at highest risk for death (HR, 1.63; 95% CI, 1.30-1.96; reference serum magnesium, 1.60-<1.90 mEq/L). Among 27,544 HD patients in the follow-up study, there were 4,531 deaths. In Cox proportional hazards models, there was a linear decline in death risk from the lowest to the highest serum magnesium category, with the best survival at serum magnesium levels≥ 2.50 mEq/L (HR, 0.68; 95% CI, 0.56-0.82). However, risk estimates were attenuated with case-mix and lab adjustment. This pattern was consistent within diabetes subgroups and for cardiovascular or noncardiovascular causes of death. Observational study with cross-sectional serum magnesium measurements and no information for oral magnesium intake. Elevated serum magnesium levels > 2.10 mEq/L were associated with better survival than low serum magnesium levels< 1.30 mEq/L in HD patients. Prospective studies may determine whether manipulation of low serum magnesium levels affects survival.

Magnesium - its role in CKD.

Magnesium containing compounds present promising oral phosphate binders for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). However, the impact of magnesium in CKD patients still remains unclear in clinical routine practice. Therefore, this publication provides a practicable overview of knowledge about the physiological role of magnesium in general and in particular in CKD patients. Prevalence of hypomagnesaemia is high in the general population and especially in intensive care unit patients, but often not being detected. Magnesium deficiency increases the risk for several diseases, like diabetes mellitus type 2, hypertension and atherosclerosis. Moderate hypermagnesaemia, however, seems to have beneficial effects on vascular calcification and mortality rates in CKD patients. On the other hand, higher serum magnesium levels are reported to be linked to lower PTH levels and results on the effects on bone are controversial. In addition, low magnesium levels are associated with low bone mass, osteoporosis and vascular calcification. In dialysis patients serum magnesium levels are dependent mainly on the dialysate magnesium concentration. To confirm the potential delay of arterial calcification and improved survival outcomes by long-term intervention with magnesium powered randomized studies are required in dialysis patients. Since a recent trial revealed that a phosphate binder containing a combination of magnesium carbonate and calcium acetate was as effective as the polymer-based agent sevelamer hydrochloride and had an equally good tolerability profile, it is time for a re-examination of the role of magnesium in CKD patients.

Hypomagnesaemia, the kidney and the vessels

The morbidity and mortality of chronic kidney disease (CKD) and dialysis patients remain excessive, despite increasing knowledge on the role of a multitude of cardiovascular risk factors. As a hallmark of this, randomized controlled trials (RCTs) in these populations failed to demonstrate survival benefit of interventions successfully targeted on well-accepted risk factors in the general population or on dialysis efficiency [1]. Extensive research has confronted the nephrology community with a complex and elusive network of pathophysiological pathways. In contrast, our knowledge of basic elements, such as magnesium, remains surprisingly scarce. Nevertheless, emerging evidence, be it mostly circumstantial, from in vitro and in vivo studies, indicates that hypomagnesaemia, or rather a magnesium deficit per se might convey nephrotoxicity together with negative cardiovascular effects. Alternatively, higher serum magnesium levels might be beneficial. This review aims to further critically appraise and outline this premise. Of importance, the interventional trials targeting magnesium status in CKD and dialysis patients are almost non-existent. Confounding by unmeasured residual subclinical disease and multicollinearity could subsequently hamper the interpretability of the observational evidence. Hypomagnesaemia might merely be considered a 'risk marker' rather than 'risk factor'. Future studies in the CKD and dialysis population therefore should meticulously address causality in order to allow the development of guidelines on optimal target values.

Magnesium in disease

Although the following text will focus on magnesium in disease, its role in healthy subjects during physical exercise when used as a supplement to enhance performance is also noteworthy. Low serum magnesium levels are associated with metabolic syndrome, Type 2 diabetes mellitus (T2DM) and hypertension; consequently, some individuals benefit from magnesium supplementation: increasing magnesium consumption appears to prevent high blood pressure, and higher serum magnesium levels are associated with a lower risk of developing a metabolic syndrome. There are, however, conflicting study results regarding magnesium administration with myocardial infarction with and without reperfusion therapy. There was a long controversy as to whether or not magnesium should be given as a first-line medication. As the most recent trials have not shown any difference in outcome, intravenous magnesium cannot be recommended in patients with myocardial infarction today. However, magnesium has its indication in patients with torsade de pointes and has been given successfully to patients with digoxin-induced arrhythmia or life-threatening ventricular arrhythmias. Magnesium sulphate as an intravenous infusion also has an important established therapeutic role in pregnant women with pre-eclampsia as it decreases the risk of eclamptic seizures by half compared with placebo.

Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels

Serum calcium levels are tightly regulated. We performed genome-wide association studies (GWAS) in population-based studies participating in the CHARGE Consortium to uncover common genetic variations associated with total serum calcium levels. GWAS of serum calcium concentrations was performed in 20 611 individuals of European ancestry for ∼2.5 million genotyped and imputed single-nucleotide polymorphisms (SNPs). The SNP with the lowest P-value was rs17251221 (P = 2.4 * 10(-22), minor allele frequency 14%) in the calcium-sensing receptor gene (CASR). This lead SNP was associated with higher serum calcium levels [0.06 mg/dl (0.015 mmol/l) per copy of the minor G allele] and accounted for 0.54% of the variance in serum calcium concentrations. The identification of variation in CASR that influences serum calcium concentration confirms the results of earlier candidate gene studies. The G allele of rs17251221 was also associated with higher serum magnesium levels (P = 1.2 * 10(-3)), lower serum phosphate levels (P = 2.8 * 10(-7)) and lower bone mineral density at the lumbar spine (P = 0.038), but not the femoral neck. No additional genomic loci contained SNPs associated at genome-wide significance (P < 5 * 10(-8)). These associations resemble clinical characteristics of patients with familial hypocalciuric hypercalcemia, an autosomal-dominant disease arising from rare inactivating mutations in the CASR gene. We conclude that common genetic variation in the CASR gene is associated with similar but milder features in the general population.

A case report: Magnesium intoxication occurring in the process of total serum magnesium decrease

Magnesium intoxication is a result of excessively high serum magnesium levels, which are generally represented by a patient's total serum magnesium concentration. This is the first case report in PubMed in which a female patient showed no signs of magnesium intoxication when her total serum magnesium concentration was 4.34 mg/dL, but showed signs of magnesium intoxication (i.e. absent-patellar reflex) when the concentration was 3.66 mg/dL. We concluded that the serum magnesium level cannot be represented by the total serum magnesium concentration to a full extent; a lower total serum magnesium concentration may still lead to magnesium intoxication.

Serum and Dietary Magnesium and Risk of Ischemic Stroke: The Atherosclerosis Risk in Communities Study

The authors sought to examine the relation between serum or dietary magnesium and the incidence of ischemic stroke among blacks and whites. Between 1987 and 1989, 14,221 men and women aged 45-64 years took part in the first examination of the Atherosclerosis Risk in Communities Study cohort. The incidence of stroke was ascertained from hospital records. Higher serum magnesium levels were associated with lower prevalence of hypertension and diabetes mellitus at baseline. During the 15-year follow-up, 577 ischemic strokes occurred. Serum magnesium was inversely associated with ischemic stroke incidence. The age-, sex-, and race-adjusted rate ratios of ischemic stroke for those with serum magnesium levels of <or=1.5, 1.6, 1.7, and >or=1.8 mEq/L were 1.0, 0.78 (95% confidence interval (CI): 0.62, 0.96), 0.70 (95% CI: 0.56, 0.88), and 0.75 (95% CI: 0.59, 0.95) (P(trend) = 0.005). After adjustment for hypertension and diabetes, the rate ratios were attenuated to nonsignificant levels. Dietary magnesium intake was marginally inversely associated with the incidence of ischemic stroke (P(trend) = 0.09). Low serum magnesium levels could be associated with increased risk of ischemic stroke, in part, via effects on hypertension and diabetes.

Hypophosphataemia: cause of the disturbed metabolism in the metabolic syndrome

The clustering of risk factors for cardiovascular disease (CVD) and non-insulin-dependent diabetes mellitus (NIDDM) in obese patients may be attributable to a disturbed metabolism caused by hypophosphataemia. A low serum phosphate (S-P) level may be a limiting factor for glucose metabolism and may account for hyperglycaemia, with an increased risk of NIDDM and hypertension and consequent increased risk of stroke. Low S-HDL levels, known to exist in the metabolic syndrome, as well as high serum triglycerides may also have been the results of phosphate depletion. The hypothesis presents a new serious disturbance which accounts for the dyslipidaemia, hyperglycaemia and the hypertension in metabolic syndrome. The proposed causal relationship between low S-P and the clustering of risk factors is based on results from a cross-sectional study of obese patients, where low S-P was associated with high body mass index (BMI), high blood glucose (B-glu), high systolic blood pressure (SBP), high diastolic blood pressure (DBP), but low serum high density lipoprotein (S-HDL) and serum magnesium (S-Mg) levels. Knowledge from experimental and clinical studies on hypophosphataemia and/or phosphate depletion are referred to when discussing the hypothesis.

Magnesium and the anaesthetist.

Magnesium plays an important role as a cofactor in many of the body's critical functions and reactions. A deficiency or excess of extracellular magnesium can produce significant signs and symptoms. Hypomagnesaemia is a common finding in hospitalised patients, especially those in critical care areas. Anaesthetising hypomagnesaemic patients may exacerbate pre-existing cardiovascular disease and increase the risk of perioperative dysrhythmias. A low serum magnesium level usually suggests a total body deficiency of magnesium. Treatment of magnesium deficiency is by parenteral magnesium and should be instituted prior to surgery. Hypermagnesaemia is often iatrogenic and is more likely in patients with renal dysfunction who are receiving oral or parenteral magnesium. The specific antidote is intravenous calcium. Anaesthetised patients with high serum magnesium levels are at risk from hypotension, potentiation of non-depolarising neuromuscular blockers, postoperative respiratory failure and cardiac arrest.

Effect of conserving annual pastures for hay on serum magnesium levels of lactating beef cows in a Mediterranean environment

Mature Friesian crossbred cows calving in April-May either continuously grazed annual pasture and received a small hay supplement in May and June, solely to prevent starvation ketosis, or had the pasture from one-third of their area conserved as hay in spring and fed back ad libitum in April, May and June. In May, deaths of cows from hypomagnesaemia occurred on the continuous grazing treatment but not on the fodder conservation treatment. Liveweight and serum magnesium levels of cows and the availability, botanical and mineral composition of the pasture on offer were therefore monitored during June, July and August. The cows on the fodder conservation treatment had higher serum magnesium levels through June, July and August. One cow on the continuous grazing treatment died of hypomagnesaemia in July, but none died on the fodder conservation treatment. After a supplement of 30 g MgSO4.7H2O and 4 kg of hay/cow.day was provided for 3 weeks in July, serum magnesium levels increased on both treatments and no further clinical cases of hypomagnesaemia occurred. Serum magnesium levels continued to increase on the continuous grazing treatment, and remained at a satisfactory level on the fodder conservation treatment and through August on pasture alone. Cation ratios (K:[Mg + Ca]) of clovers, weeds and hay at all samplings were less than 2.2, but grass sampled in July and August had cation ratios of 2.59 and 2.95, respectively. There was always a higher percentage of grass on the continuous grazing treatment. It was concluded that conservation of fodder as hay increased the serum magnesium levels of beef cows suckling calves in early winter by providing more energy and more magnesium during the period of pasture shortage in autumn-winter. Fodder conservation also appeared to contribute to increased serum magnesium levels in winter by reducing the proportion of grass in the sward.