Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

A randomized, double-blind, placebo-controlled, multicenter study assessing the efficacy of magnesium oxide monohydrate in the treatment of nocturnal leg cramps.

BACKGROUND: Magnesium supplements are widely used for prophylaxis and treatment of nocturnal leg cramps (NLC). However, there is little evidence in support of their effectiveness. The main impediment stems from the lack of assessments of cellular absorption. In the current study, we tested the efficacy and safety of a magnesium supplement - magnesium oxide monohydrate (MOMH), for which increased cellular absorption rates were demonstrated in an ex-vivo setting. METHODS: A randomized, double-blind, placebo-controlled multicenter study was conducted in hospitals and outpatient clinics in Ukraine, from February to August 2018. Eligible subjects received a capsule with MOMH 226 mg or placebo, once daily, at bedtime, for a 60-day period. The assessed parameters included frequency and duration of NLC episodes, quality of sleep, NLC-induced pain and quality of life sub-scores. The Fisher's Exact Test for comparison of groups by categorical variables was used. The Student's test or Mann-Whitney test were used for between-group comparison at different timepoints. ANCOVA followed by contrast analysis was used for comparison of groups at the end of the study. RESULTS: 175 (81%) out of 216 initially screened subjects completed the study. The number of NLC episodes has significantly decreased by the end of the study period as compared to baseline in both groups (p < 0.001 for both). There was a significant between-group difference in the magnitude of reduction in NLC episodes (p = 0.01), indicating a higher decrease in the MOMH group as compared to the placebo group (- 3.4 vs - 2.6, respectively). In addition, MOMH treatment resulted in a greater reduction in NLC duration (p < 0.007) and greater improvement in sleep quality (p < 0.001) as compared to placebo. CONCLUSIONS: MOMH was shown to be effective in the treatment of NLC as well as safe and well-tolerated. TRIAL REGISTRATION: NCT03807219 , retrospectively registered on January 16, 2019.

[UPDATED ISRAELI GUIDELINES FOR THE TREATMENT OF DYSLIPIDEMIA 2020].

INTRODUCTION: Despite the impressive decline in mortality from atherosclerotic cardiovascular diseases (ASCVD), these diseases still account for a large proportion of the overall morbidity and mortality worldwide. A vast amount of research has demonstrated the key role played by circulating lipoproteins, and especially low-density lipoprotein (LDL), in the etiology of atherosclerosis, and numerous studies have proven the efficacy of interventions that lower the atherogenic lipoproteins in reducing morbidity and mortality from ASCVD. While previous guidelines placed an emphasis on the use HMG-CoA reductase inhibitors (statins) for the treatment of dyslipidemia, recent studies have shown that other LDL cholesterol lowering drugs, including ezetimibe and the PCSK9 inhibitors, can provide additional benefit when used in combination with (and in certain cases instead of) statins. These studies have also shown that blood LDL cholesterol levels lower than previously recommended targets provide additional benefit, without evidence of a threshold beyond which the benefit ceases and without excess adverse effects. The updated guidelines were formulated by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, the Israel Society of Internal Medicine, the Israeli Heart Association, the Israeli Neurology Association and the Israel Association of Family Medicine. They provide recommendations for revised risk stratification of patients, novel target goals, and the use of evidence-based treatment and follow-up strategies with reference to specific patient sub-groups.

Periodontitis and cardiovascular diseases: Consensus report.

BACKGROUND: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Hypomagnesemia is associated with new-onset diabetes mellitus following heart transplantation.

BACKGROUND: Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT). METHODS: Between 2002 and 2017, 102 non-DM HT patients were assessed. In accordance with the mean value of all s-Mg levels recorded during the first year post-HT, patients were divided into high s-Mg (≥ 1.8 mg/dL) and low s-Mg (< 1.8 mg/dL) groups. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association. RESULTS: Baseline clinical and demographic characteristics for the high (n = 45) and low s-Mg (n = 57) groups were similar. Kaplan-Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high vs low s-Mg (85% vs 46% log-rank test, p < 0.001). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies, BMI and mean creatinine values in the first year post-HT, showed that low s-Mg was independently associated with a significant > 8-fold increased risk for NODAT (95% CI 2.15-32.63, p = 0.003). Stroke rate was significantly higher in patients with low s-Mg levels vs high s-Mg (14% vs 0, p = 0.025), as well as long term mortality (HR 2.6, 95% CI 1.02-6.77, p = 0.05). CONCLUSIONS: Low s-Mg level post-HT is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, for the risk of NODAT and for clinical outcomes should be evaluated.

Association between exposure to desalinated sea water and ischemic heart disease, diabetes mellitus and colorectal cancer; A population-based study in Israel.

BACKGROUND: Drinking water (DW) is an important dietary source of magnesium. Recently, Israel has increased its use of desalinated seawater (DSW) as DW country-wide. Its negligible magnesium content, however, raises concern that consumption of DSW may be associated with hypomagnesemia and increase the risk of ischemic heart disease (IHD), diabetes mellitus (DM), and colorectal cancer (CRC). OBJECTIVES: We tested whether there was a change in incidence of negative health outcomes (IHD, DM, and CRC) following the introduction of DSW supply in a population-based ecologic study in Israel. METHODS: A historical prospective analysis was applied to members aged 25-76 during 2004-2013 of Clalit Health Services (Clalit), the largest healthcare provider in Israel, using its electronic medical record database. Multivariable analyses were adjusted for age, sex, socioeconomic status, smoking status, and body mass index. RESULTS: An increased odds ratio was found for IHD (0.96, 95% CI 0.93-0.99 at baseline and 1.06, 95% CI 1.02-1.11 at the end of the follow-up period), but no time trend was observed. CONCLUSIONS: We found that the risk for IHD increased during the study period. The risks for DM and CRC were unchanged. Long term studies are needed for assessing the risk for CRC due to the long latency. The higher risk for IHD has practical public health implications and raise the need to add magnesium to DSW.

[ENDOTHELIAL DYSFUNCTION: A POSITION PAPER OF THE ISRAEL HEART SOCIETY].

INTRODUCTION: Prediction of cardiovascular adverse events is challenging. It became apparent that traditional coronary artery disease (CAD) risk factors are the cornerstones of the European 10-year CAD risk SCRORE and the Framingham score. However, despite their importance, the prediction value of general assessment tools such as the SCORE and Framingham options in an individual subject is limited, especially in young adults and women. The trend toward personalized medicine and individualized risk assessment during recent years is growing strong and various functional and imaging screening tests, including endothelial function studies, have been suggested to improve accuracy and provide the functional implications of these risk factors. Endothelial dysfunction is an early stage of atherosclerosis and has been associated with adverse cardiovascular outcome events, including myocardial infarction, stroke and death. The purpose of this position paper is to review the scientific background, methods available for assessment of endothelial function and the interpretation of test results. The current manuscript also suggest some meaningful clinical guidelines on potential integration of these tests into our practice.

Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. METHODS: We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. FINDINGS: Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). INTERPRETATION: Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. FUNDING: Gilead Sciences, Menarini.

Evaluation of platelet response to different clopidogrel dosing regimens in patients with acute coronary syndrome in clinical practice.

High-post clopidogrel platelet reactivity in acute coronary syndrome (ACS) patients is associated with adverse outcomes and may be related to clopidogrel dosing. Clinical studies evaluating different clopidogrel doses have resulted in conflicting conclusions. Clopidogrel dosing regimens have evolved over time, enabling us to evaluate platelet reactivity in real-life ACS patients undergoing percutaneous coronary intervention and treated with three different clopidogrel doses. Platelet reactivity was assessed with light transmitted aggregometry on the third day post clopidogrel loading in 404 consecutive ACS patients. Of them, 198 were treated with a standard regimen (300 mg loading, 75 mg/day maintenance dose), 95 with a high loading regimen (600 mg loading, 75 mg/day maintenance dose) and 111 with a high loading/high maintenance regimen (600 mg loading, 150 mg/day maintenance). Compared with the standard regimen, the high loading regimen resulted in significantly lower mean platelet reactivity to adenosine diphosphate (ADP) with a lower proportion of patients exhibiting clopidogrel non-responsiveness (11% vs. 28%, p = 0.004). Compared with the high loading regimen, the high loading/high maintenance regimen resulted in significantly lower mean platelet reactivity to ADP, but without a further drop in the number of non-responders (8.1% vs. 11%, p = 0.16). In conclusion, greater overall inhibition can be achieved with higher loading and maintenance doses in ACS patients. However, despite high clopidogrel doses, a sizable proportion of patients remained "resistant" to the effects of clopidogrel.

Bimodal response to aspirin loading in acute ST-elevation myocardial infarction.

Patients with stable coronary disease who exhibit platelet hypo-responsiveness to aspirin (ASA) have worse outcomes. Little data exist regarding platelet response to ASA in ST-elevation myocardial infarction (STEMI) patients. Our objective was to assess acute platelet response to ASA loading in STEMI patients undergoing primary percutaneous coronary intervention (PCI). The study comprised 102 consecutive patients with STEMI. All patients received a loading dose of 300 mg chewable ASA upon admission. Platelet reactivity was assessed immediately prior to primary PCI, at a median of 95(63 139) minutes after ASA loading. A bimodal response to arachidonic acid (AA) stimulation was observed, such that two distinct populations could be discerned: "good responders" had a mean AA-induced platelet aggregation of 36 ± 11% vs. 79 ± 9% for "poor responders." Despite equivalent demographic, clinical, and angiographic characteristics, good responders were significantly more likely to demonstrate early ST-segment resolution ≥70% after primary PCI (80% vs. 48%, p = 0.001), suggestive of better myocardial reperfusion. Early inhibition of AA-induced platelet aggregation post-ASA loading in the setting of STEMI is associated with better tissue reperfusion; however, a sizeable proportion of patients do not achieve significant inhibition of AA-induced platelet aggregation in response to ASA loading at the time of primary PCI.

Admission Serum Magnesium Levels Is Associated with Short and Long-Term Clinical Outcomes in COVID-19 Patients.

BACKGROUND: In the face of the global pandemic that the coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. OBJECTIVE: To evaluate the association between serum magnesium (sMg) levels on admission and clinical outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively analyzed all patients admitted to a single tertiary center with a primary de novo diagnosis of COVID-19. Patients were followed for a mean of 10 ± 7 months. Demographic, clinical and laboratory data were collected and compared between five groups of patients according to sMg quintiles on hospital admission. RESULTS: The cohort included 1522 patients (58% male, 69 ± 17 years old). A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, renal dysfunction, higher levels of inflammatory markers and stay in the intensive care unit. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4th quintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p < 0.001 for all). After adjusting for significant clinical parameters indicating severe disease and renal dysfunction, only low sMg state was independently associated with increased mortality (HR = 1.57, p < 0.001). CONCLUSIONS: Both low and high sMg levels were associated with increased mortality in a large cohort of hospitalized COVID-19 patients. However, after correction for renal dysfunction and disease severity, only low sMg maintained its prognostic ability.

Endothelial function predicts 5-year adverse outcome in patients hospitalized in an emergency department chest pain unit.

BACKGROUND: Although endothelial function is a marker for cardiovascular risk, endothelial dysfunction assessment is not routinely used in daily clinical practice. A growing challenge has emerged in identifying patients prone to cardiovascular events. We aim to investigate whether abnormal endothelial function may be associated with adverse 5-year outcomes in patients presenting to a chest pain unit (CPU). METHODS: Following endothelial function testing using EndoPAT 2000 in 300 consecutive patients without a history of coronary artery disease, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability. RESULTS: Mean 10-year Framingham risk score (FRS) was 6.6 ±â€Š5.9%; mean 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 7.1 ±â€Š7.2%; median reactive hyperemia index (RHI) as a measure of an endothelial function 2.0 and mean was 2.0 ±â€Š0.4. During a 5-year follow-up, the 30 patients who developed major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions, had higher 10-year FRS (9.6 ±â€Š7.8 vs. 6.3 ±â€Š5.6%; P  = 0.032), higher 10-year ASCVD risk (10.4 ±â€Š9.2 vs. 6.7 ±â€Š6.9%; P  = 0.042), lower baseline RHI (1.6 ±â€Š0.5 vs. 2.1 ±â€Š0.4; P  < 0.001) and a greater degree of coronary atherosclerotic lesions (53 vs. 3%, P  < 0.001) on CCTA compared with patients without MACE. Multivariate analysis demonstrated that RHI below the median was an independent predictor of 5-year MACE (odds ratio 5.567, 95% confidence interval 1.955-15.853; P  = 0.001). CONCLUSION: Our findings suggest that noninvasive endothelial function testing may contribute to clinical efficacy in triaging patients in the CPU and in predicting 5-year MACE. CLINICAL TRIALSGOV IDENTIFIER: NCT01618123.

Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients.

BACKGROUND: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. OBJECTIVE: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. METHODS: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2-Q4; sMg ≥ 1.9 mg/dL). RESULTS: The study cohort included 4552 patients (70% male, median age 69 [IQR 59-79]) who were followed for a median of 4.4 (IQR 2.4-6.6) years. The median sMg level in the low sMg group was 1.7 (1.6-1.8) and 2.0 (2.0-2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan-Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11-1.39; p < 0.001). CONCLUSIONS: Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event.

Brachial artery endothelial function predicts platelet function in control subjects and in patients with acute myocardial infarction.

Platelet activation occurs in an endothelium-dependent flow-mediated dilation (FMD) impairment environment. The aim of this study was to explore the association between platelet reactivity and brachial artery FMD in individuals without established cardiovascular disease (controls) and acute myocardial infarction (AMI) patients. We prospectively assessed brachial artery FMD in 151 consecutive subjects, 104 (69%) controls, and 47 (31%) AMI patients; 115 (76%) men, mean age 53 ± 11 years. Following overnight fasting and discontinuation of all medications for ≥ 12 h, percent change in brachial artery FMD (%FMD) and endothelium-independent, nitroglycerin-mediated vasodilation (%NTG) were assessed. Platelet aggregation was assessed by conventional aggregometry, and platelet adhesion and aggregation under flow conditions by cone-and-plate(let) technology (Impact-R). Smoking, diabetes, and hypertension were more common in AMI compared to control subjects (p < 0.01 for all). Furthermore, aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, and statin administration were more common in AMI compared to controls (p < 0.01 for all). %FMD but not %NTG was significantly lower in AMI patients compared to controls (10.2 ± 4.2% vs. 15.4 ± 4.4%; p < 0.001 and 17.2 ± 3.9% vs. 18.0 ± 3.7%, p = 0.803, respectively). %FMD was significantly and inversely associated with all platelet functions tests (p < 0.001) in all study participants. In a multivariate logistic regression (unadjusted and adjusted for age, gender, smoking status, diabetes mellitus, hypertension, hypercholesterolemia, overweight, family history, and concomitant medications), %FMD remained the best predictor of platelet function, irrespective of group allocation (AMI patients or controls). In conclusion, FMD is inversely correlated to platelet reactivity in both controls and AMI patients.

Hyperglycaemic disorders associated with PCSK9 inhibitors: a real-world, pharmacovigilance study.

AIMS: While genetic and biological studies indicated a potential association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycaemia, real-world data are limited. Therefore, we sought to investigate this association using the FDA adverse event reporting system (FAERS). METHODS AND RESULTS: The FAERS database (2015-2020) was retrospectively queried to characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. Disproportionality analyses were performed using the adjusted reporting odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were identified. Compared to the full database, PCSK9i treatment was associated with increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07-1.22), IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, adj. ROR = 1.48 (1.36-1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. ROR = 0.67 (0.60-0.74), IC025 = -0.90]. Among PCSK9i agents, evolocumab, but not alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 (1.15-1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60-0.88), IC025 = -0.38, respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared to ezetimibe [adj.ROR = 1.99 (1.35-2.94)], and less often compared to statins [adj.ROR = 0.26 (0.25-0.28)]. Notably, hyperglycaemic AEs were reported more frequently by diabetic than by non-diabetic patients (P < 0.001), mostly occurred within 6 months of treatment and were reversible upon drug discontinuation. CONCLUSION: In a real-world setting, PCSK9i treatment was associated with increased reporting of mild hyperglycaemia, but not diabetes. While initial monitoring is warranted, the favourable glycaemic safety profile compared to statins supports their essential role in the management of lipid disorders.

Statins have an early antiplatelet effect in patients with acute myocardial infarction.

Statins confer an antiplatelet effect in hypercholesterolemic subjects and in stable coronary artery disease patients. We explored the antiplatelet effects of statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. Of 120 STEMI patients, 80 (67%) received statins while 40 (33%) did not. Ex vivo platelet reactivity was studied on admission and 72 hours later by conventional aggregometry and under flow conditions (Impact R). Measures of platelet reactivity under flow conditions included aggregate size and surface coverage, signifying platelet aggregation and adhesion respectively. The effect of statins on platelet function under flow conditions and platelet aggregation was studied in?vitro in platelets from 10 STEMI patients. Platelets from each patient were incubated in?vitro with lovastatin or PBS as a control. The effect of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was also studied. Patients treated with statins were compared with those who did not have significantly lower ADP-induced platelet aggregation on the 4th day (56 ± 18% vs. 64 ± 17%, p=0.02). Platelet deposition under flow conditions as measured by surface coverage was reduced from admission to 72 hours later among statin-treated patients (19 ± 28% reduction, p<0.01), but was unchanged in non-treated patients (for comparison p<0.01). The extent of platelet inhibition was unrelated to patient characteristics, including lipid profile and type of statin administered (lipophylic vs. hydrophilic). In the in vitro study platelet incubation with statin compared with PBS resulted in a lower aggregate-size (29 ± 9 µm(2) vs. 39 ± 15 µm(2), p<0.01), and lower surface coverage (8.5 ± 4% vs. 12 ± 4%, p<0.01). The effect of the statin on both parameters was significantly blunted by L-NMMA. Incubation with statin also resulted in a reduction in collagen-induced platelet aggregation (31 ± 20% vs. 54 ± 25%, p<0.01). We concluded that in acute myocardial infarction patients, statins have an early antiplatelet effect, in addition to that afforded by standard antiplatelet therapy.

[Body magnesium--the spark of life].

Hypomagnesemia is common in hospitalized patients, especiaLLy in the eLderLy with coronary artery disease (CAD) and/or those with chronic heart failure. Hypomagnesemia is associated with the risk of hypertension, type 2 diabetes mellitus, increased mortality from all cause and CAD. Higher magnesium intake, however, has been associated with a Lower risk of developing metabolic syndrome, a problem which exists in 25% of American adults. Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves human endothelial function and inhibits platelet function, including platelet aggregation and adhesion, which potentially provides magnesium with physiologic and natural effects similar to adenosine-diphosphate inhibitors, such as clopidogrel. Data on magnesium supplementation in patients with acute myocardial infarction (AMI) are conflicting. ALthough a number of relatively small randomized cLinicaL trials have demonstrated a remarkable reduction in mortality when magnesium is administered to relativeLy high risk AMI patients, two recently published large-scale randomized cLinical trials (the Fourth International Study of Infarct Survival and Magnesium in Coronaries) failed to show any superiority of intravenous magnesium over placebo. Furthermore, the theoretical potential benefits of magnesium supplementation as a cardioprotective agent in CAD patients, its relatively low cost, easy administration, and relatively insignificant adverse effects, gives magnesium a place in treating CAD patients, especially those at high-risk and in life-threatening ventricular arrhythmias, such as Torsades de Points and intractable ventricular tachycardia.

Dietary recommendations of magnesium for cardiovascular prevention and treatment. A position paper of the Israel Heart Society and the Israel Dietetic Association.

Modern life and the Western industrial diet has enhanced the reduction of magnesium in our food, which may contribute to a marginal or absolute magnesium deficiency. Magnesium deficiency is evident in, among others, the elderly population, those after myocardial infarction and/or chronic heart failure, and diabetics. In Israel, over 60% of the drinking water originates from desalinated seawater lacking magnesium, which may cause hypomagnesemia. Magnesium deficiency can easily be treated by magnesium supplementation if we are aware of the situation. This paper summarizes the magnesium chapter in a position paper published in April 2021 by the Israeli Cardiology Society together with the Israeli Dietetic Association. It summarizes evidence-based nutritional recommendations for prevention and treatment of cardiovascular disease, with emphasis on the level of evidence and practical recommendations according to the European Society of Cardiology definitions. The best recommendation is to increase consumption of magnesium-rich food, such as leafy green vegetables (mainly spinach), nuts, avocado, whole grains, legumes (e.g., beans, peas and soy beans), chocolate and certain seafood. However, for people who do not get sufficient magnesium from their diet completing the daily amount, as needed, with supplements of up to 600 mg/day should be considered. In addition, serum magnesium levels should be checked at least every six months in patients with heart failure, people taking diuretic therapy, and people taking proton-pump inhibitors. In addition, it may be beneficial to add magnesium following myocardial infarction in people with hypertension and in heart failure patients in order to reduce cardiovascular morbidity and mortality (class of recommendation IIa, level of evidence B).

Magnesium levels in relation to rates of preterm birth: a systematic review and meta-analysis of ecological, observational, and interventional studies.

CONTEXT: Experimental studies suggest that magnesium levels in pregnant women may affect the length of gestation, as magnesium affects the activity of smooth muscle in the uterus. Little is known about the association between magnesium levels or supplementation and the rate of preterm birth. OBJECTIVE: The aim of this systematic review was to summarize the data on magnesium soil levels and preterm birth rates from ecological, observational, and interventional studies. DATA SOURCES: Soil magnesium levels were obtained from US Geological Survey data, and preterm birth rates were acquired from the March of Dimes Foundation. Relevant epidemiological and clinical studies published until April 2019 in peer-reviewed journals were retrieved from PubMed, Google Scholar, and related reference lists. STUDY SELECTION: Original studies published in English, conducted in humans, and in which magnesium (dietary/supplemental intake or biomarkers) was an exposure and preterm birth was an outcome were included. DATA EXTRACTION: Eleven studies were included in the systematic review. Meta-analysis was performed on 6 studies. Overall relative risk (RR) and corresponding 95%CIs for risk of preterm birth in relation to magnesium supplementation were estimated by a random-effects model. RESULTS: The ecological study revealed an inverse correlation between magnesium content in soil and rates of preterm birth across the United States (r = -0.68; P < 0.001). Findings from 11 observational studies generally support an inverse association between serum magnesium levels and rates of preterm birth. Of the 6 eligible randomized controlled trials, which included 3068 pregnant women aged 20 to 35 years and 352 preterm infants, the pooled RR was 0.58 (95%CI, 0.35-0.96) for women in the magnesium supplementation group compared with women in the control group. CONCLUSIONS: Accumulated evidence from ecological, observational, and interventional studies consistently indicates that adequate magnesium intake during pregnancy may help reduce the incidence of preterm birth.