Acute myocardial infarction severity, complications, and mortality associated with lack of magnesium intake through consumption of desalinated seawater.

Drinking water (DW) is an important dietary source of magnesium. Israel has recently increased desalinated seawater (DSW) production for DW, but negligible magnesium content in DSW may pose a risk of hypomagnesemia and consequential adverse cardiovascular effects. Consecutive acute myocardial infarction (AMI) patients (n = 380, age 35-75 years), hospitalized in 2015-2017 with ST-segment elevation myocardial infarction (STEMI), were divided into two groups based on their domicile region having a major supply of DSW (n = 250, 65%) or not (non-DSW; n = 130, 35%). We evaluated admission serum magnesium concentrations in patients, magnesium levels in tap water, 1-year all-cause mortality, and major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, rehospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions. Multivariate analyses were adjusted for age and sex. Serum magnesium concentrations (mean ± SD) were significantly higher among patients in the non-DSW group compared with the DSW group (1.95 ± 0.20 mg/dL and 1.81 ± 0.20 mg/dL, P < 0.001; respectively). Additionally, the mean residential DW magnesium level in the DSW group was 5.4 ± 2.2 mg/L compared with 25.1 ± 3.4 mg/L, P < 0.01 in the non-DSW group. Fewer patients (although not statistically significant) in the non-DSW group experienced major adverse cardiovascular events (MACE) or 1-year-all-cause mortality compared with the patients in the DSW group (12.4% and 20%, P = 0.065; respectively). In conclusion, in post AMI patients, we found nonsignificant higher MACE and 1-year mortality with the use of DSW.

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.

Sea water desalination and removal of iodine: effect on thyroid function.

In Israel, about 55% of drinking water is derived from desalination (DSW) which removes all iodine. A recent study from Israel demonstrated high rates of iodine deficiency among school-aged children and pregnant women. There are concerns that low iodine may lead to impaired thyroid function. However, to date, the impact of consuming DSW on body iodine status has not been studied. The objective was to assess whether the increased use of DSW is associated with increased rates of hypothyroidism. Using data from a large health fund in Israel, we compared proportions of patients with higher than normal thyroid stimulating hormone (TSH), and lower than normal T3 and T4 levels before and after a massive desalination project became operational in August 2013 in areas with high vs. low use of DSW. Over 400,000 cases were compared in 2010-2013 vs. 2014-2016. Overall, there was no increase in the proportion of individuals with higher than normal TSH levels, or lower than normal T3 and T4 levels. In conclusion, in this population-based study, following the introduction of DSW, there was no evidence of increased incidence of low thyroid function tests, and the trends were similar in both areas highly consuming, or not consuming, DSW.

The Effect of Admission Renal Function on the Treatment and Outcome of Patients with Acute Coronary Syndrome.

BACKGROUND: Chronic kidney disease is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate treatment characteristics in ACS patients according to their renal function and to assess the effect of differences in therapy on clinical outcomes. METHODS: Included were patients with ACS enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) during 2000-2013. Excluded were patients with cardiogenic shock at presentation. The estimated glomerular filtration rate (eGFR) was calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula. The distribution of the eGFRs was divided into 4 categories (<45, 45-59.9, 60-74.9, and ≥75 mL/min/1.73 m2). The primary endpoint was all-cause mortality at 1 year. RESULTS: A total of 13,194 patients with ACS were included. Patients with a reduced eGFR were less likely to be admitted to a coronary care unit and had lower rates of coronary angiograms and subsequent percutaneous coronary interventions. Furthermore, as the eGFR was lower, the patients were less frequently treated with aspirin, clopidogrel, ß-blockers, and ACE inhibitors/angiotensin receptor blockers. We demonstrated an inverse association between renal function and 1-year mortality, with the highest mortality rates observed in the group with the lowest eGFR (HR = 3.8, 95% CI 2.9-4.9, p < 0.0001). Differences in mortality remained significant following a multivariate analysis for all the baseline characteristics as well as for invasive and medical treatment (HR = 2.7, 95% CI 1.9-3.7, p < 0.0001). CONCLUSIONS: ACS patients with chronic kidney disease represent a high-risk group with an increased mortality risk. Despite this high risk, these patients are less frequently selected for an invasive treatment strategy and are less commonly treated with guideline-based medications. However, reduced renal function was associated with higher mortality regardless of the variations in therapy.

Trends in the management and outcomes of patients admitted with acute coronary syndrome complicated by cardiogenic shock over the past decade: Real world data from the acute coronary syndrome Israeli survey (ACSIS).

Registries and other cohorts have demonstrated that early revascularization improve the survival of patients presenting with Cardiogenic Shock (CS) completing Aute coronary syndrome (ACS). Our aim was to describe the change in the clinical characteristics of these patients and their management and their outcome. The study population comprised 224 patients who were admitted with ACS complicated by cardiogenic shock who were enrolled in the prospective biannual Acute Coronary Syndrome Israeli Surveys (ACSIS) between 2000 and 2013 (1.7% of all patients admitted with ACS during the study period). Survey periods were categorized as early (years 2000-2004) and late (year 2006-2013).The rate of cardiogenic shock complicated ACS declined from 1.8% between the years 2000-2004 to 1.5% during the years 2006-2013. The clinical presentation in both the early and late groups was similar. During the index hospitalization primary percutaneous coronary intervention (PPCI) was more frequently employed during the late surveys [31% vs. 58% (p<0.001)], while fibrinolysis therapy was not used in the late surveys group [27% vs. 0.0% (p=<0.001)]. Compared to patients enrolled in the early surveys, those enrolled in the late survey group experienced significantly lower mortality rates at 7-days (44% vs. 30%, respectively; p=0.03). However, this difference was no longer statistically significant at 30-days (52.8% vs. 46.4%, respectively, p=0.34) and 1-year (63% vs. 53.2%, respectively, p=0.14). Similarly, the rate of major adverse cardiac events (MACE) at 30-days was similar between the two groups (57.4% vs. 47.4%, respectively, p=0.13).Our findings indicate that patients admitted with ACS complicated by cardiogenic shock still experience very high rates of MACE and mortality during follow-up, despite a significant increase in the use of PPCI in this population over the past decade.

Seawater desalination and serum magnesium concentrations in Israel.

With increasing shortage of fresh water globally, more countries are consuming desalinated seawater (DSW). In Israel >50% of drinking water is now derived from DSW. Desalination removes magnesium, and hypomagnesaemia has been associated with increased cardiac morbidity and mortality. Presently the impact of consuming DSW on body magnesium status has not been established. We quantified changes in serum magnesium in a large population based study (n = 66,764), before and after desalination in regions consuming DSW and in regions where DSW has not been used. In the communities that switched to DSW in 2013, the mean serum magnesium was 2.065 ± 0.19 mg/dl before desalination and fell to 2.057 ± 0.19 mg/dl thereafter (p < 0.0001). In these communities 1.62% of subjects exhibited serum magnesium concentrations ≤1.6 mg/dl between 2010 and 2013. This proportion increased by 24% between 2010-2013 and 2015-2016 to 2.01% (p = 0.0019). In contrast, no such changes were recorded in the communities that did not consume DSW. Due to the emerging evidence of increased cardiac morbidity and mortality associated with hypomagnesaemia, it is vital to consider re-introduction of magnesium to DSW.

Admission plasma glucose levels within the normal to mildly impaired range and the outcome of patients with acute coronary syndrome.

BACKGROUND: Elevated admission plasma glucose levels >140 mg/dl are associated with adverse clinical outcomes in both diabetic and non-diabetic patients admitted with acute coronary syndrome (ACS). We aimed to evaluate the association between admission plasma glucose levels <140 mg/dl and the outcome of non-diabetic patients admitted with acute coronary syndrome. METHODS: The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli Survey during 2000-2013. Diabetic patients were excluded. The primary endpoint was all-cause mortality at one year. RESULTS: The 452 0 patients had a mean age of 61.7±13.5 years and were stratified into four quartiles according to admission plasma glucose (60-94, 95-105, 106-119, 120-140 mg/dl). Patients with higher admission plasma glucose were older and included a higher percentage of smokers. In addition, the higher the glucose so also did they have a poorer risk factor profile including a higher body mass index, total and low-density lipoprotein cholesterol and triglyceride levels, and lower high-density lipoprotein cholesterol levels. During the first year 5.2% of patients died. A comparison of one-year mortality according to admission plasma glucose quartiles demonstrated a significant and progressive increase in mortality risk as admission plasma glucose rose (3.5%, 4.1%, 6.1%, 6.4%, respectively, p=0.001). However, this association lost its clinical significance following a multivariate analysis ( p=0.08). CONCLUSIONS: High admission plasma glucose levels within the normal to mildly impaired range are associated with increased one-year mortality in non-diabetic acute coronary syndrome patients. However, the higher glucose level is probably not the cause for the adverse outcome but rather a marker for high risk. Our findings support the definition of 140 mg/dl as the cutoff for clinically acceptable admission glucose levels in patients with acute coronary syndrome.

CHA2DS2-VASc score and clinical outcomes of patients with acute coronary syndrome.

BACKGROUND: The CHA2DS2-VASc score has been recommended for the assessment of thromboembolic risk in patients with atrial fibrillation. HYPOTHESIS: The CHA2DS2-VASc score may be associated with adverse outcomes in patients with ACS. METHODS: Included were patients with ACS enrolled in the Acute Coronary Syndrome Israeli biennial Surveys (ACSIS) during 2000-2013. Patients were divided into 4 groups according to their CHA2DS2-VASc score (0 or 1, 2 or 3, 4 or 5, and >5). The primary endpoint was 1-year all-cause mortality. RESULTS: The 13,422 patients had a mean age of 63.5±13years and included 25.8% females. Higher CHA2DS2-VASc score was associated with a significant increase in 1-year mortality. Patients with a CHA2DS2-VASc score >5 had the highest 1-year mortality risk that was 6-fold higher compared to patients with a score of 0 to 1 (hazard ratio=6, 95% CI=4.1-8.8, p<0.0001). However, even an intermediate CHA2DS2-VASc score of 2-3 was associated with a significant 2.6-fold increase in 1-year mortality. Patients with a higher CHA2DS2-VASc score were less frequently selected for an invasive strategy with an early coronary angiogram and subsequent angioplasty and were less commonly treated with the guideline-based medications. However, differences in outcomes remained significant following a multivariate analysis suggesting that these variations in therapy can only partially explain the differences in outcomes. CONCLUSIONS: Higher CHA2DS2-VASc score identifies high-risk patients that may be overlooked by existing scores. Further studies are needed in order to evaluate whether the CHA2DS2-VASc score may be used together with the GRACE score for an improved risk assessment of ACS patients.

Desalinated seawater supply and all-cause mortality in hospitalized acute myocardial infarction patients from the Acute Coronary Syndrome Israeli Survey 2002-2013.

BACKGROUND: Consuming desalinated seawater (DSW) as drinking water (DW) may reduce magnesium in water intake causing hypomagnesemia and adverse cardiovascular effects. METHODS: We evaluated 30-day and 1-year all-cause mortality of acute myocardial infarction (AMI) patients enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) during 2002-2013. Patients (n=4678) were divided into 2 groups: those living in regions supplied by DSW (n=1600, 34.2%) and non-DSW (n=3078, 65.8%). Data were compared between an early period [2002-2006 surveys (n=2531) - before desalination] and a late period [2008-2013 surveys (n=2147) - during desalination]. RESULTS: Thirty-day all-cause-mortality was significantly higher in the late period in patients from the DSW regions compared with those from the non-DSW regions (HR=2.35 CI 95% 1.33-4.15, P<0.001) while in the early period there was no significant difference (HR=1.37 CI 95% 0.9-2, P=0.14). Likewise, there was a significantly higher 1-year all-cause mortality in the late period in patients from DSW regions compared with those from the non-DSW regions (HR=1.87 CI 95% 1.32-2.63, P<0.0001), while in the early period there was no significant difference (HR=1.17 CI 95% 0.9-1.5, P=0.22). Admission serum magnesium level (M±SD) in the DSW regions (n=130) was 1.94±0.24mg/dL compared with 2.08±0.27mg/dL in 81 patients in the non-DSW (P<0.0001). CONCLUSIONS: Higher 30-day and 1-year all-cause mortality in AMI patients, found in the DSW regions may be attributed to reduced magnesium intake secondary to DSW consumption.

Incidence and Clinical Features of Early Stent Thrombosis in the Era of New P2y12 Inhibitors (PLATIS-2).

Early stent thrombosis (EST) (≤ 30 days after stent implantation) is a relatively rare but deleterious complication of percutaneous coronary intervention (PCI). Administration of newer P2Y12 inhibitors (prasugrel and ticagrelor) combined with aspirin has been shown to reduce the incidence of sub-acute and late stent thrombosis, compared with clopidogrel. We investigated the "real life" incidence of EST in patients from a large acute coronary syndrome (ACS) national registry, where newer P2Y12 inhibitors are widely used. Patients were derived from the ACS Israeli Survey (ACSIS), conducted during 2006, 2008, 2010 and 2013. Major adverse cardiac events (MACE) at 30days were defined as all-cause death, recurrent ACS, EST and stroke.Of the 4717 ACS patients who underwent PCI and stenting, 83% received clopidogrel and 17% newer P2Y12 inhibitors. The rate of EST was similar in both groups (1.7% in the newer P2Y12 inhibitor group vs. 1.4% in the clopidogrel-treated patients, p = 0.42). Results were consistent after multivariate analysis (adjusted HR = 1.06 [p = 0.89]). MACE occurred in 6.4% in the newer P2Y12 inhibitor group compared with 9.2% in the clopidogrel group (P<0.01). However, multivariate logistic regression modeling showed that treatment with newer P2Y12 inhibitors was not significantly associated with the secondary endpoint of MACE when compared with clopidogrel therapy [OR = 1.26 95%CI (0.93-1.73), P = 0.136]. The incidence of "real life" EST at 1month is relatively low, and appears to be similar in patients who receive newer P2Y12 inhibitors as well as in those who receive clopidogrel.

Comparison of Noninvasively and Invasively Managed Patients, With or Without Revascularization in Non-ST Elevation Myocardial Infarction (from the Acute Coronary Syndrome Israeli Survey).

Patients with non-ST elevation myocardial infarction who are managed noninvasively at presentation or are catheterized but without revascularization represent a heterogeneous and understudied population. We evaluated the clinical characteristics, management strategies, and outcomes of patients with non-ST elevation myocardial infarction (NSTEMI) who were enrolled in the prospective biannual Acute Coronary Syndrome Israeli Surveys from 2004 to 2013. Patients were divided into 3 groups: no catheterization (no angio), catheterization with revascularization (angio-revascularized), and catheterization without revascularization (angio-nonrevascularized) groups. The study included 3,198 patients with NSTEMI. Coronary angiography was performed in 2,525 (79%) during the index hospitalization, of whom 1899 (59%) underwent revascularization. Evidence-based therapies were administered during the index hospitalization at a significantly higher rate to those in the angio-revascularized group compared with the other 2 groups. Multivariate analysis showed that compared with those in the angio-revascularized and angio-nonrevascularized groups, patients in the no angio group experienced a significantly higher risk for 1-year mortality (hazard ratio 2.04 [p ≤0.0001] and 1.21 [p = 0.01], respectively). The risk associated with no revascularized was consistent in each risk subset analyzed, including an older age, and increased creatinine levels. In conclusion, our data, from a large real-world contemporary experience, suggest that patients with NSTEMI who do not undergo coronary revascularization during the index hospitalization represent a greater risk and undertreated group with increased risk for long-term mortality.

Prevalence and Significance of Unrecognized Renal Dysfunction in Patients with Acute Coronary Syndrome.

BACKGROUND: Unrecognized renal insufficiency, defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) in the presence of normal serum creatinine, is common among patients with acute coronary syndrome. We aimed to determine the prevalence and clinical significance of unrecognized renal insufficiency in a large unselected population of patients with acute coronary syndrome. METHODS: The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli biennial Surveys during 2000-2013. The estimated glomerular filtration rate was calculated using the simplified Modification of Diet in Renal Disease formula. Patients were stratified into 3 groups: 1) normal renal function (estimated glomerular filtration rates ≥60 mL/min/1/73 m(2)); 2) unrecognized renal insufficiency (estimated glomerular filtration rates <60 mL/min/1/73 m(2) with serum creatinine ≤1.2 mg/dL); and 3) recognized renal insufficiency (estimated glomerular filtration rates <60 mL/min/1/73 m(2) with serum creatinine ≥1.2 mg/dL). The primary endpoint was all-cause mortality at 1 year. RESULTS: Included in the study were 12,830 acute coronary syndrome patients. Unrecognized renal insufficiency was present in 2536 (19.8%). Patients with unrecognized renal insufficiency were older and more frequently females. All-cause mortality rates at 1 year were highest among patients with recognized renal insufficiency, followed by patients with unrecognized renal insufficiency, with the lowest mortality rates observed in patients with normal renal function (19.4%, 9.9%, and 3.3%, respectively, P <.0001). Despite their increased risk, patients with renal insufficiency were less frequently referred for coronary angiography and were less commonly treated with guideline-based cardiovascular medications. CONCLUSIONS: Acute coronary syndrome patients with unrecognized renal insufficiency should be considered as a high-risk population. The question of whether this group would benefit from a more aggressive therapeutic approach should still be evaluated.

Temporal trends in all-cause mortality of smokers versus non-smokers hospitalized with ST-segment elevation myocardial infarction.

BACKGROUND/OBJECTIVES: Over the past decade, the development of novel management strategies has resulted in improved outcomes among patients hospitalized with ST-segment myocardial infarction (STEMI). The aim of the present study was to compare temporal trends in the mortality of smokers versus non-smokers admitted with STEMI in a real world setting between 2000 and 2010. METHODS: We evaluated time-dependent changes in the clinical characteristics, management strategies, and one year all-cause mortality of STEMI patients who were enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) between 2000 and 2010, categorized as smokers (n=2399) and non-smokers (n=3069). We divided the survey periods into early (2000-2004) and late (2006-2010). The primary endpoint of the study was the occurrence of one-year all-cause mortality. RESULTS: A total of 4564 STEMI patients were enrolled in the study. Compared with non-smokers, smokers were significantly younger and displayed a significantly lower rate of all-cause mortality at 30 days and 1-year. Both smokers and non-smokers who were enrolled in the late survey period received more evidence-based therapies (primary PCI and guideline-based medications) (p<0.001 for all). There was a significant reduction in the risk of 1-year all-cause mortality only among non-smokers (HR=0.664 CI 95% 0.52-0.85, p=0.0009), whereas smokers who were enrolled in more recent survey periods did not display a significant risk reduction (HR=1.08 CI 95% 0.77-1.51, p=0.67). CONCLUSION: Survival following STEMI among smokers has not improved over the past decade despite corresponding changes in management strategies. Future trials should focus on reducing the risk in smokers.

Correcting for bias in estimation of quantitative trait loci effects.

Estimates of quantitative trait loci (QTL) effects derived from complete genome scans are biased, if no assumptions are made about the distribution of QTL effects. Bias should be reduced if estimates are derived by maximum likelihood, with the QTL effects sampled from a known distribution. The parameters of the distributions of QTL effects for nine economic traits in dairy cattle were estimated from a daughter design analysis of the Israeli Holstein population including 490 marker-by-sire contrasts. A separate gamma distribution was derived for each trait. Estimates for both the alpha and beta parameters and their SE decreased as a function of heritability. The maximum likelihood estimates derived for the individual QTL effects using the gamma distributions for each trait were regressed relative to the least squares estimates, but the regression factor decreased as a function of the least squares estimate. On simulated data, the mean of least squares estimates for effects with nominal 1% significance was more than twice the simulated values, while the mean of the maximum likelihood estimates was slightly lower than the mean of the simulated values. The coefficient of determination for the maximum likelihood estimates was five-fold the corresponding value for the least squares estimates.