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Background: Little is known about the prevalence of orthostatic hypertension (OHT) and its effect on long-term mortality in the elderly. We evaluated the prevalence of OHT and its effect on mortality in hospitalized elderly patients., Methods: Out of 1852 patients admitted between 31/12/1999 and 31/12/2000 to an acute geriatric ward, 474 patients (48% males) with a mean age of 81.5 ± 6.8 years were enrolled in this study. Blood pressure (BP) was measured three times during the day in a supine and standing position. Patients with at least one increase in systolic or diastolic BP levels upon standing were diagnosed with OHT. Medical history, physical examination and laboratory parameters were retrieved from the medical records. Mortality data until 18(th) June 2014 were retrieved from the computerized system of the Ministry of the Interior., Results: Four hundred and seven patients (86%) were diagnosed with OHT. Those without OHT had a lower body mass index and were more likely males, smokers, had a higher rate of Parkinson's disease and less congestive heart failure compared with those with OHT. Patients with OHT had a better survival rate than those without OHT (P = 0.024). Hazard ratios (HRs) for mortality in those with OHT adjusted to age and multiple risk factors were: 0.67 [95% confidence interval (CI): 0.51-0.87] and 0.73 (95% CI: 0.55-0.97), respectively; a similar tendency was noticed in a sensitivity analysis by gender., Conclusion: Hospitalized elderly patients with OHT had a better survival rate than those without OHT.

Background: Pregnancy-induced hypertension (PIH) is associated with chronic hypertension (HTN) and cardiovascular complications. We investigated the factors that predict the development of chronic HTN in women with PIH., Methods: The study population comprised 108 women with PIH and 87 healthy age-matched women control subjects who gave birth during the years 1990-1994 at the Chaim Sheba Medical Center, Israel, and were followed for up to 23 years (average 20.8 ± 1.4). We analyzed the association between PIH and subsequent HTN and cardiovascular complications, aiming to identify predicting factors for the development of chronic HTN in this subject population., Results: At the time of index pregnancy, women with PIH were more likely to be overweight, had elevated blood pressure (BP) levels, a shorter gestational period, required more cesarean sections, and were more likely to deliver small infants than the control group. Compared to women with normotensive pregnancy, women with PIH had 11-fold higher age-adjusted risk of developing HTN. They also had a higher body mass index (BMI), and were more likely to develop diabetes mellitus (DM) and coronary artery disease, during follow-up. Among women with PIH, those subjects who developed HTN were older during pregnancy, had higher BMI and more deliveries before the index pregnancy., Conclusion: Our findings confirm the association between PIH and chronic HTN. In women with PIH, high BMI and more previous pregnancies are risk factors for developing HTN. Thus, obese women with multiple pregnancies who develop PIH should be more closely followed for the development of HTN., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Glycated hemoglobin (HgbA1c) is extensively used as a screening tool for the diagnosis of diabetes mellitus (DM). Although its prognostic value among diabetics has been extensively studied, similar data among non-diabetics is scarce. The aim of this study was to evaluate the association between HgbA1c and mortality in non-diabetic elderly individuals., Methods: A review of a computerized database of a large health care organization was performed. Non-diabetic individuals≥65years old with HgbA1c levels<6.5% evaluated during the years 2002-2012 were included in the analysis. Subjects were stratified into quintiles based on HgbA1c levels. Hazard ratios (HR) for mortality were compared between the quintiles., Results: The cohort included 12,937 non-diabetic individuals≥65years who did not develop DM during the follow-up period. The lowest mortality rate was observed in the fourth HgbA1c quintile [HgbA1c 5.9-6.1% (41-43mmol/mol)]. Compared with the mortality rate in the fourth quintile, mortality rate was increased in the lowest (HgbA1c<5.39%, 35mmol/mol, HR 1.21 CI 1.09-1.35) and highest (HgbA1c>6.11%, 43mmol/mol, HR 1.17 CI 1.04-1.32) HgbA1c quintiles. This association persisted after adjustment for age, gender and co-morbidities., Conclusions: The association between HgbA1c and all-cause mortality in non-diabetic elderly individuals has a U-shape form with the highest mortality in those with the lowest and highest HgbA1c levels., (Copyright © 2015. Published by Elsevier B.V.)

Inter-arm blood pressure difference (IAD) has been found to be associated with cardiovascular mortality. Its clinical significance and association with mortality in the elderly is not well defined. This study evaluated the association of IAD with mortality in a cohort of hospitalized elderly individuals. Blood pressure (BP) was measured simultaneously in both arms in elderly individuals (older than 65 years) hospitalized in a geriatric ward from October 2012 to July 2014. During the study period, 445 patients, mostly women (54.8%) with a mean age of 85±5 years, were recruited. Systolic and diastolic IAD were >10 mm Hg in 102 (22.9%) and 76 (17.1%) patients, respectively. Patients were followed for an average of 342±201 days. During follow-up, 102 patients (22.9%) died. Mortality was not associated with systolic or diastolic IAD. It is therefore questionable whether BP should be routinely measured in both arms in the elderly., (© 2015 Wiley Periodicals, Inc.)

Hypothesis: We aimed to describe the kinetics and associated prognostic implications of the cardiac troponin release curve after a primary percutaneous coronary intervention (PPCI) in patients presenting with ST-segment elevation myocardial infarction (STEMI)., Patients and Methods: We prospectively determined, in a prespecified timely manner, serial cardiac troponin I levels and obtained clinical, ECG, and echocardiographic data from 175 consecutive patients hospitalized with STEMI who underwent PPCI. The median peak troponin levels and time until troponin peaking were determined., Results: The troponin elevation curve following PPCI was single peaked, with a median value measuring 715 times the upper normal limit and a median peaking time of 8 h. Later-peaking troponin levels were associated with a TIMI flow grade of 0/1 at the initiation of angiography and with lack of at least 70% regression in the ST-elevation on the first post-PPCI ECG. Higher peak values were similarly associated with these two parameters as well as with a lower blush score and with distal embolization during PPCI. Both higher peak values and later peaking of troponin were associated independently with higher occurrence of the combined adverse cardiovascular event outcomes consisting of death, congestive heart failure, and recurrent infarction., Conclusion: The cardiac troponin elevation curve following PPCI for STEMI shows a single peak and is affected by the adequacy of myocardial reperfusion. This method can serve as a simple surrogate for risk stratification of patients with STEMI who undergo PPCI.

Early identification of patients at risk for coronary heart disease is crucial to formulate effective preventive strategies. The elevated risk of coronary artery calcium (CAC) for coronary heart disease is well established. Our aim was to estimate the relative risk of abnormal exercise electrocardiography (Ex ECG) in the presence of CAC. During the year 2001, 566 asymptomatic subjects performed a treadmill exercise test and consented to perform an unenhanced computed tomography to assess CAC. Patients were followed until December 2012. The relative risk for coronary events (acute myocardial infarction, hospitalization for unstable angina or coronary catheterization that resulted in angioplasty or coronary artery bypass surgery), of abnormal Ex ECG and presence of CAC were analyzed. An abnormal Ex ECG was found in 71 subjects (12.5%), and CAC was found in 286 subjects (50.5%). During a mean follow-up of 6.5 ± 3.3 years, 35 subjects experienced a first coronary event. In those without CAC, the rate of coronary events was low (4 of 280; 1.4%) regardless of the Ex ECG results. Subjects with both CAC and abnormal Ex ECG had the highest rate of coronary events (13 of 39; 33%). The adjusted hazard ratio for coronary events, in subjects with CAC, was 5.16 (95% confidence interval 2.52 to 10.60) in those with abnormal Ex ECG compared with those with normal Ex ECG. In conclusion, in subjects with CAC, further risk stratification can be achieved by an Ex ECG, whereas in those without CAC, an Ex ECG has less additional value in predicting coronary events., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: Perioperative urinary retention (POUR) is common among hip fracture patients. The aim of the present study was to compare the prevalence, risk factors, functional outcomes and survival rates of patients with and without POUR., Methods: This was a retrospective chart review study that was carried out in an orthogeriatric hip fracture unit. A total of 639 consecutive hip fracture patients who had hip surgery followed by a standard rehabilitation course participated in the study. Post-void residual volume (PVRV), Functional Independence Measure (FIM) scores (total and motor FIM, FIM gain) and mortality rates (90 and 365 days, end of follow up) were measured., Results: A total of 328 patients (51.3%) suffered from POUR. Diabetes (OR 1.55, 95% CI 1.04-2.31), urinary infection (OR 3.25, 95% CI 2.16-4.90) and delirium (OR 1.66. 95% CI 1.09-2.52) emerged as the best predictors for POUR. Functional gains were slightly better in patients without POUR (P = 0.037 and P = 0.023, for discharge motor and total FIM gain, respectively). There were no differences in FIM gains at discharge in male patients, whether with or without POUR. However, female patients without POUR showed significantly better motor and total FIM gains on discharge (P = 0.003 and P = 0.003, respectively), compared with females with POUR. In multiple linear regression analyses, POUR in female (but not male) patients was predictive for adverse motor FIM gain (beta = -0.089, P = 0.046). In Cox regression analysis, urinary retention was not associated with mortality rates., Conclusions: POUR is highly prevalent in elderly hip fracture patients. It adversely affects the functional outcome of female patients, but is not associated with increased mortality rates., (© 2014 Japan Geriatrics Society.)

Background: Contemporary therapiesimprove prognosis and may restore left ventricular (LV) sizeand function., Objectives: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM)., Methods: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by > or = 10% concomitant with > or = 10% decreased LV end-diastolic dimension., Results: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the SRR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, Iower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose wasrelated to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01)., Conclusions: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures.

Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the association between UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 55±7 years) were evaluated for the presence of CAC. The study population was divided into three tertiles according to their UA levels, and the prevalence of CAC was compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of UA were significantly higher in those with CAC than in those without CAC (5.6+1.2 vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs lowest UA tertile was 1.72 (95% confidence interval, 1.17-2.51). The highest UA tertile remained associated with the presence of CAC after adjustment for known cardiovascular risk factors. The results show that high serum UA levels are associated with the presence of CAC., (©2014 Wiley Periodicals, Inc.)

Background: Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]., Methods: The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects' electronic records were used to build a biochemical and clinical database., Results: Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07-4.31)., Conclusions: Anaemia is more common in diabetic patients even when eGFR > 60 mL/min., (Copyright © 2013 John Wiley & Sons, Ltd.)

The association between exaggerated blood pressure (BP) response to exercise (ExBPR) and "masked hypertension" is unclear. Medical records of patients with high-normal BP who were evaluated in the Chaim Sheba Screening Institute Ramat Gan, Israel, during the years 2002-2007 and referred for 24-hour ambulatory BP monitoring (ABPM) and exercise test were reviewed. Data on exercise tests performed in the preceding 5 years were retrieved. Reproducible ExBPR was defined when it was recorded at least twice. BP levels on 24-hour ABPM were compared between patients with a normal BP response and those with an ExBPR (systolic BP ≥200 mm Hg). Sixty-nine normotensive patients with high normal BP levels were identified. ExBPR was recorded in 43 patients and was reproducible in 28. BP levels on 24-hour ABPM were similar in patients with and without ExBPR. In patients with high-normal BP levels, ExBPR is not associated with masked hypertension., (©2014 Wiley Periodicals, Inc.)

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Coronary artery calcification (CAC) is closely related to coronary atherosclerosis. However, less is known about the clinical significance of extensive CAC (ECAC) in regard to types of first coronary events (acute vs. chronic). Diabetes mellitus (DM) represents a strong risk factor for CAD although its association with CAC is controversial. Aiming to elucidate these controversies we investigated the long-term outcome of coronary artery disease (CAD) in relation to degree of CAC in patients with and without DM from our annual cheek-up outpatient clinic., Methods: Coronary artery computed tomography (CT) was performed in 667 patients who were yearly evaluated during a mean follow-up period of 6.3 ±3.4 year. The following 4 CAC categories were established: calcium absence; total calcium score (TCS): 1-100 AU; TCS: 101-600 AU and ECAC: TCS above 600 AU. Acute event was defined as first acute myocardial infarction (MI) or a new unstable angina. First chronic event was defined as a positive stress test with a consequent elective percutaneous coronary intervention or coronary artery bypass grafting., Results: 628 subjects (94%) were free from any cardiac events, 39 (6%) experienced first cardiac event: 18 of them suffered acute and 21 chronic events. There were 67 patients with and 600 patients without DM: 78% of patients with DM presented CAC vs. 50% of patients without DM (p < 0.001).The mean TCS was 17 times higher in the chronic than in the acute events group: 914 vs. 55 AU, p < 0.001. In 95% of the patients with chronic events more than one calcified vessel was found, compared to 67% of the patients with acute events and only 30% of those without events (p < 0.001). Incidence of CAD events (all types pooled together) rose consequently from 2% in subjects without CAC to 34% in subjects with ECAC (p < 0.001). However, among the 32 subjects with ECAC, 11 (34%) developed chronic event while none of them had acute event. In contrast, none of subjects with TCS =0 or TCS 1-100 AU presented with chronic events. Subjects with TCS 101-600 AU presented 10 (9%) chronic and 5 (4.5%) acute events (p < 0.001)., Conclusions: Asymptomatic subjects with ECAC are not firstly manifested as acute coronary events but presented a high level of chronic CAD-related events during the 6.3 ±3.4 year follow-up. In contrast, first acute CAD-related events occurred mostly in subjects with mild and moderate CAC score.

Objective: To study the advantage of intracytoplasmic morphologically selected sperm injection (IMSI) versus intracytoplasmic sperm injection (ICSI) in the first artificial reproductive technology (ART) cycle and in consecutive cycles., Design: A cohort study., Setting: Single outpatient fertility center., Patient(s): Couples presenting with male factor infertility, requiring ovum micromanipulation., Intervention(s): The ICSI or IMSI was performed according to the couple's choice., Main Outcome Measure(s): Clinical intrauterine pregnancies and deliveries., Result(s): A total of 1,891 IVF-ICSI cycles and 577 IVF-IMSI cycles were included. In the first IVF treatment, pregnancy rates (PRs) were 46% and 47%, respectively, and delivery rates were 23% versus 30%, respectively. In the second cycle to follow a failed ICSI, PRs and delivery rates were significantly higher for patients who chose to shift to the IMSI technique compared with patients who chose to go through a second IVF-ICSI cycle (56% vs. 38% PRs and 28% vs. 18% delivery rates, respectively). In the following cycles a significant difference was demonstrated in both PR and delivery rates in favor of patients shifting between treatments. In a multivariate analysis an approximate threefold increased chance existed for both pregnancy and delivery only in the case of couples failing an ICSI attempt who shifted to IMSI., Conclusion(s): Our present experience supports refraining from repeated IMSI cycles. In light of improved PRs and delivery rates, we recommend promoting the IMSI method for couples who failed ICSI cycle, once or more., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To study possible differences in rehabilitation outcomes of patients with hip fracture, with and without atrial fibrillation., Methods: A retrospective cohort study comprising 1114 patients, divided into three groups: patients with sinus rhythm, paroxysmal atrial fibrillation or chronic atrial fibrillation. All patients underwent a standard orthogeriatric care comprising surgical hip repair and a rehabilitation course. Main outcome measures included functional status at discharge by the Functional Independence Measure, post-fracture functional status category and type of postdischarge living arrangement., Results:   Patients with atrial fibrillation differed from patients in sinus rhythm by female sex (P = 0.018), older age (P = 0.008) and higher rates of heart failure (P < 0.001), ischemic heart disease (P < 0.001), previous stroke (P < 0.001), and American Society of Anesthesiologists score (P < 0.001). No differences were observed among the three groups regarding Functional Independence Measure motor and total scores. In regression analysis, Mini-Mental State Examination (P < 0.001), prefracture status (P < 0.001), postsurgery motor Functional Independence Measure (P < 0.0001) and Parkinson's disease (P = 0.009) were predictive of higher motor Functional Independence Measure at discharge, whereas atrial fibrillation had no predictive value whatsoever. There were no differences among groups in magnitude of postfracture change of functional status category or type of postdischarge living arrangement., Conclusions: Discharge motor Functional Independence Measure scores, postfracture changes in functional status and in discharge placement are similar in hip fracture patients with sinus rhythm, compared with those with atrial fibrillation. Atrial fibrillation should not be considered to adversely affect the rehabilitation outcome of these patients., (© 2012 Japan Geriatrics Society.)

Background and Aims: Prediction of factors associated with survival following hip fracture is important. We studied crude and adjusted survival rates in elderly hip fracture patients with and without atrial fibrillation (AF) to assess possible risk of death associated with AF., Methods: A historical prospective cohort study, comprising 1114 consecutive patients with hip fractures. Subjects were divided into three groups: patients with sinus rhythm (SR), paroxysmal atrial fibrillation (PAF) or chronic atrial fibrillation (CAF). The main outcome measures were crude and adjusted survival rates at 30, 90 and 365 days, and end of follow-up., Results: AF patients differed from SR patients by gender (p=0.0018), age (p=0.008), heart failure (p<0.001), ischemic heart disease (p<0.001) and history of a stroke (p<0.001). The lowest death rates were observed among SR and PAF patients, whereas CAF patients had the highest rates at each follow-up time point. CAF (but not PAF or SR) patients were at a significantly higher risk of death at both 365 days and at the end of the study (HR 1.786, CI 1.011- 3.155 and HR 1.835, CI 1.302-2.585, respectively). Older age (HR 1.301, CI 1.135-1.491 and HR 1.321, CI 1.321-1.415) and male gender (HR 1.879, CI 1.271- 2.779 and HR 1.545, CI 1.251-1.909) also predicted higher risk of death at both 365 days and at the end of the study., Conclusions: Atrial fibrillation cannot be considered to adversely affect short-term survival of hip fracture patients. After 365 day, CAF was associated with a significantly higher risk of death.

Background: The most common ophthalmologic manifestation of hypertension is hypertensive retinopathy. Our study was designed to evaluate the factors that determine retinal vessel caliber in hypertensive subjects., Methods: During a 6-month period, retinal photographs were taken of participants during a routine yearly check-up. The photographs were evaluated by an ophthalmologist and the diameters of the individual retinal vessels were measured and summarized by a computer program. Data including patient's medical history, physical examination and laboratory evaluations were collected. The findings of the ophthalmologic examinations were analyzed with respect to the relevant systemic data., Results: We evaluated 285 subjects (43 women) with an average age of 62 ± 9 years (range 33-87). Hypertension was reported in 204 (71.6%) subjects and diabetes mellitus in 60 subjects (21%). The arteriolar calibers were inversely related to age (R = - 017; p = 0.01). Retinal arteriolar and venular calibers were wider in smokers and in subjects with dyslipidemia. History of hypertension was not associated with any vascular changes. However, retinal arteriolar caliber was inversely related to blood pressure levels. Diuretic treatment was associated with narrow retinal venular caliber., Conclusion: The association between different cardiovascular risk factors and hypertensive retinopathy is complex. Effective blood pressure control has a beneficial effect on the vascular changes in the retina.

The magnesium content in food consumed in the Western world is steadily decreasing. Hypomagnesemia is associated with increased incidence of diabetes mellitus, metabolic syndrome, all-cause and coronary artery disease mortality. We investigated the impact of supplemental oral magnesium citrate versus magnesium oxide on intracellular magnesium levels ([Mg2+]i) and platelet function in healthy subjects with no apparent heart disease. In a randomized, prospective, double-blind, crossover study, 41 (20 women) healthy volunteers [mean age 53±8 (range 31-75) years] received either magnesium oxide monohydrate tablets (520 mg/day of elemental magnesium) or magnesium citrate tablets (295.8 mg/day of elemental magnesium) for one month (phase 1), followed by a four-week wash-out period, and then crossover treatment for one month (phase 2). [Mg2+]i was assessed from sublingual cells through x-ray dispersion (normal values 37.9±4.0 mEq/L), serum magnesium levels, platelet aggregation, and quality-of-life questionnaires were assessed before and after each phase. Oral magnesium oxide, rather than magnesium citrate, significantly increased [Mg2+]i (34.4±3 versus 36.3±2 mEq/L, p<0.001 and 34.7±2 versus 35.4±2 mEq/L, p=0.097; respectively), reduced total cholesterol (201±37 versus 186±27 mg/dL, p=0.016 and 187±28 versus 187±25 mg/dL, p=0.978; respectively) and low-density lipoprotein (LDL) cholesterol (128±22 versus 120±25 mg/dL, p=0.042 and 120±23 versus 121±22 mg/dL, p=0.622; respectively). Noteworthy is that both treatments significantly reduced epinephrine-induced platelet aggregation (78.9±16% versus 71.7±23%, p=0.013 and 81.3±15% versus 73.3±23%, p=0.036; respectively). Thus, oral magnesium oxide treatment significantly improved [Mg2+]i, total and LDL cholesterol compared with magnesium citrate, while both treatments similarly inhibited platelet aggregation in healthy subjects with no apparent heart disease.

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.

Background: Atrial fibrillation (AF) is a major risk factor of ischemic stroke. We tested whether the adoption of the CHADS(2) score in clinical guidelines has impacted treatment strategies for stroke prevention, and examined how AF affects stroke outcome., Methods: In the setting of two national surveys [National Acute Stroke Israeli Surveys; all patients hospitalized for stroke in Israel during February-March 2004, and March-April 2007] data of patients with and without AF were analyzed with respect to patient characteristics, use of anticoagulation, stroke severity, clinical course, and long-term outcome., Results: Of 3040 patients with acute ischemic stroke, 586 patients (19%) had a history of AF. Severe strokes on admission were significantly more frequent in patients with AF, as was the proportion of total anterior circulation strokes. Ischemic stroke associated with AF predicted poor outcome at discharge (adjusted OR 1.56; 95%CI 1.24-1.96) and higher mortality rates throughout follow-up. Among patients with a CHADS(2) score ≥ 2 prior to the index stroke and without known contraindications, 41% received anticoagulation. This proportion increased to only 62% after the index stroke, even after excluding patients with severe disability and no significant increase between 2004 and 2007 was detectable. Increasing age, in-hospital infectious complications, and unfavorable functional status at discharge were independently associated with decreased likelihood of receiving anticoagulation., Conclusions: In deviation from current recommendations and in spite of the introduction of CHADS(2) criteria, anticoagulation for stroke prevention remains underutilized, despite the particularly poor outcome of strokes associated with AF., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: Adverse cardiovascular events (CVE) tend to peak during early morning post-waking hours. Our objective was to explore a possible correlation between early and late morning hours and flow-mediated dilation (FMD), and whether early morning FMD reduction contributes to a circadian pattern of cardiac and vascular vulnerability., Methods: Brachial FMD was prospectively assessed in 268 consecutive healthy subjects, 169 (63%) men, mean age 53 ± 11 years, without any concomitant medications. Following an overnight fast, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high-resolution ultrasound. All subjects were followed up by phone every 6 months for combined CVE, which included all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions., Results: The cohort was divided into Group A with FMD performed immediately post-waking, between 6:00 and 10:00 am [n=151 (56%) subjects], and Group B after 10:00 am [n=117 (46%) subjects]. Although both groups were comparable regarding baseline brachial artery diameter and the prevalence of risk factors, FMD was significantly lower in Group A compared with Group B subjects (10.4 ± 3.4% vs. 13.5 ± 3.5%, p=0.007, respectively). In a mean follow-up of 45 ± 21 months, the composite CVEs were significantly more common in subjects with ≤(n=128) vs. >(n=140) the median FMD of 11.3% [18/128 (14.1%) vs. 1/140 (0.7%), p=0.007, respectively]. Furthermore, FMD independently predicted long-term adverse CVE., Conclusions: FMD is blunted in early compared to late morning post-waking hours, and independently predicts long-term adverse CVE in healthy subjects with no apparent heart disease., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: A number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC., Methods: The study population comprised 510 patients with stable angina pectoris, mean age of 63 ± 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up., Results: CL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups (p=0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 ± 63 from baseline in the 1st (upper) quartile, and by 350 ± 44, 403 ± 41 and 480 ± 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes (p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups (p=0.4). Multivariate analysis demonstrated that only baseline TCS (p < 0.001), body mass index (p = 0.007) and age (p = 0.006) were independent predictors for the TCS changes., Conclusions: Longitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Smoking has been causally linked to cardiovascular disease, and smoking cessation after myocardial infarction (MI) has been associated with a 50% reduction in mortality. Post-MI smokers are a vulnerable population for which efforts to encourage cessation should be maximized. We examined the determinants of smoking cessation after MI., Methods: A population-based cohort of 768 Israeli smokers was followed-up longitudinally after first MI. Data were collected at study entry on demographic, socioeconomic, smoking behaviour, and clinical variables. Psychosocial measures were obtained in a subsample (n = 330). Self-reported smoking status was assessed at 3-6 months, 1-2 years, 5 years, and 10-13 years after MI. Generalized estimating equation analyses determined which factors were significant predictors of smoking status., Results: Point abstinence rates throughout follow-up ranged from 55% to 70%, while continuous abstinence rates were 59% after 1-2 years, 44% after 5 years, and 35% after 10-13 years, among survivors. Variables most strongly associated with persistent smoking were young age, long duration and high intensity of pre-MI smoking, low education, poor family income, lack of a steady partner, non-diabetic status, and short hospital stay at the index MI. Significant psychosocial predictors were low sense of coherence and high depression., Conclusions: Determinants of smoking cessation after MI are multifactorial and include demographic, socioeconomic, smoking behaviour, clinical and psychosocial measures. Post-MI hospitalization is a window of opportunity for smoking cessation interventions. Patients should be assessed for psychosocial characteristics and those with low sense of coherence and high depression should be provided with targeted help to quit.

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The goal of this study was to assess the correlation between true fetal macrosomia and abnormal oral glucose tolerance test (OGTT) in pregnant women at term gestation who had a negative glucose challenge screen (GCT) at 24-28 weeks., Study Design: In this cohort observational study, we enrolled all term pregnant patients who presented to our antenatal unit with estimated fetal weight >90th percentile (or >4,000 g) and negative 50 g GCT. The women underwent a 3-h (100 g) OGTT test. Patient's demographics, GCT and OGTT test results, mode of delivery and pregnancy outcomes were recorded and analyzed., Results: One hundred and seventy women (mean age 30.2+4.6 years, range 19-44) were recruited over 15-month period. Ten patients (5.9%) were identified as having impaired glucose metabolism at term. In this sub-group, we found no correlation between GCT values at 24-28 weeks, family history of diabetes mellitus, the patient's BMI or weight at term, and the diagnosis of impaired glucose metabolism. There was no statistically significant difference in the mean fetal weight in patients with normal and abnormal OGTT. No shoulder dystocia or third and fourth degree vaginal tears were reported among the women with suspected fetal macrosomia and impaired glucose metabolism., Conclusions: There was no correlation between true fetal macrosomia and an abnormal 3-h (100 g) OGTT at term. A larger-scale study is needed to determine the clinical significance of performing an OGTT at term for all patients with macrosomia and negative gestational diabetes screen.

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(-) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.

Background: The incidence of stroke varies among ethnically and culturally diverse groups., Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke., Methods: Patients with documented coronary heart disease were followed for 6-8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measurements of blood lipids. Among 15,052 patients, 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack., Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000), but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin resulting from factors that remain unrecognized, or with variables unassessed in this study., Conclusions: We identified an ethnic diversity in stroke risk among the Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.

Elevated homocysteine levels are associated with increased risk for mortality in patients with coronary artery disease (CAD). However, the benefit of homocysteine-lowering therapy remains controversial. The aim of this study was to examine the impact of homocysteine-lowering therapy on the long-term outcomes of patients with CAD and its interaction with the methylenetetrahydrofolate reductase genotype. The study sample included 492 patients with early-onset CAD who were genotyped for the C677T mutation in the methylenetetrahydrofolate reductase gene or screened for elevated homocysteine from January 1997 to December 2002. Folic acid > or =400 microg/day with or without additional B vitamins was administered at the attending physicians' discretion. There was no difference between treated (n = 140) and untreated patients in age, gender, or prevalence of coronary risk factors. Forty-six patients (9%) died during a median follow-up period of 115 months. Treatment was associated with significantly lower all-cause mortality in patients with homocysteine levels >15 micromol/L (4% vs 32%, p <0.001) but not in patients with lower levels (5% vs 7%, p >0.05). On Cox regression analysis, the following factors were independently associated with all-cause mortality: vitamin therapy (hazard ratio 0.33, 95% confidence interval 0.11 to 0.98, p = 0.046), elevated homocysteine level (hazard ratio 3.5, 95% confidence interval 1.31 to 9.43, p = 0.013), and older age (hazard ratio 1.1, 95% confidence interval 1.04 to 1.14, p <0.0001 for an increment of 5 years). The methylenetetrahydrofolate reductase genotype was not associated with outcomes. In conclusion, long-term folate-based vitamin therapy was independently associated with lower all-cause mortality in patients with CAD and elevated homocysteine levels. This association was not observed in patients with lower homocysteine levels.

Objectives: This study sought to explore the effect of glycemic-index dietary carbohydrates on endothelium-dependent flow-mediated dilation (FMD) in overweight and obese nondiabetic volunteers., Background: Post-prandial hyperglycemia has been recognized as a cardiovascular risk factor in both the diabetic and the general population. Endothelial dysfunction has been shown to occur in diabetic and hyperglycemic patients., Methods: We prospectively assessed brachial artery FMD in 56 healthy overweight and obese nondiabetic volunteers (38 [67.9%] men, mean age 48 +/- 6 years) on 4 separate mornings, 1 to 2 weeks apart. After overnight fasting, the percent FMD (%FMD) improvement and endothelium-independent nitroglycerin-mediated dilation (%NTG) were assessed, after which subjects received 1 of 4 group meals at each visit (placebo [water] or a carbohydrate meal of glucose, cornflakes, or high-fiber cereal). Meals were distributed in a rotating randomized fashion, such that each subject received all 4 meals once throughout the study period., Results: Fasting and 2-h post-prandial serum glucose levels were similar in all 3 meals, whereas at 30 to 90 min, serum glucose levels were significantly higher after glucose and cornflakes (high glycemic) compared with fiber (low glycemic). Baseline %FMD, not significantly different in the 3 carbohydrate-based meals, was reduced 2 h post-prandially in all groups, showing statistical significance in only high-glycemic index meals: glucose (15 +/- 9% vs. 10 +/- 8%, p < 0.01), cornflakes (13 +/- 7% vs. 9 +/- 7%, p < 0.01). No correlation was observed between the %FMD reduction rate and glucose levels throughout the study period., Conclusions: High- compared with low-glycemic carbohydrate consumption significantly suppresses FMD in nondiabetic overweight and obese volunteers, suggesting a mechanism whereby high-glycemic meals may enhance cardiovascular risk.

Background: Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. The aim of this study was to detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects without apparent coronary artery disease (CAD)., Methods: We prospectively assessed brachial flow-mediated dilation (FMD) in 435 consecutive healthy subjects: 281 (65%) men, mean age 54+/-12 years and body mass index 28+/-4 kg/m(2). After overnight fasting and discontinuation of all medications for > or =12 h, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high resolution linear array ultrasound., Results: Subjects were divided into 2 groups: below (n=221) and above (n=214) the median FMD of 10.7%, and were comparable regarding CAD risk factors, lipoproteins, fasting glucose, C-reactive protein, and concomitant medications, with a mean clinical follow-up of 32+/-2 months. Composite cardiovascular endpoints (all-cause mortality, non-fatal myocardial infarction, heart failure or angina pectoris hospitalization, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with below median FMD of 10.7%, than above (11.8% vs 4.7%, p=0.007, respectively). Univariate analysis demonstrated that median FMD significantly predicted cardiovascular events [odds ratio (OR) of 2.78 and 95% CI 1.35 to 5.71 (p=0.003)]. After multivariate analysis including conventional CAD risk factors, median FMD was the best independent predictor of long-term cardiovascular adverse events [OR of 2.70 and 95% CI 1.16 to 6.32 (p=0.011)]., Conclusions: Brachial artery median FMD independently predicts long-term adverse cardiovascular events in healthy subjects in addition to traditional risk factor assessment.

Aim: To examine the effects of sinus rhythm (SR) restoration on N-Terminal pro-BNP (NTP-BNP) in patients with atrial fibrillation (AF)., Methods: Subjects with paroxysmal and persistent AF and absence of organic heart disease were prospectively studied. Chemical or electrical restoration of SR was attempted within 48 hours (n = 37) or >3 weeks (n = 73). Clinical and laboratory (NTP-BNP, 72-hour Holter monitor, and electrocardiogram) assessment were obtained at baseline and at 1, 30, and 180 days after SR restoration. Patients were divided into three predefined "outcome groups": (a) maintenance of SR for 1 month, (b) SR with recurrent paroxysmal AF (PaAF), and (c) early (<30 days) recurrence persistent AF (RAF)., Results: Of the 110 patients enrolled, 89 had initial successful SR restoration. Baseline NTP-BNP was 936 pg/mL (interquartile range (IQR) 333-2,026); ratio between baseline and 30-day NTP-BNP was 10.2 (IQR 6.42-22.0) for SR group, 3.3 (IQR 2.45-7.34) for PaAF, and 1.07 (IQR 0.87-1.22) for RAF (P < 0.001). Patients with ratio

Background and Purpose: The role of blood lipids and lipoprotein-related variables in the prediction of ischemic stroke is less clear than that for coronary heart disease. Apolipoprotein B (Apo B), which reflects the concentration of potentially atherogenic lipoprotein particles, and apolipoprotein AI (Apo A-I), which reflects the corresponding concentration of the anti-atherogenic HDL, represent additional lipoprotein-related variables that may indicate vascular risk. We examined the association between serum concentrations of Apo B, Apo A-I, and the Apo A-I/Apo B ratio and the risk of incident ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease., Methods: Patients with documented chronic coronary heart disease and measured Apo B and Apo A-I concentration, screened for but not included in a clinical trial of lipid modification were followed over 4.8 to 8.1 years for hospitalized incident cerebrovascular events., Results: Among 3,434 patients 266 (7.7%) developed an incident ischemic cerebrovascular event. Adjusting for potential confounders, the hazard ratios (HR) for incident ischemic cerebrovascular events associated with the top versus bottom quartile of Apo B was 1.68 (95%CI, 1.18-2.40), of Apo A-I 0.71 (95%CI, 0.50-1.00), and of Apo A-I/Apo B ratio 0.51 (95%CI, 0.35-0.74)., Conclusions: These findings support the hypothesis that Apo B, Apo A-I and the Apo A-I/Apo B ratio predict incident ischemic stroke among patients with preexisting atherothrombotic disease. The potential clinical role of measuring these apolipoproteins for ischemic stroke prediction warrants further study.

Individuals involved in intense resistance training present with increased absolute left ventricular (LV) wall thickness and mass and show good systolic responses to isometric exercise. There is no consensus regarding diastolic features and no available information regarding diastolic function in athletes during isometric exertion itself. Therefore, the main aim of this study was to assess diastolic LV function at baseline and during exercise in athletes. The population consisted of 96 men (mean age 29 +/- 7 years): 48 weight lifters who trained for 15 to 20 hours/week and 48 sedentary men. All weight lifters had been active for >6 years, including the 6 months before the study. Ultrasound was performed using a commercially available Doppler echocardiographic system. Isometric exercise was performed in the supine position using a standard 2-hand bar dynamometer. The man end-diastolic volumes at rest were 97 +/- 6 ml in sedentary subjects and 101 +/- 5 ml in weight lifters, increasing to 100 +/- 6 and 118 +/- 11 ml during exercise (p = 0.06 and p <0.01, respectively). End-systolic volumes at rest were similar in the 2 groups, showing significantly greater reductions during exercise in the weight lifters. The mean absolute LV mass was 167 +/- 30 g in sedentary subjects and 202 +/- 32 g in weight lifters (p <0.0001). The mean stroke volume increased from 65 +/- 7 to 86 +/- 7 ml in sedentary subjects and from 70 +/- 6 to 107 +/- 11 ml in weight lifters (intergroup significance p = 0.05 and p <0.01, respectively). A similar pattern of response was documented for the ejection fraction (i.e., significantly greater increases during exercise in weight lifters). Regarding diastolic indexes, in the weight lifters, the mean peak early velocity at rest was 68 +/- 7 cm/s, the mean acceleration rate was 1,242 +/- 176 cm/s/s, and the mean deceleration rate was 414 +/- 44 cm/s/s. All these values were significantly higher than in sedentary subjects, with further increases during exercise (p <0.0001). In weight lifters, the mean peak atrial velocity at rest was 37 +/- 6 cm/s, the mean acceleration time was 55 +/- 4 ms, the mean isovolumic relaxation time was 63 +/- 3 ms, and the mean deceleration time was 164 +/- 4 ms; these values were lower than in sedentary subjects (p <0.0001 for all). In conclusion, intense resistance training leads to enhanced LV diastolic function at rest and during isometric exercise despite the markedly increased LV mass.

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD development in women are limited and conflicting., Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel., Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age < or = 65 years. DNA samples from 235 women served as the control., Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 +/- 7.0 years vs. 48.3 +/- 7.5 and 46.3 +/- 7.7 years, respectively, P= 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P= 0.037) and Ashkenazi control subjects (23.3%, P= 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 45 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12-13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P= 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI 0.189-1.114) and in women of other origins, 5.84 (95%CI 1.76-19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR 1.42, 95%CI 1.06-1.89)., Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Background: Exercise training can improve aerobic capacity and symptoms in congestive heart failure (CHF) patients., Aims: To test the feasibility of exercise training in advanced CHF patients, and examine the potential benefit from peripheral vascular and muscular conditioning as well as improved central hemodynamic and neurohumoral status., Methods and Results: Thirty NYHA functional class III, CHF patients (mean age 61+/-13 yr, ejection fraction 27+/-4%, VO2max 11.3+/-3.9 ml/kg/min) were enrolled. Exercise capacity, cardiovascular parameters and serum levels of brain natriuretic peptide (NT-proBNP) were determined at baseline and after 18 weeks of moderate intensity exercise training. Twenty eight (93%) patients, who completed the exercise program, experienced marked improvements in the 6 min walk (+39%) and exercise duration on the modified Bruce protocol (+66%). Smaller improvements were recorded in the cardiac index (a 15% increase), in the maximal oxygen consumption (a 13% increase in VO2max), in the left ventricular ejection fraction (an 11% increase) and in the systemic vascular resistance and pulmonary artery pressure (an 11% decrease). NT-proBNP levels were not significantly affected. They correlated with exercise capacity and VO2max on baseline measurement, but these correlations were not found after training., Conclusion: Rehabilitation is feasible, even in advanced CHF, and leads to markedly improved exercise performance, but does not affect the level of the principal neurohumoral marker of prognosis - NT-proBNP. Resting cardiovascular performance and maximal oxygen consumption improve less than functional capacity, suggesting that an important benefit is derived from muscle conditioning and improved peripheral vascular response to exercise.

Inherited disorders of hemostasis are natural models for investigating mechanisms of thrombosis and development of antithrombotic therapy. Because mice with total factor XI deficiency are protected against ischemic stroke and do not manifest excessive bleeding, we investigated the incidence of ischemic stroke in patients with severe inherited factor XI deficiency. Incidence of ischemic stroke in 115 patients aged 45 years or more with severe factor XI deficiency (activity less than 15 U/dL) was compared with incidence in the Israeli population as estimated from a stroke survey of 1528 patients. Adjustment for major risk factors of stroke (hypertension, diabetes mellitus, hypercholesterolemia, current smoking) was based on comparison of their prevalence in the stroke survey to an Israeli health survey of 9509 subjects. Incidence of myocardial infarction in the factor XI cohort was also recorded. After adjustment for the 4 major risk factors of ischemic stroke, the expected incidence of ischemic stroke was 8.56 compared with one observed (P = .003). The reduced 1:115 incidence of ischemic stroke contrasted with a 19:115 incidence of myocardial infarction, similar to the expected incidence. Thus, severe factor XI deficiency probably is protective against ischemic stroke but not against acute myocardial infarction.

Background: Patients with coronary heart disease (CHD) are at increased risk of stroke. We investigated in a large cohort of patients with CHD the relationship between functional status, as assessed by the New York Heart Association (NYHA) classification, and incident ischemic stroke., Methods: We followed up 15,524 patients with documented CHD, screened for inclusion in a clinical trial (Bezafibrate Infarction Prevention), for 4.8 to 8.1 years. Functional status at baseline was categorized according to the NYHA classification. Among 14,703 patients, free of stroke, with recorded NYHA functional class, 1086 (7.4%) developed an ischemic cerebrovascular event, of whom 604 (4.1%) patients were confirmed to have an ischemic stroke or transient ischemic attack., Results: The cumulative rate of ischemic cerebrovascular events increased from 6.7% in patients with NYHA functional class I to 9.2% and 9.7% for patients with NYHA functional classes II and III, respectively (P < .001). Adjustments were made in Cox proportional hazard models for age, sex, body mass index, past myocardial infarction, current smoking, diabetes, hypertension, peripheral vascular disease, percent of cholesterol in high-density lipoprotein, and triglyceride levels. The adjusted hazard ratios associated with NYHA functional class II and III were 1.29 (95% confidence interval 1.12-1.48) and 1.71 (95% confidence interval 1.36-2.15), respectively, as compared with patients with NYHA class I., Conclusions: Our findings indicate that stable coronary patients with even a slight limitation based on the NYHA functional class are exposed to an increased risk of ischemic stroke.

Left ventricular hypertrophy (LVH) has been associated with hypertension, although debate exists as to whether LVH is caused by elevated blood pressure (BP) or is a risk factor for its development. The present study evaluates the association between left ventricular structure and the development of hypertension in a young healthy population. We followed young healthy Israeli Air Force aviators from initial echocardiography at the start of their military service to a mean of 7.5+/-3.0 years. Data collection included annual BP measurements, height, weight, smoking habits, and lipid profile. We monitored 500 Air Force men with a mean age of 20.5+/-3.3 (range, 17-40) years and baseline BP of 125+/-13/74+/-8 mmHg. Systolic BP during follow-up was associated with baseline systolic BP, interventricular septum (IVS) thickness, and ejection fraction, whereas diastolic BP was associated only with baseline diastolic BP and body mass index. The probability that the systolic BP during follow-up would be higher than the median was twice that in those with an IVS thickness greater than the median. In conclusion, IVS thickening was associated with long-term elevation of systolic BP. Therefore, it seems that IVS thickening is not merely a result of long-term BP elevation, but may predict the development of systolic hypertension.

Background: Coronary heart disease and ischemic stroke are among the leading causes of morbidity and mortality in adults, and cerebrovascular disease is associated with the presence of symptomatic and asymptomatic CHD. Several studies noted an association between coronary calcification and thoracic aorta calcification by several imaging techniques, but this association has not yet been examined in stable angina pectoris patients with the use of spiral computed tomography., Objectives: To examine by spiral CT the association between the presence and severity of CC and thoracic aorta calcification in patients with stable angina pectoris., Methods: The patients were enrolled in ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) in Israel. The 432 patients (371 men and 61 women aged 40-89 years) underwent chest CT and were evaluated for CC and aortic calcification., Results: CC was documented in 90% of the patients (n = 392) and aortic calcification in 70% (n = 303). A significant association (P < 0.05) was found between severity of CC and severity of aortic calcification (as measured by area, volume and slices of calcification). We also found an association between the number of coronary vessels calcified and the presence of aortic calcification: 90% of patients with triple-vessel disease (n = 157) were also positive for aortic calcification (P < 0.05). Age also had an effect: 87% of patients > 65 years (n=219) were positive for both coronary and aortic calcification (P = 0.005) while only 57% < or = 65 (n = 209) were positive for both (P = 0.081)., Conclusions: Our study demonstrates a strong association between the presence and severity of CC and the presence and severity of calcification of thoracic aorta in patients with stable angina pectoris as detected by spiral CT.

Aim: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET)., Methods: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET., Results: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all)., Conclusions: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Background and Objective: T1DM and asthma are mediated by opposite arms of the cellular immune system namely T helper (Th)1 and Th2 CD4(+) cells, respectively. Our aim was to characterize the Th1/Th2 cytokine balance in patients with both T1DM and asthma., Methods: Forty-four patients, mean age 19 years were matched by gender and age, to 4 paired groups: T1DM and asthma, asthma only, T1DM only and healthy controls. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with disease-specific recombinant antigens; glutamic acid decarboxylase and house dust mite (Der p1 antigen) for T1DM and asthma, respectively, and non-specific mitogens; phytohemaglutinin (PHA), tetanus toxin and anti-CD3 mAb. ELISPOT and ELISA technique were used to determine INF-gamma, IL-2, IL-4, IL-13 and IL-10 expression., Results: Patients with T1DM and asthma demonstrated a similar cytokine pattern but lower Th1/Th2 ratio compared to patients with T1DM only. The Th2 cytokines response to Der p1 was enhanced in patients with both diseases compared to controls. The IL-10 overall secretion was higher in patients with both diseases compared to one disease only., Conclusion: The Th1 and Th2 secretory pattern of patients with T1DM and asthma combines features of both diseases suggesting a unique Th1/Th2 balance.

Background: There are no national data on the burden and management of acute cerebrovascular disease in Israel., Objectives: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines., Methods: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004., Results: During the survey period 2174 patients were admitted with acute cerebrovascular disease (mean age 71 +/- 13 years, 47% women; 89% ischemic stroke or TIA, 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of medicine and a third to neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean (+/-SD) length of hospital stay was 12 +/- 27 days for ICH and 8 +/- 11 days for ischemic stroke. Among patients with ICH, 28% died during hospitalization and 66% died or remained with severe disability while for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke., Conclusions: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.

Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG--7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG--3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL., (Copyright 2006 S. Karger AG, Basel.)

Background: Malnutrition is prevalent in elderly populations. Recommended methods of nutritional screening are often too complicated and time-consuming for routine application in frail, very old, hospitalized patients., Objective: Our aims were to identify risk factors for development of malnutrition in very old hospitalized patients and to evaluate the total Mini Nutritional Assessment (MNA) score and MNA subscores as predictors of in-hospital and long-term mortality., Design: A prospective cohort study of patients aged > or =75 y was conducted in a geriatric hospital. Assessment included demographic, clinical, and laboratory data and cognitive, functional, and nutritional status. Follow-up was conducted for < or =2.7 y., Results: Of the 414 patients studied, only 73 (17.6%) were well-nourished. Low serum albumin and phosphorus concentrations, dementia, and cerebrovascular accident (CVA) were significant risk factors for malnutrition. Survival was significantly lower in malnourished patients and patients at risk of malnutrition than in well-nourished patients (P < 0.0001). Low MNA-3 subscores (dietary habits) were significantly correlated with laboratory indexes of malnutrition and were significantly lower in patients with infections, malignancy, pressure ulcers, dementia, recent orthopedic surgery, and CVA. Multivariate analysis showed that a low MNA-3 score was an independent predictor of mortality; scores <7.5 increased the risk of death 2.05-fold., Conclusions: The prevalence of malnutrition was high in elderly hospitalized patients. Dietary habits were significant predictors of poor hospitalization outcome. A questionnaire on dietary habits can serve as a useful tool in assessing nutritional status and prognosis in elderly patients.

Purpose: White blood cell (WBC) count is a marker of inflammation and has been associated with the development of cardiovascular disease. We investigated the relationship between WBC counts and the incidence of ischemic cerebrovascular disease in a large cohort of patients with pre-existing atherothrombotic disease and defined blood lipid boundaries., Subjects and Methods: We followed up patients with documented coronary heart disease for 4.8 to 8.1 years. An extensive medical evaluation, conducted at baseline, included assessment of vascular risk factors and measures of blood lipids. Among 5435 patients with WBC counts, free of stroke, 295 developed an ischemic cerebrovascular disease (fatal and nonfatal). After review of available medical records, 186 of these cases had ischemic stroke or TIA., Results: Higher WBC counts were associated with increased risk for ischemic cerebrovascular disease. Age-adjusted hazard ratio (HR) was 1.55 with 95% confidence interval (CI) 1.16-2.07, upper WBC tertile compared with the lowest. Adjusting for clinical covariates, WBC count remained an independent predictor for ischemic cerebrovascular disease (HR = 1.39; 95% CI 1.03-1.87, upper WBC tertile compared with the lowest). A similar trend appeared for the endpoint of ischemic stroke/transient ischemic attack (TIA). Further adjustment for plasma fibrinogen did not change the association materially (HR = 1.32; 95% CI 1.01-1.80; upper tertile of WBC compared with lowest)., Conclusions: These findings support the role of WBC count as a simple inexpensive and readily available marker for risk stratification of ischemic cerebrovascular disease among patients with pre-existing atherothrombotic disease and defined blood lipid boundaries.

Purpose: To prospectively compare the results of coronary artery calcium (CAC) measurements obtained with 55- and 165-mAs electrocardiographically gated multi-detector row computed tomography (CT)., Materials and Methods: Institutional clinical study review board approval and written informed consent were obtained. Fifty-one consecutive subjects (mean age, 59 years +/- 10) were scanned consecutively by using 165 and 55 mAs. For each examination, the number of lesions, total calcium score (TCS) calculated with Agatston algorithm (130-HU threshold), and calcium mass (in milligrams) were measured. Noise was measured by averaging 1 standard deviation of the CT attenuation values in five consecutive transverse sections of the ascending aorta. Paired t test and Pearson correlation were used to compare measurements between the examinations., Results: By using 55 mAs, CAC was detected (TCS > 0) in all 33 subjects in whom CAC was initially detected with 165 mAs. The mean values of CAC measures with 165 and 55 mAs, respectively, were as follows: number of lesions, 6.2 +/- 9.6 and 6.1 +/- 9.4; TCS, 123 +/- 223 and 126 +/- 225; and calcium mass, 23.25 mg +/- 43 and 24.25 mg +/- 44 (P value was not significant for all parameters). Significant high correlation was found between the two methods for all measures (r > 0.90, P < .01). Similar results were obtained with analysis by coronary vessel. Image noise was 9.3 HU +/- 2.1 with 165 mAs and 14.7 HU +/- 3.9 with 55 mAs (P < .001), with a parallel decrease in the volume CT dose index from 12 to 4 mGy., Conclusion: Radiation dose can be reduced (eg, 55 mAs) for CAC detection and measurement at multi-detector row CT and provides results comparable to those obtained with 165 mAs.

A high plasma homocysteine level is associated with early onset of coronary artery disease (CAD), particularly in homozygotes for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Family history is a predictor of increased plasma homocysteine and may be involved in early-onset CAD. This study examined the relations among family history, plasma homocysteine, and age at onset of CAD, and the role of the MTHFR genotype in this context. We screened 284 patients who developed first symptoms of CAD at < or =65 years of age for fasting plasma homocysteine and the C677T mutation. On multiple regression analysis, homocysteine, family history, male gender, and smoking were independently associated with age at onset of CAD. However, separate analysis of patients who had the MTHFR 677 T/T genotype (n = 57) and those who did not (n = 209) showed that plasma homocysteine and family history were associated with earlier onset of CAD only in T/T homozygotes and that family history in patients who had this genotype was also associated with higher plasma homocysteine levels and a stronger association between plasma homocysteine and age at onset of CAD. In patients who had other genotypes, these associations were not observed, and earlier onset of CAD was associated only with male gender and smoking. Thus, the MTHFR genotype modifies the effects of family history and other risk factors on age at onset of CAD. In T/T homozygotes, family history is associated with earlier onset of CAD, higher plasma homocysteine levels, and a stronger association between plasma homocysteine and age at onset of CAD.

Aims: Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine., Methods and Results: One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those, 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among male patients after colchicine treatment (36 vs. 17%, P=0.046), and those with previous corticosteroid treatment (43 vs. 13%, P=0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% CI: 1.65-27.02) and male gender (OR 4.20, 95% CI: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy., Conclusion: Treatment with colchicine is highly effective in preventing recurrent pericarditis, while pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis.

In a community cohort of 833 women and men aged <60 years, employed at the time of a first acute myocardial infarction (AMI), the relation of sociodemographic, vocational, and medical variables to the following three aspects of employment was investigated longitudinally: resumption of employment anytime within 5 years after AMI, resumption of employment within 3 months of the AMI, and maintenance of employment 5 years after AMI. Different sets of characteristics of persons with a first AMI were related to the different criteria of employment. Only sociodemographic and vocational variables were related to early resumption of employment, whereas maintenance of employment 5 years after AMI was influenced by both medical and nonmedical variables. These results support the importance of examining different aspects of resumption and maintenance of employment after AMI. They also suggest that early resumption of employment after AMI and employment anytime 5 years after AMI are more a function of the sociodemographic and vocational characteristics of the person with the AMI than of that person's medical condition, whereas long-term maintenance of employment after an AMI is also related to the person's medical condition., (Copyright (c) 2005 S. Karger AG, Basel.)

Purpose: To prospectively assess the 4-year progression rate of coronary artery calcium (CAC) in patients with clinically stable coronary artery disease (CAD) with multi-detector row computed tomography (CT)., Materials and Methods: The study group consisted of 382 consecutive patients. All underwent baseline dual-sector spiral CT, and CT was repeated at 2 and 4 years later. Progression of CAC was assessed with measurement of the increase in total calcium score (TCS) and with repeated-measures analysis and multivariate linear regression models. Logistic regression model was used to predict incidence of new lesions., Results: Eighty-seven percent (333 of 382) of the study group were men, with mean age of 65 years +/- 11, and 13% (49 of 382) were women, with mean age of 68 years +/- 11. The average TCS increased after 4 years by sixfold from baseline in the 1st quartile, and by four-, two- and 1.5-fold in the 2nd, 3rd, and 4th quartiles of baseline TCS (P <.01), respectively. Multiple linear regression analysis included age; sex; natural logarithm of baseline TCS; history of hypertension, diabetes mellitus, current smoking, hypercholesterolemia, and lipid-lowering therapy with cholesterol synthesis enzyme inhibitor (statin); and family history of premature CAD. Results demonstrated that natural logarithm of baseline TCS and history of current smoking were independent predictors of the 4th-year natural logarithm of TCS levels (R(2) = 0.85, P <.001). New lesions were diagnosed in 56 (15%) patients. History of statin therapy (odds ratio = 0.35; 95% confidence interval [CI]: 0.16, 0.77; P <.01), age with an increment of 5 years (odds ratio = 0.76; 95% CI: 0.64, 0.90; P =.01), and natural logarithm of baseline TCS (odds ratio = 0.73; 95% CI: 0.62, 0.86; P <.01) were independent predictors for new calcific lesions during 4 years., Conclusion: Accelerated progression of CAC during 4 years was found in clinically stable patients with CAD., (Copyright RSNA, 2004)