A Longitudinal Assessment of the Natural Change in Haemoglobin, Haematocrit, and Mean Corpuscular Volume with Age.

INTRODUCTION: We aimed to assess the natural annual trends in the levels of haemoglobin, haematocrit, and mean corpuscular volume (MCV) in a population of adults, together with the influence of different clinical parameters on these trends. METHODS: A retrospective analysis was carried out on data from a large cohort of subjects attending a screening centre in Israel. For each subject, the yearly average change of haemoglobin, haematocrit, and MCV was calculated. Statistical analysis was performed for the whole cohort and for different subgroups. RESULTS: The study included 3,551 subjects. The average annual rates of decline were found to be -0.0550 g/dL (95% confidence interval [CI] -0.0590 g/dL to -0.0503 g/dL) and -0.097% (95% CI -0.112% to -0.083%) for haemoglobin and haematocrit, respectively. An average annual increase in the MCV level by 0.184 fL (95% CI 0.168 fL-0.200 fL) was found. Among men, the rate of decline in haemoglobin was found to be twice as high compared with women -0.06 g/dL versus -0.03 g/dL, respectively (p = 0.0063). In a multivariate analysis, gender remained the only parameter significantly associated with the annual decline of haemoglobin (p = 0.0001). CONCLUSION: An annual average decrease in the levels of haemoglobin and haematocrit together with an annual increase in MCV was found. These changes were more prominent in men.

A possible increased risk of metamizole-associated neutropenia among COVID-19 patients.

Metamizole is commonly used as analgesic and antipyretic drug. The use of metamizole is prohibited in several countries due to its rare side effect of neutropenia and even agranulocytosis. Among the many symptoms of COVID-19, fever and diffuse pain predominant and therefore it can be assumed that metamizole may be widely used in the current epidemic period. So far, there have been no reports on the safety of metamizole in COVID-19 patients. We describe a series of 3 patients who developed severe neutropenia under metamizole treatment, raising a concern of a possible increased risk of this side effect among COVID-19 patients.

Sex Differences in Folate Levels: A Cross Sectional Study of a Large Cohort from Israel.

BACKGROUND: Low folate levels are associated with megaloblastic anemia, neural tube defects, and an increased risk of cancer. Data are scarce regarding the sex aspect of this deficiency. OBJECTIVES: To assess sex differences in folate levels in a large cohort of patients and to investigate the effect of low folate levels on homocysteine concentrations. METHODS: Data were collected from medical records of patients examined at a screening center in Israel between 2000 and 2014. Cross sectional analysis was conducted on 9214 males and 4336 females. RESULTS: The average age was 48.4 ± 9.5 years for males and 47.6 ± 9.4 years for females. Average folate levels were 19.2 ± 8.6 and 22.4 ±10.3 nmol/L in males and females, respectively (P < 0.001). The prevalence of folate levels below 12.2 nmol/L was 19.5% in males compared to 11.6% in females (P < 0.001). In patients with low folate levels and normal B12 levels, homocysteine levels above 15 µmol/L were found in 32.4% of males and 11.4% of females (P < 0.001). Males had a significantly higher odds ratio (OR) of having folate levels below 12.2 nmol/L: OR 1.84 (95% confidence interval [95%CI] 1.66-2.05) in a non-adjusted model, and OR 2.02 (95%CI 1.82-2.27) adjusted for age, smoking status, body mass index, kidney function, albumin, and triglycerides levels. CONCLUSIONS: Folate levels are lower in males compared to females, which may contribute to the higher homocysteine levels found in males and thus to their increased risk of developing atherosclerosis and coronary artery disease.

Reconsidering the relation between serum homocysteine and red blood cell distribution width: a cross-sectional study of a large cohort.

PURPOSE: In a recent small sample study, red blood cell distribution width (RDW) was suggested as a predictor of homocysteine levels. The current study was aimed to reexamine this association in a large scale sample. METHODS: A retrospective cross-sectional study of healthy adults, conducted at Rabin Medical Center, during 2000-2014. Data were retrieved from the medical charts and a logistic regression controlling for interfering factors was carried out. Sensitivity analysis was implemented by exclusion of individuals with anaemia. RESULTS: Five thousand, five hundred fifty-four healthy individuals were included. Mean serum homocysteine level was 10.10 (SD 2.72) µmol/L. 34.4% of the study population had a homocysteine level higher than the upper limit of normal (10.8 µmol/L). Homocysteine showed no association with RDW (OR 1.00; 95% CI 0.97-1.03), but increased with age (OR 1.05; 95% CI 1.04-1.06) and decreased with a rise in haemoglobin (OR 0.77; 95% CI 0.71-0.83), and in the mean corpuscular volume (OR 0.86; 95% CI 0.85-0.88). Exclusion of individuals with anaemia did not reveal an association between homocysteine and RDW but found a somewhat smaller association between haemoglobin and RDW [OR 0.82; 95% CI 0.73-0.91]. CONCLUSIONS: In our large scale sample we did not find an association between RDW and serum homocysteine.

Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

BACKGROUND: Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. METHODS: A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18-65, who were provided with a routine medical evaluation during 2000-2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. RESULTS: In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p < 0.001). Deficiency prevalence was greater for men (25.5%) in comparison with women (18.9%; p < 0.001). Men were strongly associated with severe deficiency (adjusted OR 2.26; 95% CI 1.43-3.56). CONCLUSIONS: Among the healthy population, men are susceptible to vitamin B12 deficiency. This can be explained by neither diet habits nor estrogen effects. Genetic variations are therefore hypothesized to play a role.

Infective endocarditis in the setting of renal transplantation: Case report and review of the literature.

The potent immunosuppressive drugs used by transplant recipients place them at risk of infections. Data on infective endocarditis (IE) in the setting of renal transplantation (RT) are sparse. We describe a 36-year-old woman referred to a tertiary medical center for evaluation of elevated creatinine levels 1 month after a second RT. Work-up revealed the presence of all four of Duke's criteria: fever, persistent bacteremia, new-onset tricuspid regurgitation, and masses suspected to be vegetation attached to the tricuspid annulus. Symptoms resolved with antibiotic treatment and fluids. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed hypermetabolic absorption in the femoral vascular graft that had been used for hemodialysis prior to transplantation. The graft was removed by open surgery, and the patient was discharged home in good condition with continued antibiotic treatment. Review of the literature yielded 73 previously reported cases of IE in renal transplant recipients. Several differences were noted from IE in the general population: lower male predominance, younger age (<60 years), absence in most cases of a preexisting structural cardiac anomaly, and more variable causative pathogens. Our case also highlights the importance of FDG-PET/CT for detecting the source of IE and alerts clinicians to the sometimes unexpected course of the disease in renal transplant recipients.

Factors Affecting the Upper Limit of the Methotrexate (MTX) CSF Levels Achievable in Children With Brain Tumors Treated With High-dose Intravenous MTX.

BACKGROUND: Little has been published in the medical literature on serum and cerebrospinal fluid (CSF) methotrexate (MTX) levels in children with brain tumors. METHODS: Matched 24-hour serum and CSF MTX levels were studied after 113 treatments in 35 brain tumors patients. RESULTS: A correlation between the 24-hour serum levels of MTX and MTX dosage was observed after 113 treatments in all 35 patients (r=0.39, P<0.001) but no statistical difference was found between CSF MTX levels in the irradiated and nonirradiated groups (P=0.12). Nonirradiated children received a lower dose of MTX (12.3±4.8 cf 14.8±3.7) (P=0.002). The 24-hour MTX CSF levels of these 2 groups were also found to be different (the nonirradiated group 7.6±9.8 cf 12.5±0.15.3). Using the Levene test for variances we found that these variances were not equal and therefore we used the Welch test which resulted in a P-value of 0.04. However, when an analysis of covariance was performed looking at evidence of CSF disease and MTX dose the radiation difference was no longer significant (P=0.15). The 24-hour CSF MTX levels in children without evidence of active CSF disease were consistently lower than those with active disease using a mixed-model analysis (P=0.002). Although a 24-hour CSF MTX level of at least 1 µM was observed after infusions of >5 g/m MTX in previously irradiated children and after infusion of ≥10 g/m in nonirradiated children this difference did not reach statistical significance. CSF MTX levels plateau at doses of MTX 15 g/m putting in doubt the value of administering even higher doses of MTX. CONCLUSIONS: The 24-hour MTX CSF levels are higher in patients with active CSF disease. Doses of <10 gm/m in children with brain tumors may not achieve a guaranteed 24-hour MTX CSF level of 1 µM. There may be little value in a given dose of >15 g/m MTX as CSF levels plateau at this dose.

The Relationship between Cigarette Smoking and Renal Function: A Large Cohort Study.

BACKGROUND: Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood. OBJECTIVES: To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function. METHODS: We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed. RESULTS: The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P < 0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P < 0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005). CONCLUSIONS: Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.

The real-world safety of sacubitril / valsartan among older adults (≥75): A pharmacovigilance study from the FDA data.

BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.

Association between the body mass index and chronic kidney disease in men and women. A population-based study from Israel.

BACKGROUND: Any association between the body mass index (BMI) and chronic kidney disease (CKD) has so far proved inconclusive. Most studies have estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. This has recently been replaced by the more accurate Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. METHODS: In a cross-sectional study, data from a screening centre in Israel, n = 21880 (32% women) were used to assess the prevalence of CKD defined as eGFR < 60 mL/min/1.73 m(2) in relation to BMI categories. The CKD-EPI equation was used to assess the eGFR. RESULTS: CKD was found in 167 men and 45 women. Subjects with a BMI of 25-29.9 kg/m(2), compared with those with a BMI of <25 kg/m(2), had an odds ratio (OR; 95% confidence intervals) for CKD of 1.8 (1.2-2.7) and 3.4 (1.5-7.7) for men and women, respectively. Subjects with a BMI of 30-35 kg/m(2) had an OR of 2.5 (1.6-4.0) and 4.5 (1.7-11.7) for men and women, respectively. In comparable data, for subjects with a BMI > 35 kg/m(2) the OR was 2.7 (1.3-5.5) and 15.4 (6.4-36.7) for men and women, respectively. After multivariate adjustment for age, hypertension and diabetes mellitus, no association was found in men yet it persisted for women. This correlation in women, between the BMI and CKD, was attributed to the subcategory of severely obese women with a BMI of >35 kg/m(2). CONCLUSIONS: Our study is the first to suggest that morbid obesity may be an independent factor related to CKD in women.

Mortality in heart failure with worsening anemia: a national study.

BACKGROUND: Anemia is common in heart failure (HF), but there is controversy regarding its contribution to morbidity and mortality. OBJECTIVE: To examine the association of mild and severe anemia with acute HF severity and mortality. METHODS: Data were prospectively collected for patients admitted to all departments of medicine and cardiology throughout the country during 2 months in 2003 as part of the Heart Failure Survey in Israel. Anemia was defined as hemoglobin (Hb) < 12 g/dl for women and < 13 g/dl for men; Hb < 10 g/dl was considered severe anemia. Mortality data were obtained from the Israel population registry. Median follow-up was 33.6 months. RESULTS: Of 4102 HF patients, 2332 had acute HF and available hemoglobin data. Anemia was common (55%) and correlated with worse baseline HF. Most signs and symptoms of acute HF were similar among all groups, but mortality was greater in anemic patients. Mortality rates at 6 months were 14.9%, 23.7% and 26.3% for patients with no anemia, mild anemia and severe anemia, respectively (P < 0.0001), and 22.2%, 33.6% and 39.9% at one year, respectively (P < 0.0001). Compared to patients without anemia, multivariable adjusted hazard ratio was 1.35 for mild anemia and 1.50 for severe anemia (95% confidence interval 1.20-1.52 and 1.27-1.77 respectively). CONCLUSIONS: Anemia is common in patients with acuteHF and is associated with increased mortality correlated with the degree of anemia.

Hyperuricemia and metabolic syndrome: lessons from a large cohort from Israel.

BACKGROUND: There is a striking increase in the number of people with metabolic syndrome (MetS) as a result of the global epidemic of obesity and diabetes. Increasing evidence suggests that uric acid may play a role in MetS. OBJECTIVES: To assess the prevalence of MetS in a large cohort from Israel and its association with hyperuricemia using the latest three definitions of MetS. METHODS: We conducted a retrospective analysis of the database from a screening center in Israel, using the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the Harmonizing definitions of MetS, to assess 12,036 subjects with an age range of 20-80 years. RESULTS: The mean age of the study sample was 46.1 +/- 10.2 years and 69.8% were male. The prevalence of MetS was 10.6%, 18.2% and 20.2% in the revised NCEP ATP III, the IDF and the Harmonizing definitions respectively. The prevalence of hyperuricemia in subjects with MetS, for all three MetS definitions, was similar: 20.0%, 19.9% and 19.1% respectively. There was a graded increase in the prevalence of MetS among subjects with increasing levels of uric acid. The increasing trend persisted after stratifying for age and gender and after multivariate analysis (P for trend (0.001). CONCLUSIONS: This large cohort shows a high prevalence of MetS in Israel, but is still lower than the prevalence in western countries. Hyperuricemia is common in those subjects and might be considered a potential clinical parameter in the definition of MetS.

Proton pump inhibitor use and its effect on vitamin B12 and homocysteine levels among men and women: A large cross-sectional study.

BACKGROUND: Previous studies have demonstrated an association between proton pump inhibitors (PPI) use and vitamin B12 deficiency. However, data regarding PPI use and elevated serum homocysteine level, an important marker of vitamin B12 deficiency, are scant. METHODS: Data were collected from medical records of subjects examined at a screening center in Israel. Cross sectional analysis was conducted on 25,953 subjects. Levels of vitamin B12 and homocysteine were compared between subjects who consumed PPI medications and those who did not. RESULTS: The mean age of the study population was 45 years and 33% were females. Subjects who received PPI medications had a minor higher vitamin B12 levels (320 pmol/L vs 300 pmol/L, p=0.024). Levels of vitamin B12 remained higher in females receiving PPI medications after performing a stratified analysis according to subjects' gender. Homocysteine levels were higher in subjects receiving PPI medications as compared to those who did not (12.0 µmol/L vs 11.6 0 µmol/L, p<0.001). Levels remained higher in female subjects after performing a stratified analysis according to subjects' sex. There was no statistically significant difference in the prevalence of vitamin B12 deficiency (according to two cutoffs: vitamin B12≤200 or ≤140 pmol/L) as well as the prevalence of hyperhomocysteinemia (defined as homocysteine >15.0 µmol/L) between the two groups. CONCLUSIONS: According to our study, no association was found between PPI medication use and vitamin B12 deficiency or hyperhomocysteinemia. Patients receiving PPI medications had slightly higher levels of vitamin B12 and homocysteine, however these differences were too small to have any clinical relevance.

Markers of Chronic Inflammation in Overweight and Obese Individuals and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

OBJECTIVE: During the last decade, obesity has become an epidemic. As obesity is now considered a state of low-grade inflammation, the purpose of this study was to assess the prevalence of four common elements of inflammation, in individuals with increased BMI. These findings were compared to those of subjects with normal BMI. The effect of gender was also noted. METHODS: Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000-2014. Cross-sectional analysis was carried out on 7526 men and 3219 women. White blood cell count (WBC); platelet (PLT) count; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed in four BMI categories: normal, overweight, obese and morbidly obese. RESULTS: Mean (SD) age of the study sample was 47.5 (9.7) and 46.7 (9.8) years for men and women, respectively. The prevalence of each inflammatory marker increased significantly when comparing abnormal to normal BMI (p<0.0001). The odds ratio (OR) of the prevalence of increased inflammatory markers was compared between subjects with overweight, obese and morbid obesity and subjects with normal BMI. This study showed that the higher the BMI, the higher the OR. For those in the morbid obesity group, the OR for the different inflammatory markers adjusting for age, diabetes mellitus hypertension and kidney function were as follows: WBC levels, 5.1 (2.9-8.7) and 4.7 (2.4-9.1) for men and women, respectively; PLT levels, 1.7 (0.3-8.5) and 2.0 (0.6-7.2) for men and women, respectively; ESR levels, 4.2 (3.2-5.4) and 4.6 (3.2-6.6) for men and women, respectively, and CRP levels, 13.4 (10.0-18.2) and 19.2 (12.9-28.6) for men and women, respectively. CONCLUSION: Inflammatory markers are significantly higher in subjects with abnormal compared to normal BMI. This difference was found to be greater in women than in men.

Streptococcus gallolyticus endocarditis on a prosthetic tricuspid valve: a case report and review of the literature.

BACKGROUND: Streptococcus gallolyticus subspecies gallolyticus is a known pathogen that causes infective endocarditis, and most cases involve the left heart valves. We present the first reported case of prosthetic tricuspid valve endocarditis caused by this microorganism. Relevant literature is reviewed. CASE PRESENTATION: A 67-year-old Jewish female with a history of a prosthetic tricuspid valve replacement was admitted to the emergency department because of nonspecific complaints including effort dyspnea, fatigue, and a single episode of transient visual loss and fever. No significant physical findings were observed. Laboratory examinations revealed microangiopathic hemolytic anemia and a few nonspecific abnormalities. Transesophageal echocardiogram demonstrated a vegetation attached to the prosthetic tricuspid valve. The involved tricuspid valve was replaced by a new tissue valve, and Streptococcus gallolyticus subspecies gallolyticus was grown from its culture. Prolonged antibiotic treatment was initiated. CONCLUSIONS: Based on this report and the reviewed literature, Streptococcus gallolyticus should be considered as a rare but potential causative microorganism in prosthetic right-sided valves endocarditis. The patient's atypical presentation emphasizes the need for a high index of suspicion for the diagnosis of infective endocarditis.

Blood transfusion for acute decompensated heart failure--friend or foe?

BACKGROUND: In acute coronary syndromes (ACSs), blood transfusion (BT) has been associated with worse outcomes. The impact of BT among patients with acute decompensated heart failure (ADHF) remains unknown. METHODS: Propensity score analysis of patients with ADHF with and without BT in a national heart failure (HF) survey was used in this study. RESULTS: Of the 4,102 enrolled patients, 2,335 had ADHF, of whom 166 (7.1%) received BT. These patients were older (75.6% vs 73.6%, P = .04), more likely to be females (54.8% vs 43.9%, P = .007), more likely to have diabetes (59.0% vs 51.1%, P = .04) and renal dysfunction (59.0% vs 40.2%, P < .001), and more likely to receive inotropes (16.9% vs 8.0%, P < .001), but they had similar rates of ACS (41.0% vs 39.4%, P = .69) and prior HF (64.5% vs 70.0%, P = .23). Nadir hemoglobin levels were commonly <10 g/dL in BT patients (92.7% vs 8.0%); 15 BT patients had bleeding complications, of which 10 are major bleeding. Major predictors for BT were ACS (OR 1.85, 95% CI 1.15-2.96), inotropes use (OR 2.36, 95% CI 1.22-4.55), and nadir hemoglobin (OR 0.18 per 1 g/dL increase, 95% CI 0.14-0.22). In-hospital, 30-day, 1-year, and 4-year unadjusted mortality rates were higher for BT patients (10.8% vs 5.2%, P = .02; 11.0% vs 8.5%, P = .27; 39.6% vs 28.5%, P = .03; 69.5% vs 59.5%, P = .01, respectively). However, in 103 propensity-matched pairs (c-statistic 0.97), short-term mortality tended to be lower with BT (8.7% vs 14.6%, P = .20; 9.7% vs 18.4%, P = .08; 38.8% vs 42.7%, P = .59; and 72.8% vs 76.7%, P = .52, respectively). CONCLUSIONS: Acute decompensated HF patients receiving BT had worse clinical features and unadjusted outcomes, but BT per se seemed to be safe and perhaps even beneficial.

The relationship between the concentration of plasma homocysteine and chronic kidney disease: a cross sectional study of a large cohort.

BACKGROUND: High concentrations of homocysteine are considered a risk factor for developing atherosclerosis and coronary artery disease. The aim of this study was to assess the concentrations of homocysteine in subjects with chronic kidney disease (CKD). METHODS: Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000-2014. Cross sectional analysis was carried out on 17,010 subjects; 67% were men. RESULTS: Significant differences were observed between four quartiles of homocysteine concentrations and estimated glomerular filtration rate (eGFR)-the higher the homocysteine concentration, the lower the eGFR (p < 0.0001). In subjects with CKD, homocysteine plasma levels were correlated with the stage of renal impairment. Mean (SD) homocysteine concentrations in subjects with eGFR < 60 mL/min per 1.73 m2 compared to subjects with eGFR ≥ 60 mL/min per 1.73 m2 were: 16.3 (5.9) vs. 11.5 (5.5) µmol/L respectively. These findings remained significant after adjustment for age, smoking status, body mass index, hypertension and diabetes mellitus (p < 0.0001). Compared to subjects with homocysteine concentrations less than 15 µmol/L, those with homocysteine concentrations equal and above 15 µmol/L, had a significantly higher odds ratio (95% CI) of having an eGFR < 60 mL/min per 1.73 m2; non adjusted model, 8.30 (6.17-11.16); adjusted model for age smoking status, body mass index, hypertension and diabetes mellitus, 7.43 (5.41-10.21). CONCLUSION: Plasma homocysteine concentrations are higher in subjects with CKD. This may contribute to an increased risk for developing atherosclerosis and coronary artery disease in these patients.

Gender as an Independent Risk Factor for the Components of Metabolic Syndrome Among Individuals Within the Normal Range of Body Mass Index.

Background: Overweight and obesity are more common in men than in women. This explains the higher prevalence of risk factors for metabolic syndrome (MetS) found in men. We aimed to assess whether gender, per se, might be an independent risk factor for the components of MetS in a large cohort of subjects within the normal range of body mass index (BMI). Materials and Methods: Cross-sectional analysis was carried out on 9976 men and women, aged 18 to 70 years, with a BMI between 18.5 and 25.0 kg/m2 attending a screening center in Israel between the years 2000 and 2014. Results: Mean (SD) age of the study sample was 43.3 (9.6) years, 54.5% were men. Prevalence of MetS components in men and women was hypertension 5.3% and 3.0%, impaired fasting glucose (IFG) 18.1% and 7.9%, diabetes mellitus (DM) 2.4% and 1.3%, high triglyceride levels 17.7% and 9.4%, and low high-density lipoprotein (HDL) cholesterol levels 13.6% and 17.0%, respectively, P < 0.001 for all. Increased waist circumference was <1% in both genders. Multivariate analysis showed male gender to be an independent risk factor for IFG [odds ratio (OR) 2.43, 95% confidence interval (CI) 2.12-2.79], hypertriglyceridemia (OR 1.86, 95% CI 1.63-2.12), DM (OR 1.80, 95% CI 1.29-2.50), and hypertension (OR 1.46, 95% CI 1.16-1.83) but not for low HDL levels (OR 0.59, 95% CI 0.52-0.67). Conclusion: This study, on a cross-sectional sample of subjects with a normal BMI, showed male gender to be an independent risk factor for all components of the MetS, apart from the low HDL risk factor that was found to be higher in women.

Impaired fasting glucose is associated with lower glomerular filtration rate decline among men but not women -a large cohort study from Israel.

OBJECTIVES: Early stages of diabetes are associated with an increased glomerular filtration rate (GFR). Little is known, however, about the change in GFR among patients with impaired fasting glucose (IFG). We aimed to evaluate the yearly decline rate of GFR among IFG patients. METHODS: A retrospective analysis of a large cohort of subjects attending a medical screening center in Israel. Patients with diabetes mellitus and patients with decreased estimated GFR (eGFR) were excluded. We divided the cohort into 2 subgroups; Healthy controls and impaired fasting control subjects. For each group, we calculated the average yearly estimated GFR decline (ΔeGFR). The results were adjusted for age, BMI, hypertension and smoking status. RESULTS: 8176 subjects met the inclusion criteria. The median follow up time was 4.8 years (range 2.0 to 13.4). For the whole cohort (men and women), yearly ΔeGFR was -0.68 among healthy controls, and - 0.47 among IFG patients (p = .003). Among men, average yearly ΔeGFR in healthy controls and IFG patients was -0.7 and - 0.4, respectively (p = .0002). All results remained significant after adjusting for age, BMI, hypertension, smoking status and level of HDL and triglycerides. In contrast, among IFG women there was no significant difference in ΔeGFR in comparison with healthy women. CONCLUSIONS: Impaired fasting glucose is associated with a decreased rate of GFR reduction compared with healthy subjects. This effect is gender dependent - observed in men but not in women. A mechanism of glomerular hyperfiltration might be involved.