Israel Medical Association Journal

Background: Cardiac resynchronization therapy (CRT) is a non-pharmacological option for patients with heart failure and interventricular dyssynchrony. Elevated red cell distribution width (RDW) reflects higher size and heterogeneity of erythrocytes and is associated with poor outcome in patients with chronic heart failure. 

Objectives: To examine the association between RDW levels and outcomes after CRT implantation.

Methods: We conducted a cohort analysis of 156 patients (126 men, median age 69.0 years) who underwent CRT implantation in our institution during 2004–2008. RDW was measured at three time points before and after implantation. Primary outcome was defined as all-cause mortality, and secondary outcome as hospital re-admissions. We investigated the association between RDW levels and primary outcome during a median follow-up of 61 months.

Results: Ninety-five patients (60.9%) died during follow-up. Higher baseline RDW levels were associated with all-cause mortality (unadjusted HR 1.35, 95%CI 1.20–1.52, P < 0.001). On multivariate analysis adjusted for clinical, electrocardiographic and laboratory variables, baseline RDW levels were associated with mortality (HR 1.33, 95%CI 1.16–1.53). RDW levels 6 months and 12 months post-implantation were also associated with mortality (HR 1.22, 95%CI 1.08–1.38, P = 0.001; and HR 1.15, 95%CI 1.01–1.32, P = 0.02, respectively). Patients who were re-admitted to hospital during follow-up (n=78) had higher baseline RDW levels as compared to those who were not (14.9%, IQR 14.0, 16.0% vs. 14.3%, IQR 13.7, 15.0%, respectively, P = 0.03). 

Conclusion: An elevated RDW level before and after CRT implantation is independently associated with all-cause mortality. 

 

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Background: Ethiopian immigration to Israel was initiated in 1981. Most immigrants were rural dwellers who migrated first to Addis Ababa or Gondar, where they waited for eligibility status from Israel to leave Ethiopia. Soon after arriving in Israel, all immigrants were offered screening tests for human immunodeficiency virus (HIV) and syphilis.

Objectives: To evaluate the association of age, gender, marital status and length of time spent in urban areas in Ethiopia with the prevalence of HIV and syphilis seropositivity.

Methods: All adult Ethiopian immigrants who arrived at the Jerusalem immigration center between 1999 and 2002 and consented to HIV and syphilis screening tests were interviewed.

Results: Altogether, 678 immigrants (51% females) were screened; 39 (5.8 %) were seropositive for HIV and 33 (4.9%) for syphilis. The length of time the immigrants spent in Ethiopian cities before leaving for Israel was significantly associated with HIV: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.13–6.71, and syphilis seropositivity  OR 3.87, 95%CI  1.56–9.62.

Conclusions: The length of transit time Ethiopian immigrants from rural areas spend in Ethiopian cities is significantly associated with HIV and syphilis seropositivity. Efforts should be made to shorten this time in order to reduce the risk of infection

Objectives: To investigate the association between CAD and H. pylori infection using MPI.

Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD-positive group included patients with ischemia and/or myocardial infarctions (MI) on a stress MPI, coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients’ demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.

Results: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD- positive (odds ratio 1.83, 95% confidence interval 1.06–3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44–7.84, P = 0.005). No association was noted with CagA positivity.

Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors. 

Background: Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely investigated.

Objectives: To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata.

Methods: The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels.

Results: Mean CRP values were significantly higher in the AA group than the control group (1.1 ± 0.7 mg/dl vs. 0.4 ± 0.8 mg/dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 ± 10.18 ng/ml vs. 21.55 ± 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6–4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95%CI 2.2–3.1, P = 0.02) were associated with AA. 

Conclusions: We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be significant risk factor for AA occurrence.

Objectives: To report the first results from the Serbian National Cohort study, which was started in January 2000.

Methods: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), ß₂-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected.

Results: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations.

Conclusions: Patients with secondary APS had a higher prevalence of valvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS patients.

Background: Type 1 diabetes in humans is an autoimmune disease in which T cells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulin-producing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potential vanilloid receptor-1 (TRPV1) gene.

Objectives: To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes.

Methods: We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M315I), rs224534 (T469I) and rs8065080 (I585V) variants of the TRPV1 gene.

Results: There was a significant increase in the rs222747 (M315I) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M315I) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type1 diabetes was significantly associated with rs222747 (M315I), such that having diabetes increased the odds of rs222747 homozygosity (M315I) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08–2.57, P < 0.02. No difference was found in the rs224534 (T469I) and rs8065080 (I585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases.

Conclusions: Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.

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 as 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 (confidence interval 1.20–1.52 and 1.27–1.77 respectively).

Conclusions: Anemia is common in patients with acute HF and is associated with increased mortality correlated with the degree of anemia.

Objectives: To review positive temporal artery biopsiese of GCA in an attempt to correlate various histological parameters with clinical features, disease complications and outcome.

Methods: Positive biopsies from 65 GCA patients were randomly selected for review by a single pathologist. In each biopsy the following parameters were scored: intensity and location of the inflammatory infiltrate, presence of giant cells and other cell types, fragmentation and calcification of the internal elastic lamina, intimal thickening, and presence of luminal thrombus. Clinical data were obtained from the patients’ charts. Intensity of the initial systemic inflammatory reaction (ISIR) at the time of diagnosis was scored by the presence of five parameters: fever, anemia, thrombocytosis, leukocytosis, and sedimentation rate > 100 mm/hr.

Results: In cases with bilateral positive biopsy (n=27), there was good correlation between the two sides regarding intensity of inflammation (r = 0.65, P < 0.001), location of the infiltrate (r = 0.7, P < 0.001), degree of intimal thickening (r = 0.54, P < 0.001), and presence of giant cells (r = 0.83, P < 0.001). The rate of corticosteroid discontinuation tended to be quicker in patients with inflammatory infiltrates confined mainly to the adventitia, but other histological parameters did not affect this rate.

Conclusions: Inflammatory infiltrates confined to the adventitia were associated with more neuro-ophthalmic ischemic manifestations, weak/moderate ISIR at the time of diagnosis, and faster rate of corticosteroid discontinuation. No association was found between other temporal artery biopsy histological parameters and clinical features of GCA patients.

Background: Kidney disease and cardiovascular disease seem to be lethally synergistic and both are approaching the epidemic level. A reduced glomerular filtration rate is associated with increased mortality risk in patients with heart failure. Many patients with congestive heart failure are anemic. Anemia is very often associated with chronic kidney disease.

Objectives: To assess – in relation to New York Heart Association class – the prevalence of anemia and chronic kidney disease in patients with normal serum creatinine in a cohort of 526 consecutive patients with coronary artery disease undergoing percutaneous coronary interventions.

Methods: GFR[1] was estimated using the simplified MDRD formula, the Cockcroft-Gault formula, the Jeliffe and the novel CKD-EPI formula.

Results: According to the WHO definition the prevalence of anemia in our study was 21%. We observed a progressive decline in GFR and hemoglobin concentration together with a rise in NYHA[2] class. Significant correlations were observed between eGFR[3] and systolic blood pressure, diastolic blood pressure, age, NYHA class, complications of PCI[4], including bleeding, and major adverse cardiac events.

Conclusions: The prevalence of anemia and chronic kidney disease is high in patients undergoing PCI despite normal serum creatinine, particularly in higher NYHA class. Lower eGFR and hemoglobin are associated with more complications, including bleeding after PCI and higher prevalence of major adverse cardiac events. In patients with risk factors for cardiovascular disease, GFR should be estimated since renal dysfunction and subsequent anemia are important risk factors for cardiovascular morbidity and mortality.