Israel Medical Association Journal

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.

Background: Left atrial volume and exercise capacity are strong predictors of cardiovascular risk. Decreased exercise capacity is expected when LAV[1] is increased due to its association with abnormal left ventricular filling pressure. However, LAV enlargement is expected in chronic mitral regurgitation as well.

Objectives: To examine the linkage between LAV and exercise capacity in chronic MR[2] and to determine whether larger LAV has indeed better exercise capacity in patients with chronic severe degenerative MR and good LV systolic function.

Methods: The study included asymptomatic patients with severe chronic degenerative MR and normal LV[3] systolic function that underwent stress echocardiography. LAV was measured at rest using the biplane Simpson’s method and indexed to body surface area. The cutoff of good exercise capacity was determined at 7 METS.

Results: The patient group comprised 52 consecutive patients (age 60 ± 14 years, 36 males). Two subgroups (19 vs. 33 patients), age- and gender-matched, were formed according to LAVi[4] cutoff of 42 ml/m². Those with higher LAVi had lower exercise capacity (P = 0.004) albeit similar MR grade, baseline blood pressure, LV function and size. Receiver-operator curve analysis revealed indexed LAV value of ≤ 42 as 51% sensitive and 88% specific for predicting exercise capacity > 7 METS (AUC[5] = 0.7, P = 0.03). In multivariate analysis, age, gender and LAVi were identified as independent predictors of exercise capacity.

Conclusions: In asymptomatic patients with severe chronic degenerative MR and normal LV systolic function, mild enlargement of the left atrium (≤ 42 ml/m²) is associated with good exercise capacity.

Background: Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha.

Objectives: To test the hypothesis of the possible beneficial impact of IL-10[1] on mortality in systolic heart failure patients in relation to their circulating TNFα[2] levels.

Methods: We measured circulating levels of IL-10 and TNFα in 67 ambulatory systolic heart failure patients (age 65 ± 13 years).

Results: Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFα (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR[3] 3.67, 95% confidence interval 1.14–11.78).

Conclusions: Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFα had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.

Background: Computed tomographic colonography, also known as virtual colonoscopy, is a rapid, non-invasive imaging technique for the detection of colorectal masses and polyps that is becoming increasingly popular.

Objectives: To evaluate the availability, technique, standards of performance and indications for CT colonography in Israel.

Methods: A questionnaire on CT colonography was sent to all radiology departments and private institutions that perform CTC[1] in Israel. We evaluated multiple technical parameters regarding the performance and interpretation of CTC as well as radiologists' training and experience.

Results: Fourteen institutions – 7 hospitals and 7 private clinics – participated in the study. Most of the small radiology departments and nearly all of the more peripheral radiology departments do not perform CTC studies. Since 2000 and until March 2007, a total of 15,165 CTC studies were performed but only 14% (2123 examinations) were performed at public hospitals and 86% (13,042 exams) at private clinics. CTC was performed after an incomplete colonoscopy or for various contraindications to endoscopic colonoscopy in up to a third of cases. In the various institutions patients were self-referred in 20–60% of cases, more commonly in private clinics. All CTC examinations were performed on 16–64 slice CT scanners and only a small minority was performed on 4-slice scanners in 2001. All but one center used low radiation protocols. Nearly all facilities used a 2 day bowel-cleansing protocol. All except one facility did not use stool tagging or computer-aided diagnosis. All facilities inflated the colon with room air manually. All institutions used state-of-the-art workstations, 3D and endoluminal navigation, and coronal multi-planar reconstructions routinely. There are 18 radiologists in the country who perform and interpret CTC studies; half of them trained abroad. Ten of the radiologists (56%) have read more than 500 CTC studies.

Conclusions: In Israel, CTC examinations are performed by well-trained and highly experienced radiologists using the latest CT scanners and workstations and adhering to acceptable CTC guidelines.  

Background: Iron deficiency and lead poisoning are common and are often associated. This association has been suggested previously, mainly by retrospective cross-sectional studies.

Objective: To assess the impact of short-term lead exposure at indoor firing ranges, and its relationship to iron, ferritin, lead, zinc protoporphyrin, and hemoglobin concentrations in young adults.

Methods: We conducted a clinical study in 30 young healthy soldiers serving in the Israel Defense Forces. Blood samples were drawn for lead, zinc protoporphyrin, iron, hemoglobin and ferritin prior to and after a 6 week period of intensive target practice in indoor firing ranges.

Results: After a 6 week period of exposure to lead dust, a mean blood lead level increase (P < 0.0001) and a mean iron (P < 0.0005) and mean ferritin (P < 0.0625) decrease occurred simultaneously. We found a trend for inverse correlation between pre-exposure low ferritin levels and post-exposure high blood lead levels.

Conclusions: The decrease in iron and ferritin levels after short-term lead exposure can be attributed to competition between iron and lead absorption via divalent metal transport 1, suggesting that lead poisoning can cause iron depletion and that iron depletion can aggravate lead poisoning. This synergistic effect should come readily to every physician's mind when treating patients with a potential risk for each problem separately.
 

Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations