Israel Medical Association Journal

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.

Background: Arterial involvement in Behçet's syndrome is rare. Aneurysms are common among the arterial lesions, affecting various arteries but mostly the abdominal aorta. Surgical interposition graft insertion is the treatment of choice for large aneurysms. However, vasculitis in these patients is the reason for the notorious surgical complications that result in up to 50% false aneurysms in anastomotic sites. Recently, endovascular repair for abdominal aortic aneurysms has been established.

Objectives: To learn more about vascular Behçet and, specifically, to compare the results of surgical treatment and endovascular repair of AAA[1] in patients with Behçet's syndrome.

Methods: We retrieved the medical records of all 53 patients with Behçet disease admitted to Rambam Medical Center during the years 1985 and 2001 and analysed the results and follow-up of open surgery versus endovascular repair of AAA in patients with known Behçet's syndrome.

Results: Of the 53 patients with Behçet's disease 18 had vascular manifestations (34%). AAAs were encountered in 8 patients (15%) and 5 were treated. Open surgery (group 1), under general anesthesia, lasted less than 3 hours with an average aortic clamping time of 34 minutes (range 26–41 min) after which the patients were transferred to the intensive care unit for 24–48 hours. Endovascular treatment (group 2), although lasting about the same time without the need for intensive care, necessitated contrast media and fluoroscopy. The length of hospital stay was considerably shorter for patients after endovascular repair compared to open surgery (3 days vs. 6 days). Combined mortality and morbidity was higher in patients who underwent open surgery compared to endovascular repair (one death, one major amputation and three anastomotic pseudoaneurysms compared to one temporary contrast-induced nephropathy).

Conclusions: Vasculo-Behçet patients with AAA are better candidates for endovascular treatment than atherosclerotic patients. Combined morbidity (especially anastomotic pseudoaneurysms) and mortality of Behçet patients after endovascular repair is considerably lower than after open surgery.

Background: Increased levels of high density lipoprotein (over 60 mg/dl) are considered to be a risk factor for ischemic heart disease. However, some patients with high HDL[1] still develop cardiovascular diseases.

Objective: To find out why patients with very high HDL still suffer from cardiovascular diseases.

Methods: We analyzed several risk factors, such as increased lipid peroxidation, hyperhomeocysteinemia and increased release of inflammatory molecules that could be related to the development of vascular disease in patients with high serum HDL levels. Patients with HDL cholesterol levels above 75 mg/dl were selected for this study and were separated into two groups based on the presence of atherosclerotic vascular disease, i.e., those with vascular disease (patients) and those without (controls).

Results: Plasma isolated from the patient group exhibited significantly increased lipid peroxidation by 21% and decreased total antioxidant status by 17%, but there were no differences regarding their serum or their paraoxonase activity. Moreover, both groups exhibited similar levels of serum C-reactive protein, fibrinogen and homocysteine, enabling us to eliminate these risk factors in the etiology of cardiovascular disease in the patient group.

Conclusion: Increased oxidative stress could be one of the factors leading to cardiovascular diseases in patients with high serum HDL levels.

Background: Lower limb critical ischemia is a major problem in dialysed patients.

Objective: To evaluate the results of revascularization procedures, amputations and prosthetic rehabilitation in dialysed amputees.

Methods: Major amputation was carried out in 48 patients (4.5% of the dialysis population), and 24 patients entered the rehabilitation program. Widespread arterial calcification was common and led to falsely elevated ankle-brachial pressure indices in 9 of 14 limbs. Eight patients underwent revascularization. Subsequent major amputation was carried out 4 ± 4.5 months after the revascularization (above knee in 5 patients and below knee in 3). Of the 16 patients who underwent primary amputation, only 2 were above-knee amputees. Seven patients with toe or metatarsal amputation went on to a major amputation 1.8 ± 1.2 months after the distal amputation.

Results: No differences were found between diabetic and non-diabetic patients regarding the number of revascularization operations performed, the level of major amputation, or overall survival. Prosthetic rehabilitation was considered successful in 12 patients, partially successful in 8, and failed in 4 patients. Patient survival time was shortest in those patients with failed rehabilitation. A younger age confirmed favorable rehabilitation results, while long-standing diabetics and bilateral amputees were poor rehabilitation candidates. Patients who underwent primary amputation had more successful rehabilitation. A comparison between 24 dialysed amputees and 138 non-uremic amputees revealed similar rehabilitation results, although hospitalization time was longer in the dialysed patients.

Conclusions: Early definitive therapy is essential when dealing with critical ischemia. After diagnostic angiography, proximal revascularization should be performed where feasible. Primary amputation is indicated in patients with extensive foot infection or gangrene. Prosthetic rehabilitation is warranted in most dialysed amputees.
 

Patients with diabetes and/or insulin resistance syndrome are at increased risk for developing cardiovascular disease. The UKPDS raised a great debate about the relative importance of hyperglycemia in the development of cardiovascular disease. Recently, several epidemiologic studies have suggested that high postprandial blood glucose levels are associated with a significant risk for the development of cardiovascular disease as well as a grave prognosis for these patients during acute coronary events. In addition, a number of reports reinforce the thesis that postprandial hyperglycemia is a risk factor for mortality. Our review summarizes the current knowledge on the relation between blood glucose, insulin levels, and cardiovascular morbidity and mortality, relating these data to the new World Health Organization and American Diabetes Association classification of disturbed glucose metabolism.

Background: Elevated fibrinogen, considered an independent risk factor for coronary disease, stratifies an individual as high risk for coronary disease. A risk marker requires little intra-individual variability during a long period.

Objectives: To establish intra-individual variability of fibrinogen levels in patients with coronary disease.

Methods: We investigated fibrinogen levels prospectively in four blood samples drawn from 267 patients with a history of arterial disease (arterial group) and from 264 patients with cardiac valve replacements (valvular group). The samples were taken during the course of 78.7 and 78.8 days from the arterial and valvular groups respectively.

Results: Marked intra-individual dispersion with a reliability coefficient of 0.541 was found in the arterial group and 0.547 in the valvular group. The Bland-Altman test showed low probability to obtain similar results in different samples from the same individual. These results show large intra-individual variability, with similarities in the arterial as well as in the valvular group.

Conclusions: It is not possible to stratify a patient by a specific fibrinogen dosage.