Apolipoprotein E (APOE) Genotypes in the Israeli population.

BACKGROUND: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration. OBJECTIVES: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries. METHODS: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers. RESULTS: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%). CONCLUSIONS: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Low levels of low-density lipoprotein cholesterol: a negative predictor of survival in elderly patients with advanced heart failure.

OBJECTIVES: There are conflicting reports on the role of cholesterol as an adverse prognostic predictor in patients with heart failure (HF). This study aimed to examine the impact of low levels of low-density lipoprotein cholesterol (LDL-c) on cardiac mortality in a cohort of elderly patients with moderate and severe HF. METHODS: Chronic HF patients from the HF Unit at the Tel-Aviv Medical Center (n = 212, 77% males) with an average NYHA classification of 2.8, a mean age of 76.9 ± 7.3 years (range 66-91) and a mean follow-up of 3.7 years were consecutively enrolled. The cohort was divided into tertiles according to LDL-c levels: LDL <90 mg/dl (group 1), LDL 90-115 mg/dl (group 2) and LDL >115 mg/dl (group 3). RESULTS: The Cox regression analysis revealed that group 3 patients had the best outcome (p = 0.01 vs. groups 2 and 3), with 58% of them surviving longer than 50 months compared to 34% in group 1. The same trend was seen in the group of patients suffering from ischemic cardiomyopathy and in patients who were treated by statins (p = 0.04). CONCLUSION: Low LDL-c levels are associated with a reduced survival in elderly patients with clinically controlled moderate and severe HF.

Methylphenidate has positive hypocholesterolemic and hypotriglyceridemic effects: new data.

Many psychotropic drugs may affect plasma lipids profile and their metabolism, with carbamazepine being the best known among them. Methylphenidate is a piperidine derivative structurally related to amphetamines and acts as a central nervous system stimulant. Its effect on lipid metabolism has not been investigated. The authors evaluated how methylphenidate affects the lipid profile in the plasma of patients diagnosed as having attention-deficit hyperactivity disorder (ADHD). All consecutive patients undergoing treatment for ADHD at the Adolescent Psychiatric Clinic (2003-2007) were enrolled. Blood samples for total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A, apolipoprotein B, and lipoprotein (a) (Lp(a)) were collected before starting treatment and after 3 months of continuous treatment. Forty-two patients (22 men), median age 16, participated. The median total cholesterol count decreased by 9 mg/dL (P<.0002), LDL-C decreased by 5.0 mg/dL (P<.016), and triglycerides decreased by 8.0 mg/dL (P<.016). Changes in the levels of HDL-C, apolipoprotein A, and apolipoprotein B were nonsignificant, and Lp(a) levels decreased by 2.0 mg/dL (P<.0007). Methylphenidate improves the lipid profile by decreasing total cholesterol, triglycerides, LDL-C, and Lp(a).

Development of Crohn's disease in a patient with multiple sclerosis treated with copaxone.

BACKGROUND: Copaxone (glatiramer acetate) is a synthetic copolymer mimicking a portion of myelin basic protein, one of several putative autoantigens in multiple sclerosis (MS). Copaxone suppresses the production of tumor necrosis factor (TNF)-alpha, a key mediator of inflammation in MS as well as in other pathologies, such as colitis of interstitial bowel disease (IBD). Copaxone is a drug approved for the treatment of MS, and one that is very well tolerated with a high safety profile and relatively few side effects. Crohn's disease has not been associated with its administration. METHODS: We describe a patient with MS in remission who had not exhibited any signs of IBD in the past. She had been on Copaxone 20 mg/day treatment for 2 years when she first exhibited gastrointestinal symptoms. RESULTS: Our patient developed Crohn's disease while on Copaxone treatment as a consequence of long-term immunosuppression. CONCLUSIONS: Clinicians should be aware that Crohn's disease is a potential novel adverse drug effect of Copaxone.

Prediction of cardiogenic pulmonary edema onset by monitoring right lung impedance.

OBJECTIVE: To evaluate the ability of internal thoracic impedance (ITI) monitors to predict cardiogenic pulmonary edema in patients at risk. DESIGN AND SETTING: Prospective, controlled multicenter study. PATIENTS: We examined 328 consecutive patients admitted for cardiac conditions. Of these 265 patients aged 27-83 years with no clinical signs of pulmonary edema, extracardiac respiratory failure or pacemakers comprised the study cohort. INTERVENTION: Monitoring of the lung's electrical impedance was used for predicting cardiogenic pulmonary edema since accumulation of blood and fluid decreases impedance values. MEASUREMENTS AND RESULTS: Impedance of the lung is the main feature of ITI measured by the RS-207 monitor: decreased ITI prior to the clinical signs of cardiogenic pulmonary edema was used as the prediction criterion. The clinical signs used for confirmation of its prediction were dyspnea, cyanosis, pulmonary rales, crepitations, arterial hypoxemia, and radiographic evidence of pulmonary congestion in chest radiographs. Clinicians were blinded to the results of ITI measurements and radiologists were blinded to both ITI and clinical data. Thirty-seven patients developed cardiogenic pulmonary edema while being monitored. ITI decreased by more than 12% of baseline in all of them; this occurred at 30 min or longer (26 patients) and at 60 min or longer (11 patients) before the appearance of clinical signs. ITI fell by less then 10.1% of baseline in all 228 patients who did not develop the edema. CONCLUSION: Monitoring ITI is suitable for early prediction of cardiogenic pulmonary edema, before the appearance of the clinical signs.

Bezafibrates cause moderate, reversible impairment in renal function in patients without prior renal disease.

BACKGROUND/AIMS: To determine whether bezafibrates have adverse effects on renal function. METHODS: (1) A 3-year retrospective survey of 526 patients who were on bezafibrate for a while and 614 controls following fluctuations of serum creatinine levels. (2) A prospective study on 33 patients with previous evidence of bezafibrate-induced elevation in serum creatinine. The patients were examined after 3 months on bezafibrate 400 mg/day and then after 3 months without bezafibrate. Eight patients repeated the tests after 3 months on bezafibrate 200 mg/day. RESULTS: Retrospective: 295 bezafibrate-treated patients (56%) and 67 controls (11%) demonstrated fluctuations > or = 0.2 mg/dl in serum creatinine levels (p < 0.001); 113 patients (21%) and 16 controls (3%) showed fluctuations > or = 0.3 mg/dl (p < 0.001). Prospective: bezafibrate 400 mg/dl increased serum creatinine from 1.16 +/- 0.19 to 1.42 +/- 0.2 mg/dl (p < 0.001) and urea from 37 +/- 8 to 44 +/- 8 mg/dl (p < 0.001); creatinine clearance (Ccr) decreased from 104 +/- 23 to 82 +/- 27 ml/min (p < 0.001). CPK increased from 82 +/- 32 to 130 +/-58 mg/dl (p < 0.0001) and urinary myoglobin increased from 95.4 +/- 21 to 199 +/- 99 mg/dl (p < 0.0001). The 8 patients given bezafibrate 200 mg/dl experienced similar dose-dependent changes. CONCLUSIONS: Bezafibrate causes quiet common, dose-dependent and reversible changes in serum creatinine in patients with normal renal function, associated with a significant increase in serum CPK and urine myoglobin, suggestive of drug-induced mild subclinical skeletal muscle injury compromising renal function.

Multiple-shower thromboembolism in an artificial mitral valve patient.

BACKGROUND: Late acute left atrial thrombosis is a rare life-threatening complication that mostly appears with predisposing primary coagulopathy, such as Protein C, Protein S, antithrombin 3 deficiency, antiphospholipid syndrome or hyperhomocysteinemia. We present grave outcome due to lack of anticoagulation in a patient with artificial mitral valve. CASE PRESENTATION: A 47-year-old male known to have an artificial valve was hospitalized in another hospital due to an acute illness. Anti-coagulation therapy was not provided during that hospitalization. He was transferred to our hospital due to lower limb weakness and diagnosed by us as having extensive emboli disease with complete occlusion of the distal aorta. Multiple infarcts were found in the abdominal organs and leg muscles. He suffered from multiple organ failure and eventually died. CONCLUSION: Neglecting the common practice of anticoagulation to a patient with a mechanical heart valve may, in rare cases, lead to immediate catastrophic event caused by shower thrombemboli with disseminated vascular occlusion from the left atrium to the abdominal aorta causing complete occlusion, spleen, kidney and muscle infarcts.

The role of bile Acid excretion in atherosclerotic coronary artery disease.

The impact of cholesterol and different classes of lipoproteins on the development of coronary artery disease (CAD) has been investigated in extensively during the past 50 years. The cholesterol metabolism is dependent on numerous factors, including dietary fat, fractional absorption of dietary cholesterol, tissue stores of cholesterol, endogenous cholesterol synthesis, and fecal bile excretion. Several studies showed significantly lower amounts of bile acid secretion in adult patients with CAD compared to non-CAD patients. Could it be that the inability to efficiently excrete bile acids may lead to CAD development?

Anti-oxidized low-density lipoprotein antibodies in chronic heart failure.

Oxidative stress may play a significant role in the pathogenesis of heart failure (HF). Antibodies to oxidized low-density lipoprotein (oxLDL Abs) reflect an immune response to LDL over a prolonged period and may represent long-term oxidative stress in HF. The oxLDL plasma level is a useful predictor of mortality in HF patients, and measurement of the oxLDL Abs level may allow better management of those patients. Antibodies to oxLDL also significantly correlate with the New York Heart Association score. Hypercholesterolemia, smoking, hypertension, and obesity are risk factors for atherosclerotic coronary heart disease (CHD) leading to HF, but these factors account for only one-half of all cases, and understanding of the pathologic process underlying HF remains incomplete. Nutrients with antioxidant properties can reduce the susceptibility of LDL to oxidation. Antioxidant therapy may be an adjunct to lipid-lowering, angiotensin converting enzyme inhibition and metformin (in diabetes) therapy for the greatest impact on CHD and HF. Observational data suggest a protective effect of antioxidant supplementation on the incidence of HD. This review summarizes the data on oxLDL Abs as a predictor of morbidity and mortality in HF patients.

The association of bile acid excretion and atherosclerotic coronary artery disease.

BACKGROUND: Excess cholesterol is usually eliminated from the body by conversion to bile acids excreted in feces as bile salts. The excretion of large amounts of bile protects against atherosclerosis, while diminished excretion may lead to coronary artery disease (CAD). OBJECTIVE: To investigate a relationship between CAD and bile acid excretion. METHODS: Bile acid excretion was compared between 36 patients with proven CAD and 37 CAD-free individuals (controls). The groups were comparable for demographics and selected risk factors. All subjects received a 4-day standard diet that included ∼500 mg of cholesterol. Fecal bile acids from 24-hour stool collections were measured by gas liquid chromatography. RESULTS: CAD patients excreted lower amounts of total bile acids (358 ± 156 mg) than controls (617 ± 293 mg; p < 0.01) and less deoxycholic acid (188.29 ± 98.12 mg versus 325.96 ± 198.57 mg; p < 0.0001) and less lithocholic acid (115.43 ± 71.89 mg versus 197.27 ± 126.87 mg; p < 0.01). Advanced age, male gender, left ventricular ejection fraction and total bile acid levels were significant independent factors that predicted CAD (p < 0.05). Mortality, CAD and cerebrovascular accident development rates were significantly lower for the controls at the 13-year follow up. CONCLUSION: CAD patients have significantly decreased bile acid excretion levels than non-CAD patients. An impaired ability to excrete cholesterol may be an additional risk factor for CAD development.

Usefulness of total lymphocyte count as predictor of outcome in patients with chronic heart failure.

Low lymphocyte count has been considered a predictive marker of unfavorable outcomes for patients with heart failure (HF). Baseline blood samples for complete blood counts, differential counts, renal function tests. and lipid profile were prospectively obtained to assess the association between lymphocyte count and clinical outcomes in 305 patients with HF (average New York Heart Association [NYHA] class 2.8). The mean follow-up duration was 4.7 years (range 8 months to 8.4 years), and 111 patients (36%) died during the follow-up period. The mean lymphocyte count for the group was 1,803.64 ± 740.3, and the mean left ventricular ejection fraction (LVEF) was 37%. Patients with low lymphocyte counts (<1,600 median count) after 8 years had significantly lower survival rates than those with lymphocyte counts ≥1,600 (58% vs 72%, p=0.012). The prediction of poorest survival was for patients in NYHA class III or IV and with lymphocyte counts <1,600. Regression analysis showed that lymphocyte level, the LVEF, and NYHA class were predictors of mortality. Of these, NYHA class was the most prominent predictor, followed by lymphocyte count, which was even more significant than the LVEF (hazard ratio 0.76, p=0.037). In conclusion, the findings of this study demonstrate that total lymphocyte count is an important prognostic factor, inversely associated with predicted mortality. Although the total low lymphocyte count was correlated with a lower NYHA class and a lower LVEF, it emerged as an independent death risk factor in patients with chronic HF.

Baseline low-density lipoprotein cholesterol levels and outcome in patients with heart failure.

The incidence of heart failure (HF) is constantly increasing in the Western world. Treatment with statins is well established for the primary and secondary prevention of cardiac events by lowering low-density lipoprotein (LDL) cholesterol levels. There are conflicting reports on the role of LDL cholesterol as an adverse prognostic predictor in patients with advanced HF. The aim of this study was to investigate the association between LDL cholesterol levels and clinical outcomes in 297 patients with severe HF (average New York Heart Association class 2.8). The mean follow-up period was 3.7 years (range 8 months to 11.5 years), and 37% of the patients died during follow-up. The mean time to first hospital admission for HF was 25 +/- 17 months. The study group was divided according to plasma LDL level < or =89, >89 to < or =115, >115 mg/dl. Patients with the highest baseline LDL cholesterol levels had significantly improved outcomes, whereas those with the lowest LDL cholesterol levels had the highest mortality. When analyzed with respect to statin use, it emerged that the negative association between LDL cholesterol level and mortality was present only in the patients with HF who were treated with statins. In conclusion, lower LDL cholesterol levels appear to predict less favorable outcomes in patients with HF, particularly those taking statins, raising questions about the need for aggressive LDL cholesterol-lowering strategy in patients with HF, regardless of its cause.

Angioimmunoblastic T-cell lymphoma presenting as giant kidneys: a case report.

INTRODUCTION: Angioimmunoblastic T-cell lymphoma is a rare form of tumor of the lymph nodes or lymphoid tissue. In this report we describe an unusual presentation of angioimmunoblastic T-cell lymphoma consisting of giant kidneys with no nephrotic syndrome. CASE PRESENTATION: A 46-year-old Arabic man from Gaza was hospitalized in our ward due to abdominal pain and a weight loss of 20 kg during the preceding two months. The results of the physical examination and laboratory tests raised the possibility of neoplastic disease. A computerized tomographic scan of the abdomen showed huge kidneys, and a kidney biopsy showed infiltration by lymphocytes and eosinophils. The genetic examination revealed T-cell lymphoma. Diagnosis was made by a lymph node biopsy, which shows typical findings of angioimmunoblastic T-cell lymphoma. CONCLUSIONS: Angioimmunoblastic T-cell lymphoma can present with huge kidneys without nephrotic syndrome.

Seasonal changes in blood pressure and frequency of related complications in elderly Israeli patients with essential hypertension.

BACKGROUND: Earlier studies on hypertension demonstrated seasonal variations in different age groups. However, slightly greater fluctuations were found in the hypertensive elderly. OBJECTIVE: We conducted a prospective 5-year study from January 1997 to December 2001 to evaluate the seasonal variation in blood pressure and the variables of age, gender, body mass index and related complications in elderly Israeli patients with essential hypertension. METHODS: Blood pressure was measured in four seasons in 182 patients (98 men and 84 women; age range 65-91 years) treated for hypertension in our outpatient clinic. RESULTS: Both systolic and diastolic mean blood pressures were higher during winter compared to summer (165 +/- 11.6 and 90 +/- 13.7 and 134 +/- 47.3 and 74 +/- 8.5 mm Hg, respectively; p < 0.001). There were no significant seasonal differences between spring and autumn or any correlation between the seasonal winter-summer difference in blood pressure and other studied parameters. Patients aged 65-75 years were unexpectedly more sensitive to winter-summer changes than older patients. There was a correlation between a large winter-summer difference in systolic blood pressure and a body mass index between 20 and 30, but there was none in lower or higher ranges. Supplementary antihypertension treatment was required during winter in 38% of these selected patients. Complications such as myocardial infarctions and strokes occurred twice as frequently in winter than in any other season (p < 0.0001). CONCLUSIONS: Both systolic and diastolic blood pressures were highest during winter. Hypertension complications were more frequent in winter. Our results refute those of earlier studies that failed to find significant seasonal variations in blood pressure among the elderly.