Alexander Rabinovich

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 ∼500u2009mg 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 (358u2009±u2009156u2009mg) than controls (617u2009±u2009293u2009mg; pu2009<u20090.01) and less deoxycholic acid (188.29u2009±u200998.12u2009mg versus 325.96u2009±u2009198.57u2009mg; pu2009<u20090.0001) and less lithocholic acid (115.43u2009±u200971.89u2009mg versus 197.27u2009±u2009126.87u2009mg; pu2009<u20090.01). Advanced age, male gender, left ventricular ejection fraction and total bile acid levels were significant independent factors that predicted CAD (pu2009<u20090.05). 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.

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).

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?

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.

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.

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.

Internal Thoracic Impedance - A Useful Method for Expedient Detection and Convenient Monitoring of Pleural Effusion

Measurement of internal thoracic impedance (ITI) is sensitive and accurate in detecting acute pulmonary edema even at its preclinical stage. We evaluated the suitability of the highly sensitive and noninvasive RS-207 monitor for detecting pleural effusion and for demonstrating increased ITI during its resolution. This prospective controlled study was performed in a single department of internal medicine of a university-affiliated hospital between 2012-2013. One-hundred patients aged 25–96 years were included, of whom 50 had bilateral or right pleural effusion of any etiology (study group) and 50 had no pleural effusion (controls). ITI, the main component of which is lung impedance, was continuously measured by the RS-207 monitor. The predictive value of ITI monitoring was determined by 8 measurements taken every 8 hours. Pleural effusion was diagnosed according to well-accepted clinical and roentgenological criteria. During treatment, the ITI of the study group increased from 32.9±4.2 ohm to 42.8±3.8 ohm (p<0.0001) compared to non-significant changes in the control group (59.6±6.6 ohm, p = 0.24). Prominent changes were observed in the respiratory rate of the study group: there was a decrease from 31.2±4.0 to 19.5±2.4 ohm (35.2%) compared to no change for the controls, and a mean increase from 83.6±5.3%-92.5±1.6% (13.2%) in O2 saturation compared to 94.2±1.7% for the controls. Determination of ITI for the detection and monitoring of treatment of patients with pleural effusion enables earlier diagnosis and more effective therapy, and can prevent hospitalization and serious complications, such as respiratory distress, and the need for mechanical ventilation. Trial Registration The study is registered at ClinicalTrials.gov NCT01601444

Preventive treatment of alveolar pulmonary edema of cardiogenic origin

Objective To evaluate the efficacy of preventive treatment (PT) on alveolar pulmonary edema (APE) of cardiogenic origin using a monitor based on principles of internal thoracic impedance (ITI) measurements. Methods We conducted blinded clinical trials on patients with ST-elevation myocardial infarction (STEMI) and monitored whether the condition would progress to APE. ITI was measured non-invasively by the Edema Guard Monitor (EGM, model RS-207) every 30 min. The measurement threshold for the diagnosis of APE was fixed at > 12% decrease in ITI from baseline as described in our methodology. The patients were divided into one group that received standard treatment after the appearance of clinical signs of APE without considering the prediction of APE by EGM devise (Group 1), and another group of asymptomatic patients in whom development of APE was predicted by using only EGM measurements (Group 2). The latter participants PT consisted of furosemide, intravenous nitroglycerine and supplemental oxygen. Results One-hundred and fifty patients with acute STEMI were enrolled into this study. Group 1 included 100 patients (53% males, age 64.1 ± 12.6 years). Treatment was started after the clinical appearance of overt signs of APE. Group 2 included 50 patients (54% males, age 65.2 ± 11.9 years) who received PT based on EGM measurements. Group 2 had significantly fewer cases of APE (n = 4, 8%) than Group 1 (n = 100, 100%) (P > 0.001). While APE was lethal in six (6%) Group 1 patients, PT resulted in prompt resolution of APE in all four (8%) Group 2 patients. Conclusion ITI is a useful modality for early diagnosis and PT of pulmonary edema of cardiogenic origin.

Methylphenidate and Dyslipidemia

Methylphenidate is a piperidine derivative, structurally related to amphetamines and acts as a CNS stimulant. Methylphenidate has been widely used since 1937 for numerous indications including attention deficit hyperactivity disorder (ADHD), narcolepsy, cataplexy (3) and conduct disorder (4) in children and adolescents as well as adults (4). Although it has been indicated for ADHD since 1957 it has gained widespread use during the last two decades (5). Methylphenidate was found to affect brain sterol metabolism in mice by inhibition of the incorporation of its precursors, acetate and glucose, into the brain and by reduction of the brain’s sterol levels (6). This reduction was found to occur within 24 hours in the neuronal cellular membrane, the site of methylphenidate’s action (6).