Combining Ubiquinol With a Statin May Benefit Hypercholesterolaemic Patients With Chronic Heart Failure.

Heart failure (HF) is one of the most common causes of death in Western society. Recent results underscore the utility of coenzyme Q10 (CoQ10) addition to standard medications in order to reduce mortality and to improve quality of life and functional capacity in chronic heart failure (CHF). The rationale for CoQ10 supplementation in CHF is two-fold. One is the well-known role of CoQ10 in myocardial bioenergetics, and the second is its antioxidant property. Redox balance is also improved by oral supplementation of CoQ10, and this effect contributes to enhanced endothelium-dependent relaxation. Previous reports have shown that CoQ10 concentration is decreased in myocardial tissue in CHF and by statin therapy, and the greater the CoQ10 deficiency the more severe is the cardiocirculatory impairment. In patients with CHF and hypercholesterolaemia being treated with statins, the combination of CoQ10 with a statin may be useful for two reasons: decreasing skeletal muscle injury and improving myocardial function. Ubiquinol, the active reduced form of CoQ10, presents higher bioavailability than the oxidised form ubiquinone, and should be the preferred form to be added to a statin. The combination ezetimibe/simvastatin may have advantages over single statins. Since ezetimibe reduces absorption of cholesterol and does not affect CoQ10 synthesis in the liver, the impact of this combination on CoQ10 tissue levels will be much less than that of high dose statin monotherapy at any target low density lipoprotein-cholesterol (LDL-C) level to be reached. This consideration makes the ezetimibe/statin combination the ideal LDL-lowering agent to be combined with ubiquinol in CHF patients. However, particular caution is advisable with the use of strategies of extreme lowering of cholesterol that may negatively impact on myocardial function. All in all there is a strong case for considering co-administration of ubiquinol with statin therapy in patients with depressed or borderline myocardial function.

Treatment options for severe hypertriglyceridemia (SHTG): the role of apheresis.

Hypertriglyceridemia is associated with a number of severe diseases such as acute pancreatitis and coronary artery disease. In severe hypertriglyceridemia (SHTG, triglycerides > 1,000 mg/dL), rapid lowering of plasma triglycerides (TG) has to be achieved. Treatment regimes include nutritional intervention, the use of antihyperlipidemic drugs, and therapeutic apheresis. Apheretic treatment is indicated in medical emergencies such as hypertriglyceridemic pancreatitis. Reviewing the current literature, plasmapheresis appears to be a safe and useful therapeutic tool in patients suffering from SHTG. Apheretic treatment is able to remove the causative agent for pancreatic inflammation. Data suggests that the use of apheresis should be performed as early as possible in order to achieve best results. The use of plasmapheresis, however, is limited due to the rather high costs and the limited availability of the procedure.

Successful treatment of severe hypertriglyceridemia with a formula diet rich in omega-3 fatty acids and medium-chain triglycerides.

BACKGROUND: Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears to be a fast but expensive method to reduce triglyceride levels. In this study we describe the use of a new omega-3 fatty acid and medium-chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma triglyceride levels fast and effectively. METHODS: Thirty-two patients with severe hypertriglyceridemia were treated with the especially composed formula diet for a period of 7 days. RESULTS: Within this period of time, plasma triglycerides decreased from 1,601 (402-4,555) to 554 (142-2,382) mg/dl (p < 0.05). Total cholesterol levels were reduced from 417 (211-841) to 287 (165-457) mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (-8%; -12%). The formula diet as a 1-week treatment was well tolerated and accepted by the patients. CONCLUSION: This diet was successfully used as an acute treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and safely lowering plasma triglyceride levels.

Severe hypertriglyceridemia and pancreatitis: presentation and management.

PURPOSE OF REVIEW: Hypertriglyceridemia (HTG) is a well recognized cause of acute pancreatitis accounting for approximately up to 10% of all cases and even up to 50% of all cases in pregnancy. Both primary and secondary disorders of lipoprotein metabolism may be associated with hypertriglyceridemic pancreatitis (HTGP). The purpose of this review is to provide an overview of the current studies on presentation and management of HTGP. RECENT FINDINGS/CONCLUSION: Hydrolysis of triglycerides by pancreatic lipase and formation of free fatty acids that induce inflammatory changes are postulated to account for the development of HTGP, yet the exact pathophysiology remains unclear. The clinical features of patients with HTGP are generally not different from patients with acute pancreatitis of other causes, and there is some evidence that HTGP is associated with a higher severity or a higher complication rate. There is no clear evidence as to which HTG patients will develop pancreatitis. Several studies have evaluated the effect of apheresis, the benefit of insulin and/or heparin treatment and the use of different antihyperlipidemic agents in HTGP. Dietary modifications resemble the key features in the long-term management of HTG. Whether HTG may cause chronic pancreatitis in the long-term follow-up remains controversial.

Severe hypertriglyceridemia: an indication for apheresis?

OBJECTIVE: Severe hypertriglyceridemia is associated with a number of severe complications such as acute pancreatitis. Rapid lowering of excessively elevated triglyceride (TG) levels is therefore a primary medical goal in these patients. According to previous reports, immediate apheretic treatment might be an interesting option in order to rapidly lower excessively elevated TG levels. METHODS: A review of the current available literature was therefore conducted in order to provide an overview of the present data on apheretic treatment for patients with severe hypertriglyceridemia. RESULTS: A single session of plasmapheresis proofs capable of lowering TG levels by up to 70%, producing clear clinical and laboratory improval. The best clinical benefit concerning reduction in morbitity and mortality can be achieved when apheresis is used as early as possible. Even repetitive use of apheresis is reported. There is controversy on technical details, such as different apheresis techniques (plasma exchange versus double-membrane filtration), slightly favoring plasma exchange. CONCLUSIONS: In patients with severe hypertriglyceridemia plasmapheresis seems to be a safe and useful tool in rapidly lowering excessively elevated TG levels. Apheresis can be used to rapidly decrease triglyceride levels, and thus remove the causative agent for continuing damage. The indications are medical emergencies such as hypertriglyceridemic pancreatitis with excessively elevated TG levels (TG > 1000 mg/dl). If indicated, it should be used as early as possible.

Successful long-term treatment of severe hypertriglyceridemia by feedback control with lipid self-monitoring.

BACKGROUND/AIMS: Successful treatment of severe hypertriglyceridemia is difficult. Besides therapy with different drugs, dietary intervention is an important approach. However, compliance with dietary recommendations is usually bad. Lipid self-monitoring in patients might improve dietary compliance and control of lipid parameters. METHODS: Thirty-two patients with severe hypertriglyceridemia (>750 mg/dl) were primarily treated with a formula diet reducing the triglyceride levels <600 mg/dl. After this acute treatment, self-monitoring of lipid parameters was performed for 48 weeks. Twenty-five patients completed the whole study. The participants measured their lipid parameters with Accutrend GCT dry chemistry strips. Dietary records were taken and measurements of body composition, BMI, triglycerides, total cholesterol and glucose were performed. RESULTS: Triglycerides remained stable in patients with levels <300 mg/dl at the beginning of the protocol. There was a significant decline in triglycerides in those who started with levels >300 mg/dl. No severe hypertriglyceridemia (>750 mg/dl) could be observed. The energy intake decreased in all patients due to a reduction in total fat and carbohydrate consumption. The relation between carbohydrates and protein remained unchanged. Self-measurement was well tolerated and an improvement in controlling the diet was reported. CONCLUSIONS: Self-control of lipid parameters can improve the dietary compliance of patients with hypertriglyceridemia and is well tolerated.

Effect of liquid pancreatic enzymes on the assimilation of fat in different liquid formula diets.

BACKGROUND: In some diseases, patients require high-calorie tube feeding with standard enteral formulas usually administered via temporal feeding tubes. One frequent pathophysiological condition in a relevant number of these patients is exocrine pancreatic insufficiency. Patients unable to swallow capsules might benefit from a liquid pancreatic enzyme (LPE) preparation. METHODS: LPEs were prepared and mixed with different commercially available formula diets produced for enteral feeding. Lipolysis was then measured by fatty acid titration. RESULTS: Complete lipolysis by liquid enzyme preparations was observed in diverse formula diets. Fat assimilation was even complete when LPE had been prepared 3.5 hours before the experiments, showing that the enzymes had been stable up to that time. CONCLUSIONS: The use of LPEs seems to be a good therapeutic option in patients with exocrine pancreatic insufficiency and the need for permanent high-calorie enteral feeding. Pharmaceutical companies should therefore be further encouraged to develop and distribute liquid enzyme preparations.

Fecal pyruvate kinase-M2 (tumor M2-PK) measurement: a new screening concept for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a disease with major impact on public health and public health costs. Colonoscopy is purportedly the best screening tool for CRC. However, the acceptance by the general population is very poor. Therefore evaluation of additional screening tools is of great interest. PATIENTS AND METHODS: The use of M2-PK measurement in the feces has been reported in 6 studies to date. The data of these studies were analysed and critically reviewed. Additionally, 1,906 persons undergoing routine health care check-up provided stool samples for M2-PK measurement. RESULTS: The overall sensitivity of M2-PK is 77.9% for CRC. Specificity ranges from 74.3 to 83.3%. Of the 1,906 screened persons, 90.4% had results within the normal range, while 9.6% had elevated results. CONCLUSION: Measurement of tumor M2-PK in feces seems to be the most promising tool for CRC screening at the present time. In combination with colonoscopy, this test should hence be recommended for CRC screening programs.

Endoscopic sphincterotomy in patients with stenosis of ampulla of Vater: three-year follow-up of exocrine pancreatic function and clinical symptoms.

AIM: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater. METHODS: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured. RESULTS: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 microg/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) decreased significantly after ES. CONCLUSION: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function.

Effects of oral fat load on insulin output and glucose tolerance in healthy control subjects and obese patients without diabetes.

OBJECTIVE: Elevated plasma nonesterified fatty acid (NEFA) concentrations cause peripheral and hepatic insulin resistance and may play an important role in regulating glucose-induced insulin secretion. The aim of our study was to investigate the influence of physiologically elevated NEFA levels on glucose-stimulated insulin secretion in order to find evidence that NEFAs are a potential factor predisposing for type 2 diabetes and related metabolic disorders, which are known risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS: We combined an orally administered fat emulsion with an intravenous glucose tolerance test and measured the time course of NEFA, insulin, and glucose. In order to find pathological conditions we applied the experiment to healthy and obese subjects. RESULTS: The main findings are a significant increase in glucose-stimulated insulin secretion after oral fat load in both groups compared with the condition without preceding fat ingestion and a prolonged insulin secretion after fat load in obese patients compared with control subjects. CONCLUSIONS: The results provide evidence that fat ingestion modulates beta-cell function and that NEFA is a plausible mediator that acts as a link between fat and glucose metabolism by modulating glucose-stimulated insulin secretion. Under the condition of elevated plasma levels of NEFA, this mechanism may be responsible for hyperinsulinemia in obese patients and a potential target of type 2 diabetes prevention strategies.