Hyperlipidemias: Germany

Gogol M. · Chefarzt der Klinik für Geriatrie, Krankenhaus Lindenbrunn. · MMW Fortschr Med. · Pubmed #16626005 No free full text.

Abstract: At the present time, there is no adequate database for the application of statins for cholesterol lowering in geriatric patients. According to the current position adopted by the IOWiG (Institut für Qualität and Wirtschaftlichkeit im Gesundheitswesen = institute for quality and economy in health care), the usefulness of statins in patients with stable CAD or acute coronary syndrome can be affirmed. The National Institute of Clinical Excellence favors the administration of statins both in primary and secondary prevention of CAD and myocardial infarction, and also as a secondary prevention measure in non-severe stroke, PAD, unstable angina pectoris, and following revascularization procedures on the coronary arteries. Evidence for the superiority of the statins in patients older than 75 is, to date, available only for the indication of CAD in patients with elevated LDL cholesterol, but only up to the age of 80 years. Secondary prevention with statins leading to multipharmacotherapy must be rejected on account of the incalculable risk of side effects and drug interactions.

Kramer W, Glombik H. · TD Metabolism, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Building G 879, 65926 Frankfurt am Main, Germany. · Curr Med Chem. · Pubmed #16611081 No free full text.

Abstract: The enterohepatic circulation of bile acids is a major regulator of serum cholesterol homeostasis. After biosynthesis from cholesterol in the liver, bile acids are secreted with bile into the lumen of the small intestine to aid in the digestion and absorption of fat and fat-soluble vitamins. The bile acids are nearly quantitatively reabsorbed in the terminal ileum by a Na+-dependent transport system (IBAT) and are transported with portal blood to the liver and taken up by a second Na+-/bile acid cotransporter (LBAT) to be resecreted into bile. In the liver bile acids inhibit the rate-limiting enzyme for the conversion of cholesterol into bile acid: cholesterol-7alpha-hydroxylase; interruption of the enterohepatic circulation of bile acids withdraws this feedback inhibition and leads to an upregulation of hepatic LDL-receptors with a concomitant decrease of serum LDL-levels. Specific inhibitors of the ileal bile acid transporter belonging to different chemotypes have been developed in recent years for this purpose, some now entering clinical stage. To exert a profound systemic effect these compounds do not need to be available systemically but can act from the luminal side of the small intestine, which offers the advantage to avoid the well-known adverse side effects of other hypolipidemic drugs like statins due to metabolism and drug-drug interactions in the liver. This implies several aspects in compound optimization and drug development quite different from standard procedures, for example the concept of low absorption drugs was established to avoid systemic side effects. The review article covers the mechanistic and therapeutic principles of the approach and presents an overview on the molecular target, the discovery of specific inhibitors and respective optimization strategies.

Wassmann S, Nickenig G. · Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Bonn, Germany. · J Hypertens Suppl. · Pubmed #16601568 No free full text.

Abstract: BACKGROUND: Numerous studies have demonstrated that activation of the angiotensin II type 1 (AT1) receptor plays an important role in the pathogenesis of cardiovascular diseases. RESULTS: AT1-receptor activation by angiotensin II is not only involved in the regulation of blood pressure, water and sodium homeostasis, and control of other neurohumoral systems, but also leads to excessive production of reactive oxygen species and to hypertrophy, proliferation, migration, and apoptosis of vascular cells. AT1-receptor-induced oxidative stress may cause nitric oxide inactivation, lipid oxidation, and activation of redox-sensitive genes, such as chemotaxis and adhesion molecules, pro-inflammatory cytokines, and matrix metalloproteinases, all of which are involved in the initiation and progression of endothelial dysfunction and manifested atherosclerosis. The expression levels of the AT1-receptor define the biological efficacy of angiotensin II. Many agonists, such as, for example, angiotensin II, growth factors, low-density lipoprotein cholesterol, insulin, glucose, estrogen, progesterone, reactive oxygen species, cytokines, nitric oxide, and many others, are known to regulate AT1-receptor expression in vascular cells. The pathophysiological relevance of dysregulated AT1-receptor expression has been demonstrated in many cell culture and animal studies and interventional trials in humans. Hypercholesterolemia, estrogen deficiency, and diabetes mellitus are associated with enhanced vascular AT1-receptor expression, increased oxidative stress, and endothelial dysfunction. Importantly, treatment with AT1-receptor blockers may inhibit the onset and progression of vascular oxidative stress and inflammation, endothelial dysfunction, atherosclerosis, and related organ damage. CONCLUSION: Inhibition of AT1-receptor activation is presumably a primary treatment goal in patients suffering from cardiovascular risk factors or manifested atherosclerotic diseases.

Rief W, Avorn J, Barsky AJ. · Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA. · Arch Intern Med. · Pubmed #16432082 links to  free full text

Abstract: Medication-attributed adverse effects are a frequent reason for poor compliance in practice and in clinical studies and are also common in patients receiving placebo. The occurrence of adverse effects in placebo groups can clarify the assessment of adverse event reporting. We analyzed data from randomized, placebo-controlled trials of statin drugs published since 1992 with sample sizes larger than 100 subjects. Reports of adverse effects and discontinuation rates in placebo groups were evaluated. We compared data on adverse effect profiles in placebo groups between trials and with expected rates from population-based studies. We also sought to determine the range of adverse effect ascertainment methods used in different studies. Methods of ascertainment of adverse events varied widely across studies. Overall, 4% to 26% of patients in the control groups of large trials of statin drugs discontinued placebo use because of perceived adverse effects. The symptom rate in placebo groups varied substantially across trials (up to a ratio of 13:1 for possibly drug-related symptoms, eg, headache, 0.2%-2.7%, or abdominal pain, 0.9%-3.9%) and were often markedly lower than those found in the general population (eg, fatigue, 1.9%-3.4%) in trials of statin drugs vs 17.7% in the general population. In conclusion, the widely varying rates of adverse effects reported by patients taking placebo and the high prevalence of such symptoms in the general population should be considered by both trialists and clinicians. In addition, variability of adverse effect ascertainment is considerable and suggests the need for better standardization in research.

Borberg H. · German Haemapheresis Centre, Deutsches Haemapherese Zentrum, Maarweg 165, D-50 825 Köln, Germany. · Transfus Apher Sci. · Pubmed #16412691 No free full text.

Abstract: The techniques of haemapheresis originated in the development of centrifugal devices separating cells from plasma and later on plasma from cells. Subsequently membrane filtration was developed allowing for plasma-cell separation. The unspecificity of therapeutic plasma exchange led to the development of secondary plasma separation technologies being specific, semi-selective or selective such as adsorption, filtration or precipitation. In contrast on-line differential separation of cells is still under development. Whereas erythrocytapheresis, granulocytapheresis, lymphocytapheresis and stem cell apheresis are technically advanced, monocytapheresis may need further improvement. Also, indications such as erythrocytapheresis for the treatment of polycythaemia vera or photopheresis though being clinically effective and of considerable importance for an appropriate disease control are to some extent under debate as being either too costly or without sufficient understanding of the mechanism. Other forms of cell therapy are under development. Rheohaemapheresis as the most advanced technology of extracorporeal haemorheotherapy is a rapidly developing approach contributing to the treatment of microcirculatory diseases and tissue repair. Whereas the control of a considerable number of (auto-) antibody mediated diseases is beyond discussion, the indication of apheresis therapy for immune complex mediated diseases is quite often still under debate. Detoxification for artificial liver support advanced considerably during the last years, whereas conclusions on the efficacy of septicaemia treatment are debatable indeed. LDL-apheresis initiated in 1981 as immune apheresis is well established since 24 years, other semi-selective or unspecific procedures, allowing for the elimination of LDL-cholesterol among other plasma components are also being used. Correspondingly Lp(a) apheresis is available as a specific, highly efficient elimination procedure superior to techniques which also eliminate Lp(a). Quality control systems, more economical technologies as for instance by increasing automation, influencing the over-interpretation of evidence based medicine especially in patients with rare diseases without treatment alternative, more insight into the need of controlled clinical trials or alternatively improved diagnostic procedures are among others tools ways to expand the application of haemapheresis so far applied in cardiology, dermatology, haematology, immunology, nephrology, neurology, ophthalmology, otology, paediatrics, rheumatology, surgery and transfusion medicine.

Classen HG. · Pharmacology and Toxicology of Nutrition University of Hohenheim Stuttgart, Deuschland. · Rom J Intern Med. · Pubmed #16366126 No free full text.

Abstract: Magnesium orotate dihydrate (MO) has the sum formula C10H6MgN4O8 x 2H2O and a MG of 370.52. The salt is poorly soluble in water and hence does not bind gastric acid nor does it exhibit noteworthy laxative effects upon oral administration in contrast to easily dissociable Mg salts. As a source of magnesium (Mg), MO is indicated for the oral treatment of extracellular Mg deficiency. Orotic acid (OA), the second active ingredient of MO, is a key intermediate in the biosynthetic pathway of pyrimidines and is shown to improve the energy status of injured myocardium by stimulating, a.o., the synthesis of glycogen and ATP. Myocardial energy-rich phosphate levels are decreased during hypoxic conditions; subsequently, intracellular Mg is depleted and lost via the urine. Since binding sites for Mg (ATP) are provided by OA it can be classified as "Mg-fixing agent". Accordingly MO is also indicated for the treatment of Mg depletion as convincingly shown in animal experiments and also in coronary heart patients undergoing e.g. aortocoronary bypass surgery.

Schmitz G, Langmann T. · Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Straub-Allee 11, 93042 Regensburg, Germany. · Vascul Pharmacol. · Pubmed #16337220 No free full text.

Abstract: The prevention of cardiovascular disease is critically dependent on lipid-lowering therapy, including 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), cholesterol absorption inhibitors, bile acid resins, fibrates, and nicotinic acid. Although these drugs are generally well tolerated, severe adverse effects can occur in a minority of patients. Furthermore, a subset of patients does not respond to cholesterol-lowering therapy with a reduction in coronary heart disease progression. Significant progress has been made in the identification of common DNA sequence variations in genes influencing the pharmacokinetics and pharmacodynamics of statins and in disease-modifying genes relevant for coronary heart disease (CHD). Among the most promising candidate genes for pharmacogenomic analysis of statin therapy are HMG-CoA reductase as a direct target gene and other genes modulating lipid and lipoprotein homeostasis. Based on data from pharmacogenetic trials, a combined analysis of multiple genetic variants in several genes is more likely to give significant results than single gene studies in small cohorts. In the future, pharmacogenomic testing may allow risk stratification of patients to avoid serious side effects and enable clinicians to select lipid-lowering drugs with the highest efficacy resulting in the best response to therapy.

Dörr M, Völzke H. · Department of Internal Medicine B, Ernst-Moritz-Arndt-University, Greifswald, Germany. · Minerva Endocrinol. · Pubmed #16319809 No free full text.

Abstract: This review summarizes present knowledge from clinical and epidemiological studies with respect to cardiovascular complications in thyroid disorders, focusing on cardiovascular morbidity and mortality. Consistently, good evidence exists for an increased cardiovascular morbidity in overt hyperthyroidism, and an association with predictors of cardiovascular mortality like ventricular hypertrophy, ventricular dysfunction, and atrial fibrillation. As for subclinical hyperthyroidism evidence is conclusive only with respect to an up to 5.2-fold elevated risk for atrial fibrillation. The cardiovascular risk profile of overt hypothyroidism is characterized mainly by risk factors of atherosclerosis such as hypercholesterolemia and hypertension, but also by possible development of heart failure. In contrast, data on such parameters are inconsistent for subclinical hypothyroidism. Although many of these cardiovascular alterations may hypothetically worsen prognosis, results from cohort and retrospective studies do not consistently point towards increased mortality. Only for overt hyperthyroidism an up to 1.7 fold elevated risk for cardiovascular diseases and up to 1.7 fold increased cardiovascular mortality rates have been demonstrated. However, the evidence for similarly increased cardiovascular morbidity and mortality rates in subclinical hyperthyroidism and hypothyroidism is inconclusive, and the evidence is non-existent for overt hypothyroidism. Further randomized clinical studies and population-based cohort-studies are required and should consider major cardiovascular risk factors and adverse cardiovascular events and mortality.

Gouni-Berthold I, Krone W. · Department of Internal Medicine II, University of Cologne and Center of Moleclar Medicine Cologne (CMMC), Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany. · Z Kardiol. · Pubmed #16258774 No free full text.

Abstract: The relationship between serum triglyceride levels and cardiovascular disease has remained enigmatic despite four decades of research. The majority of the available evidence tends to support the role of hypertriglyceridemia as an independent risk factor for cardiovascular disease. However, there are no guidelines recommending a target triglyceride level for prevention of cardiovascular disease. The focus of lipid lowering therapy still remains the reduction of global cardiovascular risk by optimizing LDL cholesterol levels. Therapeutic options for triglyceride-lowering include lifestyle modification and pharmacological agents, such as fibrates, omega 3 fatty acids and niacin. Post-hoc analyses of the Helsinki Heart Study, Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial and Bezafibrate Infarction Prevention Study suggest a beneficial effect of the treatment of hypertriglyceridemia with fibrates, mainly in obese subjects with insulin resistance. However, in order to establish the actual clinical relevance of lowering triglyceride levels, prospective trials need to be conducted with the specific purpose of studying the effects of triglyceride reduction on clinical end points, i. e. coronary events and stroke.

Loeffler KU, Seifert P. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany. · Arch Ophthalmol. · Pubmed #16219739 No free full text.

This publication has no abstract.

Köstler E, Porst H, Wollina U. · Department of Dermatology, Academic Teaching Hospital Dresden-Friedrichstadt, 01067 Dresden, Germany. · Clin Dermatol. · Pubmed #16179179 No free full text.

Abstract: Metabolic diseases are common diseases in the Western world. Many of these diseases, including diabetes mellitus, hyperlipoproteinemia, gout, calcinosis, and hemochromatosis, are associated with skin diseases or often present with specific cutaneous signs. A knowledge of cutaneous manifestations helps to identify patients at risk, establish the internal diagnosis, and monitor the adverse effects of therapy.

Parhofer KG. · Department of Internal Medicine II, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. · Exp Clin Endocrinol Diabetes. · Pubmed #16151973 No free full text.

Abstract: Dyslipoproteinemias such as elevated LDL-cholesterol, reduced HDL-cholesterol, elevated triglycerides and elevated lipoprotein(a) play a central role in atherosclerosis. An elevated LDL concentration is pro-atherogenic because LDL are intimately linked to oxidative and inflammatory processes in the arterial wall. HDL on the other hand are anti-atherogenic because they mediate cholesterol efflux from the arterial wall, modulate the metabolism of atherogenic lipoproteins, and directly affect endothelial function. The current therapeutic focus is on LDL reduction and much less on HDL elevation, although fibrates and particularly nicotinic-acid/niacin are potent drugs to increase HDL-cholesterol and although both groups of drugs have been proven beneficial in large end-point studies. Furthermore, new HDL raising drugs are being developed. In patients with established atherosclerosis or at high risk for atherosclerosis statin-based LDL reduction will remain the cornerstone of lipid therapy, but many patients may benefit from combination therapy aiming at optimizing all lipid parameters.

Lammert F, Wang DQ. · Department of Medicine III, University Hospital Aachen and Aachen University, Germany. · Gastroenterology. · Pubmed #16083725 No free full text.

Abstract: The small intestine is a unique organ providing dietary and reabsorbed biliary cholesterol to the body. However, the molecular mechanisms whereby cholesterol is absorbed have not yet been fully understood. Recent research suggests that the newly identified Niemann-Pick C1-like 1 protein (NPC1L1) is expressed at the apical surface of enterocytes and plays a critical role in the absorption of intestinal cholesterol. Furthermore, adenosine triphosphate (ATP)-binding cassette (ABC) transporters ABCG5 and ABCG8 represent apical sterol export pumps that promote active efflux of cholesterol and plant sterols from enterocytes back into the intestinal lumen for excretion. This provides an explanation why cholesterol absorption is a selective process, with plant sterols and other noncholesterol sterols being absorbed poorly or not at all. These findings strongly support the concept that cholesterol absorption is a multistep process, which is regulated by multiple genes at the enterocyte level. The absorption efficiency of cholesterol is most likely determined by the net effect between influx and efflux of intraluminal cholesterol molecules across the brush border of the enterocyte. Combination therapy using a novel, specific, and potent cholesterol absorption (NPC1L1) inhibitor (ezetimibe) and HMG-CoA reductase inhibitors (statins) offers an efficacious new approach to the prevention and treatment of hypercholesterolemia.

Broedl UC, Rader DJ. · University of Munich, Department of InternalMedicine II, Marchioninistr. 15, 81377 Munich, Germany. · Expert Opin Biol Ther. · Pubmed #16050781 No free full text.

Abstract: Existing approaches to the treatment of refractory hypercholesterolaemia, severe hypertriglyceridaemia, low levels of high-density lipoprotein cholesterol and certain inherited disorders of intracellular lipid metabolism are ineffective in a substantial number of patients. Somatic gene therapy is considered to be a potential approach to the therapy of several of these lipid disorders. In many cases preclinical proof-of-principle studies have already been performed, and in one (homozygous familial hypercholesterolaemia) a clinical trial has been conducted. Other clinical gene therapy trials for dyslipidaemia are likely to be initiated within the next several years.

von Bergmann K, Sudhop T, Lütjohann D. · Department of Clinical Pharmacology, University of Bonn, Bonn, Germany. · Am J Cardiol. · Pubmed #15992510 No free full text.

Abstract: The recent discovery of transporters in the intestinal mucosa and the canalicular membrane has given new insights into the regulation of intestinal absorption as well as the biliary output of cholesterol and plant sterols. The 2 adenosine triphosphate (ATP)-binding cassette (ABC) half-transporters ABCG5 and ABCG8 are expressed in the mucosa cells and the canalicular membrane, and they resecrete sterols, especially absorbed plant sterols, back into the intestinal lumen and from the liver into bile. Defects of either of these cotransporters lead to the rare inherited disease of phytosterolemia, which is clinically defined by hyperabsorption and diminished biliary excretion of plant sterols. Furthermore, it has been recently demonstrated that the Niemann-Pick C1-Like 1 (NPC1L1) transporter is most likely responsible for the transport of cholesterol and plant sterols from the brush border membrane into the intestinal mucosa. Ezetimibe interferes with NPC1L1, reducing the intestinal uptake of cholesterol and plant sterols. These new findings contribute to our understanding of cholesterol and plant sterol concentrations in serum, and the effect of dietary and drug intervention to reduce serum concentrations of sterols.

Rosenberg M, Haass M. · Medizinische Universitätsklinik Heidelberg. · Internist (Berl). · Pubmed #15864508 No free full text.

Abstract: Alterations in lipid metabolism play a major role in the pathogenesis of atherosclerosis and are an important risk factor for cardiovascular events. Lowering of LDL cholesterol by statins reduces morbidity and mortality in patients with coronary artery disease (CAD), both in primary and secondary prevention. The results of large controlled trials that included more than 50,000 patients are the basis for target values promoted by current guidelines. According to the NCEP-ATP III guidelines LDL cholesterol should be lowered to less than 100 mg/dl in high risk patients (CAD or CAD equivalent) and in very high risk patients optional to less than 70 mg/dl. Up to now even in high risk patients the recommended goals are not sufficiently achieved: Up to 80% of high risk patients do not receive a statin and only a minority of those being treated with a statin have a LDL cholesterol below 100 mg/dl. Furthermore, after a major event (e.g. myocardial infarction) the quality of lipid reduction decreases over time. Further efforts are required to improve this situation as a guide-line oriented approach may help to prevent up to 100,000 myocardial infarctions and deaths alone in high risk patients in Germany.

Wieneke H, Schmermund A, Erbel R. · Klinik für Kardiologie, Universität Duisburg-Essen, Hufelandstrasse 55, 45122 Essen. · Med Klin (Munich). · Pubmed #15834527 No free full text.

Abstract: BACKGROUND: Large interventional studies have shown that the reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C) is one of the cornerstones in the prevention of coronary artery disease. However, in up to 40% of patients the recommended target of LDL-C is not reached with a monotherapy. Furthermore, risk stratification only by LDL-C disregards a substantial number of patients with dyslipidemia with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). EFFECT OF NIACIN ON LIPID METABOLISM: In consequence, niacin has gained attention as a component of a combined therapeutic approach in patients with dyslipidemia. Niacin substantially increases HDL-C and decreases triglycerides, LDL-C and lipoprotein (a). By this mechanism of action niacin exhibited, in combination with statins or bile acid-binding resins, favorable effects on the incidence of cardiovascular events in selected patients. Side effects like flush and hepatotoxicity seem to be in part dependent on the niacin formulations used. However, niacin has been shown to be a well-tolerated and safe therapy in controlled studies. CONCLUSION: On the basis of current data niacin should be considered a valuable therapy component in patients with dyslipidemia, in which a monotherapy fails to optimize an increased risk of coronary artery disease.

Csef H, Hefner J. · Medizinische Klinik und Poliklinik II, Würzburg. · MMW Fortschr Med. · Pubmed #15832759 No free full text.

Abstract: Most people throughout the world die from the consequences of cardiovascular disease. Stress and psychosocial burdens have, in the past, been underestimated with regard to the importance of their impact on the development and course of such diseases. In the INTERHEART study, psychosocial burdens occupy third place among the risk factors for developing acute myocardial infarction.The relevance of these factors is underscored by more recent studies, also with regard to the prognosis in already manifest CAH. The causes of mental stresses may be intrapsychic problems (e.g. depression). The roots may, however, also be found in the private sphere or at the workplace. On the basis of specific history-taking, relevant risk constellations can be identified for a comparatively low expenditure of time. Specific therapeutic approaches aimed at reducing and coping with stress may, in future, help prevent diseases of the heart and lower the risk of contracting a myocardial infarction.

Weber C. · Department of Molecular Cardiovascular Research, University Hospital, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany. · Circ Res. · Pubmed #15802619 links to  free full text

Abstract: It becomes increasingly evident that blood platelets do not only exert important functions in hemostasis and thrombus formation but are also involved in atherosclerotic vascular disease. A major portion of the underlying mechanisms is related to an intricate functional interaction of platelets with chemokines, which have also been implicated in atherogenesis and neointima formation: (1) Platelets can induce the secretion of chemokines in different cells of the vascular wall; (2) In combination with primary agonists, certain chemokines can potentiate platelet aggregation and adhesion; (3) Activated platelets can release and deposit chemokines and precursors on vascular cell surfaces, which trigger atherogenic recruitment of vascular cells or modulate crucial processes such as angiogenesis and lipoprotein metabolism; (4) Surface-adherent platelets can bind and present vascular cell-derived chemokines to trigger arrest of circulating mononuclear cells. The close linkage between platelets and chemokines as culprits in the pathogenesis of vascular diseases may provide a valuable target for selective interventions.

Eckert GP, Wood WG, Müller WE. · Department of Pharmacology, Biocenter Niederursel, ZAFES, University of Frankfurt, Germany. · J Neural Transm. · Pubmed #15682268 No free full text.

Abstract: Evidences from cell culture experiments and animal studies suggest a strong link between cholesterol and Alzheimer's disease (AD). This relationship is supported by retrospective epidemiological studies demonstrating that statin treatment reduced the prevalence of AD in patients suffering from hypercholesterolaemia. The alternative processing of the amyloid-precursor protein (APP) in the brain of AD patients leads to the production of the neurotoxic amyloid-beta protein (Abeta), a causative factor for AD pathology. In vitro, this mechanism is modulated by alterations in cellular cholesterol levels. Moreover, lowering cholesterol in animal experiments reduced the production of Abeta in most but not all studies. These findings led to prospective clinical trials of cholesterol-lowering statins in AD patients, even if many studies do not support elevated cholesterol levels in serum and brain as a risk factor for Alzheimer's disease. Most of these studies were negative. Thus, up to date there is insufficient evidence to suggest the use of statins for treatment in patients with AD.

Gohlke H. · Klinische Kardiologie II, Herz-Zentrum Bad Krozingen. · Dtsch Med Wochenschr. · Pubmed #15619173 No free full text.

This publication has no abstract.

Moosmann B, Behl C. · Department of Pathobiochemistry, Johannes Gutenberg University, Medical School, Duesbergweg 6, 55099 Mainz, Germany. · Trends Cardiovasc Med. · Pubmed #15542379 No free full text.

Abstract: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and peroxisome proliferator-activated receptor alpha activators (fibrates) are the backbone of pharmacologic hypercholesterolemia and dyslipidemia treatment. Many of their clinical effects, however, are still enigmatic. This article describes how a side road of the mevalonate pathway, characterized in recent years, can rationalize a major fraction of these unexplained observations. This side road is the enzymatic isopentenylation of selenocysteine-tRNA([Ser]Sec) (Sec-tRNA), the singular tRNA to decode the unusual amino acid selenocysteine. The functionally indispensable isopentenylation of Sec-tRNA requires a unique intermediate from the mevalonate pathway, isopentenyl pyrophosphate, which concomitantly constitutes the central building block for cholesterol biosynthesis, and whose formation is suppressed by statins and fibrates. The resultant inhibition of Sec-tRNA isopentenylation profoundly decreases selenoprotein expression. This effect might seamlessly explain the immunosuppressive, redox, endothelial, sympatholytic, and thyroidal effects of statins and fibrates as well as their common side effects and drug interactions.

Bosch T. · Nephrology Division, Department I of Internal Medicine, University Hospital Munich-Grosshadern, D-81377 Munich, Germany. · Transfus Apher Sci. · Pubmed #15501411 No free full text.

Abstract: Direct adsorption of lipoproteins (DALI) from whole blood is the first LDL-hemoperfusion procedure. The present paper addresses practical questions of DALI apheresis in order to optimise DALI therapy in sometimes critically ill coronary patients. The reduction of LDL and Lp(a) by DALI can be optimised by increasing the treated blood volume and the DALI adsorber volume. Hypotension (1.2% of sessions) may be minimised by fluid intake before the session, isovolemic connection of the patient to the ECC, reduced blood flow and low ACD-A ratio. Hypocalcemia may be avoided by low citrate anticoagulation (1:40) and reduced blood flow. Bradykinin release peaks at ca. 1000 ml of treated blood volume and may cause Quincke edema (tight throat), hypotension and flush. Reduction of the blood flow rate and decrease of citrate admixture as well as administration of iv. calcium may be helpful. While ACE inhibitors are contraindicated in DALI patients, sartans may be used without problems. Some "intrinsic" PTT increase is caused by adsorption of coagulation factors; undue PTT prolongations after DALI may be avoided by reduction of the heparin dosage during priming and treatment. In patients prone to alkalosis and hypokalemia, a reduction of the ACD-A ratio is recommended. Rises of adsorber inlet pressure may be due to insufficient anticoagulation and adsorber clotting or malfunctioning of the venous access. Rinsing of the adsorber with saline, administration of a heparin bolus and increase of the citrate admixture as well as a rinse and/or repositioning of the venous access are helpful measures. If these basic rules are followed, DALI LDL-apheresis is a safe, efficient, rapid and user-friendly LDL-apheresis procedure as evidenced by more than 80,000 DALI sessions successfully performed to date.

Döser S, März W, Reinecke MF, Ringleb P, Schultz A, Schwandt P, Becker HJ, Bönner G, Buerke M, Diener HC, Gohlke H, Keil U, Ringelstein EB, Steinmetz A, Gladisch R, Wehling M. · IV. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim, Ruprecht-Karls-Universität Heidelberg. · Internist (Berl). · Pubmed #15340698 No free full text.

Abstract: Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.

Nickenig G. · Department of Internal Medicine III, University Hospital of the Saarland, Homburg/Saar, Germany. · Circulation. · Pubmed #15326080 links to  free full text

This publication has no abstract.