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ZusammenfassungDie Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt.

Die vorliegende Leitlinie nimmt Bezug auf die Indikation und praktische Umsetzung der Insulintherapie bei Typ 2 Diabetes, insbesondere auch im Hinblick auf die unterschiedlichen Formen der Insulintherapie.

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

Background: Prognostic implications of blood cholesterol may differ at different stages of life. This cohort study compares the value of total cholesterol (TC) readings earlier versus later in life to predict coronary atherosclerosis, cardiovascular events, and cardiovascular death. Methods: In a cardiovascular observation study (CVOS) we performed coronary angiography and prospectively recorded cardiovascular events in 1090 patients over up to 19 years. These patients had participated in a health survey 15 years prior to the CVOS baseline. TC was measured both at the earlier health survey and at the later CVOS recruiting. Findings: Patients in the highest versus the lowest TC-category of the health survey had an OR of 4.30 [2.41-7.65] for significant CAD at angiography, a HR of 1.74 [1.10-2.76] for cardiovascular events, and a HR of 7.55 [1.05-54.49] for cardiovascular death after multivariate adjustment. In contrast, TC as measured at the baseline of the CVOS was neither significantly associated with significant CAD nor with cardiovascular events or death during follow-up. In addition, the ESC/EAS-SCORE was found to be more powerful in predicting cardiovascular mortality when using earlier instead of later TC, with a continuous net reclassification improvement of 0.301 (p

Hyper- und Dyslipidamie tragen zur kardiovaskularen Morbiditat und Mortalitat diabetischer Patienten bei. Uberzeugende Daten zeigen, dass eine medikamentose Therapie mit Statinen das kardiovaskulare Risiko von Patienten mit Diabetes senken kann. Der vorliegende Artikel stellt die Behandlungsvorschlage der Osterreichischen Diabetes Gesellschaft zum Einsatz lipidsenkender Medikamente dar.

Bei kritisch kranken Patienten kommt es haufig zum Auftreten einer Hyperglykamie, welche eindeutig mit einer gesteigerten Mortalitatsrate assoziiert ist. Der aktuell verfugbaren Datenlage entsprechend sollte eine intravenose Insulintherapie bei Blutzuckerwerten >180 mg/dl begonnen werden und ein Zielbereich zwischen meist 140–180 mg/dl angestrebt werden.

The availability of efficient lipid-lowering drugs has substantially reduced the incidence and mortality for cardiovascular disease (CVD). Despite that, CVD still represents a major cause of death and disability; efforts are thus required to prevent this disease, since reducing the established CV risk factors may slow or prevent the onset of cardiovascular events. Current guidelines recommend a healthier lifestyle for all CV risk categories, as it may have a beneficial impact on several risk factors; in individuals with a low-to-moderate hypercholesterolemia, which are not eligible for a pharmacological approach and are not far from the cholesterol target recommended for their risk category, functional foods or nutraceuticals may be considered as supplement to reduce their CV risk status. Of note, counseling and lifestyle intervention in people at moderate CV risk represents a major issue for both preventing a further risk increase and reducing the need for drugs. Studies on general populations have clearly indicated that lifestyle interventions translate into a clinical benefit, with reduction of the incidence of myocardial infarction and the risk of developing type 2 diabetes.

Elevated blood pressure remains a major cause of cardiovascular disease, disability, and premature death in Austria, with suboptimal rates of detection, treatment and control also in recent years. Management of hypertension is a common challenge for physicians with different spezializations. In an attempt to standardize diagnostic and therapeutic strategies and, ultimately, to increase the rate of patients with controlled blood pressure and to decrease the burden of cardiovascular disease, 13 Austrian medical societies reviewed the evidence regarding prevention, detection, workup, treatment and consequences of high blood pressure in general and in various clinical scenarios. The result is presented as the first national consensus on blood pressure. The authors and societies involved are convinced that a joint national effort is needed to decrease hypertension-related morbidity and mortality in our country.

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

In critical illness hyperglycemia is associated with increased mortality. Based on the currently available evidence, an intravenous insulin therapy should be initiated when blood glucose is above 180 mg/dl. After initiation of insulin therapy blood glucose should be maintained between 140 and 180 mg/dl.

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutant ...

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.

Summary In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The “Austrian Lipid Consensus – 2016 update” provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies. Furthermore, specific management in key patient groups is outlined, including subjects presenting with coronary, cerebrovascular, and/or peripheral atherosclerosis; diabetes mellitus and/or metabolic syndrome; nephropathy; and familial hypercholesterolemia.

1. Preamble : Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) [1]. Increased levels of low density lipoprotein cholesterol (LDL-C) are associated with an increased risk of coronary heart disease (CHD) and many clinical trials have shown that reducing LDL-C levels significantly reduced the CHD and CVD risk [[2], [3], [4], [5]]. Thus LDL-C-lowering is the main approach for the management of cardiovascular disease. Current guidelines suggest LDL-C levels targets based on the individual CV risk; such targets can be achieved by several means, which include both lifestyle changes and pharmacological approaches [6], with statins being the cornerstone of cardiovascular prevention. [...]

Background: The wearable cardioverter-defibrillator is a treatment option for patients at temporarily high risk of sudden cardiac death or in whom implantation of a cardioverter-defibrillator is temporarily not possible. Objectives: The aim of this study was to provide real-world data on patients receiving this therapy in a nurse-based wearable cardioverter-defibrillator training programme. Methods: A registry including all patients prescribed with a wearable cardioverter-defibrillator in Austria between 2010 and 2016. Overall, 448 patients received a wearable cardioverter-defibrillator in 48 centres. Patients received structured nurse-based wearable cardioverter-defibrillator educational initial training followed by remote monitoring. Results: Main indications were: severe non-ischaemic cardiomyopathy (21%); recent myocardial infarction and percutaneous coronary intervention (20%); and stable coronary artery disease with percutaneous coronary intervention/coronary artery bypass grafting (14%). Eleven patients (2.5%) received 22 appropriate wearable cardioverter-defibrillator shocks. Two patients (0.4%) received three inappropriate shocks. The risk of sudden cardiac death varied between different aetiologies. Eight out of 11 (73%) patients received their first wearable cardioverter-defibrillator shock within 30 days. The main reasons for termination of the wearable cardioverter-defibrillator therapy were implantable cardioverter-defibrillator implantation (55.5%) and improvement of left ventricular ejection fraction to more than 35% (33%). Conclusion: The wearable cardioverter-defibrillator is an effective and safe treatment option in patients at either transiently elevated risk of ventricular tachycardia/ventricular fibrillation or mandated postponed implantable cardioverter-defibrillator implantation, with a 2.5% shock rate over a median 54 days wearable cardioverter-defibrillator treatment period. However, both the wearable cardioverter-defibrillator shock rate and implantable cardioverter-defibrillator implantation rate vary widely depending on the wearable cardioverter-defibrillator indication. Nurse-based wearable cardioverter-defibrillator training is associated with high patient adherence, with a median wearing duration per day of 23.5 (1–24) hours.

Die Hyperglykamie ist ein haufiges Phanomen bei kritisch kranken Patienten, welches zu Komplikationen wie einer erhohten kardiovaskularen Ereignisrate bzw. einem gesteigerten Infektrisiko fuhrt. Basierend auf der aktuell verfugbaren Datenlage sollte eine blutzuckersenkende Therapie mittels intravenosem Insulin ab einem Blutzuckerwert von 180 mg/dl eingeleitet werden. Der Blutzuckerspiegel sollte zwischen 140 und 180 mg/dl gehalten werden. Bei chirurgischen Patienten sind niedrigere BZ-Werte zwischen 110 und 140 mg/dl anzustreben. Nach der Transferierung auf eine „Normal-Station“ sollte eine formelle Glukosediagnostik betrieben werden.

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

Background: Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail. Methods: Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10 +/- 2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years. Results: Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m(2) higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%Cl:0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%Cl: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m(2) higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups. Conclusion: BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases.

ZusammenfassungKürzlich wurde im Namen der American Heart Association und des American College of Cardiology eine Leitlinie zur Cholesterinsenkung und Reduktion des Risikos für arteriosklerotische Herz-Kreislauf-Erkrankungen veröffentlicht. Sie nimmt für sich in Anspruch, auf Evidenz randomisierter, kontrollierter Studien zu beruhen, und beschränkt sich deshalb auf die Behandlungsoptionen mit Statinen. Vor diesem Hintergrund gibt die Leitlinie keine Zielwerte mehr vor, sondern bezieht sich auf prozentuale Cholesterinsenkungen durch Statinmedikationen mit niedriger, moderater oder hoher Intensität, die allerdings genauso wenig als Vorgaben in randomisierten Studien geprüft worden sind wie die an der Praxis orientierten Zielwerte. Ähnliches gilt für die vier Patientengruppen, die die Leitlinie aufgrund ihres Risikos als therapiebedürftig definiert. Keine größere Statinstudie hat Probanden aufgrund eines errechneten globalen Risikos eingeschlossen, sodass auch die Zuordnungskriterien willkürlich gewählt sind. Sie würden zu einer erheblichen Ausweitung der Primärprävention mit hohen und maximalen Statindosen führen. Die Festlegung auf Statindosierungen statt Cholesterinzielwerte steht dem Prinzip einer individualisierten Behandlung entgegen. Zu begrüßen ist die Möglichkeit des neuen Risikoscores, zusätzlich zum 10-Jahres-Risiko das Lebenszeitrisiko bis zum 80. Lebensjahr zu ermitteln. Allerdings fließt dies nicht in die Behandlungsempfehlungen ein, obgleich Evidenz von Populations- und genetischen Studien darauf hinweist, dass die früh- und langzeitige moderate Senkung des Low-density-lipoprotein(LDL)- oder Non-high-density-lipoprotein(HDL)-Cholesterins eine weitaus stärkere Wirkung hat als eine intensive Behandlung im fortgeschrittenen Alter. Hinsichtlich der Sekundärprävention stimmt die neue Leitlinie mit der europäischen weitgehend überein. Die beteiligten Fachgesellschaften des D•A•CH-Bereichs empfehlen, weiterhin entsprechend den bewährten Richtlinien wie den Leitlinien der European Society of Cardiology und der European Atherosclerosis Society zu verfahren.

In critical illness hyperglycemia is associated with increased mortality. Based on the currently available evidence, an intravenous insulin therapy should be initiated when blood glucose is above 180 mg/dl. After initiation of insulin therapy blood glucose should be maintained between 140 and 180 mg/dl.

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

HINTERGRUND: Ein spital-basiertes Screening Projekt (HSP) in Osterreich dokumentierte eine LDL-C Zielwert-Erreichung von 47% der Hochrisikopatienten (Ziel 100 mg/dl bei ca. 70% der Patienten eine Therapie-Intensivierung, meist durch Wechsel auf ein hochpotentes Statin. Bei LDL-C zwischen 70–100 mg/dl erfolgt jedoch weder bei Hoch- noch bei Hochstrisikopatienten eine Therapie-Intensivierung (< 5%). SCHLUSSFOLGERUNG: Sowohl in der Praxis als auch im Spital in Osterreich besteht, weitgehend parallel zu europaischen Analysen, weiterhin betrachtliches Verbesserungspotential in der Lipidzielwert-Erreichung bei kardiovaskularen Hoch- und Hochstrisikopatienten.

Lecithin-cholesterol acyltransferase (LCAT), a key enzyme in high-density lipoprotein (HDL) metabolism, has been proposed to have atheroprotective properties by promoting reverse cholesterol transport. Overexpression of LCAT in various animal models, however, has led to conflicting results on its overall effect on lipoproteins and atherosclerosis. In this study, the effect of overexpression of LCAT in nonhuman primates on lipoprotein metabolism is examined. Human LCAT was expressed with adenovirus in squirrel monkeys (n = 8), resulting on day 4 in a 22-fold increase of LCAT activity (257 +/- 23 vs 5618 +/- 799 nmol mL(-1) h(-1), P < .0001). At its peak, LCAT was found to nearly double the level of HDL cholesterol from baseline (113 +/- 7 vs 260 +/- 24 mg/dL, P < .01). High-density lipoprotein formed after treatment with the adenovirus was larger in size, as assessed by fast protein liquid chromatography (FPLC) analysis. By kinetic studies, it was determined that there was a decrease in apolipoprotein (Apo) A-I resident time (0.373 +/- 0.027 vs 0.685 +/- 0.045 d(-1), P < .0001) and almost a doubling in the ApoA-I synthetic rate (22 +/- 2 vs 41 +/- 3 mg kg(-1) d(-1), P < .0001), but no overall change in ApoA-I levels. In addition, increased expression of LCAT was associated with a 37% reduction of ApoB levels (12 +/- 1 vs 19 +/- 1 mg/dL, P < .05) due to increased low-density lipoprotein catabolism (fractional catabolic rate = 1.7 +/- 0.1 d(-1) in controls vs 4.2 +/- 0.3 d(-1) in LCAT-treated group, P < .05). In summary, overexpression of LCAT in nonhuman primates leads to an antiatherogenic lipoprotein profile by increasing HDL cholesterol and lowering ApoB, thus making LCAT a potential drug target for reducing atherosclerosis.

BACKGROUND: The purpose of the investigation presented here was to study the effects of insulin therapy in type 2 diabetes mellitus (type 2 DM) not only on glycemic control but also on other components of the metabolic syndrome, including lipid metabolism, blood pressure, and body weight. METHODS: Twelve patients with type 2 DM were studied before and after replacement of sulphonylurea treatment with insulin for 4 months. RESULTS: Insulin therapy resulted in a significant decrease in fasting glucose levels by 26%; glycated hemoglobin decreased by 17% and fructosamine values by 19%. With insulin treatment, fasting plasma triglyceride levels decreased by 28% and total HDL cholesterol and HDL(3) cholesterol increased by 17 and 11%, respectively. Low-density lipoprotein (LDL) cholesterol showed no significant change. The magnitude of postprandial lipemia after ingestion of a standard fatty meal decreased by 38%. Insulin treatment was also accompanied by a 21% increase in lipoprotein lipase (LPL) activity in postheparin plasma and by a 20% increase in cholesteryl ester transfer protein (CETP) activity. Hepatic lipase activity was not changed significantly with insulin. Mean BMI decreased from 28.5+/-4.2 to 28.0+/-3.1 kg/m(2) (P=0.02), which is in keeping with the finding that peripheral insulin levels did not increase and which can be explained by the fact that the insulin regimen was combined with dietary counseling. Accordingly, blood pressure showed no significant change. CONCLUSION: Our study demonstrates that judicious replacement of sulfonylurea treatment with insulin therapy, together with dietary counseling, can result in a simultaneous improvement in the major stigmata of the metabolic syndrome, i.e. a significant improvement in glycemic control and lipid metabolism without unfavorable effects on body weight and blood pressure.

Phospholipid transfer protein (PLTP) plays an important role in plasma lipoprotein metabolism. However, PLTP is expressed in a wide range of tissues suggesting additional local functions. To analyze the tissue distribution of PLTP in an animal with high-level expression of the structurally and functionally related CETP, we have cloned the full-length cDNA of rabbit PLTP (1,796 bp). Rabbit PLTP cDNA shows high homology to human, murine, and porcine PLTP cDNA, averaging 86.1%, 80.4%, and 86.1%, respectively. Interestingly, the C-terminus contains a unique seven amino acid insertion not found in previously characterized mammalian PLTPs. In clear contradistinction to human PLTP, rabbit PLTP mRNA was prominent in brain. In situ hybridization studies revealed specific, high-level synthesis of PLTP mRNA in choroid plexus and ependyma, the organs responsible for production of cerebrospinal fluid. Consistent with these findings, PLTP activity in cerebrospinal fluid amounted to 23% ± 3% of that in rabbit plasma. In contrast, neither CETP mRNA nor CETP activity were detectable in rabbit brain. A role of PLTP in the central nervous system could involve some of its actions previously established in vitro, like proteolysis of apolipoproteins, and be physiologically relevant for neurodegenerative disorders such as Alzheimer's disease.—Gander, R., P. Eller, S. Kaser, I. Theurl, D. Walter, T. Sauper, A. Ritsch, J. R. Patsch, and B. Föger. Molecular characterization of rabbit phospholipid transfer protein: choroid plexus and ependyma synthesize high levels of phospholipid transfer protein. J. Lipid Res. 2002. 43: 636–645.

AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones-the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP. METHODS: PLTP activity and CETP concentration-measured by exogenous substrate assay and enzyme-linked immunosorbent assay-were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis. RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin. CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

Recent in vitro studies have provided evidence that hepatic lipase (HL) facilitates the selective uptake of HDL cholesteryl esters (CE), but the in vivo physiological relevance of this process has not been demonstrated. To evaluate the role that HL plays in facilitating the selective uptake of HDL-CE in vivo, we studied the metabolism of ( 3 H)CEt, 125 I-labeled apolipoprotein (apo) A-I, and 131 I- labeled apoA-II-labeled HDL in HL-deficient mice. Kinetic analysis revealed similar catabolism of 125 I-labeled apoA-I (as well as 131 I-labeled apoA-II) in C57BL controls and HL deficient mice, with fractional catabolic rates (FCR) of 2.17 6 0.15 and 2.16 6 0.11 d 2 1 (2.59 6 0.14 and 2.67 6 0.13 d 2 1 , respectively). In contrast, despite similar hepatic scavenger receptor BI expression, HL-deficient mice had delayed clearance of ( 3 H)CEt compared to controls (FCR 5 3.66 6 0.29 and 4.41 6 0.18 d 2 1 , P , 0.05). The hepatic accumula- tion of ( 3 H)CEt in HL-deficient mice (62.3 6 2.1% of total) was significantly less than in controls (72.7 6 3.0%), while the ( 3 H)CEt remaining in the plasma compartment in- creased (20.7 6 1.8% and 12.6 6 0.5%) ( P , 0.05, all). In summary, HL deficiency does not alter the catabolism of apoA-I and apoA-II but decreases the hepatic uptake and the plasma clearance of HDL-CE. These data establish for the first time an important role for HL in facilitating the se- lective uptake of HDL-CE in vivo. —Lambert, G., M. J. A. Amar, P. Martin, J. Fruchart-Najib, B. Foger, R. D. Shambu- rek, H. B. Brewer, Jr., and S. Santamarina-Fojo. Hepatic lipase deficiency decreases the selective uptake of HDL- cholesteryl esters in vivo. J. Lipid Res. 2000. 41: 667-672.

We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lip- olysis by using recombinant adenovirus to express native and catalytically inactive HL (HL-145G) in apolipoprotein (apo)E-deficient mice characterized by increased plasma concentrations of apoB-48-containing remnants. In the absence of apoE, the mechanisms by which apoB-48-con- taining remnants are taken up by either low density lipopro- tein (LDL)-receptor or LDL-receptor-related protein (LRP) remain unclear. Overexpression of either native or catalyti- cally inactive HL in apoE-deficient mice led to similar re- ductions ( P. 0.5) in the plasma concentrations of choles- terol (41% and 53%) and non high density lipoprotein (HDL)-cholesterol (41% and 56%) indicating that even in the absence of lipolysis, HL can partially compensate for the absence of apoE in this animal model. Although the clearance of ( 3 H)cholesteryl ether from VLDL was signifi- cantly increased (approximately 2-fold; P , 0.02) in mice expressing native or inactive HL compared to luciferase controls, the fractional catabolic rates (FCR) of ( 125 I-labeled) apoB- very low density lipoprotein (VLDL) in all three groups of mice were similar ( P. 0.4, all) indicating selec- tive cholesterol uptake. Hepatic uptake of ( 3 H)cholesteryl ether from VLDL was greater in mice expressing either na- tive HL (87%) or inactive HL-145G (72%) compared to lu- ciferase controls (56%). Our combined findings are consis- tent with a role for HL in mediating the selective uptake of cholesterol from remnant lipoproteins in apoE-deficient mice, independent of lipolysis. These studies support the concept that hepatic lipase (HL) may serve as a ligand that mediates the interaction between remnant lipoproteins and cell surface receptors and/or proteoglycans. We hypothe- size that one of these pathways may involve the interaction of HL with cell surface receptors, such as scavenger recep- tor (SR)-BI, that mediate the selective uptake of cholesteryl esters.— Amar, M. J. A., K. A. Dugi, C. C. Haudenschild, R. D. Shamburek, B. Foger, M. Chase, A. Bensadoun, R. F. Hoyt, Jr., H. B. Brewer, Jr., and S. Santamarina-Fojo. Hepatic lipase facilitates the selective uptake of cholesteryl esters from remnant lipoproteins in apoE-deficient mice. J. Lipid Res. 1998. 39: 2436-2442.

After the publication of the new guidelines of the European Society of Cardiology and the European Atherosclerosis Society for the prevention and treatment of dyslipidemias (Eur Heart J 32:1769–1818, 2011; Eur Heart J 33:1635–1701, 2012), a group of authors has recently published on behalf of the American Heart Association and the American College of Cardiology guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk (Circulation 2013). These new guidelines are supposed to replace the until now widely accepted, at least in the USA, recommendations of the National Cholesterol Education Program Adult Treatment Panel III from the years 2002 (Circulation 106:3143–3421, 2002) and 2004 (Circulation 110:227–39, 2004). Furthermore, they claim to be based mainly on hard evidence derived from the interpretation of results of prospective randomized controlled trials. This Joint Position Statement of the Society for the Prevention of Cardiovascular Diseases e. V. (D.A.CH), the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society of Cardiology concludes that the use of individualized prevention strategies based on specific indications and LDL cholesterol target concentrations, a strategy whose worth has been widely proven and accepted for more than a decade in Europe, should not be given up.

In vitro studies have shown that plasma phospholipid transfer protein (PLTP) converts isolated human high density lipoprotein-3 (HDL3) into larger HDL particles and generates lipid-poor apoA-I containing nascent HDL. To evaluate the role of PLTP in vivo we generated recombinant adenovirus vectors containing either human PLTP cDNA (rPLTP.AdV) or the reporter luciferase cDNA as a control. After intravenous infusion of 4 x 10(7) plaque-forming units (low dose) and 4 x 10(8) plaque-forming units (high dose) of rPLTP.AdV into mice, PLTP activity in plasma increased from base-line levels of 8.4 +/- 0.2 to 108 +/- 17 and from 8.9 +/- 0.6 to 352 +/- 31 micromol/ml/h, respectively, on day 4 (both p < 0.001). Thus, both low and high doses of rPLTP.AdV led to pronounced overexpression of human PLTP in mice. On day 4 after treatment, mice treated with low and high doses of rPLTP.AdV showed decreased HDL cholesterol (-54% and -91%) and apoA-I (-64% and -98%) (all p < 0.05). Kinetic studies revealed that the fractional catabolic rates of HDL labeled with [3H]phosphatidylcholine, [14C]phosphatidylcholine ether, [3H]cholesteryl ether, and 125I-labeled mouse apoA-I were increased by 8.5-, 8.7-, 3.8-, and 2.8-fold, respectively, in mice treated with low dose rPLTP.AdV (all p < 0.001). After injection of labeled HDL, mice treated with rPLTP.AdV showed an increased accumulation of labeled PC ether (+304%) and cholesteryl ether (+92%) in the liver (both p < 0.05). Two-dimensional gel electrophoresis of plasma 5 min after injection of HDL labeled with 125I-apoA-I demonstrated increased levels of newly generated pre-beta-HDL in mice overexpressing PLTP. In conclusion, HDL remodeling mediated by PLTP generates nascent, lipid-poor apoA-I in vivo and accelerates the hepatic uptake of HDL surface and core lipids in mice treated with rPLTP.AdV. Accelerated catabolism of HDL in mice overexpressing PLTP leads to low HDL levels. Our data indicate an important role for PLTP in modulating reverse cholesterol transport in vivo.

A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are abnormal in both composition and function. Liver uptake of [3H]cholesteryl ether incorporated in transgenic mouse HDL was reduced by 41% compared with control HDL, indicating ineffective transport of HDL-cholesterol to the liver and impaired reverse cholesterol transport. Analysis of this LCAT-transgenic mouse model provides in vivo evidence for dysfunctional HDL as a potential mechanism leading to increased atherosclerosis in the presence of high plasma HDL levels.

Postprandial hyperlipidaemia is a risk factor for atherosclerosis in multiple vascular beds, independently of high-density lipoprotein (HDL) cholesterol. An increased level of HDL cholesterol is a strong indicator of a low risk of atherosclerosis. Exercise decreases postprandial lipaemia and, in turn, increases levels of HDL cholesterol. The favourable effects of exercise on lipoprotein metabolism, particularly evident in the postprandial state, may thus help to decrease susceptibility to atherosclerosis in exercise-trained people.

Hyperglycemia frequently occurs in critically ill patients resulting in major complications like an increased cardiovascular event rate or an increased incidence of infections. Based on the currently available evidence insulin therapy should be initiated in patients with blood glucose levels above 180 mg/dl. Blood glucose values should be maintained between 180 and 140 mg/dl. In surgical patients lower target values ranging from 140 to 110 mg/dl should be applied. After transition to the general ward a complete workup of diabetes mellitus should be performed.

Chemically or biologically modified low-density lipoproteins (LDL) but not native unmodified LDL lead to foam cell formation in monocyte-derived macrophages. Since the magnitude of postprandial lipemia after a challenge test seems to be associated with coronary artery disease, we tested the hypothesis that in the course of postprandial lipemia, LDL appear in plasma that are capable of leading to foam cell formation even without prior modification. We incubated the macrophage-like cell line P388 with unmodified postabsorptive and postprandial LDL from 17 healthy donors and measured the cellular cholesterol and triglyceride contents and amounts of exogenous [14C]oleic acid incorporated into the cholesteryl ester fraction. Postprandial LDL induced a significantly more pronounced cholesteryl ester accumulation than did postabsorptive LDL (477 +/- 286% versus 212 +/- 173%, respectively; P < .003). The increase in cellular total cholesterol was significantly higher as a result of cell incubation with postprandial LDL (107 +/- 61%) than with postabsorptive LDL (54 +/- 40%, P < .003), whereas no increase in triglyceride content was observed (P < .589) in either case. After CuSO4 incubation and incubation with P388 cells, postprandial LDL revealed more thiobarbituric acid-reacting substances than did postabsorptive LDL (55 +/- 10 versus 28 +/- 9 nmol/mg protein, P < .018; 28 +/- 4 versus 20 +/- 3 nmol/mg protein). The increase in cellular cholesteryl ester synthesis caused by postprandial LDL was reduced by more than 50% when lipoproteins and cells were incubated in the presence of ascorbic acid (P < .007).(ABSTRACT TRUNCATED AT 250 WORDS)

The short-term effects of prolonged intense exercise on plasma lipid transport parameters including cholesterol, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and its subfractions HDL 2 cholesterol and HDL 3 cholesterol, on apolipoproteins (apos) A-I, A-II, and B, and on mass and activity of cholesteryl ester transfer protein (CETP) were studied in eight male endurance-trained athletes over the first week after a bicycle marathon. CETP mass concentration in plasma was quantified by a newly developed immunoradiometric assay (IRMA). Plasma concentrations of cholesterol, TGs, LDL cholesterol, apo B, CETP, and cholesteryl ester transfer activity (CETA) were significantly reduced in the recovery period compared with pre-exercise values (cholesterol by 20%, P P P P P P 2 cholesterol, in contrast, were significantly increased in the post-exercise period (HDL cholesterol by 12%, P 2 cholesterol by 96%, P 3 cholesterol showed a tendency to decrease in the late recovery period (by 8%, NS). Although changes in cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apo B, and CETP mass and activity were already evident in the early recovery period, HDL 2 cholesterol showed a delayed response, reaching its maximum 72 hours after initiation of exercise. In addition, significant increases in plasma levels of apo A-I and A-II were found 8 days after the marathon (by 5%, P P 2 cholesterol may be explained at least in part by the decrease in CETP after short-term exercise.

Objective: The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyses the rate-limiting step in cholesterol biosynthesis. Until now, there has been no evidence for a possible correlation between HMG-CoA reductase activity and human liver disease. The objective of this study was to test whether HMG-CoA reductase activity is altered in cryptogenic fatty liver disease. Method: We measured this enzyme activity in liver tissue of 20 patients undergoing routine transcutaneous biopsy of the liver (10 patients with cryptogenic fatty liver disease, three with alcoholic fatty liver disease, two with chronic hepatitis and five with normal histology)

Cholesteryl ester transfer protein (CETP) catalyzes the transfer of neutral lipids among plasma lipoproteins and in this way plays a prominent role in cholesterol metabolic routing and, thus, probably for atherosclerosis. Studies of this important protein in various clinical settings require the ability to accurately quantify CETP in plasma. In order to gain access to such a capability, an immunoradiometric assay (IRMA) for quantification of CETP was developed. CETP was purified from human plasma to apparent homogeneity and used for raising anti-CETP antibodies in rabbits. The specificity of the polyclonal antiserum obtained was demonstrated by inhibition assays and immunoblot analysis. Before use in the CETP-IRMA, the antibodies were affinity-purified by chromatography on CETP-Sepharose. Sensitivity of the CETP-IRMA was 0.1 ng, and intra- and interassay coefficients of variation were 2.9 and 8.0%, respectively. In 30 normolipidemic healthy subjects, the mean (+/- SD) CETP concentration was 1.1 (+/- 0.22) micrograms/ml of plasma; individual values ranged from 0.644 to 1.694 micrograms CETP/ml and agreed well with measurements of CETP activity of the same samples (r = 0.85).

A hospital-based screening project (HSP) in Austria found 47% of high-risk patients (LDL-C100 mg/dl) and 24% of very high-risk patients (LDL-C70 mg/dl) at goal. Separate data for the sexes were not reported. We analyze whether LDL-C goal attainment in patients with manifest atherosclerosis and/or diabetes on stable lipid-lowering treatment differs between private practice and hospital and between men and women.From September to November 2007, 49 Austrian centers (36 private practice, 13 hospitals) documented vascular morbidity, lipid levels, and lipid lowering treatment in patients with high risk (atherosclerosis or diabetes, n = 978) and very high risk (coronary heart disease and diabetes or acute coronary syndrome, n = 322).75% and 25% of the 1300 patients were high and very high risk, respectively. LDL-C goals of100 and70 mg/dl, respectively, were attained by 45.4% and 26.4% of patients (p0.001). A similar percentage of patients with very high risk was found in men and women (26.4% vs. 22.9%, NS) and goal attainment was not influenced by sex (high risk: 47.2% (m) vs. 43.8% (w), NS and very high risk: 29.1% (m) vs. 22.4% (w), NS). In patients with high risk, 41.6% treated in private practice vs. 57.9% treated in the hospital were at goal (p0.001). In patients with very high risk, 15.9% treated in private practice vs. 45.2% treated in the hospital were at goal (p0.001). Lower goal-attainment in private practice occurred despite significantly more intensive lipid intervention and probably reflects higher baseline LDL-C. LDL-C100 mg/dl leads to a more aggressive lipid lowering in approx. 70% of patients, irrespective of whether they are treated in private practice or in the hospital. LDL-C between 70 and 100 mg/dl, however, leads to a more aggressive lipid lowering in5% of patients, irrespective of whether they are high or very high risk.As observed in EUROASPIRE III for other European countries, there is substantial potential for improvement in lipid control in Austrian cardiovascular high-risk patients, irrespective of whether they are treated in private practice or in the hospital.

Overt hypothyroidism most often causes moderately elevated cholesterol and triglycerides; but, in genetically predisposed individuals, it can also trigger frank hyperlipidemia, e.g. type III hyperlipoproteinemia. In contrast, in subclinical hypothyroidism, T4 lowers low-density lipoprotein cholesterol (LDL-C) by only 3.5–6.0 mg/dl LDL-C for each 1 mU/l thyroid-stimulating hormone (TSH) increase from baseline, a finding barely perceptible in individual patients. In humans, T3 decreases apoB-containing IDL, LDL and chylomicron remnant particles by up-regulation of LDL receptors and despite a concomitant increase in HMGCoA reductase in the liver. In rodents, T3 also up-regulates CYP7A1, ABCG5 and ABCG8 which interact to increase bile acid synthesis and biliary elimination of cholesterol. Thyromimetics, selective for either thyroid hormone-receptor β or liver, lower both LDL-C in humans and HDL-C in mice, thereby promoting reverse cholesterol transport. Interestingly, the thyromimetic T-0681 protects cholesterol-fed rabbits from atherosclerosis. If safety concerns with TRβ-selective thyromimetics can be addressed (i.e. the observed pituitary feed-back inhibition leading to low TSH levels), this class of drugs may complement statins in tackling the burden of atherosclerosis in humans.

Increased activity of semicarbazide-sensitive plasma amine oxidase (SSAO), an enzyme converting various amines, has been implicated in the generation of endothelial damage through formation of cytotoxic reaction products. We investigated if SSAO activity is elevated in morbidly obese patients, which might contribute to the increased cardiovascular risk associated with obesity. SSAO activity was determined in 74 nondiabetic, obese patients (median body mass index [BMI]: 42.9 kg/m(2)) and in 32 healthy, non-obese controls (median BMI: 23.3 kg/m(2)) using a radiometric assay based on the conversion of [(14)C]benzylamine. SSAO and parameters of glucose and lipid metabolism were compared for subgroups of obese patients with normal (n = 49) and impaired (n = 25) glucose tolerance using nonparametric statistical tests. Median SSAO activity was 434 microU/mL in obese patients, which was significantly higher than in healthy, non-obese controls (median SSAO activity: 361 microU/mL). Median SSAO activity in patients with normal and impaired glucose tolerance was 423 and 464 microU/mL, respectively. SSAO activity was not correlated with any other clinical or laboratory parameters characteristic of the metabolic alterations associated with obesity. Elevated SSAO activity is found in nondiabetic, morbidly obese patients and might be an interesting independent risk factor for obesity-related cardiovascular morbidity. Long-term follow-up of SSAO and its possible role in pathogenic events is warranted since intervention with specific SSAO inhibitors is available.

Endothelial dysfunction is an early marker of atherosclerosis occurring in patients with type 2 diabetes mellitus. Endothelium-dependent dilation (EDD) has been shown to improve by combined therapy of insulin and metformin. Studies on endothelium-independent vasodilatory capacity, however, have had controversial results. We sought to investigate the vascular reactivity--EDD and endothelium-independent dilation--and their changes induced by the addition of insulin therapy to patients with type 2 diabetes mellitus pretreated with diet and oral hypoglycemic drugs. We therefore performed vascular studies in 21 poorly controlled type 2 diabetic patients and 11 nondiabetic control subjects by using high resolution ultrasound of the brachial artery. After 3 months of additional insulin therapy, vascular and laboratory measurements including C-reactive protein and parameters of glucose and lipoprotein metabolism were repeated. At baseline, EDD was significantly impaired in diabetic patients compared with controls (2.7 +/- 2.2% vs 7.0 +/- 1.8%, p