Aims: Mixed dyslipidaemia, characterized by low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides, is common in patients with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome. Dalcetrapib effectively increases HDL-C levels by modulating cholesteryl ester transfer protein (CETP) activity. The aim of this analysis was to investigate the lipid modifying efficacy and safety of dalcetrapib in patients with T2DM and/or metabolic syndrome.Methods: Post hoc analysis of dalcetrapib therapy in five placebo-controlled, Phase II trials (4-48 weeks of duration) involving T2DM and/or metabolic syndrome, in dyslipidaemic patients with coronary heart disease (CHD) or CHD risk equivalent.Results: Both in patients with and without T2DM and/or metabolic syndrome, dalcetrapib decreased CETP activity by 26-58% and increased HDL-C levels by 23-34%, depending on dose and duration of treatment. Dalcetrapib did not significantly affect low-density lipoprotein cholesterol (LDL-C) or apolipoprotein B levels. Treatment with dalcetrapib was generally well tolerated with a similar number of adverse events reported between patient groups and between those receiving dalcetrapib compared with placebo.Conclusions: Dalcetrapib similarly decreased CETP activity and increased HDL-C levels in patients with and without T2DM or metabolic syndrome; the ongoing Phase III dal-OUTCOMES study will help to determine if dalcetrapib's improvement in lipid levels also reduces cardiovascular morbidity and mortality.

Coexistence of thermal springs, travertine deposits and tectonic activity is a recurring feature for most geothermal areas. Although such a certainty, their relationships are debated mainly addressing on the role of the tectonic activity in triggering and controlling fluids flow and travertine deposition. In this paper, we present the results of an integrated study carried out in a geothermal area located in western Anatolia (Turkey), nearby the well-known Pamukkale area (Denizli Basin). Our study focused on the relationships among hydrothermal fluids circulation, travertine deposition and tectonic activity, with particular emphasis on the role of faults in controlling fluids upwelling, thermal springs location and deposition of travertine masses. New field mapping and structural/kinematics analyses allowed us to recognize two main faults systems (NW- and NE-trending), framed in the Neogene–Quaternary extensional tectonic evolution of western Anatolia. A geo-radar (GPR) prospection was also provided in a key-area, permitting us to reconstruct a buried fault zone and its relationships with the development of a fissure-ridge travertine deposit (Kamara fissure-ridge). The integration among structural and geophysical studies, fluids inclusion, geochemical, isotopic data and 230 Th/238 U radiometric age determination on travertine deposits, depict the characteristics of the geothermal fluids and their pathway, up to the surface. Hydrological and seismological data have been also taken in account to investigate the relation between local seismicity and fluid upwelling. As a main conclusion we found strict relationships among tectonic activity, earthquakes occurrence, and variation of the physical/chemical features of the hydrothermal fluids, presently exploited at depth, or flowing out in thermal springs. In the same way, we underline the tectonic role in controlling the travertine deposition, making travertine (mainly banded travertine) a useful proxy to reconstruct the seismological history of an area, as well as the characteristics of the parent geothermal fluids, adding an effective tool for geothermal exploration tasks.

Objective: This study compared effectiveness of rosuvastatin (RSV) with other statins on lowering LDL-C and LDL-C goal attainment among Medicare-eligible patients (age >= 65 years) and patients with age < 65 years treated in usual clinical practice to provide evidence of real-world effectiveness of statins. Methods: Retrospective cohort study was conducted in patients, newly prescribed statin therapy during August 2003 to May 2005. Patient inclusion criteria: no prior prescription for dyslipidaemic medication in the preceding 12 months, continuously enrolled for >= 15 months and >= 90-day supply of statin. Effectiveness of RSV in reducing LDL-C and attaining LDL-C goal when compared with other statins was evaluated using multivariate regression, adjusting for baseline LDL-C, age, gender, smoking, hypertension, coronary heart disease (CHD), systolic blood pressure and therapy duration. Results: Adjusted per cent LDL-C reduction was significantly greater (p < 0.05) with RSV (24.3% for >= 65 and 28.5% for < 65) compared with ATV (17.5%, 21.3%), SMV (14.8%, 18.4%), PRV (11.3%, 15.8%), FLV (10.7%, 20.6%) and LOV (13.3%, 14.4%). Among patients in both age groups at high or moderate CHD risk, a greater proportion of RSV patients attained LDL-C goal (76.0% for age group >= 65 years and 78.4% for age group < 65 years) vs. 50.5-73.0% for >= 65 and 51.3-71.5% for < 65 years of age on other statins (p < 0.0001). Conclusions: Rosuvastatin is more effective in lowering LDL-C in Medicare-eligible patients and patients < 65 years of age when compared with other statins in usual clinical practice. Moreover, RSV patients had higher LDL-C goal attainment rates when compared with other statins in high- and moderate-risk patients. The study results have implications for clinicians in selecting the optimal statin to meet individual patient care needs.

This article summarizes the final conclusions of the National Lipid Association (NLA) Statin Safety Task Force, based on a review and independent research of New Drug Application (NDA) information, US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, cohort and clinical trial results, and analysis of administrative claims database information and the assessment of its 4 Expert Panels, which focused on issues of statin safety with regard to liver, muscle, renal, and neurologic systems. Practical guidance in the form of recommendations to health professionals who manage the coronary artery disease risk of patients with statin therapy is provided.

The large administrative databases of health plans contain information on drug-related medical adverse events (AE) and constitute an increasingly powerful tool for the assessment of drug safety. We conducted a retrospective observational study using an administrative managed care claims database covering 9 million members from diverse regions of the United States. Patients aged 18 years who received >= 2 prescriptions for lipid-lowering drugs between July 1, 2000 and December 1, 2004 were included in the study. Hospitalizations with diagnosis codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9]) related to muscle, kidney, and liver were determined for patients exposed to 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), fibrates, extended-release niacin, cholesterol absorption inhibitors, or statin combination therapy. A total of 473,343 patients contributed 490,988 person-years of monotherapy and 11,624 person-years of combination dyslipidemia therapy. Rates of hospitalization due to AEs in patients on monotherapy with currently available statins were similar, whereas the incidence of hospitalization for muscle disorders increased 6.7-fold with cerivastatin therapy. Patients who received a lipid-lowering medication with a concomitant cytochrome P450 3A4 (CYP3A4) inhibitor had a 6-fold increased rate of muscle disorders, including rhabdomyolysis. Hypertension was associated with a 5-fold increase in both muscle and renal events, whereas patients with diabetes mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of the index AEs were observed in study subjects during the 6-month period before initiation of the lipid-lowering drug. Statin monotherapy as currently prescribed is generally well tolerated and safe. (c) 2006 Elsevier Inc. All rights reserved.

Lipoprotein apheresis (LA) is an extracorporeal technique which permits the unselective or specific removal of lipoproteins, namely Low Density Lipoproteins (LDL), as well as other apolipoprotein B100-containing lipoproteins from plasma. LA represents a selective upgrade (with both clinical and metabolic advantages) from conventional forms of extracorporeal therapy such as plasma-exchange (PEX) which was used in the seventies to treat severe hypercholesterolemia. The primary reason for using is the treatment of homo-, double- (or compound) and heterozygous familial hypercholesterolemia (Hoz-, DHtz,- Htz,-FH). This technique has also been shown to be efficacious in the treatment of other severe forms of hyperlipoproteinemia such as: hyperLp(a)lipoproteinemia, the familial combined hyperlipoproteinemia and other varieties associated with an elevated cardiovascular risk (CVR) when used in patients who are poor- or non-responders to pharmacological treatment following specific guidelines for the reduction of cholesterol in plasma. Patients with these severe forms of dyslipidemia and, particularly, those affected by FH are subject to coronary ischemic events and thus require an intensive, efficacious, continuous, and personalized form of therapy. A therapy based solely on current available drugs does not achieve the desired results in the Hoz- and DHtz forms of FH or in approximately 10–20% of the Htz form. For the aforementioned clinical conditions, LA treatment offers a necessary therapeutic approach. LA can also be applied in the prevention of secondary recurrence of coronary ischemic events and of arterial stenosis which appears, rather frequently after vascular surgery (coronary by-pass, percutaneous transluminal angioplasty). Clinical trials have shown that statins provide a major reduction in cardiovascular morbidity and mortality, but often fail to attain desirable LDL-cholesterol target level in Hoz- and DHtz- (Compound) FH high cardiovascular risk patients. Intolerance to statins is also relatively frequent in Htz-FH and non-FH patients. LA has effectively replaced pharmacological cholesterol-lowering therapy for decades. Young high CVR risk patients survived to adulthood thanks only to LA. More recently, promising novel compounds aimed at other molecular targets are being studied for the treatment of severe dyslipidemia: Lomitapide, Mipomersen, PCSK9 inhibitors and HDL-enhancers. It is expected that these potent new agents will be combined with LA in the treatment of the most severe forms of hyperlipidemia.

International Journal of Clinical PracticeVolume 59, Issue s148 p. 3-13 Undertreatment among high-risk dyslipidemic patients: results of a national survey of goal achievement for National Cholesterol Education Program Adult Treatment Panel III guidelines M. H. Davidson, M. H. Davidson Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 1,2 K. C. Maki, K. C. Maki Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 1 T. A. Pearson, T. A. Pearson Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 3 R. C. Pasternak, R. C. Pasternak Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 4 For The Neptune Steering Committee and Investigators, For The Neptune Steering Committee and Investigators Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author M. H. Davidson, M. H. Davidson Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 1,2 K. C. Maki, K. C. Maki Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 1 T. A. Pearson, T. A. Pearson Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 3 R. C. Pasternak, R. C. Pasternak Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author 4 For The Neptune Steering Committee and Investigators, For The Neptune Steering Committee and Investigators Radiant Development,1 Rush University Medical Center,2 Chicago, IL, University of Rochester School of Medicine,3 Rochester, NY, Massachusetts General Hospital,4 Boston, MA, USASearch for more papers by this author First published: 26 April 2005 https://doi.org/10.1111/j.1368-504X.2005.0538g.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume59, Issues148June 2005Pages 3-13 RelatedInformation