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Gouni-Berthold I.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB
Current Medicinal Chemistry | Year: 2015

Cardiovascular disease (CVD) is a leading cause of death for both women and men. Common traditional risk factors for CVD, such as hypercholesterolemia, hypertension and smoking have a high prevalence in women and in some cases a greater health impact compared with men. Nevertheless, risk factors are treated less often and less aggressively in women than in men, partly due to decreased awareness on the part of public health opinion makers, patients and physicians. About seventy five percent of all coronary heart disease deaths among women could be avoided if CVD risk factors like hypercholesterolemia, hypertension and smoking are adequately treated. This narrative review discusses the treatment of the 4 CVD risk factors, namely hypercholesterolemia, hypertension, smoking and diabetes. These risk factors were examined in the Framingham Heart study and years later they were found in the INTERHEART study to be the 4 most important risk factors for the development of CVD. © 2015 Bentham Science Publishers.

Gouni-Berthold I.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB
Nutrients | Year: 2014

The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C) plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145) and alirocumab (REGN727/SAR236553), have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk. © 2014, by the authors; licensee MDPI, Basel, Switzerland.

Gouni-Berthold I.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB
Atherosclerosis Supplements | Year: 2015

Familial hypercholesterolemia (FH) is a disease associated with very high plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. It is difficult in these high risk patients, exposed lifelong to very high LDL-C, to reach target LDL-C concentrations, which require >50% LDL-C reduction, even when on maximally tolerated statin therapy and on apheresis if available. Therefore, there is an unmet need for new therapeutic options for these patients. In 2013 two new drugs were approved for the treatment of homozygous FH, namely the apolipoprotein B synthesis inhibitor mipomersen and the microsomal transfer protein inhibitor lomitapide. Objective of this narrative review is to discuss the available evidence on the safety and efficacy profile of these new drugs. © 2015 Elsevier Ireland Ltd.

Berthold H.K.,Bielefeld Evangelical Hospital EvKB | Rizzo M.,University of Palermo | Rizzo M.,Euro Mediterranean Institute of Science and Technology | Spenrath N.,University of Cologne | And 3 more authors.
PLoS ONE | Year: 2014

Context and Objective: Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. Design and Participants: A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/ day, n = 24) or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. HDL subclasses were determined using polyacrylamide gel-tube electrophoresis. Multivariate regression models were used to determine the influence of treatment and covariates on changes in HDL subclass composition. Results: Baseline HDL subclasses consisted of 33±10% large, 48±6% intermediate and 19±8% small HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL-C and the ratio triglycerides/HDL-C, there was a significant increase in large HDL by about 3.9 percentage points (P<0.05) and a decrease in intermediate HDL by about 3.5 percentage points (P<0.01) in both simvastatin-containing treatment arms in comparison to ezetimibe. The parameters obtained after additional adjustment for the decrease in LDL-C indicated that about one third to one half of these effects could be explained by the extent of LDL-C-lowering. Conclusions: In healthy men, treatment with simvastatin leads to favorable effects on HDL subclass composition, which was not be observed with ezetimibe. Part of these differential effects may be due to the stronger LDL-C-lowering effects of simvastatin. Trial Registration: ClinicalTrials.gov NCT00317993. © 2014 Berthold et al.

Neef D.,University of Cologne | Berthold H.K.,Bielefeld Evangelical Hospital EvKB | Gouni-Berthold I.,University of Cologne
Expert Review of Clinical Pharmacology | Year: 2016

Lomitapide is a drug recently approved for the treatment of patients with homozygous familial hypercholesterolemia. In this article we discuss briefly the pharmacology of this drug followed by a comprehensive narrative review of the available preclinical and clinical data on its safety and efficacy. Only data published as full papers are presented, with the exception of one long-term open-label extension study, which is available only in abstract form. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

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