Impaired NO-dependent vasodilation of resistance vessels is an early marker of an increased risk of atherosclerosis; utility of the examination of microcirculation, however, is far less established. We have therefore tested the hypothesis that hypercholesterolemia is associated with an impaired microvascular reactivity and that this defect is at least partially reversible by lipid-lowering treatment. Twenty-seven otherwise healthy patients with severe hypercholesterolemia (HLP) were examined at rest and then after 10 weeks of atorvastatin treatment (20 mg/day). Skin microvascular reactivity (MVR) was examined by laser-Doppler flowmetry. Baseline MVR values of the studied group were compared to healthy control subjects, HLP patients with coronary artery disease (CAD) and diabetic patients with and without diabetic retinopathy. MVR was normal in HLP subjects without CAD. On the contrary, MVR was impaired in HLP patients with CAD. There was no effect of atorvastatin on MVR, despite the profound reduction of serum lipids. MVR values did not correlate with cholesterol levels. In diabetic subjects, the MVR was substantially impaired only in patients with retinopathy. In the subjects without retinopathy, MVR was either normal (type I diabetes) or moderately impaired (type II diabetes). MVR was thus normal in HLP patients without manifest vascular disease and was not influenced by lipid lowering therapy. Impairment in the MVR was only evident in subjects with HLP and severe CAD. These results suggest that microcirculation is not involved in the early vascular dysfunction induced by HLP and that MVR rather reflects changes which appear later in the course of the atherosclerotic disease., T. Štulc, Z. Kasalová, M. Prázný, M. Vrablík, J. Škrha, R. Češka., and Obsahuje bibliografii
Autosomal dominant hypercholesterolemia (ADH), more known as familial hypercholesterolemia (FH), is a lipid metabolism disorder characterized by an elevation in low-density lipoprotein cholesterol (LDL-C) and increased risk for cardiovascular disea se. In this study, we assessed a spectrum of mutations causing ADH in 3914 unrelated Czech patients with clinical diagnosis of hypercholesterolemia. Samples have been collected within the framework of the MedPed project running in the Czech Republic since 1998. So far we have found 432 patients (11.0 %) with the APOB gene mutation p.(Arg3527Gln) and 864 patients (22.1 %) with the LDLR gene mutation. In 864 probands carrying the LDLR gene mutation, 182 unique allelic variants were detected. We have identified 14 patients homozygous for mutations in the LDLR or APOB genes. We performed function analyses of p.(Leu15Pro) and p.(Gly20Arg) sequence variations., L. Tichý, L. Fajkusová, P. Zapletalová, L. Schwarzová, M. Vrablík, T. Freiberger., and Obsahuje bibliografii
There is a large body of evidence documenting the effects of long-chain polyunsaturated fatty acids with the first double bond at the third position from methyl-terminal (so called omega-3 fatty acids (FAs)) on different components of cardiovascular disease (CVD) risk. However, it may seem the more answers on the topic we learn, the more questions remain to be elucidated. There are three levels of evidence documenting the impact of fish omega-3 FAs on CVD risk. Epidemiological data have shown unequivocally the increased intake of fish is associated with lower CVD morbidity and mortality. Numerous experimental studies have shown (almost always) positive effects of omega-3 FAs on lipoprotein metabolism, coagulation and platelet function, endothelial function, arterial stiffness etc. Most importantly, there are a few prospective clinical endpoint trials (DART, JELIS, GISSI Prevenzione and GISSI-HF) that have examined the impact of omega-3 FAs supplementation on cardiovascular outcomes in different patient populations. Recent meta-analyses of these and other clinical studies have yielded somewhat conflicting results. In this review we will summarize current evidence of omega-3 FAs effects on cardiovascular risk focusing on new data from recent clinical trials as well as possible practical implications for clinical practice., M. Vrablík ... [et al.]., and Obsahuje seznam literatury
This article describes the evolution of our understanding of familial hypercholesterolemia (FH) in the Central, Eastern, and Southern Europe (CESE) region, and the dissemination of this understanding to other count ries. Using the ScreenPro FH project as an example, we would like to illustrate the progression from national objectives, to regional networking and, finally, to international collaboration via the Familial Hypercholesterolemia Studies Collaboration (FHSC) project under the leadership of the European Atherosclerosis Society (EAS). It is essential to improve our ability to diagnose FH. In this regard, the EAS and its FHSC project must be commended for their educational and organizational activities which, ab ove all, are dedicated to the creation of a global FH patient registry. In the CESE region, FH diagnostics and treatment situation are markedly different than in Western Europe or North America. Since the Czech MedPed project (Make Early Diagnoses to Preve nt Early Deaths in Medical Pedigrees) has been so successful (with results not only comparable to, but, for some parameters, even surpassing the results of many Western countries) we decided to apply the Czech experience to the CESE region. Thus, the ScreenPro FH project was created. The aim of ScreenPro FH is to create a specialist network in the CESE region. The primary objective of the ScreenPro FH project was to dramatically reduce the number of premature deaths due to clinical complications of atherosc lerosis in FH patients. At present, ScreenPro FH comprises 18 member countries with a total population of 500,000,000; which, in terms of the FH population, represents 1-2 million patients., R. Ceska, T. Freiberger, M. Vaclova, T. Aleksicova, L. Votavova, M. Vrablik., and Obsahuje bibliografii
Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results., M. Vrablik, L. Zlatohlavek, T. Stulc, V. Adamkova, M. Prusikova, L. Schwarzova, J. A. Hubacek, R. Ceska., and Obsahuje bibliografii
Hypertriglyceridemia is an important marker of increased levels of highly atherogenic rem nant -like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in c ombination with statins. Niacin and omega -3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti- sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega -3 fatty acids or niacin)., M. Vrablík, R. Češka., and Obsahuje bibliografii