Familial hypercholesterolemia (FH) is the most common autosomal dominant disorder. It is characterized by a de crease in LDL cholesterol catabolism and an early clinical manifestation of atherosclerotic vessel damage. The aim of the MedPed (Make early diagnosis to Prevent early deaths) project is an early diagnosis of FH patients in order to profit from early treat ment and prevent cardiov ascular events. Till November 30, 2016 The Czech National MedPed Database has registered 7,001 FH patients from 5,223 different families that is 17.4 % of expected patients in the Czech Republic considering 1:250 FH prevalence. The improvement in diagnostic accuracy, patient cooperation and above all familial cascade screening is enabled by FH mutation detection using the modern technology of next-generation sequencing. FH still remain undiagnosed even though the Czech Republic is on e of the most successful countries with respect to FH detection. The opportunities of international collaboration and experience sharing within international programs (e.g. EAS FHSC, ScreenPro FH etc.) will improve the detection of FH patients in the futur e and enable even more accessible and accurate genetic diagnostics., M. Vrablík, M. Vaclová, L. Tichý, V. Soška, V. Bláha, L. Fajkusová, R. Češka, M. Šatný, T. Freiberger., and Obsahuje bibliografii
Statins are the most commonly used drugs in patients with dyslipidemia. Among the patients, a significant inter-individual variability with supposed strong genetic background in statin treatment efficacy has been observed. Genome wide screenings detected variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes that are among the candidates potentially modifying response to statins. Ten variants (SNPs) within these genes (rs599838, rs646776, rs16996148, rs693, rs515135, rs4420638, rs12654264, rs6511720, rs6235, rs11206510) were analyzed in 895 (46 % men, average age 60.3±13.1 years) patients with dyslipidemia treated with equipotent doses of statins (~90 % on simvastatin or atorvastatin, doses 10 or 20 mg) and selected 672 normolipidemic controls (40 % men, average age 46.5 years). Lipid parameters were available prior to the treatment and after 12 weeks of therapy. Statin treatment resulted in a significant decrease of both total cholesterol (7.00±1.53→5.15±1.17 mmol/l, P<0.0001) and triglycerides (2.03±1.01→1.65±1.23 mmol/l, P<0.0005). Rs599838 variant was not detected in first analyzed 284 patients. After adjustment for multiple testing, there was no significant association between individual SNPs and statin treatment efficacy. Only the rs4420638 (APOE/C1/C4 gene cluster) G allele carriers seem to show more profitable change of HDL cholesterol (P=0.007 without and P=0.06 after adjustment). Results demonstrated that, although associated with plasma TC and LDL cholesterol per se, variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes do not modify therapeutic response to statins., M. Vrablík, ... [et al.]., and Obsahuje seznam literaury
Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28±35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C>T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in carriers of other important CHD risk factors. Observed association of sequence variants of the promoter of apo(a) gene with Lp(a) levels is caused in part due to linkage to a restricted range of apo(a) gene length isoforms., L. Zlatohlávek, K, Zídková, M. Vrablík, T. Haas, M. Prusíková, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
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