- MeSH
- ateroskleróza * farmakoterapie metabolismus patofyziologie prevence a kontrola MeSH
- hypolipidemika farmakologie terapeutické užití MeSH
- lidé MeSH
- lipoproteiny * klasifikace krev metabolismus škodlivé účinky MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- tuhost cévní stěny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.
- MeSH
- akutní koronární syndrom * krev farmakoterapie etiologie MeSH
- anticholesteremika terapeutické užití MeSH
- ateroskleróza * krev komplikace farmakoterapie MeSH
- hypolipidemika * terapeutické užití MeSH
- LDL-cholesterol krev MeSH
- lidé MeSH
- přehledová literatura jako téma MeSH
- statiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
Úloha LDL-cholesterolu (LDL-C) v patogenéze aterosklerózy a v následnom zvýšení rizika aterosklerotického kardiovaskulárneho ochorenia (ASKVO) je nespochybniteľná. Predmetom odborných diskusií je len skutočnosť, ako výrazne a akým spôsobom je potrebné túto hladinu znížiť. Aj tu však vo všeobecnosti panuje zhoda, že by to malo byť podmienené úrovni kardiovaskulárneho (KV) rizika konkrétneho jednotlivca. Tu sa názory začínajú od seba líšiť v otázke, ktorí sú pacienti s najvyšším KV-rizikom a ktorí sú naopak tí, ktorých farmakologicky stačí liečiť menej intenzívne? Odlišnosti existujú aj v názoroch, ako skoro začať liečbu, ako dlho v nej pokračovať a akým spôsobom. Odporúčania odborných spoločností sa vo väčšine prípadov opierajú o medicínu založenú na dôkazoch (Evidence Based Medicine – EBM), ktorá stratifikuje jednotlivých kandidátov na liečbu podľa úrovne dôkazov a tried odporúčaní. Napriek tomu existuje v klinickej praxi mnoho situácií, v ktorých postup nemusí byť úplne presne vyšpecifikovaný v odporúčaniach. Cieľom tohto prehľadu je pomôcť zlepšiť situáciu v sekundárnej prevencii aterosklerózy poukázaním na úlohu nestatínových liekov a možnosti ich použitia vzhľadom ku doposiaľ preukázaným benefitom a existujúcim limitáciám ich použitia.
The role of LDL-cholesterol (LDL-C) in the pathogenesis of atherosclerosis and in the subsequent increase in the risk of atherosclerotic cardiovascular disease (ACVD) is unquestionable. The only subject of expert debate is how significantly and in what way this level needs to be reduced. However, there is also general agreement that this should be conditional on the level of cardiovascular (CV) risk of the individual. This is where opinions start to diverge – who are the patients with the highest CV risk, and who, conversely, are those who pharmacologically just need to be treated less intensively? Differences also exist in opinions about how early to start treatment, how long to continue it, and in what manner. In most cases, the recommendations of professional societies are based on Evidence Based Medicine (EBM), which stratifies individual candidates for treatment according to the level of evidence and classes of recommendations. Nevertheless, there are many situations in clinical practice in which management may not be completely specified in the recommendations. The aim of this review is to help improve the situation in the secondary prevention of atherosclerosis by highlighting the role of non-statin drugs and the potential for their use in light of the benefits demonstrated to date and the limitations of their use.
- MeSH
- hypercholesterolemie farmakoterapie prevence a kontrola MeSH
- hypolipidemika aplikace a dávkování farmakologie klasifikace MeSH
- klinická studie jako téma MeSH
- klinické rozhodování MeSH
- kombinovaná farmakoterapie MeSH
- LDL-cholesterol * analýza účinky léků MeSH
- lidé MeSH
- rizikové faktory kardiovaskulárních chorob * MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- statiny aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Despite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians' therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study. METHODS: ODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada. RESULTS: A total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries' groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07-1.13). CONCLUSIONS: Despite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level.
- Publikační typ
- časopisecké články MeSH
Úvod: Aj napriek výrazným pokrokom v manažmente kardiovaskulárnych ochorení (KVO), predstavuje celosvetovo táto skupina ochorení najčastejšiu príčinu morbidity a mortality. Redukcia hladín LDL-cholesterolu (LDL-C) je základným pilierom primárnej, ako aj sekundárnej prevencie KVO. Cieľom tejto práce bolo sledovať koncentrácie LDL-C u pacientov vo veľmi vysokom kardiovaskulárnom (KV) riziku a popísať aká časť týchto pacientov dosahuje cieľové hodnoty LDL-C. Metodika: Táto štúdia prebiehala vo forme retrospektívnej analýzy anonymizovaných hodnôt LDL-C z rokov 2017–2019 z dát spolupracujúceho laboratória s celoslovenskou pôsobnosťou. Celkovo boli zaradení pacienti s diagnózou akútneho koronárneho syndrómu (AKS), cievnej mozgovej príhody (CMP) a všeobecne pacienti s veľmi vysokým KV-rizikom. Cieľové hodnoty LDL-C boli hodnotené na základe toho času platných odporučení ESC/EAS 2016. Výsledky: Celkovo sa spracovalo 220 657 záznamov vyšetrení LDL-C od 72 039 pacientov. U pacientov s diagnózou AKS dosahovali cieľové hodnoty LDL-C len 8–9 % pacientov v jednotlivých rokoch sledovania. Až 6–9 % pacientov malo hladiny LDL-C na úrovni ≥ 4,9 mmol/l. V prípade pacientov s diagnózou CMP dosahovalo cieľové hodnoty LDL-C len 9–10 % pacientov a 7–8 % malo hladiny ≥ 4,9 mmol/l. V skupine s veľmi vysokým KV-rizikom dosahovalo cieľové hladiny len 7 % pacientov a 7–8 % malo extrémne vysoké hodnoty LDL-C ≥ 4,9 mmol/l. V prípade uplatnenia najnovších odporučení ESC/EAS 2019 dosahovali cieľové hladiny len 2–3 % pacientov v jednotlivých skupinách a rokoch. Záver: Na základe výsledkov analýzy sme zistili, že až vyše 90 % pacientov vo veľmi vysokom KV-riziku nedosahuje cieľové hodnoty LDL-C. Títo pacienti sú naďalej vo vysokom riziku následnej KV-príhody a mali by významný benefit z intenzifikovanej hypolipemickej terapie.
Introduction: Despite significant progress in the management of cardiovascular (CV) diseases, they represent the most common cause of morbidity and mortality. LDL-cholesterol (LDL-C) reduction is a basic pillar of primary as well as secondary prevention of heart disease. The Aim of this study was to monitor LDL-C concentrations in patients at very high CV risk and to determine the prevalence of patients reaching the LDL-C target values. Methodology: This project took place in the form of a retrospective analysis of anonymized LDL-C values from 2017–2019 from the data of cooperating laboratory with nationwide operations. Overall, patients with a diagnosis of an acute coronary syndrome (ACS), stroke and a general patient with a very high CV risk were included. The LDL-C target values were evaluated based on the then valid ESC/EAS 2016 recommendations. Results: A total of 220,657 LDL-C results from 72,039 patients were obtained. In patients with ACS, LDL-C target values were achieved by only 8–9 % of patients in each year of follow-up. Up to 6–9 % of patients have LDL-C levels ≥ 4.9 mmol/L. In the case of patients with stroke, only 9–10 % of patients achieved target values and 7–8 % had levels ≥ 4.9 mmol/L. In the group with very high CV risk, only 7 % of patients reached the target levels and 7–8 % had extremely high LDL-C values ≥ 4.9 mmol/L. In the case of the application of the new ESC/EAS 2019 recommendations, the target levels were reached by only 2–3 % of patients. Conclusion: Based on the results of the analysis, we found that up to 90 % of patients at very high CV risk do not reach the target LDL-C values. These patients remain at high risk for further CV events and would benefit significantly from intensified hypolipidemic therapy.
Manažment dyslipidémií ostáva výzvou napriek objemu kvalitných dát a dostupnosti liečebných modalít. Epidémia aterosklerotického kardiovaskulárneho ochorenia je dominantnou príčinou chorobnosti a úmrtnosti vo vyspelom svete. Prienik Odporúčaní pre manažment dyslipidémií do ostatných dokumentov dokazuje význam tejto problematiky. Nové poznatky vedú k sprísneniu cieľových hodnôt pre LDL-cholesterol podľa stupňa kardiovaskulárneho rizika. Ročná mortalita po akútnom koronárnom syndróme v porovnaní s vyspelejšími krajinami neúmerne rastie. Analýza príčin poukazuje na zlý manažment rizikových faktorov po prepustení z hospitalizácie. Možnosti zlepšenia okrem iného smerujú k zmene indikačných obmedzení pre PCSK9-inhibítory.
The management of dyslipidemia remains a challenge despite the volume of EBM data and the availability of treatment modalities. The ASCVD epidemic is the dominant cause of morbidity and mortality in the developed world. The integration of the Guidelines for the Management of Dyslipidemias into other documents demonstrates the importance of this issue. New findings lead to the tightening of LDL-C target values according to CV risk levels. Annual mortality after ACS in Slovakia is rising disproportionately compared to more developed countries. The root cause analysis points to poor management of risk factors after hospital discharge. Opportunities for improvement include, inter alia, the changing of the indication restrictions for PCSK9 inhibitors.
- MeSH
- akutní koronární syndrom * patologie MeSH
- dyslipidemie * farmakoterapie MeSH
- LDL-cholesterol krev škodlivé účinky MeSH
- lidé MeSH
- management nemoci MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Slovenská republika MeSH
Klasické parametre lipidového metabolizmu (celkový, nízkodenzitný a vysokodenzitný cholesterol, triacylglyceroly – T-C, LDL-C, HDL-C) sú nenahraditeľné pri stanovení rizika a liečbe koronárnej choroby srdca (KCHS). Sú však len pomocné ukazovatele patogenézy KCHS. Metóda protónovej nukleárnej magnetickej rezonančnej spektroskopie (PNMR) poskytuje skutočný obraz o počte a rozmerov lipoproteínových častíc. Cieľom našej práce bola analýza údajov získaných metódou PNMR a ich vzťah k klasickým ukazovateľom rizika KCHS u probandov bez klinicky manifestných prejavov KCHS. Vyšetrili sme 75 náhodne vybraných probandov (vek 31–78 rokov, 69 mužov a 19 žien). Analýza lipoproteínov bola robená NIFAI PNMR spectroscopic assay (Nemecko). Metóda dáva výsledky počtu veľmi nízkodenzitných (VLDLp), celkových, malých a veľkých LDL-častíc (LDLp, SLDLp, LLDLp), celkových, malých a veľkých HDL-častíc (HDLp, SHDLp, LHDLp) a rozmerov VLDL-, LDL- a HDL-častíc (VLDLs, LDLs, HDLs). T-C, HDL-C, LDL-C, boli stanovené štandardnými metódami. Výsledky PNMR – počet častíc. VLDLp: 5,44 ± 4,68 nmol/l; LDLp, LLDLp a SLDLp: 1 610 ± 395, 698 ± 325 a 918 ± 226 nmol/l. HDLp, LHDLp a SHDLp: 40,4 ± 5,01, 35,2 ± 6,05, 5,79 ± 3,60 μmol/l. Rozmery častíc: VLDLs, LDLs a HDLs 49,8 ± 4,65, 21,0 ± 0,46 a 8,79 ± 0,53 nm. Pri analýze súladu alebo nesúladu porovnateľných výsledkov PNMR a klasických meraní sme zistili výrazné odlišnosti v zaradení vyšetrených do kategórií s nízkym, stredným a vysokým rizikom KCHS (podľa medzinárodných guidelines a podľa odporúčania poskytovateľa PNMR-metódy). Súlad medzi hodnotami LDLCH a LDLp sme našli len v 30 % prípadov a až 70 % vyšetrených bolo zaradených o jednu rizikovú triedu vyššie na základe PNMR-výsledku v porovnaní s klasickou hodnotou LDLCH. Súlad medzi HDLCH a HDLp bol v 52 % prípadov a rozdielne výsledky boli rozptýlené obidvoma smermi. Pri analýze súvislosti medzi koncentráciou remnantného cholesterolu (R-C; výpočet: R-C = T-C – LDL-C – HDL-C) sme našli významné súvislosti medzi R-C na jednej strane a VLDLp a LDLp (r = 0,63 a 0,42), počtom SLDLp (r = 0,38) a rozmermi LDL (r = 0,46) na strane druhej. Medzi integrovaným ukazovateľom inzulínovej rezistencie, triacylglycerol-glukózovým indexom a SLDLp bola významná priama a LDLs taká istá nepriama súvislosť (r = 0,76 a – 0,76). Záver: PNMR poskytuje skutočný obraz o štruktúre lipoproteínov a je perspektívnou metódou výskumu v špeciálnych situáciách, v ktorých klasické parametre neposkytujú dostatočnú informáciu o riziku KCHS.
- Publikační typ
- abstrakt z konference MeSH
Cardiovascular comorbidities are independent risk factors for mortality in dialysis patients. MicroRNA signaling has an important role in vascular aging and cardiac health, while physical activity is a primary nonpharmacologic treatment for cardiovascular comorbidities in dialysis patients. To identify the relationships between muscle function, miRNA signaling pathways, the presence of vascular calcifications and the severity of cardiovascular comorbidities, we initially enrolled 90 subjects on hemodialysis therapy and collected complete data from 46 subjects. A group of 26 subjects inactiv group (INC) was monitored during 12 weeks of physical inactivity and another group of 20 patients exercise group (EXC) was followed during 12 weeks of intradialytic, moderate intensity, resistance training intervention applied three times per week. In both groups, we assessed the expression levels of myo-miRNAs, proteins, and muscle function (MF) before and after the 12-week period. Data on the presence of vascular calcifications and the severity of cardiac comorbidities were collected from the patients' EuCliD® records. Using a full structural equitation modelling of the total study sample, we found that the higher the increase in MF was observed in patients, the higher the probability of a decrease in the expression of miR-206 and TRIM63 and the lower severity of cardiac comorbidities. A reduced structural model in INC patients showed that the higher the decrease in MF, the higher the probability of the presence of calcifications and the higher severity of cardiac comorbidities. In EXC patients, we found that the higher the increase in MF, the lower the probability of higher severity of cardiovascular comorbidities.
- MeSH
- cévní endotel metabolismus MeSH
- cvičení fyziologie MeSH
- dialýza ledvin * MeSH
- kardiovaskulární nemoci krev genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA biosyntéza krev genetika MeSH
- sedavý životní styl MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- stárnutí krev genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.
- MeSH
- akutní koronární syndrom krev farmakoterapie MeSH
- anticholesteremika škodlivé účinky terapeutické užití MeSH
- ateroskleróza krev farmakoterapie MeSH
- ezetimib škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- lipidy krev MeSH
- management nemoci MeSH
- PCSK9 inhibitory škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Individuals with Familial Hypercholesterolaemia (FH) are at very high risk of cardiovascular disease, which is associated with poor outcomes from coronavirus infections. COVID-19 puts strain on healthcare systems and may impair access to routine FH services. On behalf of the International Lipid Expert Panel (ILEP) and the European FH Patient Network (FH Europe), we present brief recommendations on the management of adult patients with FH during the COVID-19 pandemic. We discuss the implications of COVID-19 infections for FH patients, the importance of continuing lipid-lowering therapy where possible, issues relating to safety monitoring and service delivery. We summarise the evidence for additional benefits of statins and other lipid-lowering drugs during viral infections. The recommendations do not override in any way the individual responsibility of physicians to make appropriate and accurate decisions taking into account the condition of a given patient and the doses, rules, and regulations applicable to drugs and devices at the time of their prescription/use.
- MeSH
- Betacoronavirus * MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II komplikace farmakoterapie MeSH
- hypolipidemika terapeutické užití MeSH
- koronavirové infekce komplikace farmakoterapie MeSH
- lidé MeSH
- management nemoci * MeSH
- pandemie MeSH
- virová pneumonie komplikace farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
