Cardiovascular risk in myositis patients compared with the general population.

OBJECTIVES: We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. METHODS: Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. RESULTS: Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. CONCLUSION: Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

The way to data: opinions and recommendations for the provision of health data for secondary use.

Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.

Beta-blockers for Atherosclerosis Prevention: a Missed Opportunity?

PURPOSE OF REVIEW: Current guidelines for the management of arterial hypertension endorse ß-adrenergic receptor blocking agents (beta-blockers, BBs) as being particularly useful for hypertension in specific situations such as symptomatic angina, tachycardia, post-myocardial infarction, heart failure with reduced ejection fraction (HFrEF), and as an alternative to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in hypertensive women planning pregnancy or at least of child-bearing potential. One of the most common uses of BBs is in patients with a recent myocardial infarction, with or without hypertension. Although this one use is specifically in a setting of atherosclerotic cardiovascular disease (ASCVD), it is not primarily for atheroprevention, but rather for cases with impaired systolic function, and it is intended primarily to lessen adverse cardiac remodeling and worsening of congestive heart failure (CHF). The BB class consists of numerous agents which differ widely in pharmacologic properties and physiologic effects. These differences include selectivity for ß-adrenergic receptors and their subtypes, hydro- or lipophilicity, effects on blood pressure and heart rate, influence on lipoprotein and glucose metabolism, and direct impact on the artery wall, including platelet reactivity, endothelial function, infiltration of inflammatory cells and on inflammation per se, and on smooth muscle cell proliferation. Importantly, BBs are not commonly used for prevention of atherosclerosis or ASCVD per se. Many studies of early-generation BBs showed adverse effects on lipoprotein levels and metabolism of glucose and insulin and thus discouraged their use in atheroprevention. Nevertheless, newer BBs often have neutral or favorable metabolic effects on these important factors in ASCVD pathophysiology, and recent scientific studies now document direct beneficial effects of BBs on the artery wall. This document reviews both types of newer data, not only to encourage consideration of BB treatment to reduce ASCVD in the present, but also to call for future research to better explore the clinical settings in which BBs may be proven to have additional benefit in preventing ASCVD when added to the better-established treatments for dyslipidemia and diabetes. RECENT FINDINGS: Relatively recent publications have clarified the diversity among BBs regarding adverse, neutral, or favorable effects on lipoproteins (especially triglycerides (TG) and low-density lipoprotein (LDL)) and on glucose/insulin metabolism. Specifically, the newer BBs (metoprolol ER, carvedilol ER, bisoprolol, and nebivolol) are now documented to be metabolically beneficial. These new data are complex but instructive regarding potential mechanisms of the diverse effects of various BBs on metabolism. Further and more importantly, these new data refute the traditional, but now outmoded, concept that BBs are universally harmful metabolically and therefore must be used sparingly, if at all, for atheroprevention. Recent studies have also reported exciting new data regarding how certain BBs can reduce platelet adhesion and improve the function of the major cell types in the artery wall, including the endothelium, macrophages, and smooth muscle cells. Specifically, BBs can improve endothelial function by enhancing arterial vasodilation and by reducing monocyte adhesion and transmigration. Further, BBs can decrease numbers and activity of inflammatory cells, including decreasing proliferation of smooth muscle cells and their transformation into inflammatory cells. These data help with the crucial step of distinguishing among available BBs regarding their likely overall arterial effects, whether to accelerate or prevent the development of atherosclerosis. In this regard, there is even some limited published information beyond these intermediary steps, going directly to the clinically more important endpoints of atherosclerosis and ASCVD events. The negative metabolic effects observed with the use of traditional/earlier generations of BBs have discouraged use of any BBs to prevent ASCVD. These adverse effects are not seen, however, with newer BBs. Thus, BBs continue to be a useful component of combination regimens not only in the treatment of arterial hypertension, heart failure, and arrhythmia, but also potentially in the prevention of atherosclerosis and ASCVD. Despite this exciting potential, further research is greatly needed to better establish the possible benefits of the most promising BBs as they might work in combination with other better-established atheropreventive agents. Specifically, there is a need for randomized, prospective, cardiovascular outcome trials (CVOTs) in high-risk patients, adding a BB to background LDL-lowering (statins, etc.), TG-lowering (specifically icosapent ethyl, which reduces ASCVD in patients with high TG, although apparently not via TG-lowering), and/or anti-diabetic (sodium glucose transport-2 inhibitors, SGLT2i, and glucagon-like protein-1 receptor agonists, GLP1-RA) treatments, as indicated in a given subject population.

Statins and Inflammation.

PURPOSE OF REVIEW: Chronic inflammation has been recognized as one of the most important pathophysiological mechanisms' initiation and progression of atherosclerosis. Statins belong to most successful therapeutic agents in the prevention and treatment of atherothrombotic vascular disease. Their non-lipid related effects including suppression of inflammation have been repeatedly proven in both experimental and clinical settings. RECENT FINDINGS: Recently, the importance of inflammation in the process of atherosclerosis has been confirmed by interventions targeting inflammation selectively. Clinical trial with selective inhibitor of a principal inflammatory mediator interleukin 1-beta - canakinumab - confirmed the notion of direct vasculoprotective effects of primarily targeting inflammation. This has increased interest in the non-lipid, pleiotropic and, particularly, anti-inflammatory effects of statins. Anti-inflammatory effects of statins have been proven both experimentally and in clinical settings beyond any doubt. They comprise a direct positive effect on not only many cell types and pathways that are lipid independent but, also, some that are mediated by lipid modification. Undoubtedly, suppression of inflammatory response by statins contributes to their generally positive action in atherosclerosis and represents an important part of the vasculo- and atheroprotective effect of this drug class.

Nutraceuticals in the Management of Dyslipidemia: Which, When, and for Whom? Could Nutraceuticals Help Low-Risk Individuals with Non-optimal Lipid Levels?

PURPOSE OF REVIEW: The aim of this review is to summarize the available clinical efficacy and safety data related to the most studied and used lipid-lowering nutraceuticals. RECENT FINDINGS: A growing number of meta-analyses of randomized clinical trials supports the effectiveness and tolerability of some lipid-lowering nutraceuticals such as red yeast rice, plant sterols and stanols, soluble fibers, berberine, artichoke extracts, bergamot polyphenol fraction, garlic, green tea, and spiruline. No significant safety concern has been raised for the use of such products. Association of more lipid-lowering nutraceuticals and of some nutraceuticals with lipid-lowering drugs has been tested as well. Current evidence suggests that some clinically tested lipid-lowering nutraceuticals could be safely used to improve plasma lipid levels in subjects affected by mild-to-moderate dyslipidaemia with low cardiovascular risk.

Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).

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.

Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management?

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. Although the use of genetic risk scores further improves CVD prediction, the significance is not unambiguous, and some subjects at risk remain undetected. Further research directions should focus on the "second level" of genetic information, namely, regulatory molecules (miRNAs) and epigenetic changes, predominantly DNA methylation and gene-environment interactions.

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients.

BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS: In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .).

Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic.

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.

Analysis of incidence and prevalence of cardiovascular risk factors and evaluation of their control in epidemiological survey in the Czech Republic.

OBJECTIVE: The aim of this analysis was to analyze the presence of the most important cardiovascular (CV) risk factors and to discuss patterns of LDL cholesterol management in the population studied. METHODS: We enrolled 961 males, average age of 42.9 ± 4.7, and 851 females, average age of 51.2 ± 3.6. Data on personal, pharmacological and family history, and laboratory examinations were collected. Cardiovascular (CV) risk was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm with modifications according to the guidelines. RESULTS: The distribution of CV risk in the observed cohort was as follows: 24% of the subjects had low, 51% moderate, 17% high and 8% very high risk. The percentage of patients who reached target values of LDL cholesterol was dramatically lower in the groups with very high (1%) and high (3%) risk than in the groups with moderate (14%) or low risk (59%). Dyslipidemia was newly identified in 20% of both sexes. Arterial hypertension was newly diagnosed in 8% of males and 5% of females, and type 2 diabetes mellitus was newly diagnosed in 3% of both the males and females. Dyslipidemia was present in 39% of males and 41% of females; arterial hypertension in 43% of males and 45% of females, and type 2 diabetes mellitus was diagnosed in 11% of the subjects of both sexes. 49% of males and 31% of females were overweight and 32% of both genders were obese. There were 36% of male smokers and 22% of female smokers. 48% of the participants were pharmacologically treated. Non-pharmacological treatment was recommended to 62% of male and to 65% of female participants. Pharmacological intervention was started in 53% of males and 51% of females. In both gender antihypertensive treatment with angiotensin-converting enzyme (ACE) inhibitors (29% of males and 27% of females) and lipid lowering therapy with a statin (28% of males, 27% of females) were the most commonly initiated treatments. In the subgroup of the 101 patients with LDL cholesterol levels > 5 mmol/L 56% were not treated with a statin. The analysis of relationship between the positive family history of any of the followed CV risks showed significant increases of the risk for arterial hypertension, type 2 diabetes mellitus and dyslipidemia. CONCLUSION: European guidelines suggest general screening for risk factors, including analysis of lipid profiles in the population of 40-year-old males and 50-year-old or postmenopausal women. Our study documents high prevalence and incidence of CV risk factors together with insufficient control of the risk factors in Czech patients of this age range. This finding suggests that preventive examinations should be undertaken earlier (e.g., in 30-year-old males and 40-year-old women). Exact timing of the preventive check-ups to yield the best cost-benefit ratio needs to be verified.

Atherosclerosis and beta-blockade: A forgotten option?

Beta-blockers have been ranked fourth in management recommendations for arterial hypertension in the management of arterial hypertension. This “retreat” is justified by the results of studies comparing different antihypertensive strategies that documented a lesser benefit of the beta-blockers tested compared to control therapies. Obviously, even within the beta-adrenergic receptor blocking group, there are important differences between agents. Properties such as selectivity to receptors and their subtypes, hydrophilicity and resp. lipophilicity, control of blood pressure, influence of intermediate metabolism or directly influence on vascular reactivity determine the resulting potential benefit associated with therapy. The results of clinical trials are also influenced by the test population and concomitant medications. There are a number of studies documenting the benefit of beta-blockers in patients with a history of atherothrombotic events or in the context of heart failure. In the context of the treatment of (yet) uncomplicated hypertension, we are interested not only in the main effects - lowering blood pressure, but also in other potentially effects significant for the resulting effect and influencing the prognosis (favorable or undesirable). In the case of beta-blockers, the effect on atherosclerosis development, lipidogram, vascular wall quality, anti-inflammatory effects, etc. In beta-blockers, several studies have suggested that their metabolic side-effect profile is so unfavorable that they need insulin resistance in patients with dyslipidemia, diabetes or obesity always avoid. This article returns to the question of the metabolic properties of beta-blockers and their possible direct antiatherogenic action and thus the site that this drug class should have in the field of cardiovascular prevention.

Importance of fixed-dose combinations in cardiovascular prevention: the possibility of treating two diagnoses with a single pill.

In the care of a cardiovascular risk patient there is certainly a more frequent situation in which we try to influence several risk factors at the same time. Treatment of a single self-occurring risk factor is rather an exception. In most cases, we need to intervene with more risk factors, often involving combination therapy, which can achieve the desired goals more quickly and reliably. However, with the number of tablets taken by the patient, the patients willingness to take long-term and correct use decreases, which has a significant impact on the effectiveness of therapy and the development of individual cardiovascular risk. In an effort to control all risk factors for cardiovascular disease, there is a growing need to extend the availability of fixed drug formulations to suit the patients ease of use and suitably formulated with varying dose grades to meet the needs of our attending physicians. With regard to the fact that early intervention of risk factors brings greater benefits than deferred, we are looking for appropriate ways to manage it. The current intervention of arterial hypertension and dyslipidemia with safe and proven drugs seems to be one of the ways to further improve the results of the prevention of cardiovascular diseases. The new fixed combination of atorvastatin with perindopril, which is entering the Czech market right now, appears to be in many ways an ideal “tablet for cardiovascular prevention”.

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.

Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects.

Current and future trends in the treatment of dyslipidemias.

Lipid-lowering treatment is a part of prevention and treatment of vascular diseases caused by atherosclerosis. We need new strategies for modifying plasma lipoprotein levels in the light of new findings that reduce target lipid levels further lower, as well as the growing population of patients for whom existing treatments cannot be offered. The spectrum of existing drugs (new statins) is widening, pharmacological treatments (recombinant lipoproteins-bound statins), improved forms of established drugs (selective PPARα receptor modulators) are coming. The new procedures include fixed combinations of established drugs improving adherence and intensifying lipid modifying effects (statin + ezetimibe). The portfolio of lipid-lowering therapies today also includes monoclonal antibodies against PCSK9 (PCSK9 inhibitors). The main direction of future development is biotechnology using the principle of so-called antisense therapy, i.e. the use of specific oligonucleotide sequences blocking the translation of the selected protein. These novel therapies targeting, for example, apolipoprotein B, apolipoprotein CIII, or lipoprotein(a) are in various stages of clinical trials. A simi-lar (but not identical) principle is the use of RNA silencing - interference with gene expression using short sequences of double-stranded RNA (e.g. inclisiran siRNA against PCSK9). Innovations in the field of hypolipidemic pharmacotherapy in our country may also be inhibitors of microsomal triglyceride transfer protein (approved for use in homozygotes for familial hypercholesterolemia and experimentally also for familial chylomicronemia). The small molecule ATP citrate lyase inhibitor, bempedoic acid, decreases LDL-C by a further 20 % over and above the reduction achievable by a statin. In a broader sense, the novelty of hypolipidemic pharmacotherapy includes treatment options for some rare metabolic diseases (eg. enzyme replacement therapy for acid lysosomal lipase deficiency) manifested by lipoprotein metabolism abnormalities. All these new directions must aim at the common main goal of reducing the incidence of cardiovascular and gastrointestinal complications of dyslipidemia. Clinical research also aims to prove these effects.

Consensus statement of professional associations on prescribing of PCSK9-inhibitors.

A new class of drugs known as PCSK9 inhibitors (PCSK9i) provide biological treatment for hypercholesterolemia. These drugs are administered using a subcutaneous injection once in two or four weeks. PCSK9i are not a replacement of the existing hypolipidemics, they just expand the therapeutic spectrum for the critically ill and those who cannot use the standard therapy and do not reach satisfactory target values. There are essentially two indications: (1) hypercholesterolemie and mixed dyslipidemia and (2) secondary prevention of cardiovascular diseases (CVD). Statin intolerance is not the only indication for treatment. However as its presence sometimes plays an essential role as to choosing the treatment, it will be also discussed in the paragraph on reimbursement conditions. Reimbursement conditions (very simplified): the treatment will be provided at selected centres. A list of the centres is included in an annexe to this article. You will find it also on www.interna-cz.eu, on www.kardio-cz.cz and www.athero.cz. The indicative concentration of LDL-cholesterol (LDL-C) from which on PCSK9i can be prescribed as covered from the public health insurance, is the following: (1) familial hypercholesterolemia 4.0 mmol/l, (2) for secondary prevention CVD 3.0 mmol/l - Please note: the presented LDL-C level is one reached under maximum (tolerated) high intensity hypo-lipidemic therapy. High intensity hypolipidemic therapy is defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg + ezetimibe. In the case of demonstrated intolerance of both the mentioned statins the patient has to be treated with a maximum tolerated dose of statins, in combination with another hypolipidemic drug (ezetimibe). Statin intolerance is defined as intolerance of at least two successive statins, which results in their discontinuation. Statin intolerance alone is not the indication for PCSK9i treatment! The payment criteria must always be complied with. A medical officer can of course be asked to approve such treatment in exceptional cases. Key words: alirocumab - PCSK9 inhibitors centers - center therapy - evolocumab - familial hypercholesterolemia - proprotein konvertase subtilisin kexin 9 inhibitors (PCSK9i) - secondary prevention - statins intolerance.

A summary of the EAS consensus concerning the causal relationship between low-density lipoproteins and atherosclerotic cardiovascular diseases, prepared by the Board of the Czech Society for Atherosclerosis.

This article summarised opinion of the European Society for Atherosclerosis on the causal relationship between low density lipoprotein (LDL) and the development of atherosclerosis. The fact that there is a clear causal relationship between the LDL concentration and the development of atherosclerotic cardiovascular disease (ASKVO) is evidenced by congenital lipid metabolism disorders and results of prospective epidemiological studies, Mendelian randomized trials, and randomized controlled trials. It is documented that the effect of LDL exposure on ASKVO development is cumulative; the additive effect of other risk factors is also discussed. In conclusion the facts, underlying the rational approach to the therapy of patients with dyslipidemia, are summarized. Key words: atherosclerotic cardiovascular disease - LDL - low density lipoprotein - EAS.

Body Adiposity Changes After Lifestyle Interventions in Children/Adolescents and the NYD-SP18 and TMEM18 Variants.

BACKGROUND This study was carried out to determine the relationship between the common TMEM-18 (rs4854344, G>T) and NYD-SP18 (rs6971091, G>A) gene variants and weight loss after lifestyle interventions (increased physical activity in conjunction with optimal dietary intake) in overweight/obese children/adolescents. MATERIAL AND METHODS We genotyped 684 unrelated, white, non-diabetic children (age 12.7±2.1 years, average BMI at baseline 30.66±4.80 kg/m²). Anthropometric and biochemical examinations were performed before and after 4 weeks of an intensive lifestyle intervention. RESULTS The mean weight loss achieved was 5.20±2.02 kg (P<0.001). NYDSP-18 AA homozygotes had significantly higher abdominal skinfold value before and after the intervention (both, P=0.001). No significant associations between BMI decrease and the NYD-SP18 and TMEM18 variants were found. Associations between all anthropometrical and biochemical changes and genes remained non-significant after data were adjusted for sex, age, and baseline values. CONCLUSIONS Decreased body weight in overweight/obese children is not significantly influenced by the NYD-SP18 rs6971091 or TMEM18 rs4854344 polymorphisms.

[Cardiovascular risk in patients with rheumatic disease and its management]. / Kardiovaskulární riziko u pacientu s revmatickými chorobami a jeho management.

Cardiovascular disease (CVD) risk in patients with rheumatic diseases is increased by 50 % compared to the general population. This is a result of the increased inflammatory activity as well as modification of traditional CVD risk factors by the primary disease. So called lipid paradox, paradoxical decrease of concentrations of atherogenic plasma lipids due to increased inflammatory activity and their rise with successful anti-inflammatory treatment, is of particular importance. CVD risk in rheumatic diseases is further modified by drugs used for their treatment: while some treatment modalities increase the risk (e.g. glucocorticoids), others may act in an opposite direction (methotrexate, biological therapies). CVD risk stratification in patients with rheumatic diseases is uneasy; so far none of the specific scoring systems has been shown superior to traditional ones designed for the general population. Principles of cardiovascular risk intervention remain the same as for the general population: the management starts with lifestyle measures (healthy diet, increase in physical activity and smoking cessation) complemented with pharmacotherapy when indicated. Blood pressure as well as lipid lowering therapies should be led according to the same principles as in the general population and, also, to the same treatment goals. To improve CVD prevention outcomes in patients with rheumatic diseases it seems feasible to work in interdisciplinary teams led by a rheumatologist cooperating with a specialist in CVD prevention strategies (general practitioner, cardiologist, internist, diabetes specialist). A nutritional therapist and a physiotherapist are important members of the team, too. Interdisciplinary and complex CVD prevention in patients with rheumatic diseases decreases CVD morbidity.Key words: cardiovascular risk - intervention - lipid paradox - rheumatic diseases - risk factors - risk stratification.