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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., (© 2024. The Author(s).)

Background: An association between lipid measures and cognitive decline in patients with multiple sclerosis (MS) has been suggested., Objectives: This study aimed to investigate relationships between lipid profile and cognitive performance in a large observational cohort of MS patients., Materials and Methods: We included 211 patients with 316 available pairs of lipid and cognitive measures performed over follow-up. The time between lipid and cognitive measures did not exceed 90 days. Baseline data were analyzed by non-parametric Spearman rank correlation test. Repeated measures were analyzed using linear mixed models adjusted for sex, age, education level, disease-modifying therapy status, and depression., Results: Baseline analyses showed a correlation between higher low-density lipoprotein cholesterol (LDL-C) and lower Categorical Verbal Learning Test (CVLT) (rho=-0.15; p = 0.04), lower Symbol Digit Modalities Test (SDMT) (rho=-0.16; p = 0.02) and lower Brief Visuospatial Memory Test-Revised (BVMT-R) scores (rho=-0.12; p = 0.04). Higher high-density lipoprotein cholesterol (HDL-C) was negatively correlated with lower SDMT scores (rho=-0.16; p = 0.02) and lower Paced Auditory Serial Addition Test-3 (PASAT-3) scores (rho=-0.24; p = 0.03). Mixed model analyses of repeated measures showed a negative association between higher LDL-C and lower CVLT (B=-0.02; p < 0.001, Cohen´s d = 0.08) and lower BVMT-R (B=-0.01; p = 0.03, Cohen´s d=-0.12). Also, the negative association between HDL-C and PASAT-3 was confirmed in the mixed model analysis (B=-0.18; p = 0.01, Cohen´s d = 0.07). Additional adjustments of the models for disability assessed by Expanded Disability Status Scale or Normalized Brain Volume did not change the results of the models substantially., Conclusions: Our results suggest a mild negative impact of dyslipidemia on cognitive performance in patients with MS. We propose that dyslipidemia contributes, at least in part, to cognitive decline in MS patients, independent of brain atrophy., Competing Interests: Declaration of competing interest Balazs Lorincz received financial support for conference travel from Merck, Medtronic, Bayer and speaker honoraria from Sandoz. Jiri Motyl received compensation for traveling, conference fees and speaker honoraria from Sanofi Genzyme, Biogen, Novartis, and Merck. Lucie Friedova has nothing to disclose Daniel Hrych has received financial support for conference travel from Biogen. Eva Kubala Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen, and Merck Serono. Dana Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen. Manuela Vaneckova received speaker honoraria, consultant fees, and travel expenses from Biogen Idec, Novartis, Roche, Genzyme, and Teva, as well as support for research activities from Biogen Idec. Jan Krasensky received financial support for research activities from Biogen Idec. Tobias Kober and Bénédicte Maréchal are Siemens Healthineers International AG employees. Tadeas Urbas has nothing to disclose. Michal Vrablik reports fees for clinical trials, consultancy and presentations from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Mylan, Novartis, Novo Nordisk, Sanofi and Zentiva. Tomas Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme, and Merck Serono, as well as support for research activities from Biogen Idec and Sanofi., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study aimed to investigate relationships between cholesterol profile, brain volumetric MRI, and clinical measures in a large observational cohort of multiple sclerosis (MS) patients., Materials and Methods: We included 1.505 patients with 4.966 time points including complete lipid, clinical, and imaging data. The time among lipid, brain MRI and clinical measures was under 90 days. Cross-sectional statistical analysis at baseline was performed using an adjusted linear regression and analysis of longitudinal lipid and MRI measures data was performed using adjusted linear mixed models., Results: We found associations between higher high-density lipoprotein cholesterol (HDL-C) and lower brain parenchymal fraction (BPF) at cross-sectional analysis at baseline (B = -0.43, CI 95%: -0.73, -0.12, p = 0.005), as well as in longitudinal analysis over follow-up (B = -0.32 ± 0.072, χ 2  = 36.6; p = < 0.001). Higher HDL-C was also associated with higher T2-lesion volume in longitudinal analysis (B = 0.11 ± 0.023; χ 2  = 23.04; p = < 0.001). We observed a weak negative association between low-density lipoprotein cholesterol (LDL-C) levels and BPF at baseline (B = -0.26, CI 95%: -0.4, -0.11, p = < 0.001) as well as in longitudinal analysis (B = -0.06 ± 0.03, χ 2  = 4.46; p = 0.03). T2-LV did not show an association with LDL-C. We did not find any association between lipid measures and disability. The effect of lipid levels on MRI measures and disability was minimal (Cohen f2 < 0.02)., Conclusions: Our results contradict the previously described exclusively positive effect of HDL-C on brain atrophy in patients with MS. Higher LDL-C was weakly associated with higher brain atrophy but not with higher lesion burden., (© 2024. The Author(s).)

Atherosclerotic cardiovascular disease (ASCVD) is accelerated in people with diabetes. Dyslipidemia, hyperglycemia, oxidative stress, and inflammation play a role via a variety of mechanisms operative in the artery wall. In addition, some unique features predispose people with type 1 diabetes to accelerated atherosclerosis. Various organizations have created guidelines that provide advice regarding screening, risk assessment, and roadmaps for treatment to prevent ASCVD in diabetes. Management of dyslipidemia, especially with statins, has proven to be of immense benefit in the prevention of clinical CVD. However, since many patients fail to attain the low levels of low-density lipoproteins (LDL) recommended in these guidelines, supplemental therapy, such as the addition of ezetimibe, bempedoic acid or PCSK9 inhibitors, is often required to reach LDL goals. As a result, the upfront use of combination therapies, particularly a statin plus ezetimibe, is a rational initial approach. The addition to statins of drugs that specifically lower triglyceride levels has not proven beneficial, although the addition of icosapent-ethyl has been shown to be of value, likely by mechanisms independent of triglyceride lowering. Newer treatments in development, including apoC-III and ANGPTL3 inhibitors, seem promising in further reducing apoB-containing lipoproteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein (CRP) served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple mediation analysis revealed that all three potential mediators played a role in mediating the association. However, in parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43-0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31-0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003-0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Background: Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown., Methods: One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism., Results: Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (odds ratio (OR) 3.58, 95% confidence interva (CI): 1.78-7.18, P < 0.0005)., Conclusions: We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics., (Copyright © 2023. Published by Elsevier Inc.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Evidence continues to accumulate that select patients with acute low-risk pulmonary embolism (PE) can be safely discharged from the emergency department. Despite this, outpatient management continues to be uncommon. We report changes in emergency providers' stated preferences on low-risk acute PE management before and after the development and implementation of an institutional clinical pathway and decision tool., Methods: We performed an observational analysis of attending emergency physicians' stated preferences towards the management of low-risk acute PE using survey results before and after the development and implementation of an electronic health record-embedded institutional low-risk acute PE pathway., Results: Attending emergency medicine providers reported feeling more comfortable using PE risk stratification scores to identify dischargeable low-risk PE patients and also reported that they would be more likely to discharge a hypothetical patient with low-risk acute PE., Conclusion: Our results suggest that the implementation of an institutional clinical pathway with integration into the electronic health record was associated with a change in emergency physicians' stated preferences for managing patients with acute low-risk PE in the emergency department. Implementation of an evidence-based standard pathway was associated with increased comfort and familiarity with PE risk stratification, and an increased comfort with and preference for early outpatient management of low-risk PE., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022. The Author(s).)

Cardiovascular disease (CVD) is a chronic non-communicable disease (NCD) and the predominant cause of morbidity and mortality worldwide. Substantial reductions in the CVD prevalence have been achieved in recent years by the attenuation of risk factors (particularly hypertension and dyslipidaemias) in primary and secondary prevention. Despite the remarkable success of lipid lowering treatments, and of statins in particular, in reducing the risk of CVD, there is still an unmet clinical need for the attainment of guideline lipid-targets in even 2/3 of patients. Bempedoic acid, the first in-class inhibitor of ATP-citrate lyase presents a new approach to lipid-lowering therapy. By reducing the endogenous production of cholesterol, upstream of the rate-limiting enzyme HMG-CoA-reductase, i.e., the target of statins, bempedoic acid reduces circulating plasma concentrations of low-density lipoprotein cholesterol (LDL-C), and major adverse CVD events (MACE). Bempedoic acid has the potential to contribute to the reduction of CVD risk not only as monotherapy, but even further as part of a lipid-lowering combination therapy with ezetimibe, reducing LDL-C cholesterol up to 40%. This position paper of the International Lipid Expert Panel (ILEP) summarises the recent evidence around the efficacy and safety of bempedoic acid and presents practical recommendations for its use, which complement the 'lower-is-better-for-longer' approach to lipid management, which is applied across international guidelines for the management of CVD risk. Practical evidence-based guidance is provided relating to the use of bempedoic acid in atherosclerotic CVD, familial hypercholesterolaemia, and statin intolerance. Although there are still no sufficient data avilable for the role of bempedoic acid in the primary prevention of CVD, its favourable effects on plasma glucose and inflammatory markers makes this drug a rational choice in the patient-centred care of specific groups of primary prevention., Competing Interests: Declaration of Competing Interest MB: speakers bureau: Amgen, Daiichi Sankyo, KRKA, Polpharma, Mylan/Viatris, Novartis, Novo-Nordisk, Pfizer, Sanofi-Aventis, Teva, Zentiva; consultant to Adamed, Amgen, Daiichi Sankyo, Esperion, NewAmsterdam, Novartis, Novo-Nordisk, Sanofi-Aventis; Grants from Amgen, Daiichi Sankyo, Mylan/Viatris, Sanofi and Valeant; CMDO at Longevity Group (Luxemburg); PEP owns four shares in AstraZeneca PLC and has received honoraria and/or travel reimbursement for events sponsored by AKCEA, Amgen, AMRYT; MF reports having received consulting fees and/or honoraria and delivering lectures for Abbott, Amarin, Amgen, AstraZeneca, Ajanta, Kowa, Merck and Co, Organon, Pfizer, Recordati, Sanofi/Regeneron, Servier, SMB, Ultragenyx and Viatris; GL: has given talks, attended conferences, received consultancy fees and participated in trials sponsored by Abbott Laboratories, Amgen, Astra-Zeneca, Berlin Chemie, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Grindex, KRKA, MSD, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier Laboratories, Siemens Laboratories, Zentiva; PP; Grants from Akcea, Amgen. Scientific expert for: Amgen, Akcea, PRD Therapeutics; ŽR: has received honoraria from Novartis, Sanofi-Aventis and Swixx; MV has given talks, attended conferences, received consultancy fees and participated in trials sponsored by Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, KRKA, MSD, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Viatris, Zentiva; all other authors do not declare any conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: MB: speakers bureau: Amgen, Daiichi Sankyo, KRKA, Polpharma, Mylan/Viatris, Novartis, Novo-Nordisk, Pfizer, Sanofi-Aventis, Teva, and Zentiva; consultant to Adamed, Amgen, Daiichi Sankyo, Esperion, NewAmsterdam, Novartis, Novo-Nordisk, and Sanofi-Aventis; Grants from Amgen, Daiichi Sankyo, Mylan/Viatris, Sanofi, and Valeant; CMDO at Longevity Group (Luxemburg). PJ: speakers bureau, grants, and participation in trials sponsored by Amgen, Polpharma, Novartis, Novo-Nordisk, Pfizer, Sanofi-Aventis, Servier, and Zentiva. GK has given talks, attended conferences, received consultancy fees, and participated in trials sponsored by Amgen, Novartis, Sanofi, Servier, Viatris, and Amryt. EL reports grants from Hellenic Atherosclerosis Society; personal fees and non-financial support from AMGEN, personal fees from SANOFI, personal fees from LILLY, personal fees from BAYER, personal fees from NOVO-NORDISK, grants and personal fees from ASTRA-ZENECA, personal fees from BOEHRINGER INGELHEIM, personal fees from NOVARTIS, personal fees from SERVIER, and grants and personal fees from VIATRIS, outside the submitted work. FM attended conferences, symposia, has given talks, participated in trials, and received consultancy fees sponsored by Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Novartis, Sanofi, Servier, Zentiva, and Pfizer. GP: speakers bureau: Gedeon Richter and Novartis; MV has given talks, attended conferences, received consultancy fees, and participated in trials sponsored by Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, KRKA, MSD, Novartis, Novo-Nordisk, Pfizer, Sanofi, Servier, Viatris, and Zentiva. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Banach, Lewek, Pol, Rabczenko, Balanescu, Blaha, Ceska, Jankowski, Surma, Kolovou, Liberopoulos, Mitu, Mitu, Naji, Paragh, Popławska, Vrablik and Pella.)

Dyslipidemia treatment is of major importance in reducing the risk of atherosclerotic cardiovascular disease (ASCVD), which is still the most common cause of death worldwide. During the last decade, a novel lipid-lowering drug category has emerged, i.e., proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Apart from the two available anti-PCSK9 monoclonal antibodies (alirocumab and evolocumab), other nucleic acid-based therapies that inhibit or "silence" the expression of PCSK9 are being developed. Among them, inclisiran is the first-in-class small interfering RNA (siRNA) against PCSK9 that has been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. Importantly, inclisiran therapy may improve low-density lipoprotein cholesterol (LDL-C) target achievement by offering a prolonged and significant LDL-C-lowering effect with the administration of only two doses per year. The present narrative review discusses the ORION/VICTORION clinical trial program that has been designed to investigate the impact of inclisiran on atherogenic lipoproteins and major adverse cardiac events in different patient populations. The results of the completed clinical trials are presented, focusing on the effects of inclisiran on LDL-C and lipoprotein (a) (Lp(a)) levels as well as on other lipid parameters such as apolipoprotein B and non-high-density lipoprotein cholesterol (non-HDL-C). Ongoing clinical trials with inclisiran are also discussed.

Aims: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP)., Methods and Results: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was &lt;140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination., Conclusion: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS leading to demyelination and axonal degeneration. An increasing body of evidence suggests that lipid metabolism is associated with adverse clinical and MRI outcomes in MS. In this review we summarize the findings of association between low-density lipoproteins (LDL), high-density lipoproteins (HDL), their apolipoproteins and oxysterols with clinical and radiological disease activity in MS. Although the causality between disease activity in MS and abnormalities in lipid metabolism has not yet been elucidated, we suggest that advances in this field of research have the potential to improve understanding of MS pathophysiology and the identification of new treatment targets and strategies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Idiopathic inflammatory myopathies (IIM) are associated with systemic inflammation, limited mobility, and glucocorticoid therapy, all of which can lead to metabolism disturbances, atherogenesis, and increased cardiovascular (CV) risk. The aim of this study was to assess the CV risk in IIM patients and healthy controls (HC), and its association with disease-specific features., Methods: Thirty nine patients with IIM (32 females; mean age 56; mean disease duration 4.8 years; dermatomyositis: n = 16, polymyositis: n = 7, immune-mediated necrotizing myopathy: n = 8, anti-synthetase syndrome: n = 8) and 39 age-/sex-matched HC (32 females, mean age 56) without rheumatic diseases were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (Manual Muscle Test-8, Myositis Intention to Treat Activity Index, Myositis Damage Index). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry and bioelectric impedance). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications., Results: Compared to HC, there was no significant difference in IIM patients regarding blood pressure, ABI, PWV, CIMT, and the risk of fatal CV events by SCORE or SCORE2, or subclinical atherosclerosis (CIMT, carotid plaques, ABI, and PWV). The calculated CV risk scores by SCORE, SCORE2, and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to the results of carotid plaque presence and CIMT; however, none of them was demonstrated to be significantly more accurate. Other significant predictors of CV risk in IIM patients included age, disease duration and activity, systemic inflammation, lipid profile, lean body mass, and blood pressure., Conclusions: No significant differences in CV risk factors between our IIM patients and HC were observed. However, in IIM, CV risk was associated with age, disease duration, duration of glucocorticoid therapy, lipid profile, and body composition. None of the currently available scoring tools (SCORE, SCORE2, mSCORE) used in this study seems more accurate in estimating CV risk in IIM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oreska, Storkanova, Kudlicka, Tuka, Mikes, Krupickova, Satny, Chytilova, Kvasnicka, Spiritovic, Hermankova, Cesak, Rybar, Pavelka, Senolt, Mann, Vencovsky, Vrablik and Tomcik.)

Introduction: Patients with familial hypercholesterolemia (FH) are at increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Aim of study: To perform a retrospective analysis of data to assess the effects of individual lipoproteins and other risk factors (RFs) on the development of ASCVD and to compare these parameters in individuals with versus without ASCVD. Patients and methods: Our study group included a total of 1,236 patients with FH (395 men and 841 women with a mean age of 44.8 ± 16.7 years) attending a single lipid clinic. The diagnosis of FH was established using the Dutch Lipid Clinic Network score (DLCN). Among the 1236 FH patients, 1,008 of them [854 suspected with LDL receptor-mediated FH and 154 with familial defective apolipoprotein B-100 (FDB)] were genetically analysed. Their RFs were assessed based on the patients' clinical characteristics. Results: While patients with ASCVD had higher baseline LDL-C, TC, TG and Lp(a) compared with patients without this diagnosis, this ratio was just the opposite by the follow-up. The highest statistically significant differences were seen in the baseline levels of Lp(a) and, quite surprisingly, TG. Except for Lp(a), the levels of all lipid parameters declined significantly over time. While the incidence of diabetes and arterial hypertension was not higher in our group compared with the general population, these patients were at a more significant risk of ASCVD. Conclusion: Familial hypercholesterolemia is a major RF for the development of ASCVD. While our analysis confirmed the important role of LDL-C, it also corroborated a strong correlation between ASCVD and other lipid parameters, and Lp(a) and TG in particular. Familial hypercholesterolemia is not the only RF and, to reduce cardiovascular risk of their patients, physicians have to search for other potential RFs. Patients diagnosed to have FH benefit from attending a specialized lipid clinic perse., Competing Interests: VT declares no conflicts of interest. TA is a paid speaker for Amgen and Sanofi. RC has been a consultant to Akcea Therapeutics, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Egis, MSD, NovoNordisk, Sanofi, and is a board member of Amgen, Herbacos Recordati, Mylan, Novartis, Novatin, Pfizer, Promed, Roche, Sanofi, Servier; he also serves as a paid speaker for Akcea Therapeutics, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Egis, Herbacos Recordati, MSD, Mylan, Novartis, Novatin, NovoNordisk, Pfizer, Promed, Roche, Sanofi, and Servier. Richard Ceska has received honoraria from Amgen, Esperion, Kowa, Regeneron and Sanofi (PI, NC), and he reports grant support from IAS, Pfizer, and Teva. MV reports fees for clinical trials, consultancy and presentations from Amgen, Astrazeneca, Bayer, Boehringer Ingelheim, Lilly, Krka, Mylan, MSD, Novartis, Novo Nordisk, Sanofi and Zentiva., (Copyright © 2022 Altschmiedova, Todorovova, Vrablik, and Ceska.)