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Background: COVID-19 restrictions prompted changes in chronic disease management and lifestyle modifications, potentially altering cardiometabolic indicators and lipid-lowering pharmacotherapy patterns. We aimed to assess lipid-lowering drug (LLD) utilization trends during COVID-19 restrictions., Methods: We obtained nationwide outpatient drug sales and prescribing data for 01.03.2018-31.12.2022 from IQVIA™ Turkey. We evaluated average monthly LLD consumption, their costs, and quarterly prescribing levels in three periods: "before restrictions" (BfR, 01.03.2018-31.03.2020), "during restrictions" (DuR, 01.04.2020-31.03.2022), and "after restrictions" (AfR, 01.04.2022-31.12.2022). Drug utilization was measured via "defined daily dose/1000 inhabitants/day" (DID) metric., Results: LLD utilization increased from 25.4 ± 3.1 DID in BfR to 36.2 ± 6.8 DID in DuR (p < 0.001), and to 42.6 ± 5.3 DID in AfR (p < 0.001 vs. BfR). Statin consumption significantly rose from 22.0 ± 3.0 DID in BfR to 31.6 ± 6.3 DID in DuR (p < 0.001), and further to 37.6 ± 4.7 DID in AfR (p < 0.01 vs. DuR). High-intensity statin consumption elevated by 115.9% in AfR compared to baseline (p < 0.001). Prescribing of LLDs decreased from 12.5 ± 0.6 DID in BfR to 7.2 ± 1.2 DID in DuR (p < 0.001), later reached 13.6 ± 3.8 DID in AfR (p < 0.001 vs. DuR), with prescribing for ongoing users following similar trend. Expenditure on LLDs increased from €8.4 m ± 0.9 m in BfR to €11.4 m ± 2.0 m in DuR (p < 0.001) and to €12.8 m ± 1.9 m in AfR (p < 0.001 vs. BfR)., Conclusions: This study revealed a surge in consumption of LLDs in Turkey following the onset of the COVID-19 pandemic. This rise might be related to practices facilitating drug access, in addition to potentially greater adherence, or the necessity for more intense pharmacotherapy due to elevated cardiovascular risk., 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 © 2024 Elsevier Inc. All rights reserved.)

Several observations have shown that elevated levels of low-density lipoprotein cholesterol (LDL-C) are a cause of cardiovascular disease. Lowering LDL-C is a key strategy for reducing cardiovascular risk, with a continuous linear correlation between LDL-C reduction and cardiovascular benefit. Based on these observations, current guidelines have further lowered LDL-C goals and call for the use of more effective therapeutic interventions. In addition to statins, ezetimibe and the monoclonal antibodies targeting PCSK9, several new lipid-lowering agents are currently in phase 3 clinical trials to evaluate their clinical effects, and more are in development. The use of combination therapies targeting different pathways can increase the effectiveness of treatment., Competing Interests: Declaration of Competing Interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. A.L.C. has received honoraria, lecture fees, or research grants from Aegerion, Amgen, Amryt, Astrazeneca, Bayer, Daiichi-Sankyo, Eli Lilly, Genzyme, Ionis Pharmaceutical, Kowa, Mediolanum, Medscape, Menarini, Merck, Mylan, Novartis, PeerVoice, Pfizer, Recordati, Regeneron, Sanofi, Sigma-Tau, and The Corpus, outside the submitted work., (Copyright © 2023. Published by Elsevier Inc.)

Aims: To evaluate the effect of the ESC/EAS 2019 dyslipidaemia guidelines on patient management of lipid-lowering therapy in patients with acute coronary syndrome (ACS), through a survey designed to compare post-ACS patient management in 2022 with that in 2018., Methods: Online questionnaires focused on lipid profile and medications were used to gather data from 2650 ACS patients in 6 European countries, treated between March-June 2022 (ACS EuroPath IV survey). These data were compared with data collected from 2650 patients who participated in the ACS EuroPath I survey (conducted in 2018)., Results: Lipid testing was performed in 90% of patients and was done sooner after admission in 2022 versus 2018 (mean 1.4 vs 1.7 days). Increased testing for non-HDL-C, lipoprotein(a), and ApoB was observed over time. At discharge, most patients (≥90%) were receiving lipid-lowering therapy. Prescribing patterns differed, with a higher proportion of patients receiving statin plus ezetimibe combination therapy in 2022 versus 2018 (34% vs 13%). LDL-C levels were lower in 2022 versus 2018 at admission and at 1st, 2nd and 3rd post-discharge follow-up points. More patients achieved low-density lipoprotein cholesterol (LDL-C) goals in 2022 versus 2018 at the first follow-up (average 14 vs 16 weeks since discharge; <70 mg/dL [1.8 mmol/L]: 34% vs 20%; <55 mg/dL [1.4 mmol/L]: 18% vs 10%) and at subsequent follow-up points., Conclusion: LDL-C goal achievement has improved since the release of the 2019 guidelines, but lipid management in post-ACS patients remains suboptimal., Competing Interests: Declaration of Competing Interest UL has received honoraria, lecture fees or research grants from Amgen, Daiichi Sankyo, Novartis and Sanofi. ALC has received honoraria, lecture fees or research grants from: AstraZeneca, Aegerion, Amryt, Amarin, Daiichi Sankyo, Esperion, Ionis Pharmaceuticals, Kowa, Medscape, Mylan, Merck, Menarini, Novartis, Peer Voice, Pfizer, Recordati, Regeneron, Sandoz, Sanofi and The Corpus. The work of ALC relevant to this publication is supported by Ministero della salute Ricerca corrente. RDC has received honoraria, lecture fees or research grants from Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi Sankyo, Roche, Novartis, AstraZeneca, Milestone, Menarini, Guidotti, Lilly, Merck and Portola. AS has received honoraria, lecture fees or research grants from Amgen, Daiichi Sankyo, Ferrer, Getinge, Novartis, Pfizer, Sanofi and Zoll. AZ has received honoraria, consulting or lecture fees from Sanofi, Amgen and Novartis. FS has received research grants from and/or was speaker (with or without lecture fees) on a.o. (CME accredited) meetings sponsored by Amgen, Bayer, Novartis, Novo Nordisk, Sanofi Aventis, Recordati, Servier, Mylan and AstraZeneca. JWJ/his department has received research grants from and/or was speaker (with or without lecture fees) on a.o. (CME accredited) meetings sponsored by Amarin, Amgen, Athera, Biotronik, Boston Scientific, Dalcor, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, the Netherlands Heart Foundation, CardioVascular Research the Netherlands (CVON), the Netherlands Heart Institute and the European Community Framework KP7 Programme., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to develop genetic scores based on single-nucleotide polymorphisms (SNPs) related to lipid metabolism and evaluate whether they used to estimate disturbances in the circulating lipid profile biomarkers of adolescents., Methods: In a preliminary cross-sectional approach, 113 Brazilian adolescents (10-19 y of age) with cardiovascular disease risk factors were evaluated. Genetic scores from 20 SNPs related to lipid metabolism were calculated by codifying each of them as the rescaled sum of risk allele frequencies. All scores were distributed in classes between 0 (absence of risk alleles) and 10 (presence of all risk alleles) to evaluate the additive effect of risk alleles on the lipid profile outcomes in the same interval. Multiple linear regression analyses were performed to evaluate the association between each score and blood lipid profile biomarkers., Results: Significant associations between genetic scores and unfavorable outcomes in all evaluated lipid profile biomarkers were found. The mean ± SD of the genetic scores for the circulating lipid profile biomarkers in the 0 to 10 scale were 4.4 ± 2 for triacylglycerol, 5.3 ± 1.5 for total cholesterol, 5.6 ± 1.2 for high-density lipoprotein cholesterol, 4.9 ± 1.6 for low-density lipoprotein cholesterol, and 3.6 ± 1.9 for minimally modified low-density lipoprotein cholesterol. For each point obtained in each genetic score, a mean increase ± SE of 15.8 ± 4.2 mg/dL in triacylglycerol (P = 0.0001), 5.3 ± 1.7 mg/dL in total cholesterol (P = 0.0032), 4.8 ± 1.3 mg/dL in low-density lipoprotein cholesterol (P = 0.0003), and 1.1 ± 0.3 U/L in minimally modified low-density lipoprotein cholesterol (P = 0.0020) and a mean decrease of 3.7 ± 0.7 mg/dL in high-density lipoprotein cholesterol (P < 0.0001) concentrations were obtained., Conclusion: The calculated genetic scores could be used to estimate disturbances in circulating lipid profile biomarkers of adolescents and be applied in clinical practice to better target interventions to reduce cardiovascular disease risk throughout life., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The evidence of the causal role of low-density lipoprotein cholesterol in the development of atherosclerotic cardiovascular disease is well-established. The clearly identified common position of the European guidelines proclaims necessity to decrease LDL-C concentrations based on a proper risk stratification. However, current worldwide situation with the lipid management still demonstrates inadequate dyslipidemia control, that is probably related to a healthcare system issues. As the need to standardize and implement approaches following the guidelines into clinical practice remains a challenge, the EAS initiates the Lipid Clinics Network project, aiming to provide a structure to establish uniform EU-wide standards of diagnosis, management and treatment of patients with lipid disorders, based on the ESC/EAS Guidelines on management of dyslipidaemias., Competing Interests: Declaration of competing interest None relevant to the work described in this manuscript., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine comorbidities in young men with erectile dysfunction (ED) who are increasingly targeted by direct-to-consumer (DTC) internet platforms that sell phosphodiesterase-5 (PDE-5) inhibitors without comprehensive clinical evaluation; and, further, to characterize the portrayal of DTC platforms by popular news media., Methods: We retrospectively reviewed all men age ≤40 evaluated for ED at an andrology clinic during January 2016-March 2019 to obtain demographics, exam and lab findings, and treatments. Five news sources were analyzed during the study period to characterize whether articles about DTC platforms were positive, critical, or balanced/neutral., Results: We identified 388 patients, with age 29.5 ± 5.0 years, 15% rate of obesity, 20% prediabetes or diabetes, 54% dyslipidemia, and 20% hypogonadism. Serum lab findings associated with subfertility were found in 11%. Semen analysis was conducted in 64 men, of whom 40% were abnormal. Varicoceles were found in 35%. PDE-5 inhibitor was prescribed to 328 men (88%). Off-label empiric therapies included clomiphene (32.9%) or aromatase inhibitor (12.1%). Testosterone replacement was initiated in 9.7%. Analysis of news coverage revealed 18 articles, of which 61% portrayed DTC platforms exclusively in a positive light., Conclusion: Office consultation identified young men with significant comorbidities that would be missed by DTC platforms, which employ only questionnaires for health screening. DTC platforms present themselves as medical authorities without following AUA Guidelines, yet garner mostly positive press coverage. Patients engaging these platforms may falsely believe they are receiving adequate medical assessment. Urologists may do well to incorporate telemedicine to enfranchise young men with evidence-based evaluation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Niacin has been widely used as an antihyperlipidemic drug, but the flushing effect restricted its clinical application. Here, we developed novel niacin-lipoic acid dimers which lead to better lipid modulation, higher synergistic effects and less side effects. We utilized molecular docking simulation to design a novel series of niacin-lipoic acid dimers. The compound N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide (N2L) was selected for the in vitro and in vivo evaluation, including the agonist activity in CHO-hGPR109A cells, cell protective effects in HT22 and HUVECs cells, flushing effect in guinea pigs and rats, lipid modulation in C57BL/6 mice and high fat diet-rats and atherosclerotic lesions regulation in apolipoprotein E null mice. N2L worked as potent and selective agonists for the high affinity niacin receptor GPR109A. N2L retained antioxidation and cytoprotection of lipoic acid. In addition, N2L displayed a good therapeutic index regarding lipid modulation and atherosclerotic lesions regulation, and minimized niacin-induced vasodilation (flushing) effect in vivo. N2L showed effective treatment regarding to lipid regulation and atherosclerosis inhibition effects, also with excellent antioxidant effects, safety profiles and non-flushing. All these results suggest N2L promising application prospects in the drug development for the treatment of atherosclerosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Circulating oxidized phospholipids are increasingly recognized as biomarkers of atherosclerosis. Clinical association studies have been mainly performed using an immune assay based on monoclonal antibody E06, which recognizes a variety of molecular species of oxidized phosphatidylcholine (OxPC) in lipoproteins, cell membranes or covalently bound to plasma proteins. Accumulating evidence shows that individual molecular species of OxPC demonstrate different biological activities and have different half-life times. Therefore, it is likely that certain molecular species can be associated with pathology more strongly than others. This hypothesis can only be tested using LC-MS/MS allowing quantification of individual molecular species of OxPCs. In order to ensure that laborious LC-MS/MS methods do not simply replicate the results of a technically simpler E06-OxPCs assay, we have performed relative quantification of 8 truncated molecular species of OxPCs in plasma of 132 probands and compared the data with the results of the E06-OxPCs and OxLDL assays. We have found a strong correlation between individual molecular species of OxPCs but only a weak correlation of LC-MS/MS-OxPCs data with the E06-OxPCs assay and no correlation with the OxLDL assay. Furthermore, in contrast to the results of E06-OxPCs or OxLDL assays, 7 out of 8 OxPC species were associated with hypertension. The data suggest that the results of the LC-MS/MS-OxPCs assay do not replicate the results of two ELISA-based lipid oxidation tests and therefore may produce additional diagnostic information. These findings necessitate development of simplified mass spectrometric procedures for high-throughput and affordable analysis of selected molecular species of OxPCs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9-I) reduce low-density lipoprotein (LDL) cholesterol in human studies. Previous studies suggest that PCSK9-I may also affect very-low-density lipoproteins (VLDL). We therefore studied VLDL size and composition in a "real-world" study population with the use of β-quantification., Subjects and Methods: 350 patients (62 ± 11 years old, 58% men, 22% with diabetes mellitus) with different concomitant lipid lowering therapies, and in whom PCSK9-I treatment was indicated, received either evolocumab (140 mg) or alirocumab (75 or 150 mg). The major lipoprotein fractions were separated by β-quantification and lipid and apolipoprotein compositions were determined before and 4 weeks after initiation of PCSK9-I treatment., Results: After 4 weeks of PCSK9-I treatment, the ratio of triglycerides to apolipoprotein B in VLDL particles (VLDL-TG/apoB ratio) increased by 40% (p < .0001). VLDL-associated apolipoproteins E, CII, and CIII were reduced by 29.4%, 16.4%, and 12.4%, respectively (all p < .0001)., Conclusion: PCSK9-I treatment increased VLDL size (estimated by an increased VLDL-TG/apoB ratio) and reduced VLDL-associated apolipoproteins in a heterogeneous "real-world" study-population, reflecting a higher clearance of small atherogenic VLDL remnant particles by PCSK9-I. This may potentially lower cardiovascular risk in clinical routine patients beyond low-density cholesterol (LDL-C) reduction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Even with the improvement in lifestyle interventions, a better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) still persists as the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidaemias, namely hypercholesterolaemia, have a crucial and causal role in the development of atherosclerotic CVD. The clinical approach of a patient with dyslipidaemia involves a watchful diagnosis, sustained in lipid and lipoprotein laboratory procedures, which must be harmonized and standardized. Standardization of lipid test results and reports, incorporating the total CV risk and the respective target and goals of treatment approach, guarantees that clinical guidelines and good clinical practices are followed and respected, increasing the reliability of lipid disorders screening, producing more accurate diagnoses and CV risk stratification, and improving the CV prevention and the achievement the desirable treatment goals., (Copyright © 2018. Published by Elsevier B.V.)

Background and Aims: Physical activity is recommended as part of the lifestyle modification for the treatment of hyperlipidemia, however, the literature reports heterogeneous quantitative effects of exercise on serum lipids. We therefore reviewed the effects of aerobic exercise on serum lipids with special focus on the training effectiveness., Methods: Data regarding effects of endurance training (ET) on total Cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C) and triglycerides (TG) were evaluated in a selective literature search. To account for the observed heterogeneity of the training interventions, studies were analyzed according to effectiveness (duration, intensity, frequency) of training., Results: Unselected training intervention studies did not exert significant effects on serum LDL-C but showed minor positive effects on HDL-C and TG. Effective endurance training - defined as endurance training performed by an intensity of 65-75% of the heart rate reserve (corresponding to 75-85% maximum heart rate or 65-80% VO 2max ) for a duration of 40-50min per training unit on 3-4days/week over a period of 26-40weeks showed improvement of serum lipids. Effective training lowered TC by -3.75% (p=0.0006), LDL-C by -4.76% (p=0.0015), TG by -8.24% (p=0.0004) and increased HDL-C by +4.43% (p=0.0061)., Conclusion: The analysis suggests that a minimum exercise threshold is necessary to produce effects on serum lipids. Overall, the quantitative effect of physical activity on serum lipids is small., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Beyond its well-established efficacy in lowering atherogenic lipids and lipoproteins, DALI (Direct Adsorption of Lipids) apheresis has been shown to have acute anti-inflammatory and endothelium-protective effects. In the present study, we investigated long-term effects of DALI procedures on circulating oxidative stress markers., Methods: Thirteen patients involved in the study underwent regular DALI apheresis for nearly two years. At sessions 1, 40 and 80 conventional lipid status and changes of systemic oxidative stress markers (oxidized LDL, anti-oxidized LDL antibodies, advanced oxidation protein products (AOPP), and myeloperoxidase (MPO)) were examined., Results: DALI procedure efficiently reduced atherogenic lipids/lipoproteins. On day three after apheresis lipid parameters returned to pre-apheresis values. They showed no tendency to increase or to decrease over time. No significant differences were found between 1st, 40th and 80th sessions. In a similar way, levels of oxidative stress biomarkers acutely decreased after apheresis sessions and rebounded on day three after apheresis. No significant differences were observed between sessions 1, 40, and 80., Conclusion: DALI apheresis repeatedly decreases atherogenic lipid/lipoprotein profile and oxidative stress biomarker levels during each session. Among all investigated parameters no longitudinal effects over two years could be observed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aims: The objective of this study was a standardized comparison of the safety and effectiveness of the Kaneka (Kaneka Corporation, Osaka, Japan) whole blood (Liposorber DL-100) and plasma (Liposorber LA-15) lipoprotein apheresis (LA) system to optimize the individual therapy of patients with cardiovascular disease and severe dyslipidemia., Methods: Six chronic LA patients with a pre-treatment LDL-C < 6 mmol/l in steady state received a total of three treatments with the LA-15 device, followed by three treatments with the DL-100 device or vice versa. To achieve a standardized comparison the treated blood volume for any patient was kept identical for both procedures. Sampling points for total cholesterol, LDL-C, HDL-C, Lp(a), triglyceride, blood count, and bradykinin measurements were adjusted for both techniques., Results: Total cholesterol, LDL-C, HDL-C, Lp(a), and triglycerides were reduced by 59.2 ± 6.5%, 79.3 ± 6.9%, 7.1 ± 3.9%, 87.3 ± 3.1%, 22.5 ± 24.2% using the DL-100 system and by 51.4 ± 5.2%, 65.2 ± 3.7%, 2.2 ± 4.9%, 72.7 ± 2.2%, 46.5 ± 9.4% using the LA-15 system, showing that the DL-100 adsorber was significantly more effective for lowering total cholesterol (p = 0.044), LDL-C (p = 0.001), Lp(a) (p = 0.029), while triglycerides were reduced to a higher extent by the plasma system (p = 0.046) in this patient group. The regenerable LA-15 adsorber columns showed a higher removal capacity considering the difference between inflow and outflow concentrations. Bradykinin levels significantly increased up to 145 fold in the outflow lines using the plasma system (p = 0.028), but not systemically. There was no significant bradykinin generation using the whole blood adsorber., Conclusion: In conclusion, the whole blood system was faster and more effective in this LA patient group with pre apheresis LDL-C<6 mmol/l. Whether the regenerable plasma system is more effective in patients with higher LDL-C content should be evaluated in future standardized comparisons., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Numerous healthcare studies have shown that more than 90% of all patients with dyslipidaemia are not treated adequately., Objectives: The "Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen (DGFF)" [German Society of Lipidology], a non-profit professional membership organization, has already made a series of efforts to improve the care of patients suffering from dyslipidaemia. A recent outcome is the nationwide implementation and certification of Lipidological Competence Centres and Networks (LCCNs)., Methods and Results: By involving numerous external medical cooperation partners and combining the detailed work of different in-house medical specialists, the Medical Care Centre Kempten-Allgäu was able to improve both the diagnosis and treatment of patients exhibiting disorders of lipid metabolism (DLM). This local lipidological network is so successful, that it may serve as a nationwide standard model for outpatient lipidological care. Detailed organizational structures for improved lipidological care which are suitable to provide a template for future guidelines for the certification of LCCNs have been developed by the Medical Care Centre Kempten-Allgäu. Stringent requirements of implementation with respect to medical staff, content and structure, staff training, patient education and public relations as well as to documentation, quality assurance and quality improvement must be fulfilled both by the lipidological competence centre (LCC) and the cooperation partners within the lipidological network (LN). Finally, members of the health care system (e.g. health policy and health insurances) should be involved in this attempt and convinced of financial support., Conclusion: The implementation and certification of national LCCNs supported by DGFF could contribute to a comprehensive improvement in the care of patients with dyslipidaemia, resulting in prevention of cardiovascular diseases and reduction of cardiovascular sequelae., (Copyright © 2017. Published by Elsevier B.V.)

Background: Monocytes can be differentiated into subpopulations depending on their expression profile of CD14 and CD16. CD16-positive monocytes are associated with coronary artery disease. Up to now, no data exist about the effect of lipoprotein apheresis (LA) on the distribution of monocyte subpopulations., Methods: 80 patients who underwent LA at the University Hospital Dresden were included in the study. 8 out of the 80 LA patients received LA for the first time at the time point of blood analysis. Six different methods of LA were used (H.E.L.P. n = 8; Liposorber D n = 10; LF n = 14; DALI n = 17; MONET n = 11; Therasorb ® LDL n = 12). Blood samples were taken immediately before and after LA and analyzed for CD14 and CD16 expression on monocytes. A total of 42 patients with cardiovascular risk factors but no indication for LA served as control group., Results: The composition of monocyte-population was analyzed in regard to the 3 subpopulations. After LA, an increase in classical monocytes (CD14 ++ CD16 - ) (93.3% vs. 93.9%, p < 0.01) and a decrease in non-classical monocytes (CD14 + CD16 + ) (1.5% vs 1.0%; p < 0.001) were observed. LA did not change the amount of intermediate monocytes (CD14 ++ CD16 + ) (5.3% vs. 5.1%). Two methods (MONET and Therasorb ® LDL) did not influence the distribution of monocyte subpopulations. Interestingly, patients with LDL-C above 2.5 mmol/l prior LA showed increased amounts of intermediate monocytes., Conclusion: The distribution of monocyte populations is influenced by LA but depends on the distinct method of LA. Influences of LA were mainly observed in the content of classical and non-classical monocytes, whereas the intermediate monocyte population remained unaltered by LA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aim: Lipoprotein-apheresis (LA) is a therapeutic approach used against severe forms of dyslipidemia in patients who are non-responders or intolerant to pharmacological treatments. However, little is known about the potential pleiotropic effects of LA, particularly regarding the immune system and its regulation. Thus, in an attempt to analyse the potential effects of dyslipidemia and LA on the regulation of CD4 + T cells activation and lineage differentiation, we compared the CD4 + T cells cytokines secretion profiles of dyslipidemic patients before and after LA with the profiles observed in healthy donors., Methods: CD4 + T cells were isolated from 5 LA patients and 5 healthy donors and activated with anti-CD3 or anti-CD3 + anti-CD46 antibodies. The supernatants were collected after 36 h incubation and levels of secreted cytokines analysed by flow cytometry., Results: Our results revealed a deep remodelling of CD4 + T cells cytokines secretion patterns in dyslipidemic patients compared to healthy donors, as reflected by a 15 times higher IFN-γ secretion rate after CD3 + CD46 co-activation in dyslipidemic patients after LA compared to healthy subjects and 8 times higher after CD3 activation alone (p = 0.0187 and p = 0.0118 respectively). Moreover, we demonstrated that LA itself also modifies the phenotype and activation pattern of CD4 + T-cells in dyslipidemic patients., Conclusion: These observations could be of fundamental importance in the improvement of LA columns/systems engineering and in developing new therapeutic approaches regarding dyslipidemia and associated pathologies such as atherosclerosis and type 2 diabetes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: An elevated lipoprotein(a) (Lp(a)) level is observed in more than 30% of patients with stable ischemic heart disease (SIHD). We conducted an investigation of the effects of specific Lp(a) apheresis on the progression of atherosclerosis in SIHD patients with Lp(a) levels greater than 50 mg/dL., Methods: We prospectively enrolled 15 patients diagnosed with SIHD based on symptom-driven coronary angiography findings, with Lp(a) ≥50 mg/dL and a low density lipoprotein cholesterol (LDL-C) ≤2.5 mmol/L, who were on long-term statin therapy. They underwent weekly Lp(a) apheresis using Lp(a) Lipopak ® adsorption columns which contain monospecific sheep polyclonal antibodies against human Lp(a). Fifteen age and gender matched SIHD patients receiving atorvastatin monotherapy served as controls. At baseline and 18 months post-treatment, quantitative coronary angiography, intracoronary ultrasound with virtual histology and carotid ultrasound were performed. Lipid profile, including Lp(a), was measured at the scheduled visits, and before and after each apheresis procedure. Levels of high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinases (MMP)-7 and 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and 2 were determined at baseline and at the end of the study period., Results: Each specific Lp(a) apheresis procedure was carried out with two adsorption columns resulting in an average acute decrease in Lp(a) levels of 75% (from 110 ± 22 to 29 ± 16 mg/dL) without significant changes in other plasma components. Lp(a) reduction over the course of 18 months was associated with a decrease in the mean percent diameter stenosis of 5.05% and an increase in minimal lumen diameter of 14%; the mean total atheroma volume was reduced by 4.60 mm 3 (p < 0.05 for all). There was a decrease in absolute common carotid intima-media thickness in the Lp(a) apheresis group of 0.07 ± 0.15 mm both from baseline and compared with the control group (p = 0.01). Levels of hsCRP were reduced by 40% in patients on Lp(a) apheresis without significant changes in the levels of other biomarkers at the end of the study., Conclusion: Reduction of the atherosclerotic burden in coronary and carotid arteries was observed in patients treated with specific Lp(a) apheresis and statin over 18 months compared with statin therapy alone. These findings support the atherogenic role of Lp(a) and reinforce the need to assess the effects of Lp(a)-lowering on cardiovascular events and mortality. Trial Registration Clinicaltrials.gov (NCT02133807)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This review tells the story of atherosclerosis research in the beginning of the 20th century. It presents the significance of cardiovascular diseases and addresses major questions currently being discussed among lipidologists and the current thinking with respect to low LDL-cholesterol levels and HDL. It provides an overview of the period during which lipid-modifying drugs were introduced and their relevance with respect to cardiovascular outcome data and lists possible reasons why some patients develop new cardiovascular events while being treated with statins. Especially impressive is the history of the appearance of the PCSK9 inhibitors on the market - only 12 years after PCSK9 was detected; a study completed in 2017 provides evidence about the cardiovascular effects of these new drugs. Other new drugs are also mentioned: mipomersen, lomitapide, and Alipogen Tiparvovec. Some promising drugs are still in the pipeline which inhibit the synthesis of apolipoprotein CIII, apolipoprotein(a), and the PCSK9 protein. During the 1970s, specific lipoprotein apheresis began to be used in high-risk patients with homozygous familial hypercholesterolemia, severe hypercholesterolemia and elevated Lipoprotein(a) levels and this review provides evidence of the effectiveness of the extracorporeal therapy with respect to the reduction of cardiovascular events. Particularly in patients with high Lipoprotein(a) levels, apheresis has been proven capable of reducing cardiovascular events by more than 80%. The current situation with regard to lipoprotein apheresis centers and patients in Germany is described herein, and, in conclusion, an estimation of the future of the therapeutic options in lipidology is given., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported. Despite the established inverse correlation between HDL-C levels and cardiovascular risk, several clinical trials with HDL-C-increasing drugs (such as niacin, CETP inhibitors or fibrate) failed to demonstrate that a significant rise in HDL-C levels translate into a cardiovascular benefit. Statins, that are the most used lipid-lowering drugs, can also increase HDL-C levels, although this effect is highly variable among studies and statins; the most recent developed statin, pitavastatin, beside its role as LDL-C-lowering agent, increases HDL-C levels at a significantly higher extent and progressively upon treatment; such increase was observed also when patients where shifted from another statin to pitavastatin. The stratification by baseline HDL-C levels revealed that only pitavastatin significantly increased HDL-C levels in patients with baseline HDL-C ≤45 mg/dl, while no changes were observed in patients with higher baseline HDL-C levels. In the last years the hypothesis that functional properties of HDL may be more relevant than HDL-C levels has risen from several observations. The treatment with pitavastatin not only increased HDL-C levels, but also increased the phospholipid content of HDL, increased the HDL efflux capacity and their anti-oxidant properties. These observations suggest that, besides its high LDL-C-lowering effect, pitavastatin also exhibits a significantly higher ability to increase HDL-C levels and may also positively affect the quality and functionality of HDL particles., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Beyond its function in hemostasis, platelets activation has an important role in cardiovascular diseases (CVD) development. There are different clinical conditions that can mediate abnormal platelet activation and favors pathological thrombosis and CVD. These include Hypertension, diabetes and dyslipidemia, all risks factors from CVD development. Different drugs employed in the handled of these conditions have showed decreases platelet activation and related markers. This effect is in part by improved the base condition; however someone of these drugs can modulate platelet targets. We discuss about underlying mechanisms and the possible implications in the treatment of CVD., (Copyright © 2017. Published by Elsevier Inc.)

Compelling evidence supports the effectiveness of the reduction of total and LDL cholesterol (TC and LDL-C) in primarily preventing cardiovascular events, within the framework of life-long prevention programs mainly consisting in lifestyle changes. Pharmacological treatment should be introduced when lifestyle changes, including use of nutraceuticals, have failed. ESC/EAS guidelines list a number of nutraceutical compounds and functional foods which have been individually studied in randomized, controlled clinical trials (RCTs). To date only a proprietary formulation of three naturally occurring substances with putative complementary lipid-lowering properties - red yeast rice, policosanol and berberine - combined with folic acid, astaxanthin, and coenzyme Q10 (Armolipid Plus ® ) has been extensively investigated in several RCTs, 7 of which were placebo-controlled, 2 were ezetimibe comparators and 4 were "real life" studies comparing diet and Armolipid Plus to diet alone. The trials included mostly patients with mild to moderate dyslipidemia, treated for 6-48 weeks. The trials also included special populations and patients in whom statins were contraindicated or who could not tolerate them. Armolipid Plus has proved to be able to achieve significant reductions in TC (11-21%) and in LDL-C (15-31%) levels, which is equivalent to expectations from low dose statins. In patients intolerant to statins, who do not achieve their therapeutic target with ezetimibe, Armolipid Plus can achieve a further 10% improvement in TC and LDL-C. The safety and tolerability of Armolipid Plus were excellent, thought likely due to the intentional combination of low doses of its active ingredients: low enough not to be associated with untoward effects, but high enough to exert therapeutic effects in combination with other complementary substances. Consequently, in the event of intolerance to statins, Armolipid Plus offers an effective alternative, which is devoid of the safety risks associated with synthetic pharmacological therapy. In conclusion Armolipid Plus, in addition to dietary measures, could be a rational choice for individuals with mild to moderate hyperlipidemia and for all dyslipidemic patients in whom statins are not indicated or who cannot tolerate them., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The relationship between atherosclerosis and HDL is more complex than between LDL and atherosclerosis. Low HDL-cholesterol is associated with atherosclerotic disease not in a causal way but because low HDL-cholesterol reflects an increased concentration of triglyceride-rich lipoproteins. At the same time the functionality of the HDL system plays an important role in atherosclerosis prevention (for example by mediating reverse cholesterol transport). However, these two observations are not directly linked to each other. Therefore therapeutic strategies must either aim at decreasing the concentration of triglyceride-rich lipoproteins (and thereby increase HDL-cholesterol concentration) or at improving HDL function (which may or may not affect HDL-cholesterol concentration). Simply increasing HDL-cholesterol concentration without improving function or decreasing triglyceride-rich lipoproteins will not be beneficial with respect to atherosclerosis prevention., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The MightyMedic (Multidisciplinary International Group for Hemapheresis TherapY and MEtabolic DIsturbances Contrast) Working Group has been founded in 2013. The leading idea was to establish an international network of interdisciplinary nature aimed at working to cross national borders research projects, clinical trials, educational initiatives (meetings, workshops, summer schools) in the field of metabolic diseases, namely hyperlipidemias, and diabetes, preventive cardiology, and atherosclerosis. Therapeutic apheresis, its indications and techniques, is a parallel field of investigation. The first on-line survey of the Group has been completed in the first half of 2014. The survey included # 24 Centers in Italy, Germany, Greece, UK, Sweden, Japan and USA. Relevant data have been collected on current practice in diagnosis, therapy and follow-up of dyslipidemias. 240 subjects with hyperlipidemia and treated with lipoprotein apheresis have been reported in the survey, but a large percentage of patients (35%) who could benefit from this therapeutic option are still treated by conventional drug approach. Genetic molecular diagnosis is performed in only 33% of patients while Lipoprotein(a) (Lp(a)) is included in cardiovascular disease risk assessment in 71% of participating Centers. New detailed investigations and prospective multicenter studies are needed to evaluate changes induced by the impact of updated indications and strategies, as well as new treatment options, targeting standardization of therapeutic and diagnostic approaches., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in the regulation of lipoprotein metabolism, mostly through control of low-density lipoprotein receptor degradation. Depletion of cellular cholesterol causes a compensatory increase in plasma PCSK9 levels, which can diminish the cholesterol-lowering power of statins and may lead to the overproduction of intestinal lipoproteins, mainly thorough the up regulation of microsomal triglyceride transfer protein and the Niemann-Pick C1-like 1 protein, the target of ezetimibe. Thus, ezetimibe therapy may counter this unwanted effect of statins, providing an additional theoretical rationale for combining the effect of ezetimibe on intestinal cholesterol absorption and that of statins on cholesterol synthesis., (© 2015 Elsevier Ireland Ltd. All rights reserved.)

Ezetimibe exerts multiple favorable effects on the lipoprotein profile and reduces some inflammatory markers. Decreasing cholesterol synthesis with statin treatment can cause a compensatory increase in cholesterol absorption that reduces the efficacy of statin therapy, whereas addition of a cholesterol absorption inhibitor can improve outcomes. Recent evidence suggests a beneficial effect on atherosclerosis. In patients with diabetes, the effect of insulin resistance on low-density lipoprotein metabolism combined with the effect of hyperglycemia on cholesterol absorption may further diminish the favorable effects of statins. Further analysis is needed also to determine whether the stronger effects of ezetimibe seen in patients with diabetes are a consequence of an interaction of the drug with specific mechanisms., (© 2015 Elsevier Ireland Ltd. All rights reserved.)

Patients with diabetes represent a population at higher risk for cardiovascular disease. Diabetic dyslipidemia is characterized by the so-called atherogenic lipid triad, consisting of an increase in small dense low density lipoprotein particles and in triglyceride-rich lipoproteins, and a decrease in high-density lipoprotein cholesterol, with an increase in non-HDL cholesterol. Numerous trials have investigated the efficacy of add-on ezetimibe therapy for patients with type 2 diabetes and not controlled by statin therapy. The published data highly suggest that patients with type 2 diabetes may be more likely to benefit from ezetimibe/statin combination therapy. However, evidence specifically addressing hard clinical endpoints and prospective trials addressing differences in response between patients with or without diabetes are still needed., (© 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Waist circumference (WC) is highly associated with metabolic risk factor clusters (RFC) for chronic non-communicable diseases (NCDs). In this study, we evaluated the use of WC measurements to detect hyperglycemia and dyslipidemia in children and adolescents using the WC cutoff points reported in the Bogalusa Heart study and the New Zealand study., Design and Methods: Students (n=1011; aged 6 to 14years) were enrolled in a cross-sectional study. Anthropometric indices, fasting glucose, and lipid profiles were measured. The associations between WC measures and serum parameters were investigated by logistic regression models, and the clinical accuracy of the studied parameters was assessed using receiver operating characteristic (ROC) curve analysis., Results: The prevalence of increased WC was 30.2% using the New Zealand cutoff points and 13.7% using the Bogalusa cutoff values. In general, children with increased WC exhibited higher concentrations of total cholesterol, triglycerides, LDL-cholesterol, and non-HDL-cholesterol and lower levels of HDL-cholesterol. The areas under the ROC curves (AUC) of the WC measurements were 0.770 (95% CI: 0.744-0.797) and 0.600 (95% CI: 0.569-0.631) using, respectively, the New Zealand and Bogalusa cutoff points for WC, indicating the prediction of simultaneous hyperglycemia, increased levels of non-HDL-cholesterol, and reduced HDL-cholesterol for students with increased WC. There was a significant difference between AUC values (P=0.001). Furthermore, the sensitivity of using WC for detecting RFC in students was 2.0 to 2.5-fold higher with the New Zealand study cutoff values for WC than with those from the Bogalusa study. Logistic regression analysis revealed that increased WC was associated with simultaneous hyperglycemia and dyslipidemia after controlling for differences in sex and age (P<0.01 for all)., Conclusions: Children and adolescents exhibited a high prevalence of increased WC associated with other RFCs for NCDs. Increased WC may be used to screen and identify students with elevated clusters of metabolic risk factors for NCDs., (© 2013.)

Objectives: There is evidence of iron deficiency (ID) in patients treated with lipoprotein apheresis. Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous (i.v.) iron formulations., Methods: Inclusion criteria were defined as a) serum ferritin < 300 μg/l and transferrin saturation < 20%, b) ferritin < 100 μg/l. Both iron deficient alone and ID anemic (IDA) patients were included. Other causes for anemia were ruled out by thorough history-taking and examination/blood tests. Patients were treated with six different lipoprotein apheresis methods: DALI, Liposorber D, TheraSorb LDL, HELP, MONET and Lipidfiltration. 50 patients were randomized to either ferric carboxymaltose (FCM, 500-1000 mg as single shot infusion over 20 min) or ferric gluconate (FG, 62.5 mg once weekly)., Results: 50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency. Both i.v. iron formulations studied were equally safe (no serious adverse events (SAEs), 6 patients/group showed adverse events (AEs)) and both effective (clinically and with respect to laboratory data) in lipoprotein apheresis patients, however FCM led to a more rapid and steeper rise of iron parameters., Conclusions: ID and IDA are common findings in lipoprotein apheresis patients. The pathogenesis remains yet poorly understood and is probably multifactorial. Differential diagnosis of ID/IDA is as essential as differential therapy. Handled with care, older i.v. iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients. However, novel formulations like FCM can be administered rapidly at higher doses due to high complex stability, allowing faster filling of iron stores. Newer laboratory parameters (Reticulocyte-He, low/medium/high fluorescence reticulocytes (LFR/MFR/HFR)) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Objective: To determine whether previously demonstrated beneficial short-term effects on cardiovascular function in regular users of lipoprotein apheresis would be sustainable over time., Methods: Regular users of lipoprotein apheresis (n = 17) were studied between February 2009 and July 2010. All patients were examined for endothelial and autonomic function at baseline and at one year of regular treatment. Microvascular function was determined by flicker-induced vasodilation of retinal vessels using the Dynamic Vessel Analyzer. Autonomic regulation of blood pressure and heart rate upon cardiovascular perturbation by deep breathing at 0.1 Hz and orthostatic challenge was evaluated by trigonometric regressive spectral analysis., Results: The acute improvement of cardiovagal function and venular endothelial function seen after a single lipoprotein apheresis was not evident at one year of regular treatment. However, baroreflex sensitivity showed an improved recovery after orthostatic challenge as compared to baseline measurements. Initially compromised autonomic and microvascular function had not further deteriorated at one year of regular lipoprotein apheresis treatment., Conclusion: In patients with advanced atherosclerotic disease regular lipoprotein apheresis treatment maintains residual cardiovascular functioning over time., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Sarcoidosis is an inflammatory disease characterised by enhanced production of reactive oxygen species and alterations in the circulating lipid profile. Both attributes are thought to play a role in its pathogenesis. However, current knowledge regarding the significance of blood oxidative stress/anti-oxidant defence as well as alterations in lipid status parameters in sarcoidosis is scarce. The aim of our study was to assess these parameters and their inter-relationships, as well as their potential for patient-control discrimination., Design and Methods: Oxidative stress status and anti-oxidant defence parameters were determined in serum and erythrocytes and lipid status parameters were assessed in the serum of 213 treated sarcoidosis patients and 90 controls., Results: Malondialdehyde, superoxide anion, total oxidant status, prooxidant-antioxidant balance and triglycerides were significantly higher whereas total anti-oxidant status, superoxide dismutase activity and HDL-cholesterol were significantly lower in sarcoidosis patients compared with controls. Total sulfhydryl group content was higher in patients compared with controls. Serum and erythrocyte malondialdehyde exhibited the strongest ability to predict disease presence. Elevated oxidative stress was characterised by higher clinical accuracy compared with lipid status abnormality. Some oxidative stress and lipid status markers were significantly associated in sarcoidosis., Conclusions: Sarcoidosis is characterised by increased oxidative stress, diminished overall anti-oxidative protection and alterations in the circulating lipid profile. Both oxidative stress and lipid status parameters demonstrated the potential to discriminate sarcoidosis from controls which was particularly evident from the point of view of oxidative stress status parameters. Association between these parameters may indicate an increased risk for atherosclerosis development., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Blood pressure and cholesterol screening among women of reproductive age are important for early disease detection and intervention, and because hypertension and dyslipidemia are associated with adverse pregnancy outcomes., Purpose: The objective of this study was to examine associations of sociodemographic characteristics, cardiovascular disease risk factors, and healthcare access indicators with blood pressure and cholesterol screening among women of reproductive age., Methods: In 2011, prevalence estimates for self-reported blood pressure screening within 2 years and cholesterol screening within 5 years and AORs for screenings were calculated for 4837 women aged 20-44 years, using weighted 2008 National Health Interview Survey data., Results: Overall, recommended blood pressure and cholesterol screening was received by 89.6% and 63.3% women, respectively. Those who were underinsured or uninsured had the lowest screening percentage at 76.6% for blood pressure (95% CI=73.4, 79.6) and 47.6% for cholesterol (95% CI=43.8, 51.5) screening. Suboptimal cholesterol screening prevalence was also found for women who smoke (54.5%, 95% CI=50.8, 58.2); obese women (69.8%, 95% CI=66.3, 73.0); and those with cardiovascular disease (70.3%, 95% CI=63.7, 76.1), prediabetes (73.3%, 95% CI= 64.1, 80.8), or hypertension (81.4%, 95% CI=76.6, 85.4)., Conclusions: Most women received blood pressure screening, but many did not receive cholesterol screening. Universal healthcare access may improve screening prevalence., (Published by Elsevier Inc.)

Background: Anthropometric indices have been associated with dyslipidemia., Objective: To compare the abilities of BMI, waist circumference (WC) and WC/height to identify children's dyslipidemia., Methods: Students 1261 (639 male) age 9.5±2.1 years. were examined for anthropometry and lipid levels. Triglycerides ≥1.69 mmol/L and high-density lipoprotein cholesterol (HDL-C) <0.91 mmol/L were considered abnormal per American Heart Association., Results: The prevalence of abnormal triglycerides was 4.1% and HDL-C 8.1%. The areas under the receiver operator curves (ROC) were: BMI=0.87, WC=0.83, and WC/height=0.84 in predicting both low HDL-C and high triglycerides. Multiple regression analyses showed that the odds ratios (OR) were highest for WC [6.5], followed by WC/height [5.4], and BMI [4.9], for dyslipidemia., Conclusions: The results suggest that WC, WC/height, and BMI similarly predicted dyslipidemia, using ROC analyses. However, regression analyses showed that WC followed by WC/height was most predictive of dyslipidemia., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)