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A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n=7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n=5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n=7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C. [ABSTRACT FROM PUBLISHER]

Aim Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of familial hypercholesterolemia (FH) and familial combined hypercholesterolemia (FCH), resistant/intolerant to lipid lowering drugs, and hyperlipoproteinemia(a) for which drugs are not available. To assess the effect of LA on the incidence of adverse cardiac or vascular events (ACVE) at the time period of pre-initiation of apheresis and during the LA treatment. Methods We collected data of 30 patients (mean age 62 ± 8 years, males 73%), with FH, or FCH and cardiovascular disease on maximally tolerated lipid lowering therapy and LA treatment (median 5 years, interquartile range 3–8 years). Associated hyperlipoproteinemia(a) was present in 16/30 subjects. The LA treatment was performed biweekly as clinically indicated by dextran-sulfate or heparin-induced LDL precipitation apheresis. The ACVE incidence, before and after treatment, was evaluated by statistical analyses. Results The ACVE incidence occurred before and after the LA treatment inception, were 86 and 15 events respectively. Notably, 6/15 of ACVE were secondary to stent restenosis and 7/15 follow-up events occurred during the first 5 years. The AVCE rates/year were 0.58 and 0.13 respectively ( p < 0.001). Conclusions Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with FH and FCH and atherosclerotic disease at maximally tolerated lipid lowering therapy. [ABSTRACT FROM AUTHOR]

The article describes the case of a 60-year-old man with heterozygous familial hypercholesterolemia who experienced anaphylactic-like reaction between low-density lipoprotein (LDL) apheresis procedure and intake of crafted or home-made white wine. Topics discussed include the patient's medical history, diagnostic examinations performed on the patient, and side effects associated with LDL apheresis. The study shows how a careful medical history can help understand reactions during LDL apheresis.

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of low-density-lipoprotein cholesterol (LDL-C), a major risk factor for cardiovascular (CV) disease. Since the hormone leptin has been suggested as having a role in CV risk regulation, possibly by modulating LDL receptor expression through the PCSK9 pathway, nutritional status may represent a potential regulator. Thus, evaluation of PCSK9 levels in human eating disorders appears to be of interest. In this report, we evaluate the lipoprotein profile, PCSK9, and leptin levels in subjects affected by anorexia nervosa (AN) to improve our understanding of the metabolic alterations in this disease., Methods and Results: We designed a case-control observational study, enrolling 20 anorexic adolescent females and 20 adolescent females without AN as the control group, age- and sex-matched. Subjects affected by AN showed lower BMI, total cholesterol, and LDL-C in comparison to the control group, with lipoprotein levels in the normal range. Furthermore, adolescent girls with AN show significantly higher PCSK9 (+24%, p < 0.005) and lower leptin levels (-43%, p < 0.01), compared to the control group., Conclusions: The findings of increased levels of PCSK9 and reduced leptin levels among AN subjects warrant further research in order to unravel the role of the liver and adipose tissue in the management of PCSK9/LDL metabolism in adolescents affected by AN., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Background: Despite advance in pharmacotherapy of lipid disorders, lipoprotein apheresis (LA) plays a leading role in the management of severe hypercholesterolemia and in atherosclerosis prevention., Methods: Aim of this study was to retrospectively evaluate Charlson Comorbidity Index (CCI), presence of major comorbidity, and/or concomitant polypharmacy (definite as 5+ drugs daily) in patients with inherited dyslipidemias on chronic LA., Results: Since 1994, we performed more than 500 LA treatment/year and followed a total of 83 patients (age 56 [47-65] years, male 75%). In subjects with more than 5 years of LA treatment (38 patients, age 54 [45-62] years, male 66%), at the end of the observation time (9 [7-16] years), patients had higher CCI, polypharmacy, anemia, heart failure, peptic ulcer disease, and benign prostatic hyperplasia., Discussion: Even in the era of new lipid-lowering therapies, the LA treatment established itself as a safe and lifesaving intervention. Patients on chronic LA require a multidisciplinary approach to address their comorbidity and the apheresis unit's medical staff (doctors and nurses) play a pivotal role creating a bridge toward the general practitioner and other specialists for overcoming clinical issues., (© 2023 Wiley Periodicals LLC.)

"The lower, the better" is the recommended approach in the management of high LDL cholesterol. Unfortunately, this does not always achieve as in the case of a 69-year-old woman referred to our Institute for her lipid profile (LDL cholesterol 412mg/dl), bilateral xanthelasma and cutaneous xanthomas. With a maximized and personalized lipid-lowering therapies (rosuvastatin, ezetimibe, PCSK9i and lipoprotein apheresis), after only six months, the patient showed an impressive regression in her cutaneous xanthomas., (Copyright © 2023 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a breakthrough in the treatment of hypercholesterolemia. The aim of this study was to perform a multicentre prospective analysis on the effects of PCSK9i since their distribution in Italy., Methods: During the study period (July 2017 to February 2022) 246 patients (mean age 61 ± 11 years, male 73%) who were evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI (Costo Efficacia Regione Toscana Inibitori PCSK9) study. Lipid value, adverse events (AEs), major cardiovascular events (MACEs) and intima-media thickness were analysed., Results: PCSK9i therapy allowed a significant improvement in patients' lipid profile [total cholesterol -35%, P < 0.001; triglycerides -9%, P < 0.05; low-density lipoprotein (LDL) cholesterol -51%, P < 0.001; Lp(a) levels -4%, P < 0.05], maintained during the follow-up. No significant variations in intima-media thickness were observed. In the subgroup of patients with more than 1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in MACEs compared with the year before recruitment; a progressive increase in MACEs during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence of hypertension, smoking habit and peripheral vascular disease. During the follow-up, we recorded AEs in 31% of patients, which mainly resulted in reduction/discontinuation of lipid-lowering therapy for 50 patients or in discontinuation/shift of PCSK9i (respectively 8 and 6 cases)., Conclusion: Our data agree with the large evidence on the effectiveness/tolerability of PCSK9i therapy; however, although PCSK9i represents a good cholesterol-lowering therapeutic option, our study shows a progressive increase in MACEs during the late follow-up that deserve further research., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: In view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided., Data Synthesis: Lp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment., Conclusions: Awaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended., Competing Interests: Declaration of competing interest APM received personal fees from AstraZeneca, Bayer, Novartis for the participation in study committees, outside the present work. M Arca has received research grant support and lecturing fees from Alfasigma, Amarin, Amgen, Amryt, IONIS/Akcea Therapeutics, Daiichi Sankyo, Novartis, Pfizer, Regeneron and Sanofi, SOBI. ALC in the last three years has received honoraria, lecture fees or research grants from Aegerion, Akcea Therapeutics, Amarin, Amgen, Amryt Pharma, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceutical, Medscape Education, Menarini, Merck, Mylan, Novartis, PeerVoice, Pfizer, Recordati, Regeneron, Sanofi, The Corpus, Viatris. GC, MGZ, AB, CMB, CB, FC, DN, MP, AAR, TS, FS, M Averna declare no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)