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The pregnancy of a patient with homozygous familial hypercholesterolemia (HoFH) represents a challenge in the clinical setting due to the high cardiovascular risk of the mother and maternal-fetal morbidity. The lipid lowering drugs are generally contraindicated and lipoprotein apheresis (LA) is the only accepted treatment in HoFH pregnant woman. Liposorber D, an LA technique on whole blood, has good efficacy, safety, and short operative time. We present a 31-year-old Caucasian pregnant woman with HoFH clinical phenotype on lipid-lowering treatment with Lomitapide and Evolocumab, discontinued during pregnancy. In multidisciplinary team it was decided to submit the patient to LA throughout the pregnancy. Liposorber D sessions (a whole blood technique) were performed on a strict weekly frequency. The treatment resulted in massive decrease of total cholesterol (TC) and LDL cholesterol (LDL-c), with no significant side effects. The pregnancy presented a normal course and a cesarean section was performed on clinical indications unrelated to the use of LA. She gave birth to a healthy male child at 37 weeks of gestation. LA is considered the only effective, safe and accepted therapy during HoFH pregnancy. This is the first reported case of successful pregnancy treated with Liposorber D, a whole blood LA technique. LA with dextran sulfate has been an effective and safe choice for the mother and fetus. Furthermore it was reasonably well tolerated from the beginning of pregnancy management to its conclusion., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (Published by Elsevier Ltd.)

Background: Persistent chylomicronemia is a genetic recessive disorder that is classically caused by familial chylomicronemia syndrome (FCS), but it also has multifactorial causes. The disorder is associated with the risk of recurrent acute pancreatitis. Plozasiran is a small interfering RNA that reduces hepatic production of apolipoprotein C-III and circulating triglycerides., Methods: In a phase 3 trial, we randomly assigned 75 patients with persistent chylomicronemia (with or without a genetic diagnosis) to receive subcutaneous plozasiran (25 mg or 50 mg) or placebo every 3 months for 12 months. The primary end point was the median percent change from baseline in the fasting triglyceride level at 10 months. Key secondary end points were the percent change in the fasting triglyceride level from baseline to the mean of values at 10 months and 12 months, changes in the fasting apolipoprotein C-III level from baseline to 10 months and 12 months, and the incidence of acute pancreatitis., Results: At baseline, the median triglyceride level was 2044 mg per deciliter. At 10 months, the median change from baseline in the fasting triglyceride level (the primary end point) was -80% in the 25-mg plozasiran group, -78% in the 50-mg plozasiran group, and -17% in the placebo group (P<0.001). The key secondary end points showed better results in the plozasiran groups than in the placebo group, including the incidence of acute pancreatitis (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = 0.03). The risk of adverse events was similar across groups; the most common adverse events were abdominal pain, nasopharyngitis, headache, and nausea. Severe and serious adverse events were less common with plozasiran than with placebo. Hyperglycemia with plozasiran occurred in some patients with prediabetes or diabetes at baseline., Conclusions: Patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and a lower incidence of pancreatitis than those who received placebo. (Funded by Arrowhead Pharmaceuticals; PALISADE ClinicalTrials.gov number, NCT05089084.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Aims: Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the two main causes of severe hypertriglyceridemia (sHTG). FCS is a rare autosomal recessive form of sHTG, whereas MCS is mainly polygenic in nature with both common and rare variants accumulating and leading to sHTG. However, 30 to 50% of MCS patients have no identified genetic cause of sHTG. DNA methylation (DNAm) is a non-traditional heritable factor known to be associated with triglyceride (TG) levels. The aim of this study is to determine if DNAm level at three candidate genes for hypertriglyceridemia (ABCG1, CPT1A and SREBF1) could contribute to sHTG in MCS patients., Methods: A total of 114 MCS and 20 FCS patients were included in this retrospective study. DNAm levels were measured at ABCG1 (cg06500161), CPT1A (cg00574958), and SREBF1 (cg11024682) gene loci using pyrosequencing of bisulfite-treated DNA., Results: DNAm levels at ABCG1, CPT1A and SREBF1 were significantly associated with TG levels or minimal TG levels in MCS patients. Prevalence of patients with at least 2 loci with DNAm levels into the top tertile of DNAm associated with hypertriglyceridemia was significantly higher in MCS patients with genetically undefined sHTG compared to MCS patients with polygenic sHTG and FCS patients (57 % vs. 24 % vs. 0 %, respectively; p < 0.0001)., Conclusion: This study suggests for the first time that DNAm could contribute to sHTG in MCS patients. It suggests that further studies of epivariations may contribute to better understand the clinical heterogeneity seen in MCS patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AB received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals, Inc., ISIS Pharmaceuticals, The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. SBreceived research grants from Akcea, Fondation Leducq, and Fondation Yvan Morin. She has participated in clinical research protocols from Akcea, Amgen, Ionis Pharmaceuticals, Inc., The Medicines Company, Novartis, Pfizer, and Sanofi. She has served on advisory boards for Akcea, Amgen, HLS Therapeutics, Novartis, Novo Nordisk, and Sanofi, and received honoraria for symposia from Akcea, Amgen, Novo Nordisk, and Sanofi. SPG has served on advisory boards for Ultragenyx. MP, LB, LG, VD and AT have nothing to declare., (Copyright © 2025 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)