Lipoprotein apheresis: an established therapeutic modality for homozygous familial hypercholesterolemia patients refractory to PCSK9 inhibitors: a case report and literature review.

Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12-14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1-2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

The German Lipoprotein Apheresis Registry-Summary of the eleventh annual report.

BACKGROUND: In 2012, the German Lipoprotein Apheresis Registry (GLAR) was launched. Real-world data on lipoprotein apheresis (LA) treatment are now available for a time period of 11 years. All patients received the maximally tolerated lipid-lowering therapy, which included statins, ezetimibe, bempedoic acid, and either proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies or antisense therapy. METHODS AND RESULTS: During the time period from 2012 to 2022, 92 German apheresis centers collected retrospective and prospective observational data of a total of 2,301 patients undergoing regular lipoprotein apheresis (LA) treatment of hypercholesterolemia or/and Lp(a)-hyperlipoproteinemia suffering from progressive atherosclerotic cardiovascular disease (ASCVD), with complete data sets of 1.125 patients, who were the subject of this analysis. More than 61,500 LA sessions are documented in the database. In 2022, all patients treated with LA demonstrated a significant immediate median reduction rate of LDL-C (68.8 %) and Lp(a) (72.9 %). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to eleven years on LA treatment (y+1 to y+11). During the first two years of LA treatment (y+1 and y+2), a MACE reduction of 73 % was observed and continued to be low during y+3 to y+11, when all LA patients were analyzed. LA patients with only increased Lp(a) levels (Lp(a) ≥ 60 mg/dl (≥120 nmol/l) and an LDL-C < 100 mg/dl (<2.6 mmol/l)) had a higher MACE reduction (85 %; n = 443) in the first two years of LA treatment compared to LA patients with only increased LDL-C-levels (LDL-C ≥ 100 mg/dl (≥2.6 mmol/l); Lp(a) < 60 mg/dl (<120 nmol/l)) (53 %; n = 171). Adverse events of LA remained low (about 5 %) over the eleven years and mainly represented puncture problems (1.0 %). No side effects resulted in termination of LA therapy. CONCLUSIONS: The current analysis of GLAR data indicates that regular LA leads to very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid-lowering medication, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. Additionally, LA was safe with a low rate of adverse effects over an 11-year period. The number of enrolled patients and the duration of observation establish GLAR as the largest LA registry worldwide.

Real-world experience of long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia treated and not treating with lipoprotein apheresis.

BACKGROUND: Evinacumab is an inhibitor of angiopoietin-like 3 protein (ANGPTL3) that offers a new approach for correcting high low-density lipoprotein-cholesterol (LDL-C) and may reduce the need or frequency for lipoprotein apheresis (LA) in patients with homozygous familial hypercholesterolemia (HoFH). OBJECTIVE: We aimed to investigate the long-term efficacy and safety of evinacumab in patients with HoFH aged between 14 and 63 years on and off LA in real-world clinical practice. METHODS: Evinacumab was administrated intravenously (15 mg /kg Q4W) for the first 24 months in 7 patients with genetically confirmed HoFH, receiving best standard of lipid-lowering treatment and LA, followed by a subsequent compassionate extension period of approximately 12-month treatment with evinacumab without LA. Patient experience of evinacumab and health-related EuroQol (EQ-5D-3L) quality of life questionnaire were also assessed. RESULTS: Compared with baseline, evinacumab resulted in a sustained reduction in plasma LDL-C concentration of -43.4 % and -54.2 % at 30 and 36 months, respectively. All 7 HoFH patients achieved an LDL-C reduction >30 % with 3 patients having on-treatment LDL-C level < 2.5 mmol/L (96 mg/dL). Evinacumab was well-tolerated, with no major adverse reported or significant changes in liver enzyme concentrations. All FH patients agreed that evinacumab was acceptable and less physically demanding than LA. The mean utility score and EQ- visual analogue scale scores were 0.966 and 78.6, respectively, which are comparable to the Italian general population. CONCLUSIONS: Our findings suggest that evinacumab is a safe and effective treatment for high LDL-cholesterol that is acceptable to HoFH patients receiving and not receiving LA.

The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.

Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as a major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, with statins emerging as the cornerstone treatment. These interventions play a crucial role in both primary and secondary prevention by effectively reducing cardiovascular risk through lipid profile enhancements. Beyond their primary lipid-lowering effects, extensive research indicates that these therapies exhibit pleiotropic actions, offering additional health benefits. These include anti-inflammatory properties, improvements in vascular health and glucose metabolism, and potential implications in cancer management. While statins and ezetimibe have been extensively studied, newer lipid-lowering agents also demonstrate similar pleiotropic effects, even in the absence of direct cardiovascular benefits. This narrative review explores the diverse pleiotropic properties of lipid-modifying therapies, emphasizing their non-lipid effects that contribute to reducing cardiovascular burden and exploring emerging benefits for non-cardiovascular conditions. Mechanistic insights into these actions are discussed alongside their potential therapeutic implications.

Women and lipoprotein apheresis: another side of gender medicine.

AIM: In heterozygous Familial Hypercholesterolemia (FH) woman atherosclerotic cardiovascular disease occurs 20-years earlier respect woman without FH while homozygous FH women may suffer from atherosclerotic cardiovascular disease even in childhood. Lipoprotein apheresis, a therapeutic "last chance saloon", is a well-tolerated procedure that markedly lowers LDL-cholesterol and Lp(a) levels in patients who do not achieve acceptable levels with maximal lifestyle and drug therapy. METHODS AND RESULTS: The experience of LA treatment in 3 female homozygous FH patients was described. Moreover, an explore analysis on pre and post-LA hormonal levels was performed in 8 HeFH women showing a significant improvement in the atherogenic lipid profile (total cholesterol -56%, LDL cholesterol -71%, triglycerides -72%, Apo B lipoprotein -69%, Lp(a) -59%;) and a reduction of FSH and LH values (FSH - 28%, LH -31%). CONCLUSIONS: Women with FH experience specific barriers to care, including underrepresentation in research, significant underestimation of risk, and discontinuation of therapy during pregnancy. Therefore, in this study, we investigated the possible effects of LA treatment on plasma FSH and LH levels.

Long-term lipoprotein apheresis reduces cardiovascular events in high-risk patients with isolated lipoprotein(a) elevation.

BACKGROUND: Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a). METHODS: This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA. RESULTS: Mean LA treatment duration was 7.1 years (min-max: 1-19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3 %, p < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9 %, p < 0.0001). Prior LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, p = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, p = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L. CONCLUSION: In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.

Effective exosomes reduction in hypercholesterinemic patients suffering from cardiovascular diseases by lipoprotein apheresis: Exosomes apheresis.

INTRODUCTION: Extracellular vesicles (EVs) have been identified as playing a role in atherosclerosis. METHODS: A group of 37 hypercholesterolemic patients with atherosclerotic cardiovascular diseases (ASCVD) and 9 patients requiring hemodialysis (HD) were selected for the study. RESULTS: EVs were comparably reduced by various LA methods (Thermo: 87.66% ± 3.64, DALI: 87.96% ± 4.81, H.E.L.P.: 83.38% ± 11.98; represented as SEM). However, LDL-C (66%; 55%; 75%) and Lp(a) (72%; 67%; 79%) were less effectively reduced by DALI. There was no significant difference in the reduction of EVs when comparing different techniques, such as hemoperfusion (DALI; n = 13), a precipitation (H.E.L.P.; n = 5), and a double filtration procedure (Thermofiltration; n = 19). Additionally, no effect of hemodialysis on EVs reduction was found. CONCLUSIONS: The study suggests that EVs can be effectively removed by various LA procedures, and this effect appears to be independent of the specific LA procedure used, as compared to hemodialysis.

Comparison of double-filtration plasmapheresis (DFPP) versus heparin-mediated extracorporeal LDL-precipitation (HELP)-apheresis in early-onset preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a major cause of maternal and fetal mortality, and preterm birth. Previous studies indicate that lipid-apheresis may prolong pregnancy, namely heparin-mediated extracorporeal LDL-precipitation (HELP)- and dextran sulfate cellulose (DSC)-apheresis. We now report on double membrane plasmapheresis (DFPP) in early-onset preeclampsia (eoPE). STUDY DESIGN: Open pilot study assessing the prolongation of pregnancy in PE by lipoprotein-apheresis (DRKS00004527). Two women with eoPE were treated by DFPP and compared to a historical cohort of 6 patients with eoPE treated by HELP-apheresis (NCT01967355). MAIN OUTCOME MEASURES: Clinical outcome of mothers and babies and prolongation of pregnancies (time of admission to birth). RESULTS: Patient 1 (33y; 22 + 5/7GW) received 4 DFPP. Delivery day 19; birthweight 270 g; weight at discharge 2134 g on day 132. Patient 2 (35y; 21 + 4/7GW) received 2 DFPP. Delivery day 19; birthweight 465 g; weight at discharge 2540 g on day 104. DFPP was well tolerated by both patients. CONCLUSIONS: DFPP proved to be save and pregnancies remained stable as long as 19 days. Although babies were born very preterm both babies could finally be dismissed from hospital. No relevant clinical differences between DFPP and HELP-apheresis could be observed. Therefore, DFPP may extend the range of available apheresis techniques to prolong pregnancies in early-onset preeclampsia. However, further studies are necessary to gain more information. REGISTER: (DRKS00004527).

Lipoprotein Apheresis Alleviates Treatment-Resistant Peripheral Artery Disease Despite the Normal Range of Atherogenic Lipoproteins: The LETS-PAD Study.

AIM: Peripheral artery disease (PAD) severely impairs patient prognosis and quality of life (QOL). Although lipoprotein apheresis (LA) has been applied to patients with PAD and elevated serum atherogenic lipoproteins, we hypothesized that LA can be effective for treating PAD even in patients with controlled serum lipoproteins through pleiotropic anti-atherosclerotic effects beyond lipoprotein removal. This study aimed to evaluate the efficacy of LA in patients with treatment-resistant PAD and controlled serum lipoproteins focusing on QOL. METHODS: In a single-arm prospective study, 30 patients with refractory PAD who had controlled serum lipoproteins underwent sequential LA sessions using dextran sulfate adsorption columns, aiming to complete 10 sessions. The ankle-brachial pressure index (ABI) and vascular QOL (VascuQOL) score were evaluated as the primary outcomes. Secondary outcomes included reactive hyperemia index (RHI) and biological antioxidant potential (BAP) as an endothelial function test and serum antioxidative-capacity evaluation, respectively. RESULTS: ABI significantly increased after LA sessions (pre-treatment 0.60±0.09 vs. post-treatment 0.65±0.13, p=0.023). Total VascuQOL score (3.7±1.1 vs 4.6±1.1, p＜0.001) and RHI (1.70±0.74 vs 2.34±1.76, p=0.023) significantly improved after the LA sessions. BAP tended to increase after the LA sessions, and the change reached statistical significance 3 months after treatment. CONCLUSION: ABI and QOL improved after a series of LA sessions in conventional treatment-resistant PAD patients with controlled serum lipoprotein levels. Increased antioxidative capacity and ameliorated endothelial function were observed after the LA treatment.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Novel Therapeutic Approaches for the Management of Elevated Lipoprotein(a): From Traditional Agents to Future Treatment Options.

Cardiovascular disease is the leading cause of mortality worldwide. Despite the availability of effective low-density lipoprotein cholesterol (LDL-C) lowering agents, an increased cardiovascular risk is still observed in individuals with therapeutic LDL-C levels. One of these cardiovascular risk factors is elevated plasma lipoprotein(a) (Lp(a)) concentration, which maintains chronic inflammation through the increased presence of oxidized phospholipids on its surface. In addition, due to its 90 percent homology with the fibrinolytic proenzyme plasminogen, Lp(a) exhibits atherothrombotic effects. These may also contribute to the increased cardiovascular risk in individuals with high Lp(a) levels that previous epidemiological studies have shown to exist independently of LDL-C and other lipid parameters. In this review, the authors overview the novel therapeutic options to achieve effective Lp(a) lowering treatment, which may help to define tailored personalized medicine and reduce the residual cardiovascular risk in high-risk patients. Agents that increase LDL receptor expression, including statins, proprotein convertase subtilisin kexin type 9 inhibitors, and LDL production inhibitors, are also discussed. Other treatment options, e.g., cholesterolester transfer protein inhibitors, nicotinic acid derivatives, thyroid hormone mimetics, lipoprotein apheresis, as well as apolipoprotein(a) reducing antisense oligonucleotides and small interfering RNAs, are also evaluated.

Delipid extracorporeal lipoprotein filter from plasma system: a new intensive lipid lowering therapy for patients with acute ischemic stroke.

Objectives: To investigate the safety and efficacy of the delipid extracorporeal lipoprotein filter from plasma (DELP) system, a new low-density lipoprotein cholesterol (LDL-C) adsorption system, in acute ischemic stroke (AIS) patients. Patients and methods: In the present study, a total of 180 AIS patients were enrolled during March 2019 to February 2021. They were divided into DELP group (n1 = 90) and the control group (n2 = 90). The treatment protocol and vascular access of DELP treatment was established and evaluated. For the DELP group, clinical data and laboratory results including plasma lipid and safety parameters before and after the apheresis were collected and analyzed. For all participants, neurological scores were assessed and recorded. Results: For the DELP group, 90 patients including 70 males and 20 females were included. The mean LDL-C was significantly decreased from 3.15 ± 0.80 mmol/L to 2.18 ± 0.63 mmol/L (30.79%, p < 0.001) during a single DELP treatment, and decreased from 3.42 ± 0.87 mmol/L to 1.87 ± 0.48 mmol/L (45.32%, p < 0.001) after two DELP treatments. No clinically relevant changes were observed in hematologic safety parameters and blood pressure levels except for hematocrit and total protein throughout the whole period of DELP treatment. The DELP group showed improvement relative to the control group in National Institute of Health stroke scale scores (NIHSS) on the 14th and 90th day after stroke. Moreover, the DELP group had a significantly higher ratio of mRS 0 to 1 on the 90th day after stroke. Conclusion: The new LDL-C adsorption system, the DELP system, may provide a new option for intensive lipid lowering therapy in AIS patients in view of its safety, efficacy, and operation feasibility.

Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study.

AIM: We aimed to describe clinical and genetic characteristics, lipid-lowering treatment and atherosclerotic cardiovascular disease (ASCVD) outcomes over a long-term follow-up in homozygous familial hypercholesterolemia (HoFH). METHODS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is a long-term study in molecularly diagnosed FH. Data analyzed in HoFH were prospectively obtained from 2004 until 2022. ASCVD events, lipid profile and lipid-lowering treatment were determined. RESULTS: Thirty-nine HoFH patients were analyzed. The mean age was 42 ± 20 years and nineteen (49%) were women. Median follow-up was 11 years (IQR 6,18). Median age at genetic diagnosis was 24 years (IQR 8,42). At enrolment, 33% had ASCVD and 18% had aortic valve disease. Patients with new ASCVD events and aortic valve disease at follow-up were six (15%), and one (3%), respectively. Median untreated LDL-C levels were 555 mg/dL (IQ 413,800), and median LDL-C levels at last follow-up was 122 mg/dL (IQR 91,172). Most patients (92%) were on high intensity statins and ezetimibe, 28% with PCSK9i, 26% with lomitapide, and 23% with lipoprotein-apheresis. Fourteen patients (36%) attained an LDL-C level below 100 mg/dL, and 10% attained an LDL-C below 70 mg/dL in secondary prevention. Patients with null/null variants were youngers, had higher untreated LDL-C and had the first ASCVD event earlier. Free-event survival is longer in patients with defective variant compared with those patients with at least one null variant (p=0.02). CONCLUSIONS: HoFH is a severe life threating disease with a high genetic and phenotypic variability. The improvement in lipid-lowering treatment and LDL-C levels have contributed to reduce ASCVD events.

Changing from lipoprotein apheresis to evolocumab treatment lowers circulating levels of arachidonic acid and oxylipins.

Background and aims: Previous studies have shown that lipoprotein apheresis can modify the plasma lipidome and pro-inflammatory and pro-thrombotic lipid mediators. This has not been examined for treatment with protein convertase subtilisin/kexin type 9 inhibitors such as evolocumab, which are increasingly used instead of lipoprotein apheresis in treatment-resistant familial hypercholesterolemia. The aim of this study was to compare the effects of evolocumab treatment and lipoprotein apheresis on the fatty acid profile and on formation of lipid mediators in blood samples. Methods: We analyzed blood samples from 37 patients receiving either lipoprotein apheresis or evolocumab treatment as part of a previous study. Patients were stratified according to receiving lipoprotein apheresis (n = 19) and evolocumab treatment (n = 18). Serum fatty acid analysis was performed using gas chromatography flame ionization detection and plasma oxylipin analysis was done using liquid chromatography tandem mass spectrometry. Results: Changing from lipoprotein apheresis to evolocumab treatment led to lower levels of omega-6 polyunsaturated fatty acid (n-6 PUFA) including arachidonic acid, dihomo-γ-linolenic acid and linoleic acid. Moreover, several n-6 PUFA-derived oxylipins were reduced after evolocumab treatment. Conclusions: Given that arachidonic acid, either directly or as a precursor, is associated with the development of inflammation and atherosclerosis, evolocumab-mediated reductions of arachidonic acid and its metabolites might have an additional beneficial effect to lower cardiovascular risk.

Minimal impact of low-density lipoprotein apheresis on vancomycin serum concentration: A case report.

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics.

"Eve is not Adam" - differences in efficacy, safety and clinical outcomes with lipoprotein apheresis between sexes.

PURPOSE: In Familial Hypercholesterolemia (FH), female atherosclerotic cardiovascular disease occurs 20 years earlier than in women without FH. The aim of this study is to describe the differences in lipoprotein apheresis (LA), a last therapeutic option, in terms of efficacy, safety and clinical outcomes between the two sexes. MATERIALS AND METHODS: Sex related differences were analysed in 31 subjects in on LA treatment with FH and not achieving LDL-cholesterol and/or Lp(a) target values on maximum lipid-lowering therapies. Moreover, sex related differences in time to major cardiovascular event (MACE) was investigated in 68 subjects, with at least one year of follow-up. RESULTS: Among the 31 patients currently undergoing LA treatment who did not achieve LDL-cholesterol and/or Lp(a) target values, no differences in comorbidity were recorded despite a worse pre-LA treatment lipid profile (LDL-C 77 ± 60 mg/dl in males vs. 128 ± 105 mg/dl in females; p 0.025) and a longer mean inter-apheresis interval (17 ± 4 days in males vs. 19 ± 5 days in females; p 0.012) reported in females compared to males. Additionally, in comparison with men, it was found that the time between the first cardiovascular event and the beginning of LA, as well as the age at the beginning of LA, were significantly higher in females than in males (p 0.027 and 0.007, respectively). CONCLUSIONS: Sex differences in FH subjects not only affect the diagnosis and treatment but also influence varied responses to the treatment itself.

Application of Lipid Apheresis in Acute Lipogenic Pancreatitis.

INTRODUCTION: Recently, the incidence of hypertriglyceridemia-associated pancreatitis (HTG-AP) has been increasing. The pathogenesis of lipogenic pancreatitis is not fully understood. This study aimed to retrospectively analyze the laboratory data, clinical manifestations, and prognosis of patients with lipid-derived pancreatitis who received lipid purification, to explore whether lipid purification is a better treatment for acute hyperlipidemic pancreatitis. METHODS: In this study, we enrolled five subjects diagnosed with HTG-AP at the Second Xiangya Hospital of Central South University between 2021 and 2022. We collected demographic data, medical histories, clinical manifestations, and laboratory data. All patients received routine therapy. Blood lipid purification was conducted using the double filtration plasmapheresis (DFPP) method. Plasma was separated from blood cells and purified to remove cholesterol, triglycerides, and low-density lipoprotein (LDL). SPSS was used for statistical analyses. RESULTS: Following a single lipoprotein apheresis (LA) treatment, significant improvements in serum lipid levels were observed. Three patients achieved triglyceride levels below 5.65 mmol/L within 24 h, while the remaining 2 patients experienced reductions of 82% and 78%, respectively. The average triglyceride level decreased from 36.82 to 7.27 mmol/L, representing an 80% reduction from baseline. Total cholesterol decreased by 59% on average, and LDL levels decreased by 69%. Statistically significant differences were observed in triglyceride and cholesterol levels before and after treatment. Four patients exhibited increased HDL levels posttreatment, while 1 patient showed a decrease. The average HDL/TC level was 21% higher after treatment. CONCLUSION: LA in HTG-AP effectively improves clinical symptoms, rapidly lowers lipid levels, and achieves good therapeutic outcomes.

PCSK9 inhibitor use during pregnancy in a case of familial hypercholesterolemia complicated with coronary artery disease.

Limited data have been reported on the use of proprotein convertase subtilisin/kexin type 9 (PCSK 9) inhibitors during pregnancy in women with familial hypercholesterolemia (FH). Here, we present the first case of initiating evolocumab (PCSK9 inhibitor) in a compound heterozygous FH mother. The patient was a 34-year-old primipara with severe dyslipidemia and a history of coronary artery bypass surgery. An elevated low-density lipoprotein cholesterol (LDL-C) level of 420 mg/dL was detected in the first trimester and persistently increased throughout pregnancy. Evolocumab was administered at 31 and 35 weeks of gestation, showing a positive effect on stabilizing LDL-C levels. Planned delivery with labor analgesia was performed at 38 + 4 weeks. Both the mother and infant were discharged without any notable complications. Hence, evolocumab, an IgG2 monochromatic antibody with little placental permeability, may be an alternative medication with limited influence on infants. Further studies are needed to assess the safety of evolocumab administration during pregnancy.