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IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-01
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引用次数: 0
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-01
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引用次数: 0
From the Editors: Cardiovascular outcomes trials targeting lipoprotein(a) and inflammation: Results anticipated in 2026 针对脂蛋白(a)和炎症的心血管结局试验:预计2026年的结果
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-01 DOI: 10.1016/j.jacl.2025.12.019
Kevin C. Maki PhD, MNLA, P. Barton Duell MD, MNLA
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引用次数: 0
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-01
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引用次数: 0
Country-specific prevalence and clinical relevance of elevated Lp(a) as a risk enhancer in 2 Greek cohorts. 在2个希腊队列中,Lp(a)升高作为风险增强因素的国家特异性患病率和临床相关性。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-23 DOI: 10.1016/j.jacl.2025.12.016
Dimitrios Delialis, Polyxeni Manifava, Sofia-Panagiota Giannakopoulou, Christina Konstantaki, Stavros Athanasopoulos, Georgios Zervas, Panagiotis Nastatos, Georgios Mavraganis, Kateryna Sopova, Maria-Angeliki Dimopoulou, Lydia Kokkinidou, Yannis Skoumas, Christos Pitsavos, Nikolaos Rachiotis, Lasthenis Angelidakis, Dimitrios Papoutsis, Peggy Kostakou, Elisabeth Samouilidou, Achilleas A Zacharoulis, Konstantinos Stellos, Evangellos Liberopoulos, Christina Chrysochoou, Georgios Georgiopoulos, Demosthenes Panagiotakos, Kimon Stamatelopoulos

Background: National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments.

Objective: We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events.

Results: Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS).

Conclusion: Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+.

背景:需要国家流行病学数据来为国家特定的预防保健政策和新开发的治疗方法提供信息。目的:我们旨在分析希腊临床相关特殊人群的流行病学数据,以进行靶向治疗,并评估脂蛋白(a) [Lp(a)]作为风险增强因子的效用。方法:本分析纳入两个独立队列:(1)连续招募三级门诊脂质诊所评估的患者(雅典血管代谢队列[AAC], n = 1106),具有可用的外周血管标志物;(2)希腊普通人群样本(ATTICA研究[AS], n = 2682),具有可用的20年动脉粥样硬化性心血管疾病(ASCVD)事件随访数据。结果:8.3%的AS(≥50 mg/dL)和18.9%的AAC(≥125 nmol/L)患者Lp(a)升高(无ASCVD为16.0%,ASCVD为22.1%,P = 0.006)。Lp(a)水平升高与颈动脉、冠状动脉和下肢动脉粥样硬化增加相关(P结论:在8.3%的普通人群队列中观察到Lp(a)水平升高,在脂质临床队列中观察到高达23.9%的ASCVD患者中观察到Lp(a)水平升高,突出了ASCVD类别之间的风险梯度。将Lp(a)作为风险增强因子,在已验证的HellenicSCOREII+基础上改进了ASCVD风险重新分类。
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引用次数: 0
Olezarsen reduces all-cause health services utilization and improves the treatment experience of patients with familial chylomicronemia syndrome. Olezarsen减少了全因卫生服务的利用,并改善了家族性乳糜微粒血症综合征患者的治疗体验。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-19 DOI: 10.1016/j.jacl.2025.12.018
Asia Sikora Kessler, Montserrat Vera-Llonch, Ewa Karwatowska-Prokopczuk, Veronica J Alexander, Quratul Ann, Catalina Mejia Herrera, Spyros Paparrodopoulos, Shuting Xia, Erik S G Stroes, Seth J Baum, Sotirios Tsimikas

Background: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder associated with extreme hypertriglyceridemia and high risk of acute pancreatitis. Olezarsen-an antisense oligonucleotide targeting hepatic apolipoprotein C3 (APOC3) messenger RNA-reduces triglycerides and may decrease pancreatitis risk. Olezarsen 80 mg once monthly is approved in the United States as an adjunct to diet to reduce triglycerides in adults with FCS.

Objective: To assess the effect of olezarsen on all-cause healthcare resource utilization (HCRU) and overall experience of patients with genetically identified FCS enrolled in the Balance trial (NCT04568434).

Methods: Prespecified exploratory endpoints included yearly all-cause hospitalization, total inpatient days, and emergency room visits for patients treated with olezarsen (80 or 50 mg) vs placebo, as well as Patient Global Impression of Change (PGIC). Ad hoc outcomes included length of hospital stay, intensive care unit (ICU) admissions, reasons for HCRU, and all-cause HCRU according to patients' history of acute pancreatitis and for individual olezarsen doses vs placebo.

Results: Treatment with olezarsen vs placebo for 1 year was associated with an 84% reduction in all-cause hospitalizations (mean rate ratio [95% CI], 0.16 [0.05, 0.50]), 6.3 fewer total inpatient days (95% CI, -11.09, -1.53), better PGIC scores, shorter length of stay, and numerically fewer ICU admissions. Acute pancreatitis was the most frequent cause of hospitalization. Reduction in all-cause inpatient service utilization was consistent for individual dose groups and in patients with a history of acute pancreatitis.

Conclusion: In the Balance study, olezarsen reduced all-cause inpatient service utilization and improved the experience of patients with FCS.

背景:家族性乳糜小铁血症综合征(FCS)是一种罕见的遗传性疾病,与极端高甘油三酯血症和急性胰腺炎的高风险相关。olezarsenn是一种靶向肝载脂蛋白C3 (APOC3)信使rna的反义寡核苷酸,可降低甘油三酯并可能降低胰腺炎风险。Olezarsen每月一次,80毫克,在美国被批准作为降低FCS成人患者甘油三酯的辅助饮食。目的:评估olezarsen对Balance试验(NCT04568434)中基因鉴定的FCS患者全因医疗资源利用(HCRU)和整体体验的影响。方法:预先指定的探索性终点包括olezarsen(80或50 mg)与安慰剂治疗患者的年度全因住院、总住院天数和急诊室就诊次数,以及患者总体变化印象(PGIC)。特别结局包括住院时间、重症监护病房(ICU)入院情况、HCRU发生的原因,以及根据患者急性胰腺炎病史和单个olezarsen剂量与安慰剂的全因HCRU。结果:与安慰剂相比,olezarsen治疗1年与全因住院减少84%相关(平均率比[95% CI], 0.16[0.05, 0.50]),总住院天数减少6.3天(95% CI, -11.09, -1.53), PGIC评分更好,住院时间更短,ICU入院人数更少。急性胰腺炎是最常见的住院原因。各剂量组和有急性胰腺炎病史的患者全因住院服务利用率的降低是一致的。结论:在Balance研究中,olezarsen降低了全因住院服务的利用率,改善了FCS患者的体验。
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引用次数: 0
A delayed diagnosis of familial chylomicronemia syndrome in an elderly patient: Clinical implications of late-onset disease. 延迟诊断家族性乳糜微粒血症综合征在老年患者:迟发性疾病的临床意义。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-18 DOI: 10.1016/j.jacl.2025.12.017
Ilenia Calcaterra, Nicoletta Vitelli, Maria Donata Di Taranto, Carmine De Luca, Sofia Donnarumma, Vincenzina Palermo, Giovanna Cardiero, Gabriella Iannuzzo, Domenico Rendina, Giuliana Fortunato, Matteo Di Minno

Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life.

Case presentation: We describe a 70-year-old man with severe refractory hypertriglyceridemia, chronic hyperCKemia, and protein-energy malnutrition, ultimately diagnosed with FCS due to a homozygous pathogenic LPL variant (c.844G>T; p.Glu282*). Despite long-standing disease and comorbidities, treatment with volanesorsen, an antisense oligonucleotide targeting apoC-III mRNA, produced a 74% reduction in triglyceride levels and marked clinical improvement. This case underscores that FCS may remain undetected until late adulthood, particularly when confounded by diabetes or chronic kidney disease.

Conclusion: Recognition of characteristic biochemical profiles and family history is essential to avoid diagnostic delay and prevent irreversible pancreatic damage and malnutrition. Even in elderly patients, targeted therapy can substantially improve metabolic control and quality of life.

背景:家族性乳糜低血症综合征(FCS)是一种罕见的常染色体隐性遗传病,由调节脂蛋白脂肪酶活性的基因突变引起,通常在生命早期表现出来。病例介绍:我们描述了一位患有严重难愈性高甘油三酯血症、慢性高血液病和蛋白质能量营养不良的70岁男性,由于纯合子致病性LPL变异(c.844G>T; p.Glu282*)最终被诊断为FCS。尽管存在长期疾病和合共病,但volanesorsen(一种针对apoC-III mRNA的反义寡核苷酸)治疗可使甘油三酯水平降低74%,并显着改善临床。该病例强调,FCS可能直到成年晚期才被发现,特别是当与糖尿病或慢性肾脏疾病混淆时。结论:认识特征性生化特征和家族史对避免诊断延误和预防不可逆胰腺损伤和营养不良至关重要。即使在老年患者中,靶向治疗也能显著改善代谢控制和生活质量。
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引用次数: 0
Precision approach in apoA-I infusion trials: When CSL112 may actually work. apoA-I输注试验的精确方法:CSL112何时可能真正起作用。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-17 DOI: 10.1016/j.jacl.2025.12.015
Vignesh Chidambaram, Amudha Kumar, Thorsten M Leucker

In the recent ApoA-I Event Reducing in Ischemic Syndromes II trial, a plasma-derived apolipoprotein A-I (apoA-I) infusion (CSL112) demonstrated no significant reduction in major cardiovascular events in the overall postmyocardial infarction population. However, exploratory analyses revealed benefits in subgroups with both elevated low-density lipoprotein cholesterol (LDL-C) and systemic inflammation, suggesting that biologic context may be critical to therapeutic efficacy. Building on these trial findings, we highlight that the efficacy of CSL112 may depend on the coexistence of elevated LDL-C and systemic inflammation. We integrate ATP-binding cassette transporter A1 (ABCA1) biology with subgroup trial findings to propose a precision-stratification framework for future apoA-I infusion trials. We focus on the interaction of lipid burden and inflammation on ABCA1 transporter function, the impact of statin-induced transporter downregulation, and strategies for patient selection, including ex vivo efflux assays and molecular transporter profiling, and the therapeutic promise of combination therapies (apoA-I infusion with liver X receptor agonists) in patients with impaired transporter function.

在最近的ApoA-I事件减少缺血性综合征II的试验中,血浆源性载脂蛋白a- i (ApoA-I)输注(CSL112)显示,在心肌梗死后总体人群中,主要心血管事件没有显著减少。然而,探索性分析显示,低密度脂蛋白胆固醇(LDL-C)升高和全身性炎症的亚组都有益处,这表明生物学背景可能对治疗效果至关重要。基于这些试验结果,我们强调CSL112的疗效可能取决于LDL-C升高和全身性炎症的共存。我们将atp结合盒转运蛋白A1 (ABCA1)生物学与亚组试验结果结合起来,为未来的apoA-I输注试验提出了一个精确的分层框架。我们关注脂质负荷和炎症对ABCA1转运蛋白功能的相互作用,他汀类药物诱导的转运蛋白下调的影响,以及患者选择策略,包括体外排出试验和分子转运蛋白分析,以及转运蛋白功能受损患者联合治疗(apoA-I输注肝X受体激动剂)的治疗前景。
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引用次数: 0
Reply to: "Obesity and statin intolerance: Implications for LDL-C target achievement in PCSK9 inhibitor therapy". 回复:“肥胖和他汀类药物不耐受:对PCSK9抑制剂治疗中LDL-C目标实现的影响”。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-16 DOI: 10.1016/j.jacl.2025.12.014
Elena Formisano, Andrea Pasta, Livia Pisciotta
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引用次数: 0
Impact of omega-3 supplementation on lipoprotein-associated phospholipase A2 mass and activity: A systematic review and meta-analysis of randomized controlled trials. 补充omega-3对脂蛋白相关磷脂酶A2质量和活性的影响:随机对照试验的系统回顾和荟萃分析
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-12-16 DOI: 10.1016/j.jacl.2025.12.013
Luis E Simental-Mendía, Mario Simental-Mendía, Laura Jazel Barragán-Zúñiga, Paola Aguillón-Marín

Background: Omega-3 polyunsaturated fatty acid (PUFA) administration has been associated with a reduced risk of developing cardiovascular diseases. Some studies have explored the potential effect of omega-3 PUFA on lipoprotein-associated phospholipase A2 (Lp-PLA2) levels with conflicting results; while some have shown no effect, others have found reduced levels of Lp-PLA2 with omega-3 supplementation. This meta-analysis of randomized controlled trials aims to clarify the impact of omega-3 supplementation on Lp-PLA2 mass and activity.

Sources of material: The Medical Subject Headings (MeSH) terms and keywords were searched in Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases. The random- or fixed-effects model and the generic inverse variance weighting method were applied for quantitative data. The influence of each study on the overall effect size was determined using the leave-one-out method.

Abstract of findings: The meta-analysis of 16 randomized controlled trials showed a significant reduction in Lp-PLA2 mass with omega-3 intervention (weighted mean difference [WMD]: -24.05 ng/mL, 95% CI: -27.63, -20.47, P < .0001) but no significant changes in Lp-PLA2 activity (WMD: -8.54 nmol/mL/min, 95% CI: -27.25, 10.18, P = .37). A subgroup analysis by type of omega-3 supplementation revealed that either icosapent ethyl (WMD: -32.67 ng/mL, 95% CI: -34.36, -30.98, P < .00001) or other omega-3 formulations (WMD: -17.05 ng/mL, 95% CI: -22.93, -11.18, P < .00001) significantly decreased the Lp-PLA2 mass.

Conclusion: Omega-3 supplementation significantly reduces circulating levels of Lp-PLA2 mass without affecting its activity.

背景:Omega-3多不饱和脂肪酸(PUFA)的服用与降低心血管疾病的发生风险有关。一些研究探索了omega-3 PUFA对脂蛋白相关磷脂酶A2 (Lp-PLA2)水平的潜在影响,但结果相互矛盾;虽然有些人没有发现效果,但另一些人发现补充omega-3可以降低Lp-PLA2的水平。这项随机对照试验的荟萃分析旨在阐明补充omega-3对Lp-PLA2质量和活性的影响。材料来源:在Web of Science、PubMed、Scopus、谷歌Scholar和ClinicalTrials.gov数据库中搜索医学主题词(MeSH)术语和关键词。定量数据采用随机或固定效应模型和通用方差逆加权法。每项研究对总体效应大小的影响采用留一法确定。研究结果摘要:对16项随机对照试验的荟萃分析显示,omega-3干预显著降低了Lp-PLA2质量(加权平均差[WMD]: -24.05 ng/mL, 95% CI: -27.63, -20.47, P)。结论:补充omega-3可显著降低循环中Lp-PLA2质量水平,但不影响其活性。
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引用次数: 0
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Journal of clinical lipidology
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