Current opinion in lipidology最新文献_第3页

Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field? Lp(a)之战的治疗进展：我们知道什么？该领域最令人期待的新奇事物是什么？

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-06-01 Epub Date: 2025-03-19 DOI: 10.1097/MOL.0000000000000981

Marc Jean-Gilles, Baris Gencer

{"title":"Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field?","authors":"Marc Jean-Gilles, Baris Gencer","doi":"10.1097/MOL.0000000000000981","DOIUrl":"10.1097/MOL.0000000000000981","url":null,"abstract":"Purpose of review: To review the latest advances in lipoprotein(a) [Lp(a)] treatment, focusing on the impact of currently available lipid-lowering therapies and highlighting the highly anticipated and most developed RNA-based therapies.Recent findings: Lp(a) is a key genetically determined cardiovascular risk modifier linked to myocardial infarction and calcific aortic stenosis development and progression. Conventional lipid-lowering therapies have no substantial effect on circulating Lp(a) levels, leading current guidelines to focus on managing traditional cardiovascular risk factors. New therapies, including antisense oligonucleotides and small interfering RNAs, target Lipoprotein(A) [LPA] gene translation to reduce apo(a) synthesis and Lp(a) particles formation. The most advanced candidates, pelacarsen, olpasiran, and lepodisiran, have shown promising Lp(a) reductions, ranging from -35% to -101% in Phase 1 and 2 trials. Phase 3 studies will clarify their effects on cardiovascular outcomes and address concerns about extremely low Lp(a) levels and safety.Summary: The RNA-based agents pelacarsen, olpasiran, and lepodisiran represent the most advanced developments in this field. Ongoing Phase 3 trials, expected to be finalized between 2025 and 2029, will be crucial in determining their efficacy in improving cardiovascular outcomes and their safety profiles.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"130-137"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peripheral arterial disease associated with elevated lipoprotein(a): a review of the evidence and treatment approaches. 外周动脉疾病与脂蛋白升高相关(a)：证据和治疗方法综述

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-05-26 DOI: 10.1097/MOL.0000000000000999

Harpreet S Bhatia, Sonar Dalal, Elsie Ross

{"title":"Peripheral arterial disease associated with elevated lipoprotein(a): a review of the evidence and treatment approaches.","authors":"Harpreet S Bhatia, Sonar Dalal, Elsie Ross","doi":"10.1097/MOL.0000000000000999","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000999","url":null,"abstract":"Purpose of review: Peripheral arterial disease (PAD) is an atherosclerotic and thrombotic disease associated with substantial morbidity and mortality. Although risk factors for PAD are mostly modifiable, prognosis remains poor, and patients are at a high risk of cardiovascular events. This review aims to summarize current evidence surrounding the role of lipoprotein(a) (Lp[a]) in PAD and examines the available data on lipoprotein apheresis as an effective management approach for patients with PAD with elevated Lp(a).Recent findings: Evidence strongly indicates that elevated Lp(a) is a causal and independent risk factor for PAD and is associated with PAD severity and increased risk of adverse outcomes, including major adverse cardiovascular events and major adverse limb events. Proprotein convertase subtilisin/kexin type 9 inhibitors can modestly reduce Lp(a) levels, and several Lp(a)-lowering therapies are currently under investigation. Prospective cohort studies in patients with PAD with elevated Lp(a) have reported clinical benefits of lipoprotein apheresis, including reduction of cardiovascular event risk.Summary: Limited treatment options exist for patients with PAD and elevated Lp(a). Lipoprotein apheresis is currently the only treatment option approved specifically for lowering Lp(a) levels.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipoprotein(a) and peripheral artery disease: contemporary evidence and therapeutic advances. 脂蛋白(a)和外周动脉疾病：当代证据和治疗进展

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-05-21 DOI: 10.1097/MOL.0000000000000998

Shivshankar Thanigaimani, Maarisha Kumar, Jonathan Golledge

{"title":"Lipoprotein(a) and peripheral artery disease: contemporary evidence and therapeutic advances.","authors":"Shivshankar Thanigaimani, Maarisha Kumar, Jonathan Golledge","doi":"10.1097/MOL.0000000000000998","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000998","url":null,"abstract":"Purpose of review: Peripheral artery disease (PAD) is a major cause of global health burden, including amputation and impaired quality of life. This review examines the evidence implicating lipoprotein(a) [Lp(a)] in PAD, which is timely as novel therapies lowering Lp(a) are currently being tested in several clinical trials.Recent findings: Human observational studies demonstrate strong associations between elevated Lp(a) levels and increased risk of PAD incidence, severity of chronic limb-threatening ischemia, and major adverse limb events. Emerging therapies including small interfering RNA, antisense oligonucleotides, proprotein convertase subtilisin-kexin type 9 inhibitors and lipoprotein apheresis demonstrate significant Lp(a)-lowering effects. However, whether these treatments benefit patients with PAD is currently unknown.Summary: Lp(a) may be involved in PAD pathogenesis. Lp(a)-lowering therapies may significantly reduce PAD-related events and improve outcomes. Future studies are needed to test Lp(a)-lowering therapies in people with PAD and to explore how the association of Lp(a) varies in different sexes and ethnicities and understand mechanisms by which Lp(a) may contribute to limb ischemia.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

What is the phenotype of heterozygous lipoprotein lipase deficiency? 杂合脂蛋白脂肪酶缺乏症的表型是什么？

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2025-01-15 DOI: 10.1097/MOL.0000000000000974

Robert A Hegele

{"title":"What is the phenotype of heterozygous lipoprotein lipase deficiency?","authors":"Robert A Hegele","doi":"10.1097/MOL.0000000000000974","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000974","url":null,"abstract":"Purpose of review: Genetic testing of patients with severe hypertriglyceridemia often identifies a single heterozygous pathogenic variant in the LPL gene. The complex and variable phenotype associated with this genotype is the topic of this review.Recent findings: Previous research showed that heterozygosity for lipoprotein lipase deficiency is associated with reduced but variable post heparin lipolytic activity alongside inconsistent plasma lipid phenotypes ranging from normal to mild-to-moderate to severe hypertriglyceridemia. Recent research confirms and extends these observations, showing that a heterozygous individual can express a highly variable phenotype over time, depending on the presence of secondary factors. About 10% (range 8-20%) of patients with severe hypertriglyceridemia or multifactorial chylomicronemia syndrome are heterozygous for a rare pathogenic LPL variant, and a clinically relevant minority of these has recalcitrant or sustained hypertriglyceridemia.Summary: Heterozygosity for lipoprotein lipase deficiency predisposes to hypertriglyceridemia, which is sometimes severe depending on secondary factors, but is typically quite responsive to routine interventions such as diet, lifestyle and existing lipid-lowering therapies. However, many heterozygotes for pathogenic variants in LPL have completely normal plasma lipids.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"36 2","pages":"96-103"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The breadth and impact of the Global Lipids Genetics Consortium. 全球脂质遗传学联合会的范围和影响。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2024-12-09 DOI: 10.1097/MOL.0000000000000966

Jacqueline S Dron, Pradeep Natarajan, Gina M Peloso

{"title":"The breadth and impact of the Global Lipids Genetics Consortium.","authors":"Jacqueline S Dron, Pradeep Natarajan, Gina M Peloso","doi":"10.1097/MOL.0000000000000966","DOIUrl":"10.1097/MOL.0000000000000966","url":null,"abstract":"Purpose of review: This review highlights contributions of the Global Lipids Genetics Consortium (GLGC) in advancing the understanding of the genetic etiology of blood lipid traits, including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-HDL cholesterol. We emphasize the consortium's collaborative efforts, discoveries related to lipid and lipoprotein biology, methodological advancements, and utilization in areas extending beyond lipid research.Recent findings: The GLGC has identified over 923 genomic loci associated with lipid traits through genome-wide association studies (GWASs), involving more than 1.65 million individuals from globally diverse populations. Many loci have been functionally validated by individuals inside and outside the GLGC community. Recent GLGC studies show increased population diversity enhances variant discovery, fine-mapping of causal loci, and polygenic score prediction for blood lipid levels. Moreover, publicly available GWAS summary statistics have facilitated the exploration of lipid-related genetic influences on cardiovascular and noncardiovascular diseases, with implications for therapeutic development and drug repurposing.Summary: The GLGC has significantly advanced the understanding of the genetic basis of lipid levels and serves as the leading resource of GWAS summary statistics for these traits. Continued collaboration will be critical to further understand lipid and lipoprotein biology through large-scale genetic assessments in diverse populations.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"61-70"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Translating genetics into clinical practice plus nonmainstream thoughts on lipoprotein(a). 将遗传学转化为临床实践，加上对脂蛋白的非主流看法(a)。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2025-03-06 DOI: 10.1097/MOL.0000000000000972

Robert A Hegele

引用次数: 0

Genetic determinants of pancreatitis risk in hypertriglyceridemia. 高甘油三酯血症胰腺炎风险的遗传决定因素。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2024-11-08 DOI: 10.1097/MOL.0000000000000962

Martine Paquette, Simon-Pierre Guay, Alexis Baass

{"title":"Genetic determinants of pancreatitis risk in hypertriglyceridemia.","authors":"Martine Paquette, Simon-Pierre Guay, Alexis Baass","doi":"10.1097/MOL.0000000000000962","DOIUrl":"10.1097/MOL.0000000000000962","url":null,"abstract":"Purpose of review: In recent years, studies have shed light on the concept of risk heterogeneity among patients with severe hypertriglyceridemia (HTG). Several clinical risk factors for acute pancreatitis have been identified in this population, but the importance of different genetic factors above and beyond triglyceride concentration remains unclear. This review endeavours to summarize recent developments in this field.Recent findings: Recent studies suggest that the molecular basis of severe HTG (polygenic susceptibility vs. rare pathogenic variants) can modulate the risk of acute pancreatitis independently of triglyceride level. Furthermore, a pancreatitis polygenic risk score has been developed and validated using data from the largest GWAS meta-analysis of acute pancreatitis published to date. In patients with severe HTG, a high polygenic susceptibility for pancreatitis was associated with a three-fold increased risk of acute pancreatitis compared with those with a lower polygenic risk score.Summary: In the past months, there have been substantial advances in understanding the prediction of acute pancreatitis in patients with severe HTG. However, further efforts at developing risk-stratification strategies and predictive models may help identifying the patients who would benefit most from early and effective interventions to reduce the risk of pancreatitis, including treatment with APOC3 inhibitors.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"55-60"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammation in atherosclerosis: a Big Idea that has underperformed so far. 动脉粥样硬化中的炎症：一个迄今为止表现不佳的大想法。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2025-01-22 DOI: 10.1097/MOL.0000000000000973

Kevin Jon Williams

{"title":"Inflammation in atherosclerosis: a Big Idea that has underperformed so far.","authors":"Kevin Jon Williams","doi":"10.1097/MOL.0000000000000973","DOIUrl":"10.1097/MOL.0000000000000973","url":null,"abstract":"Purpose of review: For many years, inflammation has been a major concept in basic research on atherosclerosis and in the development of potential diagnostic tools and treatments. The purpose of this review is to assess the performance of this concept with an emphasis on recent clinical trials. In addition, contemporary literature may help identify new therapeutic targets, particularly in the context of the treatment of early, rather than end-stage, arterial disease.Recent findings: Newly reported clinical trials cast doubt on the efficacy of colchicine, the sole anti-inflammatory agent currently approved for use in patients with atherosclerotic cardiovascular disease (ASCVD). New analyses also challenge the hypothesis that residual ASCVD event risk after optimal management of lipids, blood pressure, and smoking arises primarily from residual inflammatory risk. Current clinical practice to initiate interventions so late in the course of atherosclerotic arterial disease may be a better explanation. Lipid-lowering therapy in early atherosclerosis, possibly combined with novel add-on agents to specifically accelerate resolution of maladaptive inflammation, may be more fruitful than the conventional approach of testing immunosuppressive strategies in end-stage arterial disease. Also discussed is the ongoing revolution in noninvasive technologies to image the arterial wall. These technologies are changing screening, diagnosis, and treatment of atherosclerosis, including early and possibly reversable disease.Summary: The burden of proof that the Big Idea of inflammation in atherosclerosis has clinical value remains the responsibility of its advocates. This responsibility requires convincing trial data but still seems largely unmet. Unfortunately, the focus on inflammation as the source of residual ASCVD event risk has distracted us from the need to screen and treat earlier.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"78-87"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Navigating variants of uncertain significance in genetic dyslipidemia: how to assess and counsel patients. 在遗传性血脂异常中导航不确定意义的变异：如何评估和咨询患者。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2024-12-18 DOI: 10.1097/MOL.0000000000000971

Hannah E Ison, Benjamin Helm, Gabriel Kringlen, Paul Crawford

{"title":"Navigating variants of uncertain significance in genetic dyslipidemia: how to assess and counsel patients.","authors":"Hannah E Ison, Benjamin Helm, Gabriel Kringlen, Paul Crawford","doi":"10.1097/MOL.0000000000000971","DOIUrl":"10.1097/MOL.0000000000000971","url":null,"abstract":"Purpose of review: Genetic testing has become an integral component of clinical care when an inherited condition is suspected. However, the interpretation of variants identified with this testing can be nuanced. Variants of uncertain significance (VUS) are variants for which there is not enough data currently available to determine if the variant is causal for disease (i.e. pathogenic) or is benign. VUS can exist on a spectrum with some leaning towards suspected pathogenicity and others leaning towards likely benign. Clinician understanding of variant interpretation can improve clinical care by providing more context around how suspicious a VUS is, determining whether additional steps should be taken to further evaluate the variant in question, and ensuring patient understanding of these results.Recent findings: Research on this topic highlights the complexities around VUS interpretation and counseling. VUS are not static: interpretations of pathogenicity change as new information is uncovered.Summary: This review aims to summarize this literature and provide insight into variant interpretation, practical steps clinicians can take to further assess a VUS, and considerations when counseling patients on these results.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"49-54"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibroblast growth factor 21: update on genetics and molecular biology. 成纤维细胞生长因子 21：遗传学和分子生物学的最新进展。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-04-01 Epub Date: 2024-10-23 DOI: 10.1097/MOL.0000000000000960

Daniel R Barros, Robert A Hegele

{"title":"Fibroblast growth factor 21: update on genetics and molecular biology.","authors":"Daniel R Barros, Robert A Hegele","doi":"10.1097/MOL.0000000000000960","DOIUrl":"10.1097/MOL.0000000000000960","url":null,"abstract":"Purpose of review: Since its discovery, most research on fibroblast growth factor 21 (FGF21) has focused on its antihyperglycemia properties. However, attention has recently shifted towards elucidating the ability of FGF21 to lower circulating lipid levels and ameliorate liver inflammation and steatosis. We here discuss the physiology of FGF21 and its role in lipid metabolism, with a focus on genetics, which has up until now not been fully appreciated.Recent findings: New developments have uncovered associations of common small-effect variants of the FGF21 gene, such as the single nucleotide polymorphisms rs2548957 and rs838133, with numerous physiological, biochemical and behavioural phenotypes linked to energy metabolism and liver function. In addition, rare loss-of-function variants of the cellular receptors for FGF21 have been recently associated with severe endocrine and metabolic phenotypes. These associations corroborate the findings from basic studies and preliminary clinical investigations into the therapeutic potential of FGF21 for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertriglyceridemia. Furthermore, recent breakthrough research has begun to dissect mechanisms of a potential FGF21 brain-adipose axis. Such inter-organ communication would be comparable to that seen with other potent metabolic hormones. A deeper understanding of FGF21 could prove to be further beneficial for drug development.Summary: FGF21 is a potent regulator of lipid and energy homeostasis and its physiology is currently at the centre of investigative efforts to develop agents targeting hypertriglyceridemia and MASLD.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"88-95"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0