Current opinion in lipidology最新文献

{"title":"Oral PCSK9 inhibitors: closing the gap between potency and practicality.","authors":"Danh Q Nguyen, Neha J Pagidipati, Ann Marie Navar","doi":"10.1097/MOL.0000000000001061","DOIUrl":"10.1097/MOL.0000000000001061","url":null,"abstract":"<p><strong>Purpose of review: </strong>Oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a new generation of lipid-lowering therapies that combine the potency of injectable PCSK9 inhibitors with the convenience of oral administration. This review examines the mechanisms, trial evidence, and implementation considerations for oral PCSK9 inhibitors that have reached phase 2 or later clinical development.</p><p><strong>Recent findings: </strong>Two oral PCSK9 inhibitors, enlicitide and laroprovstat, have demonstrated that oral PCSK9 inhibition is pharmacologically viable through distinct mechanisms of action. Enlicitide, a macrocyclic peptide that competitively blocks the PCSK9-LDL receptor interaction, achieved placebo-corrected LDL-C reductions of ~60% across three phase 3 trials, with high adherence and a favorable safety profile over 52weeks. Laroprovstat, a small molecule that inhibits PCSK9-mediated lysosomal trafficking of the LDL receptor, produced dose-dependent LDL-C reductions of up to 51% in a phase 2 trial and is advancing through phase 3 evaluation. Large cardiovascular outcomes trials remain underway for both agents.</p><p><strong>Summary: </strong>Oral PCSK9 inhibitors have the potential to improve the convenience and acceptability of PCSK9-targeted therapy. Whether these advantages translate into greater real-world uptake will depend on affordability, payer coverage, clinician adoption, and long-term adherence.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988561","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}

{"title":"CRISPR therapy for dyslipidemia.","authors":"Stephen J Nicholls","doi":"10.1097/MOL.0000000000001062","DOIUrl":"https://doi.org/10.1097/MOL.0000000000001062","url":null,"abstract":"<p><strong>Purpose of review: </strong>Several lipid and lipoprotein risk factors play an important role in the causality of atherosclerotic cardiovascular disease. Many therapies are limited by suboptimal long-term adherence. This narrative review summarizes the potential for gene editing and epigenetic therapy for the management of dyslipidemia.</p><p><strong>Recent findings: </strong>Recent advances in genomic engineering permit the ability to develop gene editing, base editing and epigenomic editing of specific regions of DNA in humans. These therapies have advanced to early phase clinical evaluation with initial reports demonstrating favorable reductions in ANGPTL3 and proprotein convertase subtilisin kexin type 9, with consequent decreases in levels of low-density lipoprotein cholesterol and triglycerides. Apart from mild-moderate infusion reactions, the early experience with these therapies appears to be well tolerated.</p><p><strong>Summary: </strong>Advances in genomic engineering have developed a number of agents with the potential for robust and durable changes to atherosclerotic lipid and lipoprotein risk factors. How these agents will enter clinical practice will require further evaluation in clinical trials.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988536","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}

{"title":"Editorial introduction.","authors":"","doi":"10.1097/MOL.0000000000001044","DOIUrl":"10.1097/MOL.0000000000001044","url":null,"abstract":"","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"37 4","pages":"v"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374967","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}

{"title":"Premature atherosclerotic cardiovascular disease in the MENA region: economic impact, barriers to care, and policy recommendations for an escalating crisis.","authors":"Radwa Ahmed Batran, Sara Tahoun, Amira Othman, Youssef M Amin, Ahmed Khalil, Ayman Bahr, Mohab Kamel, Mohamed Elsokary","doi":"10.1097/MOL.0000000000001046","DOIUrl":"10.1097/MOL.0000000000001046","url":null,"abstract":"<p><strong>Purpose of the review: </strong>Premature atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized as a major public health challenge in the Middle East and North Africa (MENA) region, where cardiovascular events occur at younger ages than in Western populations. Despite ongoing policy reforms and improvements in healthcare infrastructure, premature ASCVD remains underrecognized and insufficiently addressed. This review summarizes the epidemiology, economic burden, policy initiatives, and current barriers related to premature ASCVD in MENA, while proposing targeted interventions to support policymakers and improve health outcomes.</p><p><strong>Recent findings: </strong>Recent evidence demonstrates that premature ASCVD occurs approximately 10-12 years earlier in MENA populations than in Western countries. The high prevalence of traditional risk factors, including dyslipidemia, obesity, diabetes, hypertension, smoking, and physical inactivity, together with genetic predisposition and familial hypercholesterolemia, contributes substantially to earlier disease onset. Available economic data indicate a considerable burden associated with ischemic heart disease, stroke, and acute coronary syndromes across the region. Multiple initiatives have focused on cardiovascular risk reduction through screening programs, tobacco taxation, trans-fat elimination policies, and strengthening acute care systems. However, significant barriers persist, including healthcare inequities, fragmented health-information systems, workforce limitations, financing constraints, and insufficient implementation of preventive strategies.</p><p><strong>Summary: </strong>Premature ASCVD represents an underrecognized and growing challenge in the MENA region. Addressing this burden requires integrated policy reforms emphasizing early screening, aggressive risk-factor management, strengthened primary healthcare systems, improved digital health infrastructure, expanded workforce capacity, and sustainable financing strategies. Coordinated regional efforts are essential to reduce the long-term clinical and economic consequences of premature ASCVD.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"139-153"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263615","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}

{"title":"Heterozygosity for pathogenic variants in familial chylomicronemia syndrome genes: from carrier state to complex trait.","authors":"Robert A Hegele","doi":"10.1097/MOL.0000000000001048","DOIUrl":"10.1097/MOL.0000000000001048","url":null,"abstract":"<p><strong>Purpose of review: </strong>Biallelic loss-of-function (LOF) variants in any of five canonical genes - LPL, GPIHBP1, APOA5, APOC2 , and LMF1 - cause familial chylomicronemia syndrome (FCS), a rare and severe Mendelian disorder. Heterozygosity for these same variants is far more common but its clinical implications have only recently come into focus. Here, the past 18months of evidence on the monoallelic carrier state across the FCS genes is synthesized.</p><p><strong>Recent findings: </strong>Longitudinal studies of LPL and APOA5 heterozygotes have demonstrated that triglyceride phenotypes vary widely both between individuals and within the same individual over time, ranging from completely normal levels to severe hypertriglyceridemia. Heterozygosity contributes to 15-25% of multifactorial chylomicronemia syndrome (MCS) cases. Mechanistic data implicate dominant-negative effects for some truncating variants and saturation of compromised lipolytic reserve as unifying explanations, rather than simple haploinsufficiency. Common intermediate-effect risk alleles such as LPL p.D36N and p.N318S, and APOA5 p.S19W and p.G185C, behave differently and should not be conflated with rare LOF variants.</p><p><strong>Summary: </strong>The phenotype of FCS-gene heterozygotes is best understood as a complex trait modulated by polygenic background and secondary factors. This understanding has practical implications for cascade screening, counseling, and selection of patients who may benefit from emerging apolipoprotein C-III-targeted therapies, particularly those in the refractory MCS subgroup.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"131-138"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270663","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}

{"title":"The role of metabolic profiling and dietary intervention in the early diagnosis and prevention of atherosclerosis.","authors":"Ali Khattib, Manar Shmet, Rasha Ashkar, Tony Hayek, Soliman Khatib","doi":"10.1097/MOL.0000000000001047","DOIUrl":"10.1097/MOL.0000000000001047","url":null,"abstract":"<p><strong>Purpose of review: </strong>Atherosclerotic cardiovascular disease (ACVD) causes more than 17 million deaths annually, and traditional risk scores capture only part of individual risk. Metabolomic and lipidomic profiling has emerged as a route to better risk stratification and to mechanistic insight into how diet shapes atherogenesis. This narrative review summarizes the most replicated circulating biomarkers of ACVD and the dietary patterns that modulate them.</p><p><strong>Recent findings: </strong>Eight metabolite classes - trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAGln), short-chain fatty acids (SCFAs), lysophosphatidylcholines (LPC), ceramides, branched-chain amino acids (BCAAs), acylcarnitines, and bile acids - show consistent associations with coronary artery disease, plaque burden, and adverse cardiovascular events across recent cohort and case-control studies. Mediterranean-style and DASH dietary patterns are associated with favorable shifts in these biomarkers, including reductions in TMAO, ceramides, and BCAAs, and increases in SCFAs.</p><p><strong>Summary: </strong>Metabolomic biomarkers add biological depth to cardiovascular risk assessment and provide a measurable readout of dietary exposure. Standardized analytical protocols, validated clinical thresholds, and prospective interventional studies are needed before these markers can be used routinely for risk stratification or disease monitoring.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"154-167"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257705","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}

{"title":"Emerging regulators of endothelial lipid metabolism in atherosclerosis.","authors":"Jason S Irei, Kai Hirayama, William A Boisvert","doi":"10.1097/MOL.0000000000001031","DOIUrl":"10.1097/MOL.0000000000001031","url":null,"abstract":"<p><strong>Purpose of review: </strong>Although therapies for hyperlipidemia and hypertension have been shown to be highly effective, they have not sufficiently mitigated overall cardiovascular disease risk. Endothelial cells (ECs) are an integral mediator in the development and progression of atherosclerotic cardiovascular disease. The purpose of this review is to provide an update on the current state of endothelial lipid metabolism research, with particular emphasis on atherosclerosis.</p><p><strong>Recent findings: </strong>Although it has been known that elevated palmitic acid (PA) levels were linked to metabolic dysfunction, inflammation and cardiovascular diseases, more recent studies presented here elucidate the mechanisms behind the negative effects induced by PA. Palmitoylation was found to be detrimental in the case of pyruvate kinase isozyme M2 (PKM2) activity, but also vital for the normal functioning of endothelial ciliation and cell health. Endothelial cholesterol metabolism and hemodynamic forces have also been further confirmed to be key regulators in vessel development and endothelial homeostasis. Perturbations in these pathways promote endothelial dysfunction and maladaptive lipid accumulation.</p><p><strong>Summary: </strong>Although atherosclerosis remains a complex, multifactorial disease that arises from the coordinated dysfunction across multiple vascular and immune cell types, substantial advances have been made in identifying mechanisms behind dysfunctional endothelial lipid metabolism. Despite this, further investigation is necessary to identify high impart therapeutic targets aimed at reducing overall cardiovascular disease risk.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"113-119"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321391","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}

{"title":"Polygenic risk scores in familial hypercholesterolemia. Do they have a role?","authors":"Martine Paquette, Simon-Pierre Guay, Alexis Baass","doi":"10.1097/MOL.0000000000001029","DOIUrl":"10.1097/MOL.0000000000001029","url":null,"abstract":"<p><strong>Purpose of review: </strong>Risk assessment in patients with familial hypercholesterolemia (FH) remains an important clinical challenge. The polygenic susceptibility for plasma lipoprotein traits or coronary artery disease (CAD) can be assessed by polygenic risk scores (PRS). The purpose of this review is to discuss the potential roles of PRS in the context of FH management.</p><p><strong>Recent findings: </strong>Recent studies suggested that a high PRS for lipoprotein(a) falsely explains the phenotype in a fifth of variant-negative FH patients, whereas a larger proportion can be explained by high low-density lipoprotein cholesterol (LDL-C) PRS. The cardiovascular risk, but also the risk of type 2 diabetes, is different in patients with polygenic hypercholesterolemia compared to monogenic FH. Lastly, it has been shown that a PRS for CAD, but not for LDL-C or lipoprotein(a), was associated with increased lifelong incidence of cardiovascular disease in patients with monogenic FH, independently of clinical variables.</p><p><strong>Summary: </strong>Several studies have explored the potential clinical relevance of PRS in FH, including for diagnostic purpose and in cardiovascular risk stratification. Prior to implementation in clinical practice for cardiovascular risk stratification, future studies in FH should determine whether the polygenic information offers incremental predictive value over conventional clinical variables.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"107-112"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321413","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}

{"title":"A JAK of two trades: beneficial or adverse effects of Janus kinase inhibition for plasma LDL-cholesterol and major adverse cardiovascular events in inflammatory bowel disease patients?","authors":"Katherine Muñoz Ayala, Eleonora A M Festen, Marit Westerterp","doi":"10.1097/MOL.0000000000001040","DOIUrl":"10.1097/MOL.0000000000001040","url":null,"abstract":"<p><strong>Purpose of review: </strong>Janus kinase (JAK) inhibitors have emerged as potent anti-inflammatory drugs and are prescribed in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, cardiovascular safety concerns have emerged from RA safety trials, alongside increases in LDL cholesterol (LDL-c). Whether similar lipid changes in IBD translate into clinically meaningful cardiovascular risk remains uncertain. This review focuses on studies and mechanisms increasing LDL-c due to JAK inhibition in IBD.</p><p><strong>Recent findings: </strong>JAK inhibitors increase plasma LDL-c levels in IBD patients in a dose-dependent manner. While this has generally been attributed to JAK inhibitors decreasing inflammation, inhibition of JAK signaling also decreases hematopoiesis: the differentiation of hematopoietic stem cells into granulocyte/macrophage progenitors, and subsequently neutrophils, monocytes, and macrophages. Hematopoiesis requires LDL-c uptake, and is associated with elevated plasma LDL-c when inhibited. While statins lower LDL-c, the high prevalence of metabolic syndrome-associated type 2 diabetes in IBD patients may prompt the use of alternative lipid-lowering drugs.</p><p><strong>Summary: </strong>JAK inhibitors are associated with increased LDL-c levels in IBD patients which may be due to suppressed inflammation and decreased hematopoiesis. This review summarizes the evidence on lipid changes and cardiovascular outcomes upon JAK inhibition and discusses approaches for LDL-c management in IBD.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"37 3","pages":"120-130"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765307","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}

{"title":"Lipoprotein(a) in familial hypercholesterolemia.","authors":"Ali K Jaafar, Steeve Bourane, Gilles C Lambert, Kevin Chemello","doi":"10.1097/MOL.0000000000001032","DOIUrl":"10.1097/MOL.0000000000001032","url":null,"abstract":"<p><strong>Purpose of review: </strong>Elevated concentrations of both low-density lipoprotein (LDL)-cholesterol and lipoprotein(a) [Lp(a)] is probably the most detrimental lipid profile in terms of cardiovascular health. Our primary objective was to review the reports published before January 2026 pertaining to the metabolism of lipoprotein(a) and associated cardiovascular disease (CVD) risk specifically in familial hypercholesterolemia.</p><p><strong>Recent findings: </strong>Lp(a) has consistently been found elevated in familial hypercholesterolemia (FH) cohorts. To a large extent, this results from the fact that elevated Lp(a) increases the likelihood for a patient to be clinically diagnosed as FH. For long, increases in Lp(a) concentrations observed in FH patients have been regarded as the consequence of impaired Lp(a) plasma clearance by the LDL receptor. However, recent studies strongly advocate against a significant role for the LDL receptor in mediating Lp(a) hepatic uptake. The molecular mechanisms by which Lp(a) is cleared from blood still remain elusive. Finally, mounting clinical evidence indicates that lowering LDL-C pharmacologically will not offset the specific cardiovascular risk stemming from elevated Lp(a) in FH.</p><p><strong>Summary: </strong>It is highly recommended to systematically measure Lp(a) in FH patients. These patients should be treated with high-dose statins, when necessary, in combination with a proprotein convertase subtilisin/kexin type 9 inhibitor to reach LDL-C therapeutic goals. Hopefully, the Lp(a) lowering therapies currently under development will prove instrumental for adequate treatment of FH patients with concomitantly elevated Lp(a) in coming years.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"93-99"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321408","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}