Current opinion in lipidology最新文献_第2页

Oral agents for lowering lipoprotein(a). 降低脂蛋白（a）的口服药物。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-12-01 Epub Date: 2024-09-25 DOI: 10.1097/MOL.0000000000000953

Stephen J Nicholls, Adam J Nelson, Laura F Michael

{"title":"Oral agents for lowering lipoprotein(a).","authors":"Stephen J Nicholls, Adam J Nelson, Laura F Michael","doi":"10.1097/MOL.0000000000000953","DOIUrl":"10.1097/MOL.0000000000000953","url":null,"abstract":"Purpose of review: To review the development of oral agents to lower Lp(a) levels as an approach to reducing cardiovascular risk, with a focus on recent advances in the field.Recent findings: Extensive evidence implicates Lp(a) in the causal pathway of atherosclerotic cardiovascular disease and calcific aortic stenosis. There are currently no therapies approved for lowering of Lp(a). The majority of recent therapeutic advances have focused on development of injectable agents that target RNA and inhibit synthesis of apo(a). Muvalaplin is the first, orally administered, small molecule inhibitor of Lp(a), which acts by disrupting binding of apo(a) and apoB, in clinical development. Nonhuman primate and early human studies have demonstrated the ability of muvalaplin to produce dose-dependent lowering of Lp(a). Ongoing clinical trials will evaluate the impact of muvalaplin in high cardiovascular risk and will ultimately need to determine whether this strategy lowers the rate of cardiovascular events.Summary: Muvalaplin is the first oral agent, developed to lower Lp(a) levels. The ability of muvalaplin to reduce cardiovascular risk remains to be investigated, in order to determine whether it will be a useful agent for the prevention of cardiovascular disease.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"275-280"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343275","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

Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity. 胆固醇酯转移蛋白抑制剂：降低发病风险和促进长寿的途径。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-12-01 Epub Date: 2024-10-17 DOI: 10.1097/MOL.0000000000000955

Michael H Davidson, Andrew Hsieh, John J P Kastelein

{"title":"Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity.","authors":"Michael H Davidson, Andrew Hsieh, John J P Kastelein","doi":"10.1097/MOL.0000000000000955","DOIUrl":"10.1097/MOL.0000000000000955","url":null,"abstract":"Purpose of review: To review the evidence and describe the biological plausibility for the benefits of inhibiting cholesteryl ester transfer protein (CETP) on multiple organ systems through modification of lipoprotein metabolism.Recent findings: Results from observational studies, Mendelian randomization analyses, and randomized clinical trials support the potential of CETP inhibition to reduce atherosclerotic cardiovascular disease (ASCVD) risk through a reduction of apolipoprotein B-containing lipoproteins. In contrast, raising high-density lipoprotein (HDL) particles, as previously hypothesized, did not contribute to ASCVD risk reduction. There is also an expanding body of evidence supporting the benefits of CETP inhibition for safeguarding against other conditions associated with aging, particularly new-onset type 2 diabetes mellitus and dementia, as well as age-related macular degeneration, septicemia, and possibly chronic kidney disease. The latter are likely mediated through improved functionality of the HDL particle, including its role on cholesterol efflux and antioxidative, anti-inflammatory, and antimicrobial activities.Summary: At present, there is robust clinical evidence to support the benefits of reducing CETP activity for ASCVD risk reduction, and plausibility exists for the promotion of longevity by reducing risks of several other conditions. An ongoing large clinical trial program of the latest potent CETP inhibitor, obicetrapib, is expected to provide further insight into CETP inhibition as a therapeutic target for these various conditions.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"35 6","pages":"303-309"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589794","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

Editorial introductions. 编辑介绍。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-12-01 Epub Date: 2024-11-07 DOI: 10.1097/MOL.0000000000000956

引用次数: 0

Are the lipid-lowering effects of incretin-based therapies relevant for cardiovascular benefit? 基于增量素的疗法的降脂效果与心血管益处相关吗？

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1097/MOL.0000000000000949

Teba Alnima, Mark M Smits, Nordin M J Hanssen

{"title":"Are the lipid-lowering effects of incretin-based therapies relevant for cardiovascular benefit?","authors":"Teba Alnima, Mark M Smits, Nordin M J Hanssen","doi":"10.1097/MOL.0000000000000949","DOIUrl":"10.1097/MOL.0000000000000949","url":null,"abstract":"Purpose of review: This review examines the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on lipid profiles in individuals with type 2 diabetes mellitus and/or obesity, crucial for optimizing cardiovascular risk management.Recent findings: GLP-1RAs affect lipid levels by reducing intestinal apolipoprotein B48 production and mesenteric lymph flow, while increasing catabolism of apolipoprotein B100. It remains unknown whether these effects are direct or indirect, but the improvements in lipid levels are strongly correlated to the drug-induced weight loss. Clinical trials demonstrate improvements in lipid profiles, with different effects per agent and dose. We deem it unlikely that improved lipid levels are sufficient to explain the beneficial effects of GLP-1RA on cardiovascular risk, especially given the improvement of many other risk factors (body weight, glycemic control, inflammation) while using these agents. Posthoc mediation analyses of large cardiovascular outcome trials may shed some light on the relative importance of each risk factor.Summary: GLP-1RAs improve lipid profiles in clinical trials, but their complete cardiovascular benefits likely involve multifactorial mechanisms beyond lipid modulation.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"259-267"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855114","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

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 : 2024-11-28 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":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implementation science and genetic testing for familial hypercholesterolemia. 实施科学和家族性高胆固醇血症基因检测。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-11-26 DOI: 10.1097/MOL.0000000000000967

Karen Birkenhead, David Sullivan, Gerald F Watts, Mitchell N Sarkies

{"title":"Implementation science and genetic testing for familial hypercholesterolemia.","authors":"Karen Birkenhead, David Sullivan, Gerald F Watts, Mitchell N Sarkies","doi":"10.1097/MOL.0000000000000967","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000967","url":null,"abstract":"Purpose of review: Familial hypercholesterolemia is a treatable genetic disorder of cholesterol metabolism. Genetic testing is the most specific method for diagnosing familial hypercholesterolemia, but it remains underutilized. Implementation science aims to bridge the gap between evidence and practice and, thereby, support improved familial hypercholesterolemia care. This review presents the current evidence on the use of implementation science to improve the use of genetic testing for familial hypercholesterolemia.Recent findings: Recent research has focused on developing implementation strategies to improve the use of genetic testing, particularly cascade testing of at-risk blood relatives of known familial hypercholesterolemia cases. Stakeholder informed strategies aimed at improving communication between families and detection of familial hypercholesterolemia in primary care have been developed and implemented. Findings demonstrate implementation science methods can help remove barriers and improve the uptake of cascade genetic testing.Summary: Significant gaps in familial hypercholesterolemia care emphasize the importance of practical and realistic approaches to improve the detection of this preventable cause of premature heart disease, and recent efforts using implementation science have shown some promising results. More implementation science studies are needed that address the considerable gaps in familial hypercholesterolemia care, including the underutilization of genetic testing, so that all individuals receive the best clinical care.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726696","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

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 : 2024-11-11 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":"https://doi.org/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":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","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

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 : 2024-10-18 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":"https://doi.org/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":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct roles of size-defined HDL subpopulations in cardiovascular disease. 高密度脂蛋白亚群在心血管疾病中的不同作用。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-10-17 DOI: 10.1097/MOL.0000000000000959

W Sean Davidson, Tomas Vaisar, Jay W Heinecke, Karin E Bornfeldt

{"title":"Distinct roles of size-defined HDL subpopulations in cardiovascular disease.","authors":"W Sean Davidson, Tomas Vaisar, Jay W Heinecke, Karin E Bornfeldt","doi":"10.1097/MOL.0000000000000959","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000959","url":null,"abstract":"Purpose of review: Doubts about whether high-density lipoprotein-cholesterol (HDL-C) levels are causally related to atherosclerotic cardiovascular disease (CVD) risk have stimulated research on identifying HDL-related metrics that might better reflect its cardioprotective functions. HDL is made up of different types of particles that vary in size, protein and lipid composition, and function. This review focuses on recent findings on the specific roles of HDL subpopulations defined by size in CVD.Recent findings: Small HDL particles are more effective than larger particles at promoting cellular cholesterol efflux because apolipoprotein A-I on their surface better engages ABCA1 (ATP binding cassette subfamily A member 1). In contrast, large HDL particles bind more effectively to scavenger receptor class B type 1 on endothelial cells, which helps prevent LDL from moving into the artery wall. The specific role of medium-sized HDL particles, the most abundant subpopulation, is still unclear.Summary: HDL is made up of subpopulations of different sizes of particles, with selective functional roles for small and large HDLs. The function of HDL may depend more on the size and composition of its subpopulations than on HDL-C levels. Further research is required to understand how these different HDL subpopulations influence the development of CVD.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496782","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

Complex actions of sodium glucose transporter-2 inhibitors on lipids, calcific atherosclerosis, and bone density. 钠葡萄糖转运体-2 抑制剂对血脂、钙化性动脉粥样硬化和骨密度的复杂作用。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-10-01 Epub Date: 2024-07-18 DOI: 10.1097/MOL.0000000000000942

Stuti Pradhan, Sophia Kalanski, Yin Tintut, Linda L Demer

{"title":"Complex actions of sodium glucose transporter-2 inhibitors on lipids, calcific atherosclerosis, and bone density.","authors":"Stuti Pradhan, Sophia Kalanski, Yin Tintut, Linda L Demer","doi":"10.1097/MOL.0000000000000942","DOIUrl":"10.1097/MOL.0000000000000942","url":null,"abstract":"Purpose of review: Inhibitors of sodium-glucose cotransporter-2 (SGLT2) lower renal glucose reabsorption and, thus, are used to treat patients with type 2 diabetes mellitus. Clinical trials coincidentally showed that SGLT2 inhibitors also benefitted patients with heart failure. This review explores the impact of SGLT2 inhibitors on other aspects of cardiovascular disease and skeletal health.Recent findings: In some, but not all, clinical and preclinical studies, SGLT2 inhibitors are found to reduce serum levels of free fatty acids and triglycerides. Their effects on total and low-density lipoprotein cholesterol and cardiac function also vary. However, SGLT2 inhibitors reduce lipid accumulation in the liver, kidney, and heart, and alter expression of lipid metabolism genes. Effects on free fatty acid uptake in abdominal fat depots depend on the location of adipose tissue. In male, but not female, mice, SGLT2 inhibitors reduce the atherosclerotic lesions and aortic calcium deposition. With respect to skeletal health, recent literature has reported conflicting associations with the risks of fracture and amputation.Summary: Studies suggest that SGLT2 inhibitors reduce tissue lipid accumulation, and in a sex-dependent manner, atherosclerosis and vascular calcification. However, their effects on lipid levels and bone health are complex and remain to be established.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"253-257"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757726","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