Опубликована: Янв. 1, 2024
Язык: Английский
Journal of the American Heart Association, Год журнала: 2024, Номер 13(6)
Опубликована: Март 8, 2024
Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval nonstatin therapies LDL-C lowering over past 2 decades, these medications are underused, and most patients still not at guideline-recommended goals. Barriers include poor adherence, clinical inertia, concern side effects, cost, complex prior authorization processes. With disease-related mortality increasing globally, there remains need additional therapeutic options as part an disease prevention strategy. Following identification PCSK9 (proprotein convertase subtilisin/kexin type 9) promising target, inclisiran was developed using natural process RNA interference robust, sustained hepatic synthesis. Twice-yearly maintenance subcutaneous (following initial loading doses Day 1 90) reduces circulating levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety tolerability have been assessed, with studies underway evaluate effects on outcomes provide effectiveness data. In 2021, <20 years after discovery PCSK9, became first approved in United States established or familial hypercholesterolemia has since use primary hyperlipidemia. This article reviews journey from bench bedside, including early development, trial program, key characteristics inclisiran, practical points its clinic.
Язык: Английский
Процитировано
13
Journal of Clinical Medicine, Год журнала: 2024, Номер 13(3), С. 751 - 751
Опубликована: Янв. 28, 2024
Lipoprotein(Lp)(a) is a variant of low-density lipoprotein (LDL), bound to apolipoprotein B100, whose levels are associated with significant increase in the risk atherosclerosis-related cardiovascular events, but also aortic stenosis and atrial fibrillation. Since plasma Lp(a) commonly considered resistant lifestyle changes, we critically reviewed available evidence on effect weight loss, dietary supplements, physical activity this factor. In our review, observed that relevant body relatively high intake saturated fatty acids, consumption red wine, intense exercise seems be significantly lower levels. On contrary, foods rich trans-unsaturated acids increased With regard coenzyme Q10, L-Carnitine, flaxseed exert mild lowering Lp(a).
Язык: Английский
Процитировано
5
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3537 - 3537
Опубликована: Март 21, 2024
Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be independent risk factor atherosclerotic cardiovascular disease (ASCVD). plasma levels are considered 70–90% genetically determined through the codominant expression LPA gene. Therefore, almost stable during individual’s lifetime. This lifelong stability, together with difficulties in measuring standardized manner, may account for scarcity available drugs targeting Lp(a). In this review, we synopsize latest data regarding structure, metabolism, factors affecting circulating Lp(a), as well laboratory determination measurement its role pathogenesis ASCVD thrombosis, potential use various therapeutic agents particular, discuss novel agents, such antisense oligonucleotides (ASOs) small interfering RNAs (siRNAs) that currently being developed target The promising muvalaplin, oral inhibitor formation, is then further analyzed.
Язык: Английский
Процитировано
5
Critical Reviews in Clinical Laboratory Sciences, Год журнала: 2025, Номер unknown, С. 1 - 22
Опубликована: Март 1, 2025
Cardiovascular disease (CVD) is the leading cause of mortality in United States and globally. This review describes changes CVD lipid lipoprotein biomarker measurements that occurred line with evolution clinical practice guidelines for risk assessment treatment. It also discusses level comparability these practice. Comparable reliable are achieved through assay standardization, which not only depends on correct test calibration but factors such as analytical sensitivity, selectivity, susceptibility to can affect measurement process, stability system over time. The current status standardization traditional newer biomarkers discussed, approaches setting achieving goals low-density cholesterol (LDL-C), high-density (HDL-C), total (TC), triglycerides (TG), lipoprotein(a) (Lp(a)), apolipoproteins (apo) A-I B, non-HDL-C. Appropriate levels blood lipids maintained by Centers Disease Control Prevention's (CDC) Biomarkers Standardization Program (CDC BSP) using performance recommended National Cholesterol Education Program. agreement be dependent characteristics analytes differences principles between reference procedures assays. technical limitations observed apolipoproteins. Additionally, apoB Lp(a) may more accurately capture residual risk, respectively, than lipids, thus prompting recommend apolipoprotein measurements. further CDC's approach apoA-I B past 11 years. systems previously a single laboratory, no longer exist, requiring creation new systems, currently underway. situation emphasizes importance collaborative network laboratories, Reference Methods Laboratory Network (CRMLN), ensure sustainability. CDC supporting International Federation Clinical Chemistry Medicine's (IFCC) work establish lipoproteins. Ensuring reliability remains critical effective implementation improving patient care. Utilizing experience gained three decades, BSP will continue improve emerging together stakeholders.
Язык: Английский
Процитировано
0
Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)
Опубликована: Июнь 8, 2024
Abstract Background The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate using genetic evidence. Methods Mendelian randomization (MR) analyses were conducted summary-level genome-wide association studies (GWASs) in European East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, lipoprotein[a]) lipid-modifying (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, used as exposures. AF was an outcome. inverse variance weighted method applied primary method. Summary-data-based performed for further validation expression quantitative trait loci data. Mediation explore indirect effect coronary heart disease. Results In population, MR demonstrated that elevated levels lipoprotein(a) increased risk. Moreover, focusing on targets revealed genetically proxied gene LPA , which simulates effects intervention by reducing lipoprotein(a), exhibited This validated independent datasets. There no consistent significant observed other traits when analyzed different finding also corroborated between AF. disease plays a mediating role this association. However, statistically evidence support these associations. Conclusions study provided Lp(a) may be factor represent promising pharmacological preventing population.
Язык: Английский
Процитировано
4
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1026 - 1026
Опубликована: Янв. 25, 2025
Pharmaceutical advancements and an improved understanding of pathophysiology have enabled innovative therapies for chronic conditions like dyslipidemia. This condition is marked by abnormalities in lipid homeostasis. Nucleic acid therapeutics, including antisense oligonucleotides small interfering RNAs, are novel management strategies that silence genes targeting mRNA. Antisense modify mRNA to inhibit protein production, whereas RNAs induce degradation via the RNA-induced silencing complex (RISC), thus offering promising treatments dyslipidemia atherosclerotic cardiovascular disease. Chemical modifications improve their stability targeting. RNA-based PCSK9, Lp(a), ApoC-III, ANGPTL3 hold transformative potential treating effectively. article discusses latest data from completed ongoing trials on RNA dyslipidemia, inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, solbinsiran. Each therapy targets specific molecules while also significantly impacting other parameters. The results these indicate improvements risk reduction, with studies expected further refine role agents effective management.
Язык: Английский
Процитировано
0
Lipids in Health and Disease, Год журнала: 2025, Номер 24(1)
Опубликована: Фев. 21, 2025
Lipid metabolism is a well-regulated process essential for maintaining cellular functions and energy homeostasis. Dysregulation of lipid associated with various conditions, including cardiovascular diseases, neurodegenerative disorders, metabolic syndromes. This review explores the mechanisms underlying metabolism, emphasizing roles key species such as triglycerides, phospholipids, sphingolipids, sterols in physiology pathophysiology. It also examines genetic environmental factors contributing to dysregulation challenges diagnosing managing lipid-related disorders. Recent advancements lipid-lowering therapies, PCSK9 inhibitors, ezetimibe, bempedoic acid, olpasiran, provide promising treatment options. However, these are accompanied by related cost, accessibility, patient adherence. The highlights need personalized medicine approaches address interplay between genetics metabolism. As lipidomics advanced diagnostic tools continue progress, deeper understanding disorders could pave way more effective therapeutic strategies.
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Март 13, 2025
Background Calcific aortic valve stenosis (CAVS) is a common cardiovascular condition associated with significant adverse events and high mortality rates. Unfortunately, there are currently no effective pharmacological treatments to halt or prevent its progression. Through our analysis of global trends treatment strategies, we have identified valuable insights promising therapeutic possibilities. Additionally, by utilizing bibliometric visualization techniques, provide comprehensive overview the current research landscape in this field. Method According design idea, used Web Science database select publications on related treatments. VOSviewer CiteSpace analysis, total 787 articles been analyzed September 2024. We also summarize explore most prolific authors, countries, journals institutions that publish articles. Results A visual collected reveals Canada United States highest publication volumes Among institutions, Harvard University U.S. leads count, followed Laval California The top three hotspots stenosis, calcification, journal number area Frontiers Cardiovascular Medicine, Catheterization Interventions Arteriosclerosis, Thrombosis Vascular Biology. Furthermore, CAVS spans various directions focuses, including approaches, pathogenesis, diagnostic methods. Conclusion Research into has advanced significantly over years. While interventional surgical replacement remains mainstay for they insufficient fully meet needs patient. Emerging priorities now focus improving diagnostics, exploring innovative therapies, uncovering disease mechanisms, developing novel drugs. These findings highlight evolving demands field underscore need continued address these challenges.
Язык: Английский
Процитировано
0
Prostaglandins & Other Lipid Mediators, Год журнала: 2025, Номер 178, С. 106994 - 106994
Опубликована: Апрель 17, 2025
Язык: Английский
Процитировано
0
Journal of International Medical Research, Год журнала: 2024, Номер 52(7)
Опубликована: Июль 1, 2024
The role of lipoprotein (a) [Lp(a)] in cerebrovascular disease is a topic importance. In this narrative review, pertinent studies have been leveraged to comprehensively examine relationship from diverse perspectives. Lp(a) shares structural traits with low-density cholesterol. synthesized by hepatocytes, and its plasma levels are genetically determined the LPA gene, which produces apolipoprotein (a). Numerous epidemiological confirmed positive correlation between elevated serum occurrence or recurrence events, especially ischemic strokes, adults. It should be noted that strength varies among marginal Mendelian randomization studies. Regarding pediatric patients, screening currently limited those relevant medical history. seems play significant pathogenesis arterial stroke children because environmental thrombotic atherogenic factors generally not present. Phase 3 trials novel targeting agents, such as pelacarsen olpasiran, anticipated demonstrate their efficacy reducing incidence stroke. Given richness literature, new guidelines regarding management targeted populations warranted provide more effective primary secondary prevention.
Язык: Английский
Процитировано
3