Cogent Engineering, Год журнала: 2025, Номер 12(1)
Опубликована: Фев. 18, 2025
Язык: Английский
Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2024, Номер 44(3), С. 741 - 754
Опубликована: Фев. 1, 2024
BACKGROUND: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each tunica. We aimed first identify, in a spatially resolved manner, specific changes plaque, media, adventitia, and cardiac tissue between control atherosclerotic murine aortas. Second, we assessed their translatability human plasma for cardiovascular risk estimation. METHODS: In this observational study, mass spectrometry imaging (MSI) was applied identify region-specific differences (n=11) aortas from low-density lipoprotein receptor–deficient mice, via histology-guided virtual microdissection. Early advanced plaques were compared same animals. Progression metabolites further analyzed by MSI 9 carotids targeted subjects with elective coronary artery bypass grafting (cardiovascular group, n=27) group (n=27). RESULTS: identified 362 local mice (log2 fold-change ≥1.5; P ≤0.05). lipid composition of is altered presents generalized accumulation glycerophospholipids, except lysolipids. Lysolipids (among other glycerophospholipids) found at elevated levels all 3 layers LPC(18:0) (lysophosphatidylcholine; =0.024) LPA(18:1) (lysophosphatidic acid; =0.025) be significantly as mouse-matched early plaques. Higher both species also observed fibrosis-rich areas advanced- versus early-stage samples. They reduced ( <0.001 =0.031, respectively), showing significant association (odds ratio, 0.479 [95% CI, 0.225–0.883]; =0.032) diagnostic potential (area under curve, 0.778 0.638–0.917]). CONCLUSIONS: An phospholipid metabolism occurs atherosclerosis, affecting aorta adjacent heart tissue. Plaque-progression lipids LPA(18:1), on tissue, reflect plasma.
Язык: Английский
Процитировано
7
Journal of Clinical Medicine, Год журнала: 2024, Номер 13(14), С. 4160 - 4160
Опубликована: Июль 16, 2024
This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, regulatory significantly impede access LLTs, exacerbating disparities in healthcare infrastructure affordability. We highlight importance policy reforms, including pricing regulations reimbursement policies, enhancing affordability streamlining processes. Innovative funding models, such as value-based outcome-based payment arrangements, have been recommended make novel LLTs more accessible. Public health interventions, community-based programs telemedicine, can be utilized reach underserved populations improve medication adherence. Education advocacy initiatives led by patient groups providers play a crucial role raising awareness empowering patients. Despite access, present big opportunity reduce burden ASCVD, emphasizing need collaborative efforts among policymakers, providers, industry stakeholders, address these globally.
Язык: Английский
Процитировано
6
Global Heart, Год журнала: 2024, Номер 19(1)
Опубликована: Янв. 1, 2024
Familial hypercholesterolaemia (FH), a common monogenic disorder, is preventable cause of premature coronary artery disease and death.Up to 35 million people worldwide have FH, but most remain undetected undertreated.Several clinical guidelines addressed the gaps in care little focus has been given implementation science practice.The International Atherosclerosis Society (IAS) developed an evidence-informed guidance for detection management patients with supplemented strategies optimize contextual models care.The partitioned into detection, sections.Detection deals screening, diagnosis, genetic testing counselling.Management includes risk stratification, treatment adults children heterozygous homozygous FH during pregnancy, use lipoprotein apheresis.Specific general strategies, guided by processes specified Expert Recommendations Implementing Change taxonomy, are provided.Core generic improving care.Nation-specific cholesterol awareness campaigns should be utilized promote better FH.Integrated underpinned health policy adapted meet local, regional national needs.Clinical centres excellence important taking referrals from community.General practitioners work seamlessly multidisciplinary teams.All health-care providers must receive training essential skills caring families FH.Management supported shared decision-making service improvement driven patient-reported outcomes.Improvements services require sharing existing resources that can support care.Advocacy ensure sustainable funding.Digital technologies quality registries special value.Finally, academic-service partnerships need identify set priorities research.This new IAS on complements recent World Heart Federation Cholesterol Roadmap.
Язык: Английский
Процитировано
5
Diabetes Obesity and Metabolism, Год журнала: 2024, Номер 26(8), С. 3223 - 3237
Опубликована: Май 17, 2024
Abstract Aims To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety inclisiran across glycaemic body mass index (BMI) strata. Materials Methods Participants were randomized 1:1 to receive 300 mg sodium or placebo twice yearly, after initial 3‐month doses up 18 months, with background oral lipid‐lowering therapy. Analyses stratified by status (normoglycaemia, prediabetes, diabetes) BMI (<25, ≥25 <30, ≥30 <35, ≥35 kg/m 2 ). Co‐primary endpoints percentage time‐adjusted change in low‐density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. Results Baseline characteristics balanced between treatment arms Percent LDL (placebo‐corrected) baseline Day 510 ranged −47.6% −51.9% −48.8% −54.4% glycaemic/BMI strata, respectively. Similarly, changes 90 540 −46.8% −52.0% −48.6% −53.3% Inclisiran led significant reductions proprotein convertase subtilisin/kexin type 9 other atherogenic lipids lipoproteins versus The proportions individuals achieving thresholds <1.8 mmol/L <1.4 increased increasing Across higher proportion had mild/moderate treatment‐emergent adverse events (TEAEs) at injection site (2.8%–7.7%) (0.2%–2.1%). Conclusion provided substantial sustained lowering modest excess transient mild‐to‐moderate TEAEs site.
Язык: Английский
Процитировано
5
Journal of the American College of Cardiology, Год журнала: 2024, Номер 84(20), С. 2026 - 2036
Опубликована: Окт. 9, 2024
Язык: Английский
Процитировано
5
The Lancet, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
5
Brain stimulation, Год журнала: 2023, Номер 16(3), С. 867 - 878
Опубликована: Май 1, 2023
Objective.Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many 30–40% patients. Neuromodulation, including deep brain stimulation (DBS), has emerged a potential therapy persistent disabling disease, however it yet gained widespread adoption. In 2016, American Society Stereotactic Functional Neurosurgery (ASSFN) convened meeting with leaders field to discuss roadmap path forward. A follow-up 2022 aimed review current state identify critical barriers milestones progress.Design.The ASSFN on June 3, Atlanta, Georgia included from fields neurology, neurosurgery, psychiatry along colleagues industry, government, ethics, law. The goal was field, assess or setbacks interim six years, suggest future participants focused five areas interest: interdisciplinary engagement, regulatory pathways trial design, disease biomarkers, ethics surgery, resource allocation/prioritization. proceedings are summarized here.Conclusion.The surgical made significant progress since our last expert meeting. Although weakness threats development novel exist, identified strengths opportunities promise move through methodically rigorous biologically-based approaches. experts agree that law, patient multidisciplinary teams will be any growth this area.
Язык: Английский
Процитировано
11
Pharmacological Research, Год журнала: 2023, Номер 194, С. 106857 - 106857
Опубликована: Июль 17, 2023
Familial hypercholesterolaemia (FH) is a common autosomal semi-dominant and highly penetrant disorder of the low-density lipoprotein (LDL) receptor pathway, characterised by lifelong elevated levels cholesterol (LDL-C) increased risk atherosclerotic cardiovascular disease (ASCVD). However, many patients with FH are not diagnosed do attain recommended LDL-C goals despite maximally tolerated doses potent statin ezetimibe. Over past decade, several cholesterol-lowering therapies such as those targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) or angiopoietin-like 3 (ANGPTL3) monoclonal antibody ribonucleic acid (RNA) approaches have been developed that promise to close treatment gap. The availability new complementary modes action lipid metabolism has enabled guideline-recommended goals. Emerging for include liver-directed gene transfer LDLR, vaccines key proteins involved in metabolism, CRISPR-based editing PCSK9 ANGPTL3, but further clinical trials required. In this review, current emerging strategies lowering LDL-C, ASCVD risk-stratification, well implementation care reviewed.
Язык: Английский
Процитировано
11
PharmacoEconomics, Год журнала: 2023, Номер 42(1), С. 91 - 107
Опубликована: Авг. 22, 2023
We aimed to assess the cost effectiveness of four different lipid-lowering strategies for primary prevention coronary heart disease initiated at ages 30, 40, 50, and 60 years from UK National Health Service perspective. developed a microsimulation model comparing initiation strategy current standard care (control). included 458,692 participants Biobank study. The were: (1) low/moderate-intensity statins; (2) high-intensity (3) statins ezetimibe; (4) inclisiran. main outcome was incremental cost-effectiveness ratio each compared control, with 3.5% annual discounting using 2021 GBP (£); ratios were willingness-to-pay threshold £20,000–£30,000 per quality-adjusted life-year. most effective intervention, ezetimibe, projected lead gain in life-years 0.067 person 30 0.026 age years. Initiating therapy 40 all strategies, £2553 (95% uncertainty interval: 1270, 3969), £4511 (3138, 6401), £11,107 (8655, 14,508), £1,406,296 (1,121,775, 1,796,281) life-year gained 1–4, respectively. Incremental lower male individuals (vs female individuals) people higher lower) low-density lipoprotein-cholesterol. For example, statin use had an £5891 (3822, 9348), £2174 (772, 4216), dominant (i.e. saving; −2,760, 350) lipoprotein-cholesterol ≥ 3.0, 4.0 5.0 mmol/L, Inclisiran not any sub-group its price. Low-density lowering early is more cost-effective than late intervention increased increasing lifetime risk disease.
Язык: Английский
Процитировано
11
Atherosclerosis, Год журнала: 2024, Номер 391, С. 117472 - 117472
Опубликована: Фев. 15, 2024
Background and aimsInclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation.MethodsFor each participant in the ORION-10 ORION-11 trials comparing placebo, baseline 10-year risk was estimated using SMART equation. The time-adjusted LDL-C difference from observed 90–540 days after assumed persist used estimate potential reduction risk. Impact on 500,000 ORION-like individuals simulated Monte-Carlo.ResultsMean predicted major vascular among patients randomized (n = 1288) versus placebo 1264) 2.66 mmol/L 2.60 24.9% 24.6%, respectively. Placebo-corrected absolute −1.32 (95% CI −1.37 −1.26; p < 0.001), which 18.1% 24.7% (absolute [95% CI], −6.99% [−7.33 −6.66]; 0.001) NNT 15. Extrapolating inclisiran-treated individuals, model large shifts towards lower quintiles fewer remaining high-risk categories; 3350 471 (≥80% risk), 11,793 3332 (60–<80% 52,142 22,665 (40–<60% 197,752 141,014 (20–<40% more moving into lowest category (<20%) 234,963 332,518.ConclusionsMeaningful gains health might be achieved over 10 years by at-scale approaches capable providing substantial sustained reductions beyond those achievable statins.
Язык: Английский
Процитировано
4