Residual risk

剩余风险
  • 文章类型: Journal Article
    目标:2016年,法国允许男男性行为者(MSM)献血,如果他们在过去12个月内没有与男性发生性关系。2020年4月,由于没有观察到对血液安全的负面影响,这一限制放宽至4个月。本研究评估了减少这一推迟期对流行病学监测指标的影响。
    方法:本研究比较了第二次延迟变化之前(P1)和之后(P2)两个30个月之间的感染监测指标。
    结果:总体而言,79例捐赠的人免疫缺陷病毒(HIV)检测呈阳性(P1中49例,P2中30例),322用于丙型肝炎病毒(HCV)(185和137),622为乙型肝炎病毒(HBV)(355和267),1684为梅毒(799和885)。除梅毒:HIV外,P1和P2之间的阳性捐赠率下降(0.07/10,000捐赠与0.04;p>0.5),HCV(0.25vs.0.20;p<0.05),HBV(0.49vs.0.39;p<0.01)和梅毒(1.10vs.1.29;p<0.001)。对于所有三种病毒,输血传播的残余风险没有增加:艾滋病毒(1/7800,000捐赠与1/10,500,000),HCV(1/25,200,000vs.1/47,300,000)和HBV(1/6,400,000vs.1/6,000,000)。
    结论:在2020年4月减少MSM的延期期限并未对剩余风险产生负面影响,仍然很低,或者积极的捐赠率,除了梅毒,这需要仔细监测。为了确保平等获得献血,自2022年3月以来,MSM已被允许在与其他献血者相同的条件下献血(即,过去4个月内不超过一个性伴侣)。
    OBJECTIVE: In 2016, France allowed men who have sex with men (MSM) to donate blood if they had not had sex with men in the previous 12 months. In April 2020, this restriction was relaxed to 4 months due to the lack of negative impact observed on blood safety. This study assesses the impact of reducing this deferral period on epidemiological surveillance indicators.
    METHODS: This study compares infection surveillance indicators between two 30-month periods before (P1) and after (P2) this second deferral change.
    RESULTS: Overall, 79 donations tested positive for human immunodeficiency virus (HIV) (49 in P1 and 30 in P2), 322 for hepatitis C virus (HCV) (185 and 137), 622 for hepatitis B virus (HBV) (355 and 267) and 1684 for syphilis (799 and 885). Positive donation rates decreased between P1 and P2, except for syphilis: HIV (0.07/10,000 donations vs. 0.04; p > 0.5), HCV (0.25 vs. 0.20; p < 0.05), HBV (0.49 vs. 0.39; p < 0.01) and syphilis (1.10 vs. 1.29; p < 0.001). For all three viruses, residual risks of transmission by transfusion did not increase: HIV (1/7,800,000 donations vs. 1/10,500,000), HCV (1/25,200,000 vs. 1/47,300,000) and HBV (1/6,400,000 vs. 1/6,000,000).
    CONCLUSIONS: Reducing the deferral period for MSM in April 2020 did not negatively impact residual risks, which remained very low, or the rate of positive donations, except for syphilis, which requires careful monitoring. To ensure equal access to blood donation, MSM have been allowed to donate blood under the same conditions as other donors since March 2022 (i.e., no more than one sexual partner in the last 4 months).
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  • 文章类型: Journal Article
    历史上,动脉粥样硬化性心血管疾病(ASCVD)风险缓解主要集中在低密度脂蛋白胆固醇(LDL-C).在这篇叙述性综述中,我们探讨了LDL-C以外的残余ASCVD风险状况,重点是高甘油三酯血症。针对高甘油三酯血症的治疗方法和解决其他残余ASCVD危险因素的新方法的最新临床试验。
    在他汀类药物或前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂治疗的患者中,尽管LDL-C较低,但高甘油三酯血症仍然是严重的ASCVD风险。大量基于人群的观察性研究一致证明了高甘油三酯血症与ASCVD之间的关联。低高密度脂蛋白胆固醇的共存使这种关系变得复杂。尽管显着改善了致动脉粥样硬化的血脂异常,最近的临床试验结果令人怀疑使用贝特类药物在药理学上降低甘油三酯浓度的效用。另一方面,纯化二十碳五烯酸(EPA),但不与二十二碳六烯酸(DHA)组合,产生了有利的ASCVD结果。这些试验的结果表明,ASCVD风险调节涉及替代途径。已经提出了几种其他药物疗法来解决其他针对炎症的ASCVD风险因素。血栓和代谢因子。
    高甘油三酯血症在已经接受LDL-C降低治疗的患者中存在显著的残余ASCVD风险。从药理学上降低甘油三酯的结果是矛盾的。贝特类药物的作用以及EPA和DHA的组合受到质疑,但现在有令人信服的证据表明,在高甘油三酯血症患者的亚组中,纯EPA可以降低ASCVD的风险。临床指南应根据最近的临床试验证据进行更新。针对非常规ASCVD风险的新型药物需要进一步评估。
    UNASSIGNED: Historically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceridaemia and novel modalities addressing other residual ASCVD risk factors.
    UNASSIGNED: Hypertriglyceridaemia remains a significant ASCVD risk despite low LDL-C in statin or proprotein convertase subtilisin/kexin type 9 inhibitor-treated patients. Large population-based observational studies have consistently demonstrated an association between hypertriglyceridaemia with ASCVD. This relationship is complicated by the co-existence of low high-density lipoprotein cholesterol. Despite significantly improving atherogenic dyslipidaemia, the most recent clinical trial outcome has cast doubt on the utility of pharmacologically lowering triglyceride concentrations using fibrates. On the other hand, purified eicosapentaenoic acid (EPA), but not in combination with docosahexaenoic acid (DHA), has produced favourable ASCVD outcomes. The outcome of these trials suggests alternate pathways involved in ASCVD risk modulation. Several other pharmacotherapies have been proposed to address other ASCVD risk factors targeting inflammation, thrombotic and metabolic factors.
    UNASSIGNED: Hypertriglyceridaemia poses a significant residual ASCVD risk in patients already on LDL-C lowering therapy. Results from pharmacologically lowering triglyceride are conflicting. The role of fibrates and combination of EPA and DHA is under question but there is now convincing evidence of ASCVD risk reduction with pure EPA in a subgroup of patients with hypertriglyceridaemia. Clinical guidelines should be updated in line with recent clinical trials evidence. Novel agents targeting non-conventional ASCVD risks need further evaluation.
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  • 文章类型: Journal Article
    平均而言,LDL颗粒是空腹条件下血清中最多的脂蛋白。由于许多原因,它一直是世界各地降脂指南的主要目标。在过去的30年里,我们目睹了血脂异常指南的每次迭代都发生了显着变化,在动脉粥样硬化性心血管疾病(ASCVD)高风险和极高风险患者中,LDL-胆固醇(LDL-C)目标变得越来越低。世界各地,目标达成率很低,因此,ASCVD患病率仍然高得令人无法接受。LDL-C降低不足是当代心血管(CV)医学中的主要问题。即使是最精明的临床医生也担心的另一个问题是“残余风险”,这意味着即使LDL-C适当降低后仍存在的额外风险。近年来,残余风险的一个重要新组成部分已经出现:富含甘油三酯的脂蛋白或残余脂蛋白.在甘油三酯代谢紊乱的患者中,这些LDL颗粒的前体可能具有过大的重要性(例如,遗传变异,胰岛素抵抗,和糖尿病),并且可能比LDL物种更具动脉粥样硬化。因此,为了降低急性CV事件的总风险,现在是在风险评估和治疗方法中纳入含apoB脂蛋白的整个范围的时候了.
    On average, LDL particles are the most populous lipoprotein in serum under fasting conditions. For many reasons, it has been the primary target of lipid-lowering guidelines around the world. In the past 30 years, we have witnessed remarkable changes in each iteration of dyslipidaemia guidelines, with LDL-cholesterol (LDL-C) targets becoming lower and lower among patients at high and very high risk for atherosclerotic cardiovascular disease (ASCVD). The world over, goal attainment rates are low, and hence, ASCVD prevalence remains unacceptably high. Inadequate LDL-C lowering is a major issue in contemporary cardiovascular (CV) medicine. Another issue that vexes even the most astute clinician is that of \'residual risk\', meaning the excess risk that remains even after LDL-C is appropriately reduced. In recent years, an important new component of residual risk has emerged: triglyceride-enriched lipoproteins or remnant lipoproteins. These precursors to LDL particles can assume outsized importance among patients with derangements in triglyceride metabolism (e.g. genetic variants, insulin resistance, and diabetes mellitus) and may be more atherogenic than LDL species. Consequently, to reduce total risk for acute CV events, the time has come to include the entire spectrum of apoB-containing lipoproteins in approaches to both risk evaluation and treatment.
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  • 文章类型: Journal Article
    慢性冠脉综合征(CCS)患者持续性低度炎症对预后的影响研究不足。REAL-CAD(冠状动脉疾病中使用匹伐他汀的积极或适度降脂治疗的随机评估)研究证明了更高强度匹伐他汀对日本CCS患者的益处。
    这项对REAL-CAD研究的预设亚分析旨在评估CCS患者高敏C反应蛋白(hs-CRP)所代表的持续性低度炎症的预后效果。
    本分析涉及随机分组后6个月无事件发生的患者,其hs-CRP水平在基线和6个月时可获得(n=10,460)。主要终点是心血管死亡率的复合,心肌梗塞,中风,不稳定型心绞痛住院。Landmark分析根据基线和6个月时hs-CRP的中位数水平(均为0.5mg/L)评估了4组持续炎症对预后的影响。这4组包括持续低的患者,升高(增加),减少,和持续高的hs-CRP。
    调整后的Cox比例风险分析表明,与以hs-CRP持续低作为参考的组相比,hs-CRP持续高的组的主要终点风险增加(调整后的HR:1.48,95%CI:1.18-1.89;P=0.001),但在升高(HR:1.07,95%CI:0.77-1.49,P=0.68)和降低(HR:0.92;95%CI:0.66-1.27;P=0.60)hs-CRP组中的风险相似。
    该研究表明,持续的低度炎症与不良预后相关,并强调需要解决CCS患者的残余炎症风险。(在冠状动脉疾病中使用匹伐他汀的积极或适度降脂治疗的随机评价[REAL-CAD];NCT01042730)。
    UNASSIGNED: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS.
    UNASSIGNED: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients.
    UNASSIGNED: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP.
    UNASSIGNED: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP.
    UNASSIGNED: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).
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  • 文章类型: Journal Article
    2型糖尿病(T2D)和动脉粥样硬化性心血管疾病(ASCVD)患者的脂质相关风险和残余心血管风险仍然很高。在实施降低这些风险的多能有效疗法方面存在显著的治疗差距。
    这项研究评估了专门的,旨在通过简化管理和优化治疗策略解决治疗差距的独立心脏代谢诊所.
    我们回顾性地收集了前400例T2D和ASCVD患者的数据,这些患者在诊所接受了治疗,并进行了至少一次随访。这些患者主要针对其心脏代谢风险进行管理,并接受强化降脂治疗。包括非他汀类药物的辅助治疗。
    显著发现包括增加胰高血糖素样肽-1受体激动剂(GLP1RA)和钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)的使用至84%和65%,分别,94%的患者最终接受一种治疗,55%的患者接受双重治疗。降脂治疗的增加导致89%的患者达到低密度脂蛋白胆固醇水平低于患者特定的强化阈值。
    这种护理模式有效地管理高风险患者的需求,实现显著强化降脂治疗和广泛使用心脏代谢药物,并强调了该诊所作为类似高危人群模型的潜力。
    UNASSIGNED: Lipid-related risk and residual cardiovascular risk remain high in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Significant treatment gaps exist in implementation of pluripotent and effective therapies that reduce these risks.
    UNASSIGNED: This study evaluates the efficacy and impact of a dedicated, standalone cardiometabolic clinic designed to address treatment gaps through streamlined management and optimization of treatment strategies.
    UNASSIGNED: We retrospectively collected data from the first 400 patients with T2D and ASCVD who underwent treatment at the clinic and presented for at least one follow-up visit. These patients were primarily managed for their cardiometabolic risks and received intensified lipid-lowering therapies, including adjunct non-statin therapies.
    UNASSIGNED: Significant findings included increased use of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) to 84 % and 65 %, respectively, with 94 % of patients eventually on one therapy and 55 % on dual therapy. Increases in lipid-lowering therapies led to 89 % of patients achieving low-density lipoprotein cholesterol levels below patient-specific thresholds for intensification.
    UNASSIGNED: This care model effectively manages high-risk patient needs, achieving significant intensification of lipid-lowering therapies and broad use of cardiometabolic drugs, and highlights the clinic\'s potential to serve as a model for similar high-risk populations.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    分析了9个月以上主要来源地区的生可可豆(n=870)中的沙门氏菌。在71中检测到(约8.2%)样品,除一个样品(4.1×104CFU/g)外,污染水平为0.3-46MPN/g。使用患病率和浓度数据作为输入,通过定量微生物风险评估(QMRA)方法计算了可可加工中的热处理对比利时随机巧克力消费者感染沙门氏菌病风险评估的影响.从生可可豆到可可液到假设的最终产品(70-90%黑巧克力片)的模块化过程风险模型,是为了了解生产过程中沙门氏菌浓度的变化。在豆子或笔尖蒸汽过程中进行不同的热处理,模拟了笔尖烘烤或液体灭菌(沙门氏菌减少0-6对数)。根据FAO/WHO沙门氏菌剂量反应模型和比利时的巧克力消费数据,估计了每次服务的沙门氏菌病风险和人口水平的每年病例。当沙门氏菌减少5对数时,估计每份平均风险为3.35×10-8(95%CI:3.27×10-10-1.59×10-7),估计每年的沙门氏菌病病例(1170万人口)为88例(95%CI:<1-418)。估计每份平均风险为3.35×10-9(95%CI:3.27×10-11-1.59×10-8),估计每年的沙门氏菌病病例为9例(95%CI:<1-42),减少6个对数。当前的QMRA模型仅考虑了可可工艺中单步热处理中沙门氏菌的减少。在其他工艺步骤(例如研磨)期间获得的失活可能发生,但未被考虑。由于目的是使用QMRA作为评估可可加工中对数减少的工具,不包括来自加工环境和成分的后污染.在可可工艺的单步热处理中,沙门氏菌最少减少5log,被认为是足够的。
    Salmonella in raw cocoa beans (n = 870) from main sourcing areas over nine months was analyzed. It was detected in 71 (ca. 8.2%) samples, with a contamination level of 0.3-46 MPN/g except for one sample (4.1 × 104 CFU/g). Using prevalence and concentration data as input, the impact of thermal treatment in cocoa processing on the risk estimate of acquiring salmonellosis by a random Belgian chocolate consumer was calculated by a quantitative microbiological risk assessment (QMRA) approach. A modular process risk model from raw cocoa beans to cocoa liquor up to a hypothetical final product (70-90% dark chocolate tablet) was set up to understand changes in Salmonella concentrations following the production process. Different thermal treatments during bean or nib steam, nib roasting, or liquor sterilization (achieving a 0-6 log reduction of Salmonella) were simulated. Based on the generic FAO/WHO Salmonella dose-response model and the chocolate consumption data in Belgium, salmonellosis risk per serving and cases per year at population level were estimated. When a 5 log reduction of Salmonella was achieved, the estimated mean risk per serving was 3.35 × 10-8 (95% CI: 3.27 × 10-10-1.59 × 10-7), and estimated salmonellosis cases per year (11.7 million population) was 88 (95% CI: <1-418). The estimated mean risk per serving was 3.35 × 10-9 (95% CI: 3.27 × 10-11-1.59 × 10-8), and the estimated salmonellosis cases per year was 9 (95% CI: <1-42), for a 6 log reduction. The current QMRA model solely considered Salmonella reduction in a single-step thermal treatment in the cocoa process. Inactivation obtained during other process steps (e.g. grinding) might occur but was not considered. As the purpose was to use QMRA as a tool to evaluate the log reduction in the cocoa processing, no postcontamination from the processing environment and ingredients was included. A minimum of 5 log reduction of Salmonella in the single-step thermal treatment of cocoa process was considered to be adequate.
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  • 文章类型: Journal Article
    目的:目前对脂蛋白(a)[Lp(a)]和脂蛋白相关磷脂酶A2(Lp-PLA2)与卒中复发的联合相关性知之甚少。
    方法:在这项前瞻性多中心队列研究中,纳入了10,675例Lp(a)和Lp-PLA2的连续急性缺血性卒中(IS)和短暂性脑缺血发作(TIA)患者。使用Cox比例风险模型和Kaplan-Meier曲线评估1年内卒中复发与Lp(a)和Lp-PLA2的相关性。通过乘法和加法量表评估Lp(a)和Lp-PLA2与中风复发之间的相互作用。
    结果:观察到Lp(a)和Lp-PLA2与卒中复发风险的显著联合关联。多变量cox回归分析显示Lp(a)升高(≥50mg/dL)和Lp-PLA2(≥175.1ng/ml)与卒中复发风险独立相关(调整后风险比:1.42;95%CI:1.15-1.76)。在Lp(a)和Lp-PLA2之间观察到显著的乘法[(exp(β3):1.63,95%CI:1.17-2.29,P=0.004]和加性相互作用(RERI:0.55,95%CI:0.20-0.90,P=0.002;AP:0.39,95CI,0.24-0.53)。
    结论:我们的结果表明Lp(a)和Lp-PLA2与IS/TIA患者卒中复发的风险有共同的关联。同时存在Lp(a)和Lp-PLA2升高的患者中风复发的风险更大。
    OBJECTIVE: Currently little is known about the joint association of lipoprotein (a) [Lp(a)] and Lipoprotein-associated phospholipase A2 (Lp-PLA2) with stroke recurrence.
    METHODS: In this prospective multicenter cohort study, 10,675 consecutive acute ischemic stroke (IS) and transient ischemic attack patients (TIA) with Lp(a) and Lp-PLA2 were enrolled. The association of stroke recurrence within 1 year with Lp(a) and Lp-PLA2 was assessed using Cox proportional hazards models and Kaplan-Meier curves. The interaction between Lp(a) and Lp-PLA2 with stroke recurrence was evaluated by multiplicative and additive scales.
    RESULTS: A significant joint association of Lp(a) and Lp-PLA2 with the risk of stroke recurrence was observed. Multivariate cox regression analysis demonstrated that the combination of elevated Lp(a) (≥ 50 mg/dL) and Lp-PLA2 (≥175.1 ng/ml) was independently associated with the risk of stroke recurrence (adjusted hazard ratio: 1.42; 95 % CI: 1.15-1.76). Both significant multiplicative [(exp(β3):1.63, 95 % CI: 1.17-2.29, P = 0.004] and additive interaction (RERI:0.55, 95 % CI: 0.20-0.90, P = 0.002; AP: 0.39, 95 %CI, 0.24-0.53) were observed between Lp(a) and Lp-PLA2.
    CONCLUSIONS: Our results indicated that Lp(a) and Lp-PLA2 have a joint association with the risk of stroke recurrence in IS/TIA patients. Patients with concomitant presence of elevated Lp(a) and Lp-PLA2 have greater risk of stroke recurrence.
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  • 文章类型: Journal Article
    四联疗法对射血分数降低的心力衰竭患者有效,提供显著的临床益处,包括降低死亡率。临床医生现在正处于一个专注于如何在疾病轨迹的早期阶段启动和滴定象限治疗的时代,包括心力衰竭住院期间。然而,射血分数降低的心力衰竭患者仍面临死亡和心力衰竭住院的显著"残余风险".尽管四联疗法得到了有效的实施,高死亡率和再住院率在射血分数降低的心力衰竭中持续存在,许多患者由于低血压和肾功能不全等副作用而无法最大限度地治疗。在这种情况下,伊伐布雷定,Vericiguat,和omecamtivmecarbil除了四联疗法外,还可能具有辅助作用(请注意,omecamtivmecarbil目前尚未批准用于临床)。然而,伊伐布雷定和维利吉瓜的当代使用量在全球范围内相对较低,可能部分原因是对这些疗法的作用和成本的认识不足。这篇综述为临床医生提供了直接的指导,用于床边评估这些药物的潜在候选药物。四重疗法,有强有力的证据可以降低死亡率,应始终优先执行。作为二线疗法,对于尽管β受体阻滞剂的最大耐受剂量仍无法达到最佳心率控制(静息时≥70bpm)的患者,可以考虑伊伐布雷定。Vericiguat可以考虑用于高风险患者,尽管正在接受正交治疗,但最近经历了恶化的心力衰竭事件,但其N末端B型利钠肽前体水平不应超过8000pg/mL.在未来,omecamtivmecarbil可考虑用于严重心力衰竭(纽约心脏协会III至IV级,射血分数≤30%,和心力衰竭住院在6个月内),当目前的象限治疗是有限的,尽管这仍然是假设产生的,在批准之前需要进一步调查。
    Quadruple therapy is effective for patients with heart failure with reduced ejection fraction, providing significant clinical benefits, including reduced mortality. Clinicians are now in an era focused on how to initiate and titrate quadrable therapy in the early phase of the disease trajectory, including during heart failure hospitalization. However, patients with heart failure with reduced ejection fraction still face a significant \"residual risk\" of mortality and heart failure hospitalization. Despite the effective implementation of quadruple therapy, high mortality and rehospitalization rates persist in heart failure with reduced ejection fraction, and many patients cannot maximize therapy due to side effects such as hypotension and renal dysfunction. In this context, ivabradine, vericiguat, and omecamtiv mecarbil may have adjunct roles in addition to quadruple therapy (note that omecamtiv mecarbil is not currently approved for clinical use). However, the contemporary use of ivabradine and vericiguat is relatively low globally, likely due in part to the under-recognition of the role of these therapies as well as costs. This review offers clinicians a straightforward guide for bedside evaluation of potential candidates for these medications. Quadruple therapy, with strong evidence to reduce mortality, should always be prioritized for implementation. As second-line therapies, ivabradine could be considered for patients who cannot achieve optimal heart rate control (≥ 70 bpm at rest) despite maximally tolerated beta-blocker dosing. Vericiguat could be considered for high-risk patients who have recently experienced worsening heart failure events despite being on quadrable therapy, but they should not have N-terminal pro-B-type natriuretic peptide levels exceeding 8000 pg/mL. In the future, omecamtiv mecarbil may be considered for severe heart failure (New York Heart Association class III to IV, ejection fraction ≤ 30%, and heart failure hospitalization within 6 months) when current quadrable therapy is limited, although this is still hypothesis-generating and requires further investigation before its approval.
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  • 文章类型: Journal Article
    在SPARCL(通过积极降低胆固醇水平预防中风)试验中,在近期卒中或短暂性脑缺血发作(TIA)且无已知冠状动脉疾病的患者中,将阿托伐他汀(80mg/d)与安慰剂进行比较.
    本研究旨在评估脂蛋白(a)[Lp(a)]对卒中/TIA幸存者随后的脑血管和心血管事件的影响。
    Lp(a)水平和载脂蛋白(a)[apo(a)]同工型大小通过液相色谱质谱法在基线时从2,814名SPARCL参与者(1,418名随机接受阿托伐他汀和1,396名安慰剂)收集的样本中进行测定。在每个治疗臂中,将最高四分位数(≥84.0nmol/L)的患者与Lp(a)浓度最低四分位数的患者进行比较.将apo(a)同工型大小最低四分位数(≤25.9KringleIV域)的患者与最高四分位数的患者进行比较。使用Cox比例回归模型计算多变量调整后的HR。
    Lp(a)浓度或apo(a)亚型大小与卒中复发风险之间没有显着关联,SPARCL的主要结果,随机分配给阿托伐他汀或安慰剂的患者的脑血管事件。相比之下,在随机接受阿托伐他汀治疗的患者中,Lp(a)浓度升高和apo(a)亚型短与冠状动脉事件风险增加呈正相关且独立相关(HR:1.607[95%CI:1.007-2.563]和HR:2.052[95%CI:1.303-3.232]).在随机接受安慰剂治疗的患者中没有发现这种关联(HR:1.025[95%CI:0.675-1.555]和HR:1.097[95%CI:0.735-1.637])。
    Lp(a)有助于他汀类药物治疗的卒中/TIA幸存者的残余冠状动脉疾病风险,为在该卒中人群中使用针对Lp(a)的疗法铺平了道路。(立普妥在预防中风中,对于以前有过中风的患者[SPARCL];NCT00147602)。
    UNASSIGNED: In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol levels) trial, atorvastatin (80 mg/d) was compared to placebo in patients with recent stroke or transient ischemic attack (TIA) and no known coronary artery disease.
    UNASSIGNED: This study aimed to assess the contribution of lipoprotein(a) [Lp(a)] to subsequent cerebrovascular and cardiovascular events in stroke/TIA survivors.
    UNASSIGNED: Lp(a) levels and apolipoprotein(a) [apo(a)] isoform size were determined by liquid-chromatography mass spectrometry in samples collected at baseline from 2,814 SPARCL participants (1,418 randomized to atorvastatin and 1,396 to placebo). Within each treatment arm, patients in the highest quartile (≥84.0 nmol/L) were compared with those in the lowest quartiles of Lp(a) concentrations. Patients in the lowest quartile (≤25.9 Kringle IV domains) of apo(a) isoform sizes were compared with those in the highest quartiles. Multivariable-adjusted HRs were calculated using Cox proportional regression models.
    UNASSIGNED: There was no significant association between Lp(a) concentrations or apo(a) isoform sizes and the risk of recurrent stroke, the primary outcome of SPARCL, or cerebrovascular events in patients randomized to atorvastatin or placebo. In contrast, in patients randomized to atorvastatin, elevated Lp(a) concentrations and short apo(a) isoforms were positively and independently associated with an increased risk of coronary events (HR: 1.607 [95% CI: 1.007-2.563] and HR: 2.052 [95% CI: 1.303-3.232]). No such association was found in patients randomized to placebo (HR: 1.025 [95% CI: 0.675-1.555] and HR: 1.097 [95% CI: 0.735-1.637]).
    UNASSIGNED: Lp(a) contributes to the residual coronary artery disease risk of statin-treated stroke/TIA survivors, paving the way for use of therapies targeting Lp(a) in this population with stroke. (Lipitor In The Prevention Of Stroke, For Patients Who Have Had A Previous Stroke [SPARCL]; NCT00147602).
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