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Recent updates on therapeutic targeting of lipoprotein(a) with RNA interference. 利用 RNA 干扰对脂蛋白(a)进行靶向治疗的最新进展。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-03-26 DOI: 10.1097/HCO.0000000000001144
Aravind Sekhar, Ashani Kuttan, Richard A Lange

Purpose of review: RNA interference (RNAi)-based therapies that target specific gene products have impacted clinical medicine with 16 FDA approved drugs. RNAi therapy focused on reducing plasma lipoprotein(a) [Lp(a)] levels are under evaluation.

Recent findings: RNAi-based therapies have made significant progress over the past 2 decades and currently consist of antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Chemical modification of the RNA backbone and conjugation of siRNA enables efficient gene silencing in hepatocytes allowing development of effective cholesterol lowering therapies. Multiple lines of evidence suggest a causative role for Lp(a) in atherosclerotic cardiovascular disease, and recent analyses indicate that Lp(a) is more atherogenic than low density lipoprotein- cholesterol (LDL-C). These findings have led to the 'Lp(a) hypothesis' that lowering Lp(a) may significantly improve cardiovascular outcomes. Four RNAi-based drugs have completed early phase clinical trials demonstrating >80% reduction in plasma Lp(a) levels. Phase 3 clinical trials examining clinical outcomes with these agents are currently underway.

Summary: Currently, four RNAi-based drugs have been shown to be effective in significantly lowering plasma Lp(a) levels. Clinical outcome data from phase 3 trials will evaluate the Lp(a) hypothesis.

目的:以 RNA 干扰(RNAi)为基础、靶向特定基因产物的疗法已影响到临床医学,美国食品及药物管理局已批准 16 种药物。目前正在对重点降低血浆脂蛋白(a)[Lp(a)]水平的 RNAi 疗法进行评估:基于 RNAi 的疗法在过去 20 年中取得了重大进展,目前包括反义寡核苷酸 (ASO) 和小干扰 RNA (siRNA)。通过对 RNA 主干进行化学修饰并连接 siRNA,可在肝细胞中实现高效的基因沉默,从而开发出有效的降低胆固醇疗法。多种证据表明,脂蛋白(a)在动脉粥样硬化性心血管疾病中具有致病作用,最近的分析表明,脂蛋白(a)比低密度脂蛋白胆固醇(LDL-C)更容易导致动脉粥样硬化。这些发现提出了 "脂蛋白(a)假说",即降低脂蛋白(a)可显著改善心血管疾病的预后。目前已有四种基于 RNAi 的药物完成了早期临床试验,结果显示血浆脂蛋白(a)水平降低了 80% 以上。摘要:目前,已有四种基于 RNAi 的药物被证明能有效大幅降低血浆脂蛋白(a)水平。第三阶段试验的临床结果数据将对脂蛋白(a)假说进行评估。
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引用次数: 0
Bad behavior in healthcare: an insidious threat to patients, staff, and organizations. 医疗保健领域的不良行为:对患者、员工和机构的隐性威胁。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-03-20 DOI: 10.1097/HCO.0000000000001139
Liz Crowe, Christine M Riley

Purpose of review: 'Bad' or unprofessional behavior (UPB) destroys communication, teamwork, and professional wellbeing, presenting a significant threat to patients and staff. Understanding what constitutes 'bad' or UPB and creating broad accountability for its cessation is imperative to patient-centered care and the survival of the multidisciplinary health workforce.

Recent findings: Despite organizational and legislative commitments to provide well tolerated work environments, UPB is endemic in healthcare and continues to harm patients, staff, and organizations. Historically, categories of UPB have been researched separately which dilutes the problem. Typically, these behaviors cluster, are interchangeable, and are committed by same perpetrators. Women, junior staff, and minority groups remain the most prevalent targets. Even low intensity UPBs among health staff dramatically impacts risk to patient lives, limits quality care, and destroys staff wellbeing. Targeted interventions must address all five roles impacted by UPBs: the target, patients, bystanders, the perpetrator, and the organization to effectively eliminate UPBs. Organizational leaders must demonstrate and uphold organizational values and be swift in addressing UPB to limit the impact on teams and patients.

Summary: UPB in the healthcare setting presents a multifactorial threat to patients, staff, and organizations. To ensure the delivery of high-quality patient care, and the wellbeing of the health workforce it is crucial to understand the insidious impact of UPB and target interventions across all five roles.

审查目的:不良 "或不专业行为(UPB)会破坏沟通、团队合作和职业健康,对患者和员工构成重大威胁。了解什么是 "不良 "或不专业行为,并建立广泛的责任制来制止这种行为,对于以患者为中心的医疗服务和多学科医疗队伍的生存都是至关重要的:尽管医疗机构和立法机构承诺提供良好的工作环境,但UPB在医疗机构中仍普遍存在,并继续对患者、员工和医疗机构造成伤害。从历史上看,UPB 的类别被分开研究,从而淡化了这一问题。通常情况下,这些行为会聚集在一起,可以相互替换,而且是由相同的行为人实施的。妇女、初级工作人员和少数群体仍然是最普遍的目标。即使是医务人员中强度较低的 UPBs,也会极大地影响患者的生命风险、限制护理质量并破坏员工的身心健康。有针对性的干预措施必须针对受 UPBs 影响的所有五个角色:目标、患者、旁观者、施暴者和组织,才能有效消除 UPBs。组织领导者必须展示和维护组织价值观,并迅速处理 UPB,以限制对团队和患者的影响。摘要:医疗环境中的 UPB 对患者、员工和组织构成了多因素威胁。为确保为患者提供高质量的护理服务,并保障医务人员的健康,了解 UPB 的潜在影响并有针对性地对所有五种角色采取干预措施至关重要。
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引用次数: 0
Resistant hypertension. 抵抗性高血压。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-03-04 DOI: 10.1097/HCO.0000000000001134
Farnoosh Shariati, Nitin Tandan, Carl J Lavie

Purpose of review: Resistant hypertension (RH) is characterized by persistently elevated blood pressure despite the concurrent use of three antihypertensive medications, including a diuretic, at optimal doses. This clinical phenomenon poses a significant burden on healthcare systems worldwide due to its association with increased cardiovascular disease morbidity and mortality.

Recent findings: Ongoing studies on device-based treatment of RH, with aim to reduce sympathetic nervous system outflow, have shown promising evidence in management of RH which may in turn decrease the incidence of composite cardiovascular outcome faced by the affected population.

Summary: This paper aims to provide a comprehensive overview of RH, and review some of the diagnostic and therapeutic approaches in management of RH.

审查目的:难治性高血压(RH)的特点是,尽管同时使用了包括利尿剂在内的三种最佳剂量的降压药物,但血压仍持续升高。由于这种临床现象与心血管疾病发病率和死亡率的增加有关,因此给全球医疗系统带来了沉重负担:摘要:本文旨在提供有关 RH 的全面概述,并回顾 RH 治疗中的一些诊断和治疗方法。
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引用次数: 0
From remnant cholesterol to lipoprotein(a) - emerging risk factors for cardiovascular diseases beyond low density lipoprotein. 从残余胆固醇到脂蛋白(a)--低密度脂蛋白之外新出现的心血管疾病风险因素。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-06-06 DOI: 10.1097/HCO.0000000000001142
Debabrata Mukherjee, Dimitri P Mikhailidis
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引用次数: 0
Predictive utility of remnant cholesterol in atherosclerotic cardiovascular disease. 残余胆固醇对动脉粥样硬化性心血管疾病的预测作用。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-03-08 DOI: 10.1097/HCO.0000000000001140
Spencer D Proctor, Maggie Wang, Donna F Vine, Paolo Raggi

Purpose of review: Remnant cholesterol (RC) is the cholesterol carried in lipoproteins derived from the catabolism of chylomicrons and very low-density lipoproteins. Evidence supporting the causal relationship of RC with atherosclerotic cardiovascular disease (ASVD) is accumulating rapidly. The number of impactful contributions to this field are increasing and provide a pathophysiological insight into the current residual cardiovascular risk beyond low-density cholesterol (LDL)-cholesterol (LDL-C). They also raise the question of whether RC should be used in prediction models and become the target of new therapeutic interventions. The intent of this review is to highlight the recent advances on the role of RC in atherogenesis and the validation of RC as a predictor of ASVD.

Recent findings: Numerous prospective and retrospective cohorts helped validate a significant causal relationship of RC with various forms of ASVD, independent of LDL-C. A recent large Mendelian randomization study reinforced the existence of this relationship and showed that the risk of atherosclerotic events was driven nearly entirely by a direct effect of RC.

Summary: Both available and accumulating evidence suggest that a lifelong reduction in RC could translate into a substantial reduction in ASVD risk. The data support a revision of current guidelines to incorporate RC as an independent risk factor for ASVD. We propose that early screening of RC should be implemented and that RC lowering should become the target of future drug developments.

综述的目的:残余胆固醇(RC)是乳糜微粒和极低密度脂蛋白分解产生的脂蛋白中携带的胆固醇。支持残余胆固醇与动脉粥样硬化性心血管疾病(ASVD)之间因果关系的证据正在迅速积累。该领域有影响力的研究成果越来越多,它们从病理生理学角度揭示了当前低密度胆固醇(LDL)-胆固醇(LDL-C)之外的残余心血管风险。这些研究还提出了一个问题:RC 是否应被用于预测模型并成为新的治疗干预措施的目标。本综述旨在突出 RC 在动脉粥样硬化发生过程中的作用以及 RC 作为 ASVD 预测指标的验证方面的最新进展:大量前瞻性和回顾性队列研究帮助验证了 RC 与各种形式的 ASVD 之间的显著因果关系,而与低密度脂蛋白胆固醇无关。最近的一项大型孟德尔随机研究进一步证实了这种关系的存在,并表明动脉粥样硬化事件的风险几乎完全由 RC 的直接影响所驱动。总结:现有和不断积累的证据表明,终生降低 RC 可大幅降低 ASVD 风险。这些数据支持对现行指南进行修订,将 RC 作为 ASVD 的一个独立风险因素。我们建议对 RC 进行早期筛查,并将降低 RC 作为未来药物开发的目标。
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引用次数: 0
Short and long-term complications of hypertensive disorders of pregnancy: lifelong cardiovascular risks we cannot ignore. 妊娠高血压疾病的短期和长期并发症:我们不能忽视的终生心血管风险。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-02-21 DOI: 10.1097/HCO.0000000000001122
Cara E Saxon, Julia Bast, Josephine C Chou

Purpose of review: Hypertensive disorders of pregnancy (HDP) pose a significant threat to maternal cardiovascular health, with emerging research shedding light on the enduring risks beyond the gestational period. This review highlights updates regarding cardiovascular risks associated with HDP and their implications for long-term health.

Recent findings: Patients with a history of HDP are at an elevated risk of developing chronic hypertension, ischemic heart disease, stroke, valvular heart disease, and heart failure.Not surprisingly, patients with HDP experience higher rates of maternal and fetal adverse events in the antepartum and immediate postpartum periods, with high readmission rates for cardiovascular complications. The high risk of chronic hypertension after a HDP then leads to the development of subclinical disease over 5-10 years with overt cardiovascular disease becoming most prevalent in the decades following pregnancy. Early hypertension management in the antepartum and postpartum periods has lifelong health benefits and highlights the need for seamless postpartum transitions with close blood pressure monitoring and cardiovascular risk mitigation.

Summary: HDP significantly increases the risk of short and long-term adverse cardiovascular events. Integrated healthcare models that assess and address postpartum cardiovascular risk are necessary to improve the cardiovascular health and longevity of those effected by HDP.

综述的目的:妊娠期高血压疾病(HDP)对孕产妇的心血管健康构成重大威胁,新的研究揭示了妊娠期后的长期风险。本综述重点介绍与 HDP 相关的心血管风险及其对长期健康影响的最新进展:有 HDP 病史的患者罹患慢性高血压、缺血性心脏病、中风、瓣膜性心脏病和心力衰竭的风险较高。毫不奇怪,HDP 患者在产前和产后发生母体和胎儿不良事件的比例较高,因心血管并发症再次入院的比例也很高。HDP 后的高慢性高血压风险会导致 5-10 年的亚临床疾病的发展,而明显的心血管疾病在妊娠后的几十年中最为常见。产前和产后的早期高血压管理对健康有终生的益处,并强调了产后无缝过渡的必要性,密切监测血压并降低心血管风险。评估和应对产后心血管风险的综合医疗保健模式对于改善受 HDP 影响的人群的心血管健康和长寿十分必要。
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引用次数: 0
Updates in the management of cancer therapy-related hypertension. 癌症治疗相关高血压的最新管理方法。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-07-01 Epub Date: 2024-02-23 DOI: 10.1097/HCO.0000000000001127
Prerna Gupta, Mario Enrico Canonico, Christian Faaborg-Andersen, Nicole Prabhu, Lavanya Kondapalli, Raymundo A Quintana

Purpose of review: To provide a comprehensive review of hypertension among patients with cancer. Several cancer therapies cause hypertension which has resulted in a growing and vulnerable population of patients with difficult to control hypertension which has significant downstream effects.

Recent findings: Hypertension affects up to 50% of cancer patients and higher comorbidity when compared to the general population. Many anticancer therapies can cause hypertension through their treatment effect. Antihypertensive treatment is crucial given cardiovascular mortality is a leading cause of death among cancer patients. It is already known that hypertension is poorly controlled in the general population, and there are additional challenges in management among patients with cancer. Patients with cancer suffer from multimorbidity, are on multiple medications creating concern for drug interactions, and often have blood pressure lability, which can worsen clinical inertia among patients and their providers. It is crucial to effectively treat hypertension in cancer patients to mitigate downstream adverse cardiovascular events.

Summary: In recent years, there have been significant changes in management guidelines of hypertension and simultaneously as influx of new cancer therapeutics. We provide an update on hypertension treatment among patients with cancer on different chemotherapeutic agents.

综述目的:全面回顾癌症患者的高血压情况。几种癌症疗法都会引起高血压,这导致越来越多的患者易患难以控制的高血压,并产生了严重的下游影响:与普通人群相比,多达 50% 的癌症患者患有高血压,且合并症较高。许多抗癌疗法可通过其治疗效果引发高血压。心血管疾病是癌症患者死亡的主要原因,因此抗高血压治疗至关重要。众所周知,普通人群的高血压控制不佳,而癌症患者的高血压管理则面临更多挑战。癌症患者身患多种疾病,服用多种药物,这就造成了药物相互作用的问题,而且他们的血压往往不稳定,这可能会加重患者及其医疗服务提供者的临床惰性。摘要:近年来,随着癌症新疗法的涌现,高血压管理指南也发生了重大变化。我们提供了使用不同化疗药物的癌症患者高血压治疗的最新情况。
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引用次数: 0
Metabolic basis of cardiac dysfunction in cancer patients. 癌症患者心脏功能障碍的代谢基础。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-05-01 Epub Date: 2024-02-21 DOI: 10.1097/HCO.0000000000001118
Jane C Figueiredo, Neil Adri Bhowmick, Anja Karlstaedt

Purpose of review: The relationship between metabolism and cardiovascular diseases is complex and bidirectional. Cardiac cells must adapt metabolic pathways to meet biosynthetic demands and energy requirements to maintain contractile function. During cancer, this homeostasis is challenged by the increased metabolic demands of proliferating cancer cells.

Recent findings: Tumors have a systemic metabolic impact that extends beyond the tumor microenvironment. Lipid metabolism is critical to cancer cell proliferation, metabolic adaptation, and increased cardiovascular risk. Metabolites serve as signals which provide insights for diagnosis and prognosis in cardio-oncology patients.

Summary: Metabolic processes demonstrate a complex relationship between cancer cell states and cardiovascular remodeling with potential for therapeutic interventions.

综述的目的:新陈代谢与心血管疾病之间的关系是复杂和双向的。心脏细胞必须调整代谢途径,以满足生物合成需求和能量需求,从而维持收缩功能。在癌症期间,这种平衡受到增殖的癌细胞代谢需求增加的挑战:肿瘤对全身代谢的影响超出了肿瘤微环境。脂质代谢对癌细胞增殖、代谢适应和心血管风险增加至关重要。代谢物可作为信号,为心血管肿瘤患者的诊断和预后提供洞察力。摘要:代谢过程显示了癌细胞状态与心血管重塑之间的复杂关系,具有治疗干预的潜力。
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引用次数: 0
Clinical impact of genetic testing for lipid disorders. 血脂紊乱基因检测的临床影响。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-05-01 Epub Date: 2024-02-29 DOI: 10.1097/HCO.0000000000001133
Emir Muzurović, Sanja Borozan, Manfredi Rizzo

Purpose of review: Genetic testing is increasingly becoming a common consideration in the clinical approach of dyslipidemia patients. Advances in research in last decade and increased recognition of genetics in biological pathways modulating blood lipid levels created a gap between theoretical knowledge and its applicability in clinical practice. Therefore, it is very important to define the clinical justification of genetic testing in dyslipidemia patients.

Recent findings: Clinical indications for genetic testing for most dyslipidemias are not precisely defined and there are no clearly established guideline recommendations. In patients with severe low-density lipoprotein cholesterol (LDL-C) levels, the genetic analysis can be used to guide diagnostic and therapeutic approach, while in severe hypertriglyceridemia (HTG), clinicians can rely on triglyceride level rather than a genotype along the treatment pathway. Genetic testing increases diagnostic accuracy and risk stratification, access and adherence to specialty therapies, and cost-effectiveness of cascade testing. A shared decision-making model between the provider and the patient is essential as patient values, preferences and clinical characteristics play a very strong role.

Summary: Genetic testing for lipid disorders is currently underutilized in clinical practice. However, it should be selectively used, according to the type of dyslipidemia and when the benefits overcome costs.

审查目的:基因检测正日益成为临床治疗血脂异常患者的常见考虑因素。近十年来,研究取得了进展,人们越来越认识到遗传学在调节血脂水平的生物通路中的作用,这就造成了理论知识与临床实践应用之间的差距。因此,明确血脂异常患者基因检测的临床合理性非常重要:大多数血脂异常基因检测的临床适应症尚未明确界定,也没有明确的指导建议。对于低密度脂蛋白胆固醇(LDL-C)水平严重的患者,基因分析可用于指导诊断和治疗方法;而对于严重的高甘油三酯血症(HTG)患者,临床医生在治疗过程中可依赖甘油三酯水平而非基因型。基因检测提高了诊断的准确性和风险分层、特殊疗法的可及性和依从性,以及级联检测的成本效益。由于患者的价值观、偏好和临床特征起着非常重要的作用,因此医疗服务提供者与患者之间的共同决策模式至关重要。然而,应根据血脂异常的类型,在利大于弊的情况下有选择性地使用基因检测。
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引用次数: 0
Genetic causes of lymphatic disorders: recent updates on the clinical and molecular aspects of lymphatic disease. 淋巴疾病的遗传原因:淋巴疾病临床和分子方面的最新进展。
IF 2.3 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-05-01 Epub Date: 2024-03-13 DOI: 10.1097/HCO.0000000000001116
Catharine Bowman, Stanley G Rockson

Purpose of review: The lymphatic system facilitates several key functions that limit significant morbidity and mortality. Despite the impact and burden of lymphatic disorders, there are many remaining disorders whose genetic substrate remains unknown. The purpose of this review is to provide an update on the genetic causes of lymphatic disorders, while reporting on newly proposed clinical classifications of lymphatic disease.

Recent findings: We reviewed several new mutations in genes that have been identified as potential causes of lymphatic disorders including: MDFIC, EPHB 4 , and ANGPT2. Furthermore, the traditional St. George's Classification system for primary lymphatic anomalies has been updated to reflect the use of genetic testing, both as a tool for the clinical identification of lymphatic disease and as a method through which new sub-classifications of lymphatic disorders have been established within this framework. Finally, we highlighted recent clinical studies that have explored the impact of therapies such as sirolimus, ketoprofen, and acebilustat on lymphatic disorders.

Summary: Despite a growing body of evidence, current literature demonstrates a persistent gap in the number of known genes responsible for lymphatic disease entities. Recent clinical classification tools have been introduced in order to integrate traditional symptom- and time-based diagnostic approaches with modern genetic classifications, as highlighted in the updated St. George's classification system. With the introduction of this novel approach, clinicians may be better equipped to recognize established disease and, potentially, to identify novel causal mutations. Further research is needed to identify additional genetic causes of disease and to optimize current clinical tools for diagnosis and treatment.

回顾的目的:淋巴系统具有多种关键功能,可限制重大疾病的发病率和死亡率。尽管淋巴系统疾病影响巨大、负担沉重,但仍有许多疾病的遗传基础尚不清楚。本综述旨在提供淋巴系统疾病遗传原因的最新信息,同时报告新提出的淋巴系统疾病临床分类:我们回顾了几种新的基因突变,这些基因突变已被确定为淋巴系统疾病的潜在病因,包括最近的发现:我们回顾了几种新的基因突变,这些基因突变已被确定为淋巴疾病的潜在病因,包括:MDFIC、EPHB4 和 ANGPT2。此外,针对原发性淋巴异常的传统圣乔治分类系统也进行了更新,以反映基因检测的应用,这既是临床识别淋巴疾病的一种工具,也是在此框架内建立淋巴疾病新亚分类的一种方法。最后,我们重点介绍了最近开展的临床研究,这些研究探讨了西罗莫司、酮洛芬和阿司咪唑等疗法对淋巴疾病的影响。摘要:尽管证据越来越多,但目前的文献显示,导致淋巴疾病实体的已知基因数量一直存在缺口。新近推出的临床分类工具将传统的基于症状和时间的诊断方法与现代基因分类相结合,最新的圣乔治分类系统就是其中之一。随着这种新方法的引入,临床医生可以更好地识别已确定的疾病,并有可能确定新的致病突变。我们还需要进一步研究,以确定更多的遗传致病原因,并优化当前的临床诊断和治疗工具。
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引用次数: 0
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Current Opinion in Cardiology
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