【周五】经典高分文献阅读·NEJM 征服动脉粥样硬化性心血管疾病- 50年的进展(2)

2021
03/05

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A Half-Century of Progress in Health: The National Academy of Medicine at 50

半个世纪的健康进步:50岁的国家医学研究院

Conquering Atherosclerotic Cardiovascular Disease — 50 Years of Progress

征服动脉粥样硬化性心血管疾病- 50年的进展

Gary H. Gibbons, M.D., Christine E. Seidman, M.D., and Eric J. Topol, M.D.



翻译:猫,校对:叮当丸子麻



The trajectory发展轨迹 of cardiovascular disease is shaped by the interaction between polygenic factors and environmental influences. Longitudinal studies 纵向研究have provided evidence that during childhood and early adulthood, exposure to neighborhood-level factors such as social deprivation 社会剥夺and racial segregation种族隔离, limited access to a healthy diet, lack of opportunities for regular exercise, and suboptimal次选的 health care can affect the trajectory of cardiovascular disease over the life course. The influence of social determinants of health and the exacerbation of health inequities have prevented further progress against cardiovascular disease.Addressing inequities will be an important next step in efforts to alleviate the burdens of cardiovascular disease. This step will require a collective approach involving academic researchers, clinicians, and many other partners that engages the community to test strategies for achieving optimal uptake and continued sustainability of proven interventions.


心血管疾病的发展轨迹是由多基因因素和环境影响的相互作用形成的。纵向研究提供证据表明,在儿童和成年早期,暴露在社区水平因素如社会剥夺和种族隔离,缺乏健康饮食,缺乏定期锻炼的机会,和次优医疗会影响心血管疾病在生命历程的轨迹。健康的社会决定因素的影响和健康不平等的加剧阻碍了在防治心血管疾病方面取得进一步进展。解决不平等问题将是努力减轻心血管疾病负担的下一步重要步骤。这一步骤将需要一个包括学术研究人员、临床医生和许多其他合作伙伴在内的集体方法,这些合作伙伴参与社区,以测试策略,以实现已证实的干预措施的最佳吸收和持续可持续性。


As biomedicine enters the age of precision health, we anticipate that genomic science will continue to expand our understanding of the biologic systems and molecular networks that mediate the development and clinical manifestation of cardiovascular disease. New methods of immune phenotyping and “multiomic” characterization of the epigenome, transcriptome, metabolome, and microbiome will probably accelerate the discovery of biomarkers生物标记物 and the identification of new targets靶点 for therapeutic intervention治疗干预. We also expect that investigators will advance our understanding of the ways in which the social determinants of health “get under the skin” to modulate the epigenome and other biologic systems to promote resilience or accelerate disease development. We look forward to the development of biomarkers, personal sensor technology个人传感器技术, and artificial-intelligence apps人工智能应用程序 that will continuously monitor biologic systems, permit real-time implementation of personalized dietary recommendations个性化饮食建议, and reinforce the importance of healthy lifestyle habits健康生活方式 for the prevention of cardiovascular disease.


随着生物医学进入精准健康时代,我们预计基因组科学将继续扩大我们对介导心血管疾病发展和临床表现的生物系统和分子网络的理解。免疫表型的新方法和表观基因组、转录组、代谢组和微生物组的“多组学”表征可能会加速生物标志物的发现和治疗干预的新靶点的确定。我们也希望研究人员能够加深我们对健康的社会决定因素如何“深入皮肤”来调节表观基因组和其他生物系统以促进恢复力或加速疾病发展的理解。我们期待生物标志物、个人传感器技术和人工智能应用的发展,它们将持续监测生物系统,允许实时实施个性化饮食建议,并加强健康的生活方式习惯对预防心血管疾病的重要性。


We envision that the next chapter of this story will involve building on advances in genomics,systems biology, and data sciences to better predict cardiovascular disease onset in early adulthood. In contrast to the current focus on slowing the progression of advanced plaques after middle age, future therapeutic options should be targeted at earlier stages of the disease process, 未来的治疗方案应针对疾病过程的早期阶段,with the intent of preempting the progression of cardiovascular disease. Recent proof-of-concept studies have demonstrated the feasibility of in vivo genetic engineering with nanoparticle-delivery technology to introduce PCSK9 mutations with salutary effects within the liver that cause sustained reductions in LDL cholesterol levels. The next 50 years of efforts to conquer cardiovascular disease will probably leverage new tools and technologies, from biologics and small-molecule drugs to preventive strategies including genome editing从生物制剂和小分子药物到预防策略,包括基因组编辑. This endeavor will require a multilevel, systems-based approach to preempt disease at its earliest stages and exert a long-term, cumulative benefit throughout the lifespan.


我们预计这个故事的下一章将涉及基因组学的发展,统生物学和数据科学来更好地预测成年早期心血管疾病的发生。目前的重点是减缓中年后晚期斑块的进展,反之,未来的治疗选择应针对疾病进程的早期阶段,目的是预防心血管疾病的进展。最近的概念验证研究已经证明了体内基因工程的可行性,通过纳米颗粒传递技术引入PCSK9突变,在肝脏内产生有益作用,从而持续降低LDL胆固醇水平。未来50年攻克心血管疾病的努力可能会利用新的工具和技术,从生物制剂和小分子药物到包括基因组编辑在内的预防策略。这一努力将需要一种多层次的、基于系统的方法,在疾病的早期阶段先发制人,并在整个生命周期中发挥长期累积的效益。


The past half-century of progress in alleviating the burdens of cardiovascular disease gives us great optimism给了我们很大的乐观 as we look ahead to emerging opportunities to further enhance cardiovascular health. Achieving this goal will require disciplined and continuous reinvestment 有纪律和持续的再投资in discovery science, translational research, and development leading to interventions that benefit public health. This cycle enriches our understanding of the causal factors of disease — both molecular mediators and social factors — as powerful targets of action for improving patient care and public health. There will be a persistent need for advances in the science of health delivery to develop innovative strategies that propel people to adopt healthier lifestyle habits, prompt communities to make structural investments to support healthier neighborhoods, and promote the effective adoption of evidence-based solutions基于证据的解决方案 in various real-world contexts. As the NAM National Academy of Medicine (NAM pursues scientific advances during the next five decades, the success story won’t be complete until cardiovascular disease no longer represents an important cause of morbidity or death.


过去半个世纪在减轻心血管疾病负担方面取得的进展给我们带来了极大的乐观,我们期待着进一步增强心血管健康的新机遇。要实现这一目标,就需要有纪律地、持续地对发现科学、转化研究和发展进行再投资,从而产生有利于公共卫生的干预措施。这一循环丰富了我们对疾病的因果因素(包括分子介质和社会因素)的理解,这些因素是改善病人护理和公共卫生的有力行动目标。我们将持续需要卫生服务科学的进步,以制定创新战略,推动人们采取更健康的生活方式习惯,促使社区进行结构性投资,以支持更健康的社区,并促进在各种现实环境中有效采用循证解决方案。随着NAM在未来50年里追求科学进步,除非心血管疾病不再是发病率或死亡的一个重要原因,否则成功的故事不会完成。

1972:Michael Brown和Joseph Goldstein开始研究LDL受体的发现

1973:Akira Endo发现第一个抗胆固醇的他汀类药物

1977:第一次经皮冠状动脉腔内成形术是在一个病人身上进行的

1978:The Bethesda会议证实,在美国,心脏病、冠心病和先天性心脏病的死亡率有所降低

1981:FDA批准了第一个ACE抑制剂(卡托普利)

1986:第一个可自我扩张的冠状动脉支架是通过非手术植入患者体内的

1987:第一个商业上可用的他汀(洛伐他汀)是由FDA批准的

1958年的《联邦航空法》第404条进行修订,包括禁止在2小时或更少的国内航班上吸烟

1988:詹姆斯·布莱克爵士因发明β受体阻滞剂而获得诺贝尔生理学或医学奖

1991:妇女健康倡议启动在研究心血管疾病、癌症和骨质疏松症的妇女健康倡议启动

1994:HeartMate左心室辅助系统已获FDA批准

1996:Framingham心脏研究人员得出结论,早期和更积极的高血压治疗对预防充血性心力衰竭至关重要。SHEP试验确定了治疗老年人单纯收缩期高血压的益处

1997-1998:DASH和TONE的试验表明,生活方式的改变可以显著降低成年人的血压,并使一些老年人不再需要服用抗高血压药物

1998:Framingham风险评分是为了评估10年冠心病风险

2003:人类基因组计划完成PCSK9基因的突变被发现导致高胆固醇血症

2005:组织成立了一个健康的社会决定因素委员会,以审查关于健康不平等的证据,提出社会辩论,并建议改善全球健康的政策

2006:研究发现,PCSK9基因的功能缺失变异与低密度脂蛋白胆固醇和总体冠心病风险的降低有关

2008:基因型评分用于评估心血管疾病的风险

2009:家庭预防吸烟和烟草控制法案被签署成为法律,赋予食品和药物管理局管理烟草产品的生产、分销和销售的权力

2011:经导管主动脉瓣置换术(TAVR)经FDA批准用于治疗有禁止风险的主动脉狭窄患者

2015:SPRINT试验证实了强化血压控制对非糖尿病高危患者的益处

2017:PCSK9抗体抑制剂,与标准疗法一起,被发现可以显著降低LDL胆固醇水平和心血管事件的发生率


本文由作者自行上传,并且作者对本文图文涉及知识产权负全部责任。如有侵权请及时联系(邮箱:nanxingjun@hmkx.cn
关键词:
动脉粥样硬化,心血管疾病,基因组,生物,预防,治疗

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