Pub Date : 2024-08-07DOI: 10.1038/s41569-024-01069-z
Irene Fernández-Ruiz
Acute ischaemic stroke induces persistent innate immune memory through epigenetic changes in myeloid progenitors in the bone marrow, and this innate immune training contributes to cardiac remodelling and dysfunction in the long term, according to a new study.
{"title":"Stroke triggers an innate immune memory that drives cardiac dysfunction","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-024-01069-z","DOIUrl":"10.1038/s41569-024-01069-z","url":null,"abstract":"Acute ischaemic stroke induces persistent innate immune memory through epigenetic changes in myeloid progenitors in the bone marrow, and this innate immune training contributes to cardiac remodelling and dysfunction in the long term, according to a new study.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 10","pages":"663-663"},"PeriodicalIF":41.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1038/s41569-024-01066-2
Irene Fernández-Ruiz
A new small-molecule inhibitor of vasohibins reduces myocardial stiffness and improves diastolic relaxation in a rat model of HFpEF.
一种新的血管抑制素小分子抑制剂可降低心肌僵硬度并改善高频心衰大鼠模型的舒张松弛。
{"title":"Potential new therapeutic target for HFpEF","authors":"Irene Fernández-Ruiz","doi":"10.1038/s41569-024-01066-2","DOIUrl":"10.1038/s41569-024-01066-2","url":null,"abstract":"A new small-molecule inhibitor of vasohibins reduces myocardial stiffness and improves diastolic relaxation in a rat model of HFpEF.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 10","pages":"664-664"},"PeriodicalIF":41.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-25DOI: 10.1038/s41569-024-01058-2
Luisa C. C. Brant, J. Jaime Miranda, Rodrigo M. Carrillo-Larco, David Flood, Vilma Irazola, Antonio Luiz P. Ribeiro
In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region. Cardiovascular diseases are the leading cause of death in Latin America and the Caribbean (LAC), precipitated by the unique milieu of population growth, rapid urbanization, socioeconomic disparities and prevalent cardiometabolic risk factors. Brant and colleagues summarize trends in cardiometabolic health in LAC and discuss tailored, innovative solutions to address the growing burden of disease in the region.
{"title":"Epidemiology of cardiometabolic health in Latin America and strategies to address disparities","authors":"Luisa C. C. Brant, J. Jaime Miranda, Rodrigo M. Carrillo-Larco, David Flood, Vilma Irazola, Antonio Luiz P. Ribeiro","doi":"10.1038/s41569-024-01058-2","DOIUrl":"10.1038/s41569-024-01058-2","url":null,"abstract":"In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region. Cardiovascular diseases are the leading cause of death in Latin America and the Caribbean (LAC), precipitated by the unique milieu of population growth, rapid urbanization, socioeconomic disparities and prevalent cardiometabolic risk factors. Brant and colleagues summarize trends in cardiometabolic health in LAC and discuss tailored, innovative solutions to address the growing burden of disease in the region.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 12","pages":"849-864"},"PeriodicalIF":41.7,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1038/s41569-024-01065-3
Gregory B. Lim
A new study indicates that proteins in the sarcomere complex are stochastically removed and degraded and are replaced by newly translated proteins. Sarcomere turnover occurs at a similar rate within cardiomyocytes and across the heart and slows with ageing.
{"title":"Cardiac sarcomere turnover by unidirectional replacement of proteins","authors":"Gregory B. Lim","doi":"10.1038/s41569-024-01065-3","DOIUrl":"10.1038/s41569-024-01065-3","url":null,"abstract":"A new study indicates that proteins in the sarcomere complex are stochastically removed and degraded and are replaced by newly translated proteins. Sarcomere turnover occurs at a similar rate within cardiomyocytes and across the heart and slows with ageing.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 9","pages":"600-600"},"PeriodicalIF":41.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1038/s41569-024-01047-5
Paul D. Morris, Ryan A. Anderton, Karina Marshall-Goebel, Joseph K. Britton, Stuart M. C. Lee, Nicolas P. Smith, Frans N. van de Vosse, Karen M. Ong, Tom A. Newman, Daniel J. Taylor, Tim Chico, Julian P. Gunn, Andrew J. Narracott, D. Rod Hose, Ian Halliday
For more than 60 years, humans have travelled into space. Until now, the majority of astronauts have been professional, government agency astronauts selected, in part, for their superlative physical fitness and the absence of disease. Commercial spaceflight is now becoming accessible to members of the public, many of whom would previously have been excluded owing to unsatisfactory fitness or the presence of cardiorespiratory diseases. While data exist on the effects of gravitational and acceleration (G) forces on human physiology, data on the effects of the aerospace environment in unselected members of the public, and particularly in those with clinically significant pathology, are limited. Although short in duration, these high acceleration forces can potentially either impair the experience or, more seriously, pose a risk to health in some individuals. Rather than expose individuals with existing pathology to G forces to collect data, computational modelling might be useful to predict the nature and severity of cardiovascular diseases that are of sufficient risk to restrict access, require modification, or suggest further investigation or training before flight. In this Review, we explore state-of-the-art, zero-dimensional, compartmentalized models of human cardiovascular pathophysiology that can be used to simulate the effects of acceleration forces, homeostatic regulation and ventilation–perfusion matching, using data generated by long-arm centrifuge facilities of the US National Aeronautics and Space Administration and the European Space Agency to risk stratify individuals and help to improve safety in commercial suborbital spaceflight. During commercial spaceflight, individuals who might have underlying cardiovascular disease will be exposed to increased gravitational and acceleration (G) forces. In this Review, Morris and colleagues explore the use of computational models to simulate the effects of G forces on human cardiovascular pathophysiology to risk-stratify individuals and help to improve safety in commercial suborbital spaceflight.
60 多年来，人类一直在太空中旅行。迄今为止，大多数宇航员都是政府机构的专业宇航员，他们之所以被选中，部分原因是他们具有超强的身体素质和没有疾病。现在，公众也可以参加商业航天飞行，其中许多人以前由于体能不佳或患有心肺疾病而被排除在外。虽然已有关于重力和加速度（G）对人体生理影响的数据，但关于航空航天环境对未经选择的公众，特别是对那些患有临床重大疾病的人的影响的数据却很有限。虽然持续时间很短，但这些高加速度力可能会损害某些人的体验，更严重的是会对其健康构成威胁。与其让已有病变的人暴露在 G 力下以收集数据，不如通过计算建模来预测心血管疾病的性质和严重程度，因为这些疾病的风险足以限制飞行、要求改装或建议在飞行前进行进一步的调查或培训。在这篇综述中，我们利用美国国家航空航天局和欧洲空间局的长臂离心机设施生成的数据，探讨了最先进的零维、分区人体心血管病理生理学模型，这些模型可用于模拟加速度力、稳态调节和通气-灌注匹配的影响，从而对个人进行风险分层，帮助提高商业亚轨道航天飞行的安全性。
{"title":"Computational modelling of cardiovascular pathophysiology to risk stratify commercial spaceflight","authors":"Paul D. Morris, Ryan A. Anderton, Karina Marshall-Goebel, Joseph K. Britton, Stuart M. C. Lee, Nicolas P. Smith, Frans N. van de Vosse, Karen M. Ong, Tom A. Newman, Daniel J. Taylor, Tim Chico, Julian P. Gunn, Andrew J. Narracott, D. Rod Hose, Ian Halliday","doi":"10.1038/s41569-024-01047-5","DOIUrl":"10.1038/s41569-024-01047-5","url":null,"abstract":"For more than 60 years, humans have travelled into space. Until now, the majority of astronauts have been professional, government agency astronauts selected, in part, for their superlative physical fitness and the absence of disease. Commercial spaceflight is now becoming accessible to members of the public, many of whom would previously have been excluded owing to unsatisfactory fitness or the presence of cardiorespiratory diseases. While data exist on the effects of gravitational and acceleration (G) forces on human physiology, data on the effects of the aerospace environment in unselected members of the public, and particularly in those with clinically significant pathology, are limited. Although short in duration, these high acceleration forces can potentially either impair the experience or, more seriously, pose a risk to health in some individuals. Rather than expose individuals with existing pathology to G forces to collect data, computational modelling might be useful to predict the nature and severity of cardiovascular diseases that are of sufficient risk to restrict access, require modification, or suggest further investigation or training before flight. In this Review, we explore state-of-the-art, zero-dimensional, compartmentalized models of human cardiovascular pathophysiology that can be used to simulate the effects of acceleration forces, homeostatic regulation and ventilation–perfusion matching, using data generated by long-arm centrifuge facilities of the US National Aeronautics and Space Administration and the European Space Agency to risk stratify individuals and help to improve safety in commercial suborbital spaceflight. During commercial spaceflight, individuals who might have underlying cardiovascular disease will be exposed to increased gravitational and acceleration (G) forces. In this Review, Morris and colleagues explore the use of computational models to simulate the effects of G forces on human cardiovascular pathophysiology to risk-stratify individuals and help to improve safety in commercial suborbital spaceflight.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 10","pages":"667-681"},"PeriodicalIF":41.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1038/s41569-024-01063-5
Malcolm Irving
Contraction of the heart is driven by cyclical interactions between myosin and actin filaments powered by ATP hydrolysis. The modular structure of heart muscle and the organ-level synchrony of the heartbeat ensure tight reciprocal coupling between this myosin ATPase cycle and the macroscopic cardiac cycle. The myosin motors respond to the cyclical activation of the actin and myosin filaments to drive the pressure changes that control the inflow and outflow valves of the heart chambers. Opening and closing of the valves in turn switches the myosin motors between roughly isometric and roughly isotonic contraction modes. Peak filament stress in the heart is much smaller than in fully activated skeletal muscle, although the myosin filaments in the two muscle types have the same number of myosin motors. Calculations indicate that only ~5% of the myosin motors in the heart are needed to generate peak systolic pressure, although many more motors are needed to drive ejection. Tight regulation of the number of active motors is essential for the efficient functioning of the healthy heart - this control is commonly disrupted by gene variants associated with inherited heart disease, and its restoration might be a useful end point in the development of novel therapies.
心脏的收缩是由肌球蛋白和肌动蛋白丝在 ATP 水解作用下的周期性相互作用驱动的。心肌的模块化结构和心脏搏动的器官级同步性确保了肌球蛋白 ATP 酶周期与宏观心脏周期之间紧密的相互耦合。肌球蛋白马达响应肌动蛋白丝和肌球蛋白丝的周期性激活，驱动压力变化，从而控制心腔的流入和流出瓣膜。瓣膜的打开和关闭反过来在大致等长和大致等张收缩模式之间切换肌球蛋白马达。尽管两种肌肉中的肌球蛋白丝具有相同数量的肌球蛋白马达，但心脏中肌球蛋白丝的峰值应力远小于完全激活的骨骼肌。计算表明，产生收缩压峰值只需要心脏中约 5% 的肌球蛋白马达，而驱动射血则需要更多的肌球蛋白马达。对活跃肌球蛋白马达数量的严格调控对健康心脏的高效运作至关重要--这种调控通常会被与遗传性心脏病相关的基因变异所破坏，恢复这种调控可能是开发新型疗法的一个有用终点。
{"title":"Functional control of myosin motors in the cardiac cycle.","authors":"Malcolm Irving","doi":"10.1038/s41569-024-01063-5","DOIUrl":"https://doi.org/10.1038/s41569-024-01063-5","url":null,"abstract":"<p><p>Contraction of the heart is driven by cyclical interactions between myosin and actin filaments powered by ATP hydrolysis. The modular structure of heart muscle and the organ-level synchrony of the heartbeat ensure tight reciprocal coupling between this myosin ATPase cycle and the macroscopic cardiac cycle. The myosin motors respond to the cyclical activation of the actin and myosin filaments to drive the pressure changes that control the inflow and outflow valves of the heart chambers. Opening and closing of the valves in turn switches the myosin motors between roughly isometric and roughly isotonic contraction modes. Peak filament stress in the heart is much smaller than in fully activated skeletal muscle, although the myosin filaments in the two muscle types have the same number of myosin motors. Calculations indicate that only ~5% of the myosin motors in the heart are needed to generate peak systolic pressure, although many more motors are needed to drive ejection. Tight regulation of the number of active motors is essential for the efficient functioning of the healthy heart - this control is commonly disrupted by gene variants associated with inherited heart disease, and its restoration might be a useful end point in the development of novel therapies.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":" ","pages":""},"PeriodicalIF":41.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1038/s41569-024-01057-3
Ester Cerdeira Sabino, Maria Carmo P. Nunes, Johannes Blum, Israel Molina, Antonio Luiz P. Ribeiro
Trypanosomiases are diseases caused by various species of protozoan parasite in the genus Trypanosoma, each presenting with distinct clinical manifestations and prognoses. Infections can affect multiple organs, with Trypanosoma cruzi predominantly affecting the heart and digestive system, leading to American trypanosomiasis or Chagas disease, and Trypanosoma brucei primarily causing a disease of the central nervous system known as human African trypanosomiasis or sleeping sickness. In this Review, we discuss the effects of these infections on the heart, with particular emphasis on Chagas disease, which continues to be a leading cause of cardiomyopathy in Latin America. The epidemiology of Chagas disease has changed substantially since 1990 owing to the emigration of over 30 million Latin American citizens, primarily to Europe and the USA. This movement of people has led to the global dissemination of individuals infected with T. cruzi. Therefore, cardiologists worldwide must familiarize themselves with Chagas disease and the severe, chronic manifestation — Chagas cardiomyopathy — because of the expanded prevalence of this disease beyond traditional endemic regions. Infection with Trypanosoma spp. can cause Chagas disease or human African trypanosomiasis. In this Review, Sabino and colleagues discuss the effects of these infections on the heart, with particular emphasis on the pathogenesis, diagnosis and treatment of Chagas cardiomyopathy.
{"title":"Cardiac involvement in Chagas disease and African trypanosomiasis","authors":"Ester Cerdeira Sabino, Maria Carmo P. Nunes, Johannes Blum, Israel Molina, Antonio Luiz P. Ribeiro","doi":"10.1038/s41569-024-01057-3","DOIUrl":"10.1038/s41569-024-01057-3","url":null,"abstract":"Trypanosomiases are diseases caused by various species of protozoan parasite in the genus Trypanosoma, each presenting with distinct clinical manifestations and prognoses. Infections can affect multiple organs, with Trypanosoma cruzi predominantly affecting the heart and digestive system, leading to American trypanosomiasis or Chagas disease, and Trypanosoma brucei primarily causing a disease of the central nervous system known as human African trypanosomiasis or sleeping sickness. In this Review, we discuss the effects of these infections on the heart, with particular emphasis on Chagas disease, which continues to be a leading cause of cardiomyopathy in Latin America. The epidemiology of Chagas disease has changed substantially since 1990 owing to the emigration of over 30 million Latin American citizens, primarily to Europe and the USA. This movement of people has led to the global dissemination of individuals infected with T. cruzi. Therefore, cardiologists worldwide must familiarize themselves with Chagas disease and the severe, chronic manifestation — Chagas cardiomyopathy — because of the expanded prevalence of this disease beyond traditional endemic regions. Infection with Trypanosoma spp. can cause Chagas disease or human African trypanosomiasis. In this Review, Sabino and colleagues discuss the effects of these infections on the heart, with particular emphasis on the pathogenesis, diagnosis and treatment of Chagas cardiomyopathy.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 12","pages":"865-879"},"PeriodicalIF":41.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1038/s41569-024-01056-4
James W. S. Jahng, Mark P. Little, Hyunsoo J. No, Billy W. Loo Jr, Joseph C. Wu
Ionizing radiation is widely used in various industrial and medical applications, resulting in increased exposure for certain populations. Lessons from radiation accidents and occupational exposure have highlighted the cardiovascular and cerebrovascular risks associated with radiation exposure. In addition, radiation therapy for cancer has been linked to numerous cardiovascular complications, depending on the distribution of the dose by volume in the heart and other relevant target tissues in the circulatory system. The manifestation of symptoms is influenced by numerous factors, and distinct cardiac complications have previously been observed in different groups of patients with cancer undergoing radiation therapy. However, in contemporary radiation therapy, advances in treatment planning with conformal radiation delivery have markedly reduced the mean heart dose and volume of exposure, and these variables are therefore no longer sole surrogates for predicting the risk of specific types of heart disease. Nevertheless, certain cardiac substructures remain vulnerable to radiation exposure, necessitating close monitoring. In this Review, we provide a comprehensive overview of the consequences of radiation exposure on the cardiovascular system, drawing insights from various cohorts exposed to uniform, whole-body radiation or to partial-body irradiation, and identify potential risk modifiers in the development of radiation-associated cardiovascular disease. In this Review, Wu and co-workers describe the consequences of radiation exposure on the cardiovascular system, drawing insights from individuals exposed to whole-body radiation (including nuclear and medical workers) and from patients with cancer undergoing radiation therapy.
{"title":"Consequences of ionizing radiation exposure to the cardiovascular system","authors":"James W. S. Jahng, Mark P. Little, Hyunsoo J. No, Billy W. Loo Jr, Joseph C. Wu","doi":"10.1038/s41569-024-01056-4","DOIUrl":"10.1038/s41569-024-01056-4","url":null,"abstract":"Ionizing radiation is widely used in various industrial and medical applications, resulting in increased exposure for certain populations. Lessons from radiation accidents and occupational exposure have highlighted the cardiovascular and cerebrovascular risks associated with radiation exposure. In addition, radiation therapy for cancer has been linked to numerous cardiovascular complications, depending on the distribution of the dose by volume in the heart and other relevant target tissues in the circulatory system. The manifestation of symptoms is influenced by numerous factors, and distinct cardiac complications have previously been observed in different groups of patients with cancer undergoing radiation therapy. However, in contemporary radiation therapy, advances in treatment planning with conformal radiation delivery have markedly reduced the mean heart dose and volume of exposure, and these variables are therefore no longer sole surrogates for predicting the risk of specific types of heart disease. Nevertheless, certain cardiac substructures remain vulnerable to radiation exposure, necessitating close monitoring. In this Review, we provide a comprehensive overview of the consequences of radiation exposure on the cardiovascular system, drawing insights from various cohorts exposed to uniform, whole-body radiation or to partial-body irradiation, and identify potential risk modifiers in the development of radiation-associated cardiovascular disease. In this Review, Wu and co-workers describe the consequences of radiation exposure on the cardiovascular system, drawing insights from individuals exposed to whole-body radiation (including nuclear and medical workers) and from patients with cancer undergoing radiation therapy.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 12","pages":"880-898"},"PeriodicalIF":41.7,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/s41569-024-01039-5
Brian A. Ference, Eugene Braunwald, Alberico L. Catapano
The trapping of LDL and other apolipoprotein B-containing lipoproteins within the artery wall causes atherosclerosis. As more LDL becomes trapped within the artery wall over time, the atherosclerotic plaque burden gradually increases, raising the risk of an acute cardiovascular event. Therefore, the biological effect of LDL on the risk of atherosclerotic cardiovascular disease (ASCVD) depends on both the magnitude and duration of exposure. Maintaining low levels of LDL-cholesterol (LDL-C) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and, by delaying the age at which mature atherosclerotic plaques develop, substantially reduces the lifetime risk of ASCVD events. Summing LDL-C measurements over time to calculate cumulative exposure to LDL generates a unique biomarker that captures both the magnitude and duration of exposure, which facilitates the estimation of the absolute risk of having an acute cardiovascular event at any point in time. Titrating LDL-C lowering to keep cumulative exposure to LDL below the threshold at which acute cardiovascular events occur can effectively prevent ASCVD. In this Review, we provide the first comprehensive overview of how the LDL cumulative exposure hypothesis can guide the prevention of ASCVD. We also discuss the benefits of maintaining lower LDL-C levels over time and how this knowledge can be used to inform clinical practice guidelines as well as to design novel primary prevention trials and ASCVD prevention programmes. In this Review, Catapano and colleagues discuss the evidence supporting the LDL cumulative exposure hypothesis and how measuring cumulative LDL exposure can be used to estimate risk and contribute to the prevention of atherosclerotic cardiovascular disease.
{"title":"The LDL cumulative exposure hypothesis: evidence and practical applications","authors":"Brian A. Ference, Eugene Braunwald, Alberico L. Catapano","doi":"10.1038/s41569-024-01039-5","DOIUrl":"10.1038/s41569-024-01039-5","url":null,"abstract":"The trapping of LDL and other apolipoprotein B-containing lipoproteins within the artery wall causes atherosclerosis. As more LDL becomes trapped within the artery wall over time, the atherosclerotic plaque burden gradually increases, raising the risk of an acute cardiovascular event. Therefore, the biological effect of LDL on the risk of atherosclerotic cardiovascular disease (ASCVD) depends on both the magnitude and duration of exposure. Maintaining low levels of LDL-cholesterol (LDL-C) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and, by delaying the age at which mature atherosclerotic plaques develop, substantially reduces the lifetime risk of ASCVD events. Summing LDL-C measurements over time to calculate cumulative exposure to LDL generates a unique biomarker that captures both the magnitude and duration of exposure, which facilitates the estimation of the absolute risk of having an acute cardiovascular event at any point in time. Titrating LDL-C lowering to keep cumulative exposure to LDL below the threshold at which acute cardiovascular events occur can effectively prevent ASCVD. In this Review, we provide the first comprehensive overview of how the LDL cumulative exposure hypothesis can guide the prevention of ASCVD. We also discuss the benefits of maintaining lower LDL-C levels over time and how this knowledge can be used to inform clinical practice guidelines as well as to design novel primary prevention trials and ASCVD prevention programmes. In this Review, Catapano and colleagues discuss the evidence supporting the LDL cumulative exposure hypothesis and how measuring cumulative LDL exposure can be used to estimate risk and contribute to the prevention of atherosclerotic cardiovascular disease.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"21 10","pages":"701-716"},"PeriodicalIF":41.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1038/s41569-024-01045-7
Florentina Porsch, Christoph J. Binder
Autoimmune diseases are associated with a dramatically increased risk of atherosclerotic cardiovascular disease and its clinical manifestations. The increased risk is consistent with the notion that atherogenesis is modulated by both protective and disease-promoting immune mechanisms. Notably, traditional cardiovascular risk factors such as dyslipidaemia and hypertension alone do not explain the increased risk of cardiovascular disease associated with autoimmune diseases. Several mechanisms have been implicated in mediating the autoimmunity-associated cardiovascular risk, either directly or by modulating the effect of other risk factors in a complex interplay. Aberrant leukocyte function and pro-inflammatory cytokines are central to both disease entities, resulting in vascular dysfunction, impaired resolution of inflammation and promotion of chronic inflammation. Similarly, loss of tolerance to self-antigens and the generation of autoantibodies are key features of autoimmunity but are also implicated in the maladaptive inflammatory response during atherosclerotic cardiovascular disease. Therefore, immunomodulatory therapies are potential efficacious interventions to directly reduce the risk of cardiovascular disease, and biomarkers of autoimmune disease activity could be relevant tools to stratify patients with autoimmunity according to their cardiovascular risk. In this Review, we discuss the pathophysiological aspects of the increased cardiovascular risk associated with autoimmunity and highlight the many open questions that need to be answered to develop novel therapies that specifically address this unmet clinical need. In this Review, Porsch and Binder discuss the evidence for and mechanisms of the increased and premature risk of atherosclerotic cardiovascular disease in patients with autoimmune disease, with particular focus on systemic lupus erythematosus and rheumatoid arthritis.
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