To the Editor:Coronary heart disease(CHD)continues to be a predominant cause of mortality in China even after recommended optimal management.Residual inflammatory risk(RIR)portends increased risk of recurrent cardiova...To the Editor:Coronary heart disease(CHD)continues to be a predominant cause of mortality in China even after recommended optimal management.Residual inflammatory risk(RIR)portends increased risk of recurrent cardiovascular events.As an indicator of pro-inflammatory nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)–interleukin(IL)-1β–IL-6 pathway activation,high-sensitivity C-reactive protein(hsCRP)has demonstrated significant value as a predictor of major adverse cardiovascular and cerebrovascular events(MACCEs).Due to the ethnic differences,East Asian populations exhibited lower hsCRP levels.It was confirmed by our previous single-center study,in which the median of hsCRP was 1 mg/L at 1-month follow-up,and the 1-month hsCRP>1 mg/L showed a better prediction of the risk of MACCE.展开更多
Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key par...Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.展开更多
COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection likely ranks among the deadliest diseases in human history.As with other coronaviruses,SARS-CoV-2 infection damages not only the ...COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection likely ranks among the deadliest diseases in human history.As with other coronaviruses,SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2(ACE2),a receptor for SARS-CoV-2.COVID-19 has upended lives worldwide.Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications,while patients have avoided hospital visits because of limited resources and the fear of infection,thereby increasing out-hospital mortality due to delayed diagnosis and treatment.Clinical observations show that sex,age,and race all influence the risk for SARS-CoV-2 infection,as do hypertension,obesity,and pre-existing cardiovascular conditions.Many hospitalized COVID-19 patients suffer cardiac injury,acute coronary syndromes,or cardiac arrhythmia.SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis,endothelial cell damage and dysfunction,oxidative stress and reactive oxygen species production,vasoconstriction,fibrotic and thrombotic protein expression,vascular permeability and microvascular dysfunction,heart inflammatory cell accumulation and activation,and a cytokine storm.Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors,angiotensin receptor blockers,steroids,aspirin,statins,and PCSK9 inhibitors.This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.展开更多
文摘背景：以前的血管内超声（intravascular ultrasound，IVUS）试验证实，他汀治疗可减缓或阻止动脉粥样硬化的进展，但是迄今尚无应用动脉粥样斑块体积百分比（percent atheroma volume，PAV）证实粥样硬化消退的确切证据。PAV是最严格的评价病变进展和消退的IVUS测量指标。
目标：评价极高强度他汀治疗是否能逆转IVUS确定的冠状动脉粥样硬化。
设计和地点：于美国、加拿大、欧洲和澳大利亚53个社区和3级保健中心进行前瞻性开标盲法终点试验（A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden，ASTEROID）。应用马达驱动回撤IVUS评价基线和治疗24个月时冠状动脉粥样斑块负荷。每对基线和随访IVUS测量结果均进行盲法分析。
病例：从2002年11月到2003年10月，507例患者有基线IVUS检查结果，并接受至少1个剂量的研究药物。在24个月后，349例患者具有可用于评估的系列IVUS检查结果。
干预：所有患者均接受瑞舒伐他汀40ms／d强化治疗。
主要观测指标：预先设定了两个一级疗效指标：PAV变化和基线最严重病变10min节段动脉粥样斑块体积变化。二级疗效指标为整个动脉标准化总斑块体积的变化。结果：平均（SD）LDL—C水平由基线时的130．4（34．3）ms／dL降至60．8（20．0）ms／扎，平均下降了53．2％（P〈0．001）。平均（SD）HDL-C水平从基线时的43．1（11．1）ms／dL升至49．0（12．6）ms／dL，平均增加了14．7％（P〈0．001）。整个血管PAV平均（SD）变化为-0．98％（3．15％），中位数为-0．79％（97．5％CI，-1．21％～-0．53％）（与基线比较，P〈0．001）。最严重病变10min节段斑块体积平均（SD）变化为-6．1（10．1）mm^3，中位数为-5．6mm^3（97．5％CI，-6．8～-4．0mm^3）（与基线比较，P〈0．001）。总斑块体积变化中位数降低了6．8％，平均减少了-14．7（25．7）mm^3，中位数为-12．5mm^3（95％CI，-15．1～-10．5mm^3）（与基线比较，P〈0．001）。不良事件少见，与其他他汀试验相似。
结论：应用瑞舒伐他汀40ms／d进行极高强度他汀治疗可使LDL-C平均水平达到60．8ms／dL，使HDL—C增加14．7％。这导致所有3个预先设定的IVUS斑块负荷指标均显示动脉粥样硬化消退。因此，将LDL-C降至低于目前指南规定的水平，同时显著提高HDL-C，可以使冠心病患者动脉粥样硬化斑块消退。这些变化对临床预后的影响尚需进一步研究确定。
基金supported by grants from the Noncommunicable Chronic Diseases—National Science and Technology Major Project(No.2025ZD0548400)the National Key Research and Development Program(No.2022YFC2503501)+3 种基金Chinese Society of Cardiology’s Foundation(No.CSCF2023A04)Hubei Technology Innovation Project(No.2024BCB046)Key Research and Development Program of Wuhan(No.2024020702030092)to Xiang ChengThe National Heart,Lung,and Blood Institute(Nos.1R01HL134892 and 1R01HL163099-01),the RRM Charitable Fund,and the Simard Fund to Peter Libby.
文摘To the Editor:Coronary heart disease(CHD)continues to be a predominant cause of mortality in China even after recommended optimal management.Residual inflammatory risk(RIR)portends increased risk of recurrent cardiovascular events.As an indicator of pro-inflammatory nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)–interleukin(IL)-1β–IL-6 pathway activation,high-sensitivity C-reactive protein(hsCRP)has demonstrated significant value as a predictor of major adverse cardiovascular and cerebrovascular events(MACCEs).Due to the ethnic differences,East Asian populations exhibited lower hsCRP levels.It was confirmed by our previous single-center study,in which the median of hsCRP was 1 mg/L at 1-month follow-up,and the 1-month hsCRP>1 mg/L showed a better prediction of the risk of MACCE.
基金supported by the National Heart,Lung,and Blood Institute (HL151627 and HL157073 to Guo-Ping Shi,HL134892 and HL163099 to Peter Libby)the National Institute of Neurological Disorders and Stroke (AG063839 to Guo-Ping Shi).
文摘Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.
基金Dr.Shi receives funding support from the National Heart,Lung,and Blood Institute(R01HL151627)the National Institute of Neurological Disorders and Stroke(R01AG063839)+1 种基金Dr.Libby receives funding support from the National Heart,Lung,and Blood Institute(1R01HL134892)the American Heart Association(18CSA34080399),and the RRM Charitable Fund,and the Simard Fund.
文摘COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection likely ranks among the deadliest diseases in human history.As with other coronaviruses,SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2(ACE2),a receptor for SARS-CoV-2.COVID-19 has upended lives worldwide.Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications,while patients have avoided hospital visits because of limited resources and the fear of infection,thereby increasing out-hospital mortality due to delayed diagnosis and treatment.Clinical observations show that sex,age,and race all influence the risk for SARS-CoV-2 infection,as do hypertension,obesity,and pre-existing cardiovascular conditions.Many hospitalized COVID-19 patients suffer cardiac injury,acute coronary syndromes,or cardiac arrhythmia.SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis,endothelial cell damage and dysfunction,oxidative stress and reactive oxygen species production,vasoconstriction,fibrotic and thrombotic protein expression,vascular permeability and microvascular dysfunction,heart inflammatory cell accumulation and activation,and a cytokine storm.Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors,angiotensin receptor blockers,steroids,aspirin,statins,and PCSK9 inhibitors.This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.
