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Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study 基于人群的 LIFE-成人研究中蛋白质与亚临床心血管特征的关系
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-21 DOI: 10.1016/j.atherosclerosis.2024.118613
Tarcyane Garcia , Agnese Petrera , Stefanie M. Hauck , Ronny Baber , Kerstin Wirkner , Holger Kirsten , Janne Pott , Anke Tönjes , Sylvia Henger , Markus Loeffler , Annette Peters , Markus Scholz

Background and aims

Understanding molecular processes of the early phase of atherosclerotic cardiovascular disease conditions is of utmost importance for early prediction and intervention measures.

Methods

We measured 92 cardiovascular-disease-related proteins (Olink, Cardiovascular III) in 2024 elderly participants of the population-based LIFE-Adult study. We analysed the impact of 27 covariables on these proteins including blood counts, cardiovascular risk factors and life-style-related parameters. We also analysed protein associations with 13 subclinical cardiovascular traits comprising carotid intima media thickness, plaque burden, three modes of Vicorder-based pulse-wave velocities, ankle-brachial index and ECLIA-based N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

Results

Estimated glomerular filtration rate, triglycerides and sex where the most relevant covariables explaining more than 1 % variance of 49, 22 and 20 proteins, respectively. A total of 43 proteins were significantly associated with at least one of the analysed subclinical cardiovascular traits. NT-pro-BNP, brachial-ankle pulse-wave velocity (baPWV) and parameters of carotid plaque burden accounted for the largest number of associations. Association overlaps were relatively sparse. Only growth/differentiation factor 15, low density lipoprotein receptor and interleukin-1 receptor type 2 are associated with these three different cardiovascular traits. We confirmed several literature findings and found yet unreported associations for carotid plaque presence (von-Willebrand factor, galectin 4), carotid intima-media thickness (carboxypeptidase A1 andB1), baPWV (cathepsin D) and NT-proBNP (cathepsin Z, low density lipoprotein receptor, neurogenic locus homolog protein 3, trem-like transcript 2). Sex-interaction effects were observed, e.g. for spondin-1 and growth/differentiation factor 15 likely regulated by androgen response elements.

Conclusions

We extend the catalogue of proteome biomarkers possibly involved in early stages of cardiovascular disease pathologies providing targets for early risk prediction or intervention strategies.
背景和目的了解动脉粥样硬化性心血管疾病早期阶段的分子过程对于早期预测和干预措施至关重要。方法我们测量了基于人群的 LIFE-Adult 研究中 2024 名老年参与者的 92 种心血管疾病相关蛋白(Olink,心血管 III)。我们分析了 27 个协变量对这些蛋白质的影响,包括血细胞计数、心血管风险因素和生活方式相关参数。我们还分析了蛋白质与 13 种亚临床心血管特征的关系,包括颈动脉内膜厚度、斑块负荷、基于 Vicorder 的三种模式脉搏波速度、踝肱指数和基于 ECLIA 的脑钠肽 N 端前体(NT-proBNP)。共有 43 种蛋白质与所分析的亚临床心血管特征中的至少一种显著相关。NT-pro-BNP、肱踝脉搏波速度(baPWV)和颈动脉斑块负荷参数的相关性最大。关联重叠相对较少。只有生长/分化因子 15、低密度脂蛋白受体和白细胞介素-1 受体 2 型与这三种不同的心血管特征相关。我们证实了一些文献的研究结果,并发现颈动脉斑块的存在(von-Willebrand因子、galectin 4)、颈动脉内膜厚度(羧肽酶A1和B1)、baPWV(cathepsin D)和NT-proBNP(cathepsin Z、低密度脂蛋白受体、神经源性基因座同源蛋白3、trem-like转录本2)与之相关,但尚未报道。结论我们扩展了可能参与心血管疾病病理早期阶段的蛋白质组生物标志物目录,为早期风险预测或干预策略提供了目标。
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引用次数: 0
Lipids, lipoproteins, and apolipoproteins: Associations with cognition and dementia 血脂、脂蛋白和脂蛋白:与认知能力和痴呆症的关系
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-21 DOI: 10.1016/j.atherosclerosis.2024.118614
Ida Juul Rasmussen , Jiao Luo , Ruth Frikke-Schmidt
Due to increasing lifespan and aging populations globally there has been a steep rise in late-life dementia, which is now the second most common cause of death in high-income countries. In general, dementia can be divided into two major groups: Alzheimer's disease (AD) and vascular-related dementia (VD). AD is pathologically characterised by senile plaques containing amyloid-β and neurofibrillary tangles composed of hyperphosphorylated tau, whereas VD is dominated by vascular pathology such as cerebral small vessel disease, major strokes, and white matter lesions. Recently, the importance of vascular components in AD is increasingly recognized and it is estimated that up to 45 % of all dementia cases can be prevented by preventing or treating midlife cardiovascular risk factors such as physical inactivity, diabetes, and hypertension. Even though the brain contains approximately 25 % of the total body cholesterol pool, and several genetic variants related to the lipid metabolism have been identified in genome-wide associations studies of AD, the role of lipids, lipoproteins, and apolipoproteins in dementia risk is less well-known.
In this review, we go through the current literature on lipids, lipoproteins, and apolipoproteins and risk of dementia. We conclude that the evidence is primarily insufficient or conflicting, possibly due to nonoptimal study designs. The future calls for large, prospective studies of midlife measurements of lipids, lipoproteins, and apolipoproteins and one-sample, individual level data Mendelian randomization studies to overcome survival bias. However, the current literature suggests that it is safe to say that what is good for the heart is good for the brain.
由于全球寿命延长和人口老龄化,晚年痴呆症的发病率急剧上升,目前已成为高收入国家的第二大常见死因。一般来说,痴呆症可分为两大类:阿尔茨海默病(AD)和血管相关性痴呆(VD)。阿尔茨海默病的病理特征是含有淀粉样蛋白-β的老年斑和由高磷酸化 tau 组成的神经纤维缠结,而血管性痴呆则以血管病变为主,如脑小血管疾病、重大中风和白质病变。最近,血管病变在老年痴呆症中的重要性日益得到认可,据估计,通过预防或治疗中年期心血管风险因素(如缺乏运动、糖尿病和高血压),可预防高达 45% 的痴呆症病例。尽管大脑中的胆固醇约占人体胆固醇总量的 25%,而且在注意力缺失症的全基因组关联研究中发现了一些与脂质代谢有关的基因变异,但脂质、脂蛋白和载脂蛋白在痴呆症风险中的作用却鲜为人知。我们得出的结论是,证据主要不足或相互矛盾,这可能是由于非最佳研究设计造成的。未来需要对血脂、脂蛋白和脂蛋白的中年测量进行大型前瞻性研究,并进行单样本、个体水平数据的孟德尔随机研究,以克服生存偏倚。不过,目前的文献表明,可以肯定地说,对心脏有益的东西就是对大脑有益的东西。
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引用次数: 0
The German Lipoprotein Apheresis Registry-Summary of the eleventh annual report 德国脂蛋白分离登记处--第十一次年度报告摘要
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-19 DOI: 10.1016/j.atherosclerosis.2024.118601
V.J.J. Schettler , N. Selke , S. Jenke , T. Zimmermann , G. Schlieper , W. Bernhardt , F. Heigl , P. Grützmacher , I. Löhlein , R. Klingel , B. Hohenstein , W. Ramlow , A. Vogt , U. Julius , Scientific Board of GLAR for the German Apheresis Working Group

Background

In 2012, the German Lipoprotein Apheresis Registry (GLAR) was launched. Real-world data on lipoprotein apheresis (LA) treatment are now available for a time period of 11 years. All patients received the maximally tolerated lipid-lowering therapy, which included statins, ezetimibe, bempedoic acid, and either proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies or antisense therapy.

Methods and Results

During the time period from 2012 to 2022, 92 German apheresis centers collected retrospective and prospective observational data of a total of 2,301 patients undergoing regular lipoprotein apheresis (LA) treatment of hypercholesterolemia or/and Lp(a)-hyperlipoproteinemia suffering from progressive atherosclerotic cardiovascular disease (ASCVD), with complete data sets of 1.125 patients, who were the subject of this analysis. More than 61,500 LA sessions are documented in the database. In 2022, all patients treated with LA demonstrated a significant immediate median reduction rate of LDL-C (68.8 %) and Lp(a) (72.9 %). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to eleven years on LA treatment (y+1 to y+11). During the first two years of LA treatment (y+1 and y+2), a MACE reduction of 73 % was observed and continued to be low during y+3 to y+11, when all LA patients were analyzed. LA patients with only increased Lp(a) levels (Lp(a) ≥ 60 mg/dl (≥120 nmol/l) and an LDL-C < 100 mg/dl (<2.6 mmol/l)) had a higher MACE reduction (85 %; n = 443) in the first two years of LA treatment compared to LA patients with only increased LDL-C-levels (LDL-C ≥ 100 mg/dl (≥2.6 mmol/l); Lp(a) < 60 mg/dl (<120 nmol/l)) (53 %; n = 171). Adverse events of LA remained low (about 5 %) over the eleven years and mainly represented puncture problems (1.0 %). No side effects resulted in termination of LA therapy.

Conclusions

The current analysis of GLAR data indicates that regular LA leads to very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid-lowering medication, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. Additionally, LA was safe with a low rate of adverse effects over an 11-year period. The number of enrolled patients and the duration of observation establish GLAR as the largest LA registry worldwide.
背景2012年,德国脂蛋白分离注册中心(GLAR)成立。目前已有11年来的脂蛋白分离(LA)治疗的真实数据。所有患者都接受了最大耐受性降脂治疗,包括他汀类药物、依折麦布、贝美多酸和9型丙蛋白转换酶亚基酶/kexin(PCSK9)抗体或反义疗法。方法和结果在2012年至2022年期间,德国的92个无细胞疗法中心共收集了2301名接受常规脂蛋白无细胞疗法(LA)治疗的高胆固醇血症或/和Lp(a)-高脂蛋白血症的进展性动脉粥样硬化性心血管疾病(ASCVD)患者的回顾性和前瞻性观察数据,其中有1125名患者的完整数据集是本次分析的对象。数据库中记录了 61,500 多次 LA 治疗。2022 年,所有接受 LA 治疗的患者的低密度脂蛋白胆固醇(LDL-C)(68.8%)和脂蛋白(a)(72.9%)的即时中位数下降率都非常显著。对患者数据进行了分析,以了解LA治疗开始前1年和2年(y-2和y-1)以及LA治疗11年(y+1至y+11)的主要冠状动脉事件(MACE)发生率。在 LA 治疗的前两年(y+1 和 y+2),观察到 MACE 减少了 73%,在 y+3 至 y+11 期间,对所有 LA 患者进行分析时,MACE 减少率仍然很低。仅 Lp(a) 水平升高(Lp(a) ≥ 60 mg/dl (≥120 nmol/l)和 LDL-C < 100 mg/dl (< 2.6毫摩尔/升))的LA患者相比,LDL-C水平仅升高(LDL-C ≥ 100 mg/dl (≥2.6 mmol/l);Lp(a) < 60 mg/dl (<120 nmol/l))的LA患者在LA治疗的头两年中MACE减少率更高(85%;n = 443)(53%;n = 171)。十一年来,LA 的不良反应仍然很少(约 5%),主要是穿刺问题(1.0%)。结论目前对 GLAR 数据的分析表明,对于低密度脂蛋白胆固醇(LDL-C)和/或脂蛋白(a)水平较高、有进行性 ASCVD 和最大耐受性降脂药物(包括 9 型丙蛋白转换酶亚基酶/kexin (PCSK9) 抑制剂)的患者,定期服用 LA 可降低心血管事件的发生率。此外,在长达11年的时间里,LA安全性高,不良反应发生率低。GLAR登记的患者人数和观察时间使其成为全球最大的LA登记机构。
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引用次数: 0
The age-dependent development of abnormal cardiac metabolism in the peroxisome proliferator-activated receptor α-knockout mouse. 过氧化物酶体增殖激活受体α基因敲除小鼠心脏代谢异常的发展与年龄有关。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-17 DOI: 10.1016/j.atherosclerosis.2024.118599
Michael S Dodd, Lucy Ambrose, Vicky Ball, Kieran Clarke, Carolyn A Carr, Damian J Tyler

Background and aims: Peroxisome proliferator-activated receptor α (PPARα) is crucial for regulating cardiac β-oxidation in the heart, liver, and kidney. Ageing can induce cardiac metabolic alterations, but the role of PPARα has not been extensively characterised. The aim of this research was to investigate the role of PPARα in the aged heart.

Methods: Hyperpolarized [1-13C]pyruvate was used to evaluate in vivo cardiac carbohydrate metabolism in fed and fasted young (3 months) and old (20-22 months) PPARα knockout (KO) mice versus controls. Cine MRI assessed cardiac structural and functional changes. Cardiac tissue analysis included qRT-PCR and Western blotting for Pparα, medium chain acyl-CoA dehydrenase (MCAD), uncoupling protein (UCP) 3, glucose transporter (GLUT) 4 and PDH kinase (PDK) 1,2, and 4 expression.

Results: PPARα-KO hearts from both young and old mice showed significantly reduced Pparα mRNA and a 58-59 % decrease in MCAD protein levels compared to controls. Cardiac PDH flux was similar in young control and PPARα-KO mice but 96 % higher in old PPARα-KO mice. Differences between genotypes were consistent in fed and fasted states, with reduced PDH flux when fasted. Increased PDH flux was accompanied by a 179 % rise in myocardial GLUT4 protein. No differences in PDK 1, 2, or 4 protein levels were observed between fed groups, indicating the increased PDH flux in aged PPARα-KO mice was not due to changes in PDH phosphorylation.

Conclusions: Aged PPARα-KO mice demonstrated higher cardiac PDH flux compared to controls, facilitated by increased myocardial GLUT4 protein levels, leading to enhanced glucose uptake and glycolysis.

背景和目的:过氧化物酶体增殖激活受体α(PPARα)是调节心脏、肝脏和肾脏中心脏β氧化作用的关键。衰老可诱发心脏代谢改变,但 PPARα 的作用尚未得到广泛表征。研究方法:使用超极化[1-13C]丙酮酸评估幼年(3 个月)和老年(20-22 个月)PPARα 基因敲除(KO)小鼠与对照组的体内心脏碳水化合物代谢。显像核磁共振成像评估了心脏结构和功能的变化。心脏组织分析包括 Pparα、中链酰基-CoA 脱氢酶(MCAD)、解偶联蛋白(UCP)3、葡萄糖转运体(GLUT)4 和 PDH 激酶(PDK)1、2 和 4 表达的 qRT-PCR 和 Western 印迹检测:结果:与对照组相比,年轻和年老小鼠的 PPARα-KO 心脏的 Pparα mRNA 显著减少,MCAD 蛋白水平下降了 58-59%。年轻对照组和 PPARα-KO 小鼠的心脏 PDH 通量相似,但老年 PPARα-KO 小鼠的 PDH 通量比对照组高 96%。基因型之间的差异在进食和禁食状态下是一致的,禁食时 PDH 通量降低。PDH 通量增加的同时,心肌 GLUT4 蛋白也增加了 179%。喂养组之间的 PDK 1、2 或 4 蛋白水平没有差异,这表明老龄 PPARα-KO 小鼠 PDH 通量的增加不是由于 PDH 磷酸化的变化:结论:与对照组相比,老年 PPARα-KO 小鼠表现出更高的心脏 PDH 通量,心肌 GLUT4 蛋白水平的增加促进了 PDH 通量的增加,从而导致葡萄糖摄取和糖酵解的增强。
{"title":"The age-dependent development of abnormal cardiac metabolism in the peroxisome proliferator-activated receptor α-knockout mouse.","authors":"Michael S Dodd, Lucy Ambrose, Vicky Ball, Kieran Clarke, Carolyn A Carr, Damian J Tyler","doi":"10.1016/j.atherosclerosis.2024.118599","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118599","url":null,"abstract":"<p><strong>Background and aims: </strong>Peroxisome proliferator-activated receptor α (PPARα) is crucial for regulating cardiac β-oxidation in the heart, liver, and kidney. Ageing can induce cardiac metabolic alterations, but the role of PPARα has not been extensively characterised. The aim of this research was to investigate the role of PPARα in the aged heart.</p><p><strong>Methods: </strong>Hyperpolarized [1-<sup>13</sup>C]pyruvate was used to evaluate in vivo cardiac carbohydrate metabolism in fed and fasted young (3 months) and old (20-22 months) PPARα knockout (KO) mice versus controls. Cine MRI assessed cardiac structural and functional changes. Cardiac tissue analysis included qRT-PCR and Western blotting for Pparα, medium chain acyl-CoA dehydrenase (MCAD), uncoupling protein (UCP) 3, glucose transporter (GLUT) 4 and PDH kinase (PDK) 1,2, and 4 expression.</p><p><strong>Results: </strong>PPARα-KO hearts from both young and old mice showed significantly reduced Pparα mRNA and a 58-59 % decrease in MCAD protein levels compared to controls. Cardiac PDH flux was similar in young control and PPARα-KO mice but 96 % higher in old PPARα-KO mice. Differences between genotypes were consistent in fed and fasted states, with reduced PDH flux when fasted. Increased PDH flux was accompanied by a 179 % rise in myocardial GLUT4 protein. No differences in PDK 1, 2, or 4 protein levels were observed between fed groups, indicating the increased PDH flux in aged PPARα-KO mice was not due to changes in PDH phosphorylation.</p><p><strong>Conclusions: </strong>Aged PPARα-KO mice demonstrated higher cardiac PDH flux compared to controls, facilitated by increased myocardial GLUT4 protein levels, leading to enhanced glucose uptake and glycolysis.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"118599"},"PeriodicalIF":4.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The singular French PCSK9-p.Ser127Arg gain-of-function variant: A significant player in cholesterol levels from a 775-year-old common ancestor 独特的法国 PCSK9-p.Ser127Arg 功能增益变体:775年前共同祖先胆固醇水平的重要影响因素
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-13 DOI: 10.1016/j.atherosclerosis.2024.118596
Yara Azar , Thomas E. Ludwig , Hugo Le Bon , Thea Bismo Strøm , Olivier Bluteau , Mathilde Di-Filippo , Alain Carrié , Hedi Chtioui , Sophie Béliard , Oriane Marmontel , Annie Fonteille , Maite Gebhart , Noël Peretti , Philippe Moulin , Jean Ferrières , Alain Pradignac , Michel Farnier , Antonio Gallo , Cécile Yelnik , Dirk Blom , Mathilde Varret

Background and aims

PCSK9 is a key regulator of LDL-cholesterol levels. PCSK9 gain of function variants (GOFVs) cause autosomal dominant hypercholesterolemia (ADH). The first described PCSK9-GOFV, p.Ser127Arg, almost exclusively reported in France, represents 67 % of the PCSK9 French GOFVs due to a founder effect. Few other carriers are reported in South Africa and Norway. This study aims to estimate when the common ancestor lived and to describe a cohort of p.Ser127Arg carriers.

Methods

Eight families and 14 p.Ser127Arg carriers were genotyped and phenotyped. Haplotypes were constructed using 11 microsatellites around PCSK9 and 6 intragenic single nucleotide polymorphisms (SNPs). To add to the biological analysis, eight additional p.Ser127Arg carriers, 12 carriers of other PCSK9-GOFVs, 93 LDLR loss of function variant (LOFV) carriers and 49 non-carriers subjects were phenotyped.

Results

The most common ancestor of p.Ser127Arg was estimated to have lived 775 years ago [95 % CI: 575-1075]. French Protestants exiled after the revocation of the Edict of Nantes in 1685 AD likely brought the variant to South Africa and Norway. As expected for ADH subjects, carriers of LDLR-LOFV, the p.Ser127Arg, or other PCSK9-GOFVs showed significantly higher LDL-C levels than that of the non-carriers. Interestingly, LDL-C levels are higher for LDLR-LOFVs and for the reduced secreted p.Ser127Arg than for secreted PCSK9-GOFVs, suggesting a greater effect of the p.Ser127Arg. Conversely, HDL-C was significantly lower for LDLR-LOFV and p.Ser127Arg carriers.

Conclusions

This first report from a large cohort of PCSK9-p.Ser127Arg carriers provides observations suggesting a stronger hypercholesterolemic potential of the mutated pro-PCSK9 compared with the secreted mature protein. This work also provides additional data to support the association between PCSK9 and HDL metabolism, and molecular evidence that this variant appeared in France around 1248 AD (Graphical Abstract = Fig. 1).
背景和目的PCSK9是低密度脂蛋白胆固醇水平的关键调节因子。PCSK9 功能增益变异(GOFV)会导致常染色体显性高胆固醇血症(ADH)。第一个描述的 PCSK9-GOFV 是 p.Ser127Arg,几乎只在法国有报道,由于创始人效应,它占 PCSK9 法国 GOFV 的 67%。南非和挪威很少有其他携带者的报道。本研究旨在估计共同祖先的生活时间,并描述 p.Ser127Arg 携带者的队列。方法对 8 个家庭和 14 个 p.Ser127Arg 携带者进行了基因分型和表型分析。利用 PCSK9 周围的 11 个微卫星和 6 个基因内单核苷酸多态性 (SNP) 构建了单倍型。为了补充生物学分析,还对另外 8 名 p.Ser127Arg 携带者、12 名其他 PCSK9-GOFVs 携带者、93 名 LDLR 功能缺失变异体 (LOFV) 携带者和 49 名非携带者进行了表型分析。结果p.Ser127Arg 的最常见祖先估计生活在 775 年前[95 % CI:575-1075]。公元1685年南特敕令废除后流亡的法国新教徒很可能将该变异体带到了南非和挪威。正如 ADH 受试者所预期的那样,LDLR-LOFV、p.Ser127Arg 或其他 PCSK9-GOFV 携带者的低密度脂蛋白胆固醇水平明显高于非携带者。有趣的是,与分泌型 PCSK9-GOFV 相比,LDLR-LOFV 和分泌减少的 p.Ser127Arg 的 LDL-C 水平更高,这表明 p.Ser127Arg 的作用更大。结论这是对一大群 PCSK9-p.Ser127Arg 携带者的首次报道,观察结果表明,与分泌型成熟蛋白相比,突变的原 PCSK9 具有更强的高胆固醇血症潜力。这项研究还提供了更多数据,支持 PCSK9 与高密度脂蛋白代谢之间的联系,并提供了分子证据,证明该变异体在公元 1248 年左右出现在法国(图解摘要 = 图 1)。
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引用次数: 0
In Memoriam: Akira Endo (1933-2024) 悼念:远藤明(1933-2024)
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-13 DOI: 10.1016/j.atherosclerosis.2024.118545
Alberico L. Catapano
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引用次数: 0
The association between trimethylamine N-oxide levels and coronary microvascular dysfunction and prognosis in patients with ST-elevation myocardial infarction 三甲胺 N-氧化物水平与 ST 段抬高型心肌梗死患者冠状动脉微血管功能障碍和预后之间的关系
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-12 DOI: 10.1016/j.atherosclerosis.2024.118597
Ali Aldujeli , Tsung-Ying Tsai , Ayman Haq , Vacis Tatarunas , Scot Garg , Diarmaid Hughes , Ieva Ciapiene , Ramunas Unikas , Faisal Sharif , Vaiva Lesauskaite , Yoshinobu Onuma , Patrick W. Serruys

Background and aims

Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients.

Methods

This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation.

Results

TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46–0.64; p = 0.426), and 0.80 (95 % CI 0.73–0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors.

Conclusion

TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD.
背景和目的冠状动脉微血管功能障碍(CMD)是ST段抬高型心肌梗死(STEMI)后的常见病,会导致不良的临床结局。然而,其诊断仍很困难,其机制也难以捉摸。本研究探讨了肠道微生物群代谢物三甲胺N-氧化物(TMAO)作为诊断STEMI患者CMD的潜在生物标记物的作用。方法这项前瞻性观察性研究共纳入了210名接受初级经皮冠状动脉介入治疗(PCI)的STEMI多支血管冠状动脉疾病患者。在PCI术后基线、3个月和12个月时测量TMAO水平,在3个月时评估冠状动脉生理功能。主要终点是3个月时的CMD发生率,次要终点是12个月时的主要不良心脑血管事件(MACCE)。结果TMAO水平从基线到3个月期间有所变化,随后趋于稳定。基线 TMAO 和 3 个月时 TMAO 的 ROC 曲线下面积分别为 0.55 (95 % CI 0.46-0.64; p = 0.426) 和 0.80 (95 % CI 0.73-0.87; p < 0.001)。3个月时TMAO诊断CMD的最佳临界值为3.91,在推导队列和验证队列中具有相似的敏感性和特异性。TMAO≥3.91的患者MACCE发生率更高(41.4% vs 10.7%;p < 0.001)。结论TMAO是一种可靠的CMD生物标记物,与MACCE的发病率显著相关。TMAO具有指导临床决策的潜力,并表明肠道微生物群与CMD之间存在相互作用。
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引用次数: 0
Vascular disease and ischemic stroke in patients with atrial fibrillation: Temporal trends and age-related differences. 心房颤动患者的血管疾病和缺血性中风:时间趋势和年龄差异。
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-08 DOI: 10.1016/j.atherosclerosis.2024.118590
Konsta Teppo, Elin Karlsson, Tuomas Kiviniemi, Olli Halminen, Ossi Lehtonen, Elis Kouki, Jari Haukka, Pirjo Mustonen, Jukka Putaala, Miika Linna, Juha Hartikainen, K E Juhani Airaksinen, Mika Lehto

Background and aims: We examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF).

Methods: The registry-based FinACAF study covered all patients with AF in Finland during 2007-2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed.

Results: We identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10-1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed.

Conclusions: The association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.

背景与目的我们研究了心房颤动(房颤)患者血管疾病患病率及其与缺血性中风(IS)风险相关性的时间趋势和年龄差异:以登记为基础的 FinACAF 研究涵盖了 2007-2018 年间芬兰的所有房颤患者。采用泊松回归法计算了IS的发病率比(IRR),并评估了血管疾病与年龄和日历年期间的交互作用:我们发现了 229,565 名房颤患者(50.0% 为女性;平均年龄 72.7 岁)。任何血管疾病的总患病率为 28.6%,2007 年至 2018 年患病率有所上升,主要是 75 岁以上的患者。总体而言,5909 名患者(2.6%)在确诊房颤后的第一年内经历了 IS。在研究期间,有血管疾病和无血管疾病患者的粗IS率均持续下降,有血管疾病患者的IS率始终较高。在 65 岁以下的患者中,血管疾病与较高的 IS 发生率独立相关(调整后 IRR,95% 置信区间为 1.35 (1.10-1.66)),而在老年患者中,只有外周动脉疾病与 IS 相关,其他血管疾病与 IS 无关。在日历年期间和血管疾病与IS率之间没有观察到相互作用:随着时间的推移,血管疾病与IS之间的关系保持稳定,血管疾病与较高的IS发病率独立相关,尤其是在65岁以下的房颤患者中。
{"title":"Vascular disease and ischemic stroke in patients with atrial fibrillation: Temporal trends and age-related differences.","authors":"Konsta Teppo, Elin Karlsson, Tuomas Kiviniemi, Olli Halminen, Ossi Lehtonen, Elis Kouki, Jari Haukka, Pirjo Mustonen, Jukka Putaala, Miika Linna, Juha Hartikainen, K E Juhani Airaksinen, Mika Lehto","doi":"10.1016/j.atherosclerosis.2024.118590","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118590","url":null,"abstract":"<p><strong>Background and aims: </strong>We examined temporal trends and age-related differences in the prevalence of vascular diseases and in their association with ischemic stroke (IS) risk in patients with atrial fibrillation (AF).</p><p><strong>Methods: </strong>The registry-based FinACAF study covered all patients with AF in Finland during 2007-2018. Incidence rate ratios (IRRs) of IS were computed with Poisson regression, and the interaction of vascular diseases with age and calendar year period was assessed.</p><p><strong>Results: </strong>We identified 229,565 patients (50.0 % female; mean age 72.7 years) with incident AF. The overall prevalence of any vascular disease was 28.6 %, and the prevalence increased from 2007 to 2018, primarily among patients over 75 years. Overall, 5909 (2.6 %) patients experienced IS within the first year after AF diagnosis. Crude IS rate decreased continuously during the study period in both patients with and without vascular diseases, with the rates remaining consistently higher in patients with vascular diseases. Vascular diseases were independently associated with higher IS incidence among patients under 65 years (adjusted IRR with 95 % confidence interval 1.35 (1.10-1.66)), while among older patients, only peripheral artery disease was associated with IS, and other vascular conditions had no association with IS. No interactions between the calendar year period and vascular diseases with IS rate were observed.</p><p><strong>Conclusions: </strong>The association between vascular diseases and IS has remained stable over time and vascular diseases were independently associated with higher incidence of IS particularly in patients with AF under the age of 65.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"118590"},"PeriodicalIF":4.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arterial inflammation on [18F]FDG PET/CT in melanoma patients treated with and without immune checkpoint inhibitors: CHECK-FLAME I 接受和未接受免疫检查点抑制剂治疗的黑色素瘤患者[18F]FDG PET/CT 上的动脉炎症:CHECK-FLAME I
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-07 DOI: 10.1016/j.atherosclerosis.2024.118595
Elissa A.S. Polomski , Ellen W. Kapiteijn , Julius C. Heemelaar , Anne V. van der Kolk , Timo M. Kalisvaart , Alina van de Burgt , Petra Dibbets-Schneider , Floris H.P. van Velden , Tom T.P. Seijkens , J. Lauran Stöger , J. Wouter Jukema , Lioe-Fee de Geus-Oei , M. Louisa Antoni

Background and aims

Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment. However, ICIs may increase the immune response to non-tumor cells, possibly resulting in increased arterial inflammation, raising the risk of atherosclerotic events. Nevertheless, malignancies may induce a pro-inflammatory state and the association between ICIs and arterial inflammation remains to be clarified. This study aims to assess differences in increase in arterial inflammation between patients with advanced melanoma treated with ICIs compared to a control group without ICIs.

Methods

Patients with advanced melanoma who underwent [18F]FDG PET/CT scans at baseline, 6 months (T1) and 18 months (T2) were included in this retrospective observational study. Arterial inflammation was evaluated in eight segments by calculating the target-to-background ratio (TBR). The primary study outcome was the difference in increase in mean TBRmax between patients treated with and without ICIs.

Results

We included 132 patients of whom 72.7 % were treated with ICIs. After exclusion for the use of anti-inflammatory medication, patients treated with ICIs showed a significant increase in mean TBRmax between baseline and T1 from 1.29 ± 0.12 to 1.33 ± 0.13 (p = 0.017), while in the control group, no change in mean TBRmax (1.30 ± 0.12 to 1.28 ± 0.10, p = 0.22) was observed (p = 0.027). During longer follow-up, mean TBRmax remained stable in both groups. Arterial inflammation increased significantly after ICI therapy in patients without active inflammation (p < 0.001) and in patients without calcifications (p = 0.013).

Conclusions

A significant increase in arterial inflammation as measured on [18F]FDG PET/CT was observed in patients with advanced melanoma treated with ICIs only in the first six months after initiation of therapy, whereas no changes were observed in the control group. Moreover, arterial inflammation was mainly increased in patients without pre-existing inflammatory activity and with non-calcified lesions.

背景和目的免疫检查点抑制剂(ICIs)彻底改变了癌症治疗。然而,免疫检查点抑制剂可能会增加对非肿瘤细胞的免疫反应,从而可能导致动脉炎症加剧,增加动脉粥样硬化事件的风险。然而,恶性肿瘤可能会诱发促炎症状态,而 ICIs 与动脉炎症之间的关联仍有待明确。本研究旨在评估接受 ICIs 治疗的晚期黑色素瘤患者与未接受 ICIs 治疗的对照组患者之间动脉炎症增加的差异。方法这项回顾性观察研究纳入了在基线、6 个月(T1)和 18 个月(T2)接受 [18F]FDG PET/CT 扫描的晚期黑色素瘤患者。通过计算目标与背景比值(TBR)对八个节段的动脉炎症进行了评估。主要研究结果是接受和未接受 ICIs 治疗的患者平均 TBRmax 的增加差异。在排除使用抗炎药物的情况后,接受 ICIs 治疗的患者的平均 TBRmax 在基线和 T1 之间有显著增加,从 1.29 ± 0.12 增加到 1.33 ± 0.13(p = 0.017),而对照组的平均 TBRmax 没有变化(从 1.30 ± 0.12 增加到 1.28 ± 0.10,p = 0.22)(p = 0.027)。在较长时间的随访中,两组的平均 TBRmax 均保持稳定。结论 在接受 ICIs 治疗的晚期黑色素瘤患者中,仅在开始治疗后的前 6 个月内,[18F]FDG PET/CT 检测到动脉炎症显著增加,而对照组未观察到任何变化。此外,动脉炎症主要在无炎症活动和无钙化病灶的患者中增加。
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引用次数: 0
Is colchicine on its way to a place in the polypill for cardiovascular prevention? 秋水仙碱是否即将成为预防心血管疾病的多用途药物?
IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-05 DOI: 10.1016/j.atherosclerosis.2024.118594
Fernando Botto, Sebastián Garcia-Zamora
{"title":"Is colchicine on its way to a place in the polypill for cardiovascular prevention?","authors":"Fernando Botto,&nbsp;Sebastián Garcia-Zamora","doi":"10.1016/j.atherosclerosis.2024.118594","DOIUrl":"10.1016/j.atherosclerosis.2024.118594","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118594"},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Atherosclerosis
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