European Journal of Clinical Investigation最新文献_第7页

Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery 减肥手术后内源性 GLP-1 对动脉僵化和肾血流动力学的作用。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-22 DOI: 10.1111/eci.14256

D. Moriconi, R. M. Bruno, E. Rebelos, S. Armenia, S. Baldi, L. Bonvicini, S. Taddei, M. Nannipieri

Background

Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic.

Methods

Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery).

Results

Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1_(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014).

Conclusions

Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.

背景：心血管试验显示，GLP-1 受体激动剂（GLP-1 RAs）对 2 型糖尿病（T2D）患者的心血管预后有积极影响。然而，内源性 GLP-1 对动脉僵化和肾功能的具体影响仍未得到充分研究。本研究旨在探讨减肥手术后内源性 GLP-1 反应对动脉僵化和肾血流动力学的影响：方法：研究人员纳入了 30 名计划接受 Roux-en-Y 胃旁路手术（RYGB）的病态肥胖且无 T2D 患者。在手术前和手术后 1 年分别进行了临床参数、3 小时口服葡萄糖耐量试验（OGTT）及血糖、GLP-1 和胰岛素连续采样、颈动脉-股动脉脉搏波速度（cf-PWV）、颈动脉舒张系数（carotid-DC）和肾阻力指数（RRI）测量。根据参与者手术后 GLP-1 的增加情况（手术前与手术后的中位增加率分别为 104% 和 1%），将其分为高反应组和低反应组：结果：与低反应组相比，手术后高反应组的 cf-PWV 降低幅度更大（p = .033），颈动脉直流增加幅度更大（p = .043）。这些改善与体重减轻或血压变化无关。高反应组的 RRI 有所下降（p = .034），尽管这种关联受到脉压改善的影响。最后，多变量逐步回归分析表明，GLP1 增加的百分比（Δ-GLP1(AUC)%）是预测 cf-PWV 百分比下降的最佳指标（p = .014）：结论：RYGB术后内源性GLP-1反应的升高与动脉僵化和肾脏阻力的改善有关，这表明GLP-1对心血管和肾脏有潜在的益处。这些发现强调了内源性 GLP-1 在影响血管和肾血流动力学方面的潜在作用，而与传统的体重减轻无关。

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引用次数: 0

Procedural and clinical outcomes of patients undergoing a TAVI in TAVI procedure: Rationale and design of the multicentre, prospective, observational ReTAVI registry 接受 TAVI 手术的患者的手术和临床结果：多中心、前瞻性、观察性 ReTAVI 登记的原理和设计。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-20 DOI: 10.1111/eci.14241

Radoslaw Parma, Michael Joner, Francesco Saia, Thomas Cuisset, Victoria Delgado, Josep Rodes-Cabau, Thomas Modine, Eric Van Belle, Luca Nai Fovino, Uri Landes, Hector Alfonso Alvarez-Covarrubias, Mohamed Abdel-Wahab, Jose Luis Zamorano, Matthias Eden, Filippo Cademartiri, Joanna Nawara Skipirzepa, Jana Kurucova, Daniel Greinert, Peter Bramlage, Giuseppe Tarantini

Background

Transcatheter aortic valve implantation (TAVI) is increasingly being used in younger patients and those with lower peri-procedural risk, meaning more patients will live long enough to experience structural valve deterioration (SVD) of the bioprosthesis, indicating repeated TAVI. Experience of repeated TAVI—transcatheter heart valve (THV) implantation into an index THV is limited. This registry aims to assess the peri-procedural and short-term safety, efficacy and durability of repeated TAVI.

Methods

The ReTAVI Prospective observational registry is an investigator-initiated, multicentre, international, prospective registry of patients undergoing repeated TAVI using balloon-expandable SAPIEN prosthesis to evaluate procedural and short-term safety, efficacy and durability as well as anatomical and procedural factors associated with optimal results. The registry will enrol at least 150 patients across 60 high-volume centres. Patients must be ≥18 years old, have had procedural success with their first TAVI, have index THV device failure, intend to undergo repeated TAVI and be considered suitable candidates by their local Heart Team. All patients will undergo a 30-day and 12-month follow-up. The estimated study completion is 2025.

Conclusions

The registry will collect pre-, peri-, postoperative and 12-months data on patients undergoing repeated TAVI procedures with THVs for failure of the index THV and determine VARC-3-defined efficacy and safety at 30 days and functional outcome at 12 months. The registry will expand existing data sets and identify patient characteristics/indicators related to complications and clinical benefits for patients with symptomatic severe calcific degenerative aortic stenosis.

背景：经导管主动脉瓣植入术（TAVI）越来越多地用于年轻患者和手术周风险较低的患者，这意味着更多患者将活到生物假体结构性瓣膜退化（SVD），从而需要重复进行 TAVI。重复TAVI-经导管心脏瓣膜（THV）植入指数THV的经验有限。该登记旨在评估重复 TAVI 的围手术期和短期安全性、有效性和耐久性：ReTAVI前瞻性观察登记是一项由研究者发起的多中心、国际性、前瞻性登记，登记对象为使用球囊扩张型SAPIEN假体进行重复TAVI的患者，目的是评估程序和短期安全性、有效性和耐久性，以及与最佳效果相关的解剖和程序因素。该登记将在 60 个高流量中心登记至少 150 名患者。患者年龄必须≥18岁，首次TAVI手术成功，THV设备出现指数性故障，打算再次进行TAVI手术，并被当地心脏团队视为合适人选。所有患者都将接受 30 天和 12 个月的随访。预计研究将于 2025 年完成：该登记处将收集因指数 THV 失败而接受 THV 重复 TAVI 手术的患者的术前、围手术期、术后和 12 个月的数据，并确定 30 天时 VARC-3 定义的疗效和安全性以及 12 个月时的功能预后。该登记将扩展现有数据集，并确定与无症状严重钙化变性主动脉瓣狭窄患者的并发症和临床获益相关的患者特征/指标。

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引用次数: 0

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy 基于冬眠心肌疗法的 CTO 患者血管再通疗效。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-17 DOI: 10.1111/eci.14237

Wenjie Chen, Zhiyong Du, Yanwen Qin, Ze Zheng, Jinghua Liu, Yuchen Shi

Background

The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and ¹⁸F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT).

Methods

A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI).

Results

After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008–1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008–1.043, p = .005).

Conclusion

HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

背景：经皮冠状动脉介入治疗（PCI）治疗慢性全闭塞（CTO）的效果仍不确定，尤其是对缺血性左心室功能障碍患者而言。本研究旨在评估通过单光子发射计算机断层扫描（SPECT）和18F-FDG正电子发射断层扫描（PET）确定的冬眠心肌（HM），并比较PCI和最佳药物治疗（OMT）的益处：一项回顾性研究收集了332名CTO和缺血性左心室功能障碍患者的数据。该研究通过倾向得分匹配（PSM）分析对接受 PCI 或 OMT 的患者进行了比较，倾向得分匹配分析采用最近邻匹配算法，以 1:2 的匹配方案进行。研究的主要终点是主要心脏不良事件（MACE）的发生率，其定义为心脏死亡、因心衰恶化（WHF）再入院、血管重建和心肌梗死（MI）的综合结果：PSM后，PCI组和OMT组共有246人。经过 Cox 回归，发现冬眠心肌/总灌注缺损（HM/TPD）是一个独立的风险因素（危险比（HR）：1.03，95% 置信区间（CI）：1.008-1.052，P = .007）。HM/TPD 的临界值为 38%。亚组分析结果表明，对于 HM/TPD >38% 的患者，OMT 组发生 MACE 的风险更高（p = .035）。在对单血管 CTO 病变患者进行敏感性分析后发现，HM/TPD 仍然是一个独立的预测因素（HR 1.025，95% CI 1.008-1.043，p = .005）：结论：HM/TPD是MACE的独立预测因子，对于HM/TPD大于38%的患者，与OMT相比，CTO-PCI的MACE风险更低。但仍需通过大规模研究进一步验证。

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引用次数: 0

Dutch cardio-oncology cohort: Incident cardiovascular disease predisposes to a higher cancer mortality rate 荷兰心血管肿瘤队列：心血管疾病易导致癌症死亡率升高。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-17 DOI: 10.1111/eci.14255

Yvonne Koop, Laura Yousif, Rudolf A. de Boer, Michiel L. Bots, Wouter C. Meijers, Ilonca Vaartjes

Background

Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. Given their high prevalence, it is important to understand the disease burden of cancer mortality in CVD patients.

Objective

We aimed to evaluate whether patients with incident CVD have a higher risk of malignancy-related mortality, compared to the general population without CVD.

Methods

We performed a national population-based cohort study selecting patients with incident CVD in the Netherlands between 01 April 2000 and 31 December 2005. A reference cohort was selected from the Dutch population using age, sex and ethnicity. Mortality follow-up data were evaluated after data linkage of national registries from Statistics Netherlands until 31 December 2020.

Results

A total of 2,240,879 individuals were selected with a mean follow-up of 12 years (range 0.4–21.0), of which 738,666 patients with incident CVD with a mean age of 71 ± 15 years. Malignancy mortality per 1000 person years was 84 for the reference group and 118 for patients with CVD, with the highest rate of 258 in patients with heart failure. Patients with CVD had a higher malignancy mortality risk, compared to the reference group: HR 1.35 (95%CI 1.33–1.36). Highest risks were observed in patients with venous diseases (HR 2.27, 95%CI 2.17–2.36) and peripheral artery disease (HR 1.87, 95%CI 1.84–2.01).

Conclusion

Results show that CVD predisposes to a higher cancer mortality rate. Of all CVD subtypes, HF patients have the highest cancer mortality rate and the hazards were highest in patients with venous diseases and peripheral artery disease.

背景：心血管疾病（CVD）和癌症是全球两大主要死因。鉴于这两种疾病的高发病率，了解心血管疾病患者癌症死亡率的疾病负担非常重要：我们的目的是评估与无心血管疾病的普通人群相比，心血管疾病患者是否有更高的恶性肿瘤相关死亡风险：我们进行了一项全国人群队列研究，选择了 2000 年 4 月 1 日至 2005 年 12 月 31 日期间荷兰的心血管疾病患者。根据年龄、性别和种族从荷兰人口中选择了一个参考队列。在对荷兰统计局的全国登记数据进行链接后，对截至2020年12月31日的死亡率随访数据进行了评估：结果：共选取了 2,240,879 人，平均随访 12 年（范围 0.4-21.0），其中 738,666 人为心血管疾病患者，平均年龄为 71 ± 15 岁。参照组的恶性肿瘤死亡率为84/1000人年，心血管疾病患者为118/1000人年，其中心力衰竭患者的恶性肿瘤死亡率最高，为258/1000人年。与参照组相比，心血管疾病患者的恶性肿瘤死亡风险更高：HR 1.35（95%CI 1.33-1.36）。静脉疾病（HR 2.27，95%CI 2.17-2.36）和外周动脉疾病（HR 1.87，95%CI 1.84-2.01）患者的风险最高：结果表明，心血管疾病易导致癌症死亡率升高。在所有心血管疾病亚型中，高血压患者的癌症死亡率最高，而静脉疾病和外周动脉疾病患者的危险性最高。

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引用次数: 0

The acute effect of exercise on the endothelial glycocalyx in healthy adults: A systematic review and meta-analysis 运动对健康成年人内皮糖萼的急性影响：系统回顾与荟萃分析。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-15 DOI: 10.1111/eci.14240

Alicia Saz-Lara, Iván Cavero-Redondo, Andrea del Saz-Lara, Eva Rodríguez-Gutiérrez, Bruno Bizzozero-Peroni, Carlos Pascual-Morena

Background

In recent years, it has been demonstrated that when the endothelial glycocalyx, composed of proteoglycans, glycosaminoglycans and glycoproteins, is altered or modified, this property is lost, playing a fundamental role in cardiovascular pathologies. Cardiovascular risk factors can destroy the endothelial glycocalyx layer. Exercise has a positive effect on cardiovascular risk factors, but little is known about its direct effect on the integrity of the endothelial layer.

Methods

The Cochrane Library, PubMed, Web of Science and Scopus databases were searched from their inception to June 30, 2022. The DerSimonian and Laird method was used to compute pooled effect size estimates and their respective 95% confidence intervals for the acute effect of exercise (within 24 h) on the endothelial glycocalyx and its components in healthy adults.

Results

Ten studies were included in the meta-analysis, with a total of 252 healthy subjects. The types of exercise included were resistance training, interval training, resistance training and maximal incremental exercise, with a duration range of 30–60 min. Glycocalyx assessment times included ranged from 0 to 90 min post-exercise. Our findings showed that endothelial glycocalyx increases after acute effect of exercise in healthy population (.56, 95% CI: .38, .74). The acute effect of exercise on endothelial glycocalyx components were .47 (95% CIs: .27, .67) for glycosaminoglycans, .67 (95% CIs: .08, 1.26) for proteoglycans and .61 (95% CIs: .35, .86) for glycoproteins.

Conclusions

In a healthy population, various types of exercise showed an acute improvement of the endothelial glycocalyx and its individual components.

背景：近年来的研究表明，当由蛋白聚糖、糖胺聚糖和糖蛋白组成的内皮糖萼层发生改变或修饰时，这种特性就会丧失，从而在心血管病变中扮演重要角色。心血管风险因素会破坏内皮糖萼层。运动对心血管风险因素有积极影响，但对运动对内皮层完整性的直接影响却知之甚少：方法：对 Cochrane 图书馆、PubMed、Web of Science 和 Scopus 数据库从开始到 2022 年 6 月 30 日进行了检索。采用 DerSimonian 和 Laird 方法计算运动（24 小时内）对健康成人内皮糖萼及其组成部分的急性影响的集合效应大小估计值及其各自的 95% 置信区间：荟萃分析共纳入了 10 项研究，涉及 252 名健康受试者。运动类型包括阻力训练、间歇训练、阻力训练和最大增量运动，持续时间范围为 30-60 分钟。糖萼评估时间从运动后 0 分钟到 90 分钟不等。我们的研究结果表明，在健康人群中，运动产生急性效应后内皮糖萼会增加（.56，95% CI：.38，.74）。运动对内皮糖萼成分的急性影响分别为：糖胺聚糖为.47（95% CIs：.27, .67），蛋白聚糖为.67（95% CIs：.08, 1.26），糖蛋白为.61（95% CIs：.35, .86）：结论：在健康人群中，各种类型的运动都能急性改善内皮糖萼及其各个组成部分。

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引用次数: 0

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients 透析患者的蛋白转化酶枯草酶/kexin 9 型（PCSK9）与临床疗效。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-11 DOI: 10.1111/eci.14235

Claudia Torino, Federico Carbone, Patrizia Pizzini, Sabrina Mezzatesta, Graziella D'Arrigo, Mercedes Gori, Luca Liberale, Margherita Moriero, Cristina Michelauz, Federica Frè, Simone Isoppo, Aurora Gavoci, Federica La Rosa, Alessandro Scuricini, Amedeo Tirandi, Davide Ramoni, Francesca Mallamaci, Giovanni Tripepi, Fabrizio Montecucco, Carmine Zoccali

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies.

Methods

The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis.

Results

During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HR_{for1ln unit increase}: 1.23, 95% CI 1.06–1.43, p =.008) and CV mortality (HR_{for1ln unit increase}: 1.26, 95% CI 1.03–1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HR_{for 1 ln unit increase}: 1.16, 95% CI .99–1.36, p =.07; CV mortality, HR_{for1ln unit increase}: 1.18, 95% CI .95–1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HR_{for1ln unit increase}: 1.88, 95% CI 1.27–2.78, p =.002; Men, HR_{for1ln unit increase}: 1.07, 95% CI .83–1.38, p =.61; p for effect modification: .02).

Conclusions

PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.

背景：Protein convertase subtilisin/kexin type 9 (PCSK9)是一种加速低密度脂蛋白受体降解的因子，在一般人群中与心血管（CV）事件风险的性别相关，在非洲黑人和韩国血液透析患者的两项相对较小的研究中与全因和CV死亡率相关。在这些研究中，性别对影响的修饰作用尚未得到检验：该研究从卡拉布里亚地区透析流行病学工作组前瞻性登记队列（PROGREDIRE）中招募了 1188 名透析患者。PCSK9 采用比色酶联免疫吸附测定法进行测定。主要结果为全因死亡率和心血管疾病死亡率。统计分析包括 Cox 回归分析和效应修正分析：在中位 2.9 年的随访期间，494 例死亡中 278 例与心血管疾病相关。在未经调整的分析中，PCSK9水平与全因死亡率（HRfor1ln unit increase：1.23，95% CI 1.06-1.43，p =.008）和CV死亡率（HRfor1ln unit increase：1.26，95% CI 1.03-1.54，p =.03）的增加相关。经多变量调整后，这些关联不再显著（全因死亡率，增加 1 ln 单位的 HR：1.16，95% CI：1.03-1.54，P = 008）：1.16，95% CI .99-1.36，p =.07；CV 死亡率，HR for1ln unit increase：1.18，95% CI .95-1.46，P =.14）。然而，在完全调整的交互作用分析中，女性的这一结果风险增加了一倍（女性，HRfor1ln unit increase：1.88，95% CI 1.27-2.78，p =.002；男性，HRfor1ln unit increase：1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02）：PCSK9水平与血液透析患者的全因死亡率无关，但与对普通人群的研究一样，除其他风险因素外，该人群中的女性发生心血管事件的风险会增加一倍。

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引用次数: 0

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials 口服醋酸甲羟孕酮加共轭马雌激素对女性血脂状况影响的综合荟萃分析：随机对照试验的启示。

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-10 DOI: 10.1111/eci.14211

Yi Lin Zhang, Lei Xie, Fen lan Wu, Xiaomei Ding, Benjamin Hernández-Wolters, Mihnea-Alexandru Găman, Hamed Kord-Varkaneh

Background

Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods

We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively.

Results

A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = −11.93 mg/dL; 95% CI: −13.42, −10.44; p < .001) and LDL-C (WMD = −16.61 mg/dL; 95% CI: −17.97, −15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG).

Conclusions

MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

背景：由于雌激素失去了保护心血管的作用，绝经与心血管风险升高有关。绝经后妇女通常会接受激素替代疗法（HRT），以控制更年期症状和纠正激素失衡；然而，激素替代疗法会影响血清脂质浓度。目前，关于醋酸甲羟孕酮加共轭马雌激素（MPACEE）对女性血脂的影响的数据尚不确定，因为迄今为止所进行的调查得出的结果相互矛盾。因此，我们通过对随机对照试验（RCTs）进行系统回顾和荟萃分析，旨在明确 MPACEE 处方对女性血清脂质值的影响：方法：我们采用基于 DerSimonian 和 Laird 方法的随机效应模型来确定干预对血脂状况影响的综合估计值。加权平均差（WMD）及其相应的 95% 置信区间（CI）的计算分别依赖于 MPACEE 组和对照组的平均值和标准差：共有 53 项研究纳入了荟萃分析，其中 68 项研究涉及总胆固醇（TC），70 项研究涉及低密度脂蛋白胆固醇（LDL-C）和甘油三酯（TG），69 项研究涉及高密度脂蛋白胆固醇（HDL-C）。服用 MPACEE 可显著降低 TC（WMD = -11.93 mg/dL；95% CI：-13.42, -10.44；P 结论：MPACEE 可影响血清胆固醇和甘油三酯：服用 MPACEE 可提高 HDL-C 和 TG 水平，降低 LDL-C 和 TC 值，从而影响女性的血清脂质浓度。因此，患有高胆固醇血症的绝经后女性可能会从这种类型的 HRT 中受益。

{"title":"Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials","authors":"Yi Lin Zhang, Lei Xie, Fen lan Wu, Xiaomei Ding, Benjamin Hernández-Wolters, Mihnea-Alexandru Găman, Hamed Kord-Varkaneh","doi":"10.1111/eci.14211","DOIUrl":"10.1111/eci.14211","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = −11.93 mg/dL; 95% CI: −13.42, −10.44; <i>p</i> < .001) and LDL-C (WMD = −16.61 mg/dL; 95% CI: −17.97, −15.26; <i>p</i> < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; <i>p</i> < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; <i>p</i> < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.</p>\u0000 ","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Soluble receptor of advanced glycation end product as a biomarker in neurocognitive and neuropsychiatric disorders: A meta-analysis of controlled studies 作为神经认知和神经精神疾病生物标志物的高级糖化终产物可溶性受体：对照研究荟萃分析

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-05-03 DOI: 10.1111/eci.14232

Ghazaleh Nameni, Shima Jazayeri, Somaye Fatahi, Sanaz Jamshidi, Marsa Zaroudi

Background & Objectives

Currently, there is a significant focus on the decrease of soluble receptor of advanced glycation end products (sRAGE) in neurocognitive and neuropsychiatric disorders. sRAGE plays a decoy role against the inflammatory response of advanced glycation end products (AGE), which has led to increased interest in its role in these disorders. This meta-analysis aimed to investigate the significant differences in sRAGE levels between neurocognitive and neuropsychiatric disorders compared to control groups.

Method

A systematic review was conducted using the PUBMED, Scopus and Embase databases up to October 2023. Two reviewers assessed agreement for selecting papers based on titles and abstracts, with kappa used to measure agreement and finally publications were scanned according to controlled studies. Effect sizes were calculated as weighted mean differences (WMD) and pooled using a random effects model. Heterogeneity was assessed using I², followed by subgroup analysis and meta-regression tests. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale.

Results

In total, 16 studies were included in the present meta-analysis. Subjects with neurocognitive (n = 1444) and neuropsychiatric (n = 444) disorders had lower sRAGE levels in case–control (WMD: −0.21, 95% CI: −0.33, −0.10; p <.001) and cross-sectional (WMD: −0.29, 95% CI = −0.44, −0.13, p <.001) studies with high heterogeneity and no publication bias. In subgroup analysis, subjects with cognitive impairment (WMD: −0.87, 95% CI: −1.61, −0.13, p =.000), and age >50 years (WMD: −0.39, 95% CI: −0.74, −0.05, p =.000), had lower sRAGE levels in case–control studies. Also, dementia patients (WMD: −0.41, 95% CI: −0.72, −0.10, p =.014) with age >50 years (WMD: −0.33, 95% CI: −0.54, −0.13, p = 0.000) and in Asian countries (WMD: −0.28, 95% CI: −0.42, −0.13, p =.141) had lower sRAGE levels in cross-sectional studies.

Conclusion

This meta-analysis revealed a significant reduction in sRAGE in neurocognitive and neuropsychiatric disorders particularly in Asians and moderate age.

背景& 目的目前，高级糖化终产物可溶性受体（sRAGE）在神经认知和神经精神疾病中的降低受到了广泛关注。sRAGE在高级糖化终产物（AGE）的炎症反应中发挥着诱饵作用，这使得人们对其在这些疾病中的作用越来越感兴趣。本荟萃分析旨在研究神经认知障碍和神经精神障碍患者的sRAGE水平与对照组相比存在的显著差异。方法使用PUBMED、Scopus和Embase数据库对截至2023年10月的研究进行了系统综述。两名审稿人根据标题和摘要对论文的选择进行评估，用卡帕（kappa）来衡量一致性，最后根据对照研究对出版物进行扫描。效应大小以加权平均差（WMD）计算，并使用随机效应模型进行汇总。使用 I2 评估异质性，然后进行亚组分析和元回归测试。采用纽卡斯尔-渥太华质量评估量表进行质量评估。结果本次荟萃分析共纳入 16 项研究。在病例对照（WMD：-0.21，95% CI：-0.33，-0.10；p <.001）和横断面（WMD：-0.29，95% CI=-0.44，-0.13，p <.001）研究中，神经认知障碍（n = 1444）和神经精神障碍（n = 444）受试者的 sRAGE 水平较低，异质性较高，无发表偏倚。在亚组分析中，在病例对照研究中，认知障碍受试者（WMD：-0.87，95% CI：-1.61，-0.13，p =.000）和 50 岁受试者（WMD：-0.39，95% CI：-0.74，-0.05，p =.000）的 sRAGE 水平较低。此外，年龄在 50 岁（WMD：-0.33，95% CI：-0.54，-0.13，p = 0.000）和亚洲国家（WMD：-0.28，95% CI：-0.42，-0.13，p = 0.000）的痴呆症患者（WMD：-0.41，95% CI：-0.72，-0.10，p =.014）的 sRAGE 水平较低。结论这项荟萃分析表明，神经认知和神经精神障碍患者的 sRAGE 水平显著降低，尤其是亚洲人和中年人。

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引用次数: 0

Oxidative stress, defective proteostasis and immunometabolic complications in critically ill patients 重症患者的氧化应激、蛋白稳态缺陷和免疫代谢并发症

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-04-27 DOI: 10.1111/eci.14229

Francesco Galli, Desirée Bartolini, Claudio Ronco

Oxidative stress (OS) develops in critically ill patients as a metabolic consequence of the immunoinflammatory and degenerative processes of the tissues. These induce increased and/or dysregulated fluxes of reactive species enhancing their pro-oxidant activity and toxicity. At the same time, OS sustains its own inflammatory and immunometabolic pathogenesis, leading to a pervasive and vitious cycle of events that contribute to defective immunity, organ dysfunction and poor prognosis. Protein damage is a key player of these OS effects; it generates increased levels of protein oxidation products and misfolded proteins in both the cellular and extracellular environment, and contributes to forms DAMPs and other proteinaceous material to be removed by endocytosis and proteostasis processes of different cell types, as endothelial cells, tissue resident monocytes-macrophages and peripheral immune cells. An excess of OS and protein damage in critical illness can overwhelm such cellular processes ultimately interfering with systemic proteostasis, and consequently with innate immunity and cell death pathways of the tissues thus sustaining organ dysfunction mechanisms. Extracorporeal therapies based on biocompatible/bioactive membranes and new adsorption techniques may hold some potential in reducing the impact of OS on the defective proteostasis of patients with critical illness. These can help neutralizing reactive and toxic species, also removing solutes in a wide spectrum of molecular weights thus improving proteostasis and its immunometabolic corelates. Pharmacological therapy is also moving steps forward which could help to enhance the efficacy of extracorporeal treatments. This narrative review article explores the aspects behind the origin and pathogenic role of OS in intensive care and critically ill patients, with a focus on protein damage as a cause of impaired systemic proteostasis and immune dysfunction in critical illness.

重症患者体内的氧化应激（OS）是免疫炎症和组织变性过程的代谢结果。这些过程会导致活性物质通量增加和/或失调，从而增强其促氧化活性和毒性。与此同时，OS 自身的炎症和免疫代谢发病机制也在持续，导致免疫缺陷、器官功能障碍和预后不良等一系列问题的普遍存在和恶性循环。蛋白质损伤是 OS 影响的一个关键因素；它会在细胞内外环境中产生更多的蛋白质氧化产物和折叠错误的蛋白质，并形成 DAMPs 和其他蛋白质物质，通过不同类型细胞（如内皮细胞、组织常住单核巨噬细胞和外周免疫细胞）的内吞和蛋白稳态过程清除。危重病人体内过量的操作系统和蛋白质损伤会使这些细胞过程不堪重负，最终干扰全身的蛋白稳态，进而干扰组织的先天免疫和细胞死亡途径，从而维持器官功能障碍机制。基于生物相容性/生物活性膜和新型吸附技术的体外疗法在减少操作系统对危重症患者蛋白稳态缺陷的影响方面具有一定的潜力。这些技术有助于中和反应性物质和毒性物质，还能清除各种分子量的溶质，从而改善蛋白稳态及其免疫代谢核心物。药理治疗也在向前迈进，这有助于提高体外治疗的疗效。这篇叙述性综述文章探讨了重症监护和危重病人中操作系统的起源和致病作用，重点是蛋白质损伤作为危重病人全身蛋白稳态受损和免疫功能失调的原因。

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引用次数: 0

Predictive value of quality of life as measured by KCCQ in heart failure patients: A meta-analysis KCCQ 对心力衰竭患者生活质量的预测价值：荟萃分析

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2024-04-26 DOI: 10.1111/eci.14233

Guoying Kao, Gang Xu, Ying Zhang, Chuanwei Li, Jun Xiao

Background

Studies on the predictive ability of disease-specific health quality of life (QoL) in patients with heart failure (HF) have produced conflicting results. To address these gaps in knowledge, we conducted a meta-analysis to evaluate the predictive value of QoL measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with HF.

Materials and Methods

We searched PubMed, and Embase databases to identify studies investigating the predictive utility of baseline QoL measured by the KCCQ in HF patients. The outcome measures were all-cause mortality and HF hospitalisation. The predictive value of QoL was expressed by pooling the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the bottom versus the top category of KCCQ score or for per 10-point KCCQ score decrease.

Results

Twelve studies reporting on 11 articles with a total of 34,927 HF patients were identified. Comparison of the bottom with the top KCCQ score, the pooled adjusted HR was 2.34 (95% CI 2.10–2.60) and 2.53 (95% CI 2.23–2.88) for all-cause mortality and HF hospitalisation, respectively. Additionally, a 10-point decrease in KCCQ score was associated with a 12% (95% CI 7%–16%) increased risk of all-cause mortality and a 14% (95% CI 13%–15%) increased risk of HF hospitalisation.

Conclusions

Poor health-related QoL as determined by the lower KCCQ score, was associated with an increased risk of all-cause mortality and HF hospitalisation in patients with HF. Measuring disease-specific health-related QoL using the KCCQ score may provide valuable predictive information for HF patients.

背景关于心力衰竭（HF）患者疾病特异性健康生活质量（QoL）预测能力的研究结果相互矛盾。为了填补这些知识空白，我们进行了一项荟萃分析，以评估堪萨斯城心肌病问卷（KCCQ）对心力衰竭患者 QoL 的预测价值。结果指标为全因死亡率和高血压住院率。QoL的预测价值通过汇总KCCQ得分最低与最高类别的调整后危险比（HRs）和95%置信区间（CIs）或KCCQ得分每降低10分的调整后危险比（HRs）和95%置信区间（CIs）来表示。将 KCCQ 评分从低到高进行比较，汇总调整后的全因死亡率和心房颤动住院率分别为 2.34 (95% CI 2.10-2.60) 和 2.53 (95% CI 2.23-2.88)。此外，KCCQ评分每降低10分，全因死亡风险增加12%（95% CI 7%-16%），HF住院风险增加14%（95% CI 13%-15%）。使用KCCQ评分测量疾病特异性健康相关生活质量可为高血压患者提供有价值的预测信息。

{"title":"Predictive value of quality of life as measured by KCCQ in heart failure patients: A meta-analysis","authors":"Guoying Kao, Gang Xu, Ying Zhang, Chuanwei Li, Jun Xiao","doi":"10.1111/eci.14233","DOIUrl":"10.1111/eci.14233","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Studies on the predictive ability of disease-specific health quality of life (QoL) in patients with heart failure (HF) have produced conflicting results. To address these gaps in knowledge, we conducted a meta-analysis to evaluate the predictive value of QoL measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with HF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We searched PubMed, and Embase databases to identify studies investigating the predictive utility of baseline QoL measured by the KCCQ in HF patients. The outcome measures were all-cause mortality and HF hospitalisation. The predictive value of QoL was expressed by pooling the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the bottom versus the top category of KCCQ score or for per 10-point KCCQ score decrease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve studies reporting on 11 articles with a total of 34,927 HF patients were identified. Comparison of the bottom with the top KCCQ score, the pooled adjusted HR was 2.34 (95% CI 2.10–2.60) and 2.53 (95% CI 2.23–2.88) for all-cause mortality and HF hospitalisation, respectively. Additionally, a 10-point decrease in KCCQ score was associated with a 12% (95% CI 7%–16%) increased risk of all-cause mortality and a 14% (95% CI 13%–15%) increased risk of HF hospitalisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Poor health-related QoL as determined by the lower KCCQ score, was associated with an increased risk of all-cause mortality and HF hospitalisation in patients with HF. Measuring disease-specific health-related QoL using the KCCQ score may provide valuable predictive information for HF patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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