Complemental impact of LDL-cholesterol levels and microbiota-derived metabolites on coronary plaque burden and composition

低密度脂蛋白胆固醇水平和微生物群衍生代谢物对冠状动脉斑块负荷和成分的互补影响

• 批准号: 437213406
• 负责人: Dr. Iryna Dykun
• 金额: --
• 依托单位: Klinik für Kardiologie und Angiologie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/437213406?language=en
• 关键词: Complemental; impact; LDL; cholesterol; levels

In patients with cardiovascular diseases, lipid lowering therapy is the key cornerstone for prevention of disease progression. Despite definite thresholds as indicated in the guidelines, a linear relationship between LDL-cholesterol levels and reduction of risk for subsequent cardiovascular events exists. However, existing literature on randomized controlled trials only evaluated different treatment strategies instead of individual LDL-cholesterol levels. In contrast, the potency of a given treatment with regard to achieved LDL-levels varies considerably on an individual patient level. Currently data is lacking, whether the individual LDL-level or the treatment strategy leads to improved patient outcome. In addition, despite the advances in reducing CVD burden with modification of traditional CVD risk factors, significant residual risks remain. One of the factors that might contribute to the progression of atherosclerosis and development of CVD are infectious pathogens. Present studies have shown that trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, is a predictor of incident CVD events, independent of traditional CVD risk factors. However, robust data investigating the association of microbiota-derived metabolites with coronary atherosclerosis burden is currently lacking. The aim of this project is to determine, whether LDL-cholesterol levels influence the change in coronary plaque volume over time, irrespective of the treatment regime. In addition, in the present project, the applicant aims to investigate the association of TMAO levels as microbiota-derived metabolite with adverse coronary plaque characteristics beyond lipid levels. The present project consists of two major parts that will be performed at the Cleveland Clinic Coordinating Center for Clinical Research. Within part A, a post-hoc pooled analysis of 10 prospective randomized controlled trials with over 5,500 patients on medical therapy with serial IVUS examinations will be performed. Within part B of the project, the applicant will evaluate the association of TMAO as microbiota-derived metabolite with coronary plaque burden and composition, as quantified by IVUS and virtual histology, in a prospective database of patients from the Cleveland Clinic. The applicant will further assess the complemental impact of cholesterol levels and microbiota-derived metabolites on coronary plaque burden and composition. The results drawn from this project will give substantial insights regarding the understanding of the influence of lipid lowering treatment strategies and LDL-levels on disease progression in patients with coronary artery disease. In addition, the project will further assess the association of the gut microbiome on coronary atherosclerosis. Combining the information from both parts, the project may direct towards individualized therapy decisions in primary and secondary prevention of coronary artery disease

在心血管疾病患者中，降脂治疗是防止疾病进展的关键基石。尽管指南中指出了明确的阈值，但低密度脂蛋白-胆固醇水平与随后心血管事件风险的降低之间存在线性关系。然而，现有的关于随机对照试验的文献只评估了不同的治疗策略，而没有评估个体的低密度脂蛋白-胆固醇水平。相比之下，特定治疗的效力与达到的低密度脂蛋白水平在个体患者水平上有很大的不同。目前缺乏数据，无论是个人的低密度脂蛋白水平还是治疗策略导致患者预后的改善。此外，尽管通过修改传统的心血管疾病风险因素在减少心血管疾病负担方面取得了进展，但仍然存在重大的残余风险。可能导致动脉粥样硬化进展和心血管疾病发展的因素之一是感染性病原体。目前的研究表明，三甲胺N-氧化物(TMAO)是肠道微生物区系的代谢物，是心血管事件的预测因子，独立于传统的心血管疾病危险因素。然而，目前还缺乏研究微生物代谢产物与冠状动脉粥样硬化负担之间关系的可靠数据。该项目的目的是确定，无论治疗方案如何，低密度脂蛋白-胆固醇水平是否会影响冠状动脉斑块体积随时间的变化。此外，在本项目中，申请人的目标是调查作为微生物区系衍生代谢物的TMAO水平与血脂水平以外的不良冠状动脉斑块特征的相关性。本项目由两个主要部分组成，将在克利夫兰临床研究协调中心进行。在A部分中，将对10个前瞻性随机对照试验进行事后汇总分析，这些试验涉及5500多名患者，他们接受了一系列IVUS检查的药物治疗。在该项目的B部分，申请者将在克利夫兰诊所患者的预期数据库中，评估作为微生物衍生代谢物的TMAO与冠状动脉斑块负荷和成分的关联，通过静脉内超声和虚拟组织学进行量化。申请者将进一步评估胆固醇水平和微生物衍生代谢物对冠状动脉斑块负荷和组成的互补影响。从这个项目中得出的结果将为理解降脂治疗策略和低密度脂蛋白水平对冠心病患者疾病进展的影响提供实质性的见解。此外，该项目还将进一步评估肠道微生物群与冠状动脉粥样硬化的关系。结合来自这两个部分的信息，该项目可能会针对冠状动脉疾病的一级和二级预防做出个性化的治疗决策。

项目成果

Early Resolution of New-Onset Left Bundle Branch Block After Transcatheter Aortic Valve Implantation With the SAPIEN 3 Valve.

使用 SAPIEN 3 瓣膜经导管主动脉瓣植入后新发左束支传导阻滞的早期解决

• DOI: 10.1016/j.amjcard.2021.12.032
• 期刊: The American journal of cardiology
• 作者: Isogai T;Dykun I;Agrawal A;Shekhar S;Tarakji KG;Wazni OM;Kalra A;Krishnaswamy A;Reed GW;Kapadia SR;Puri R.
• 通讯作者: Puri R.