Clinical associations and their significance of inflammatory markers with incidence, severity of disease and prognosis in heart failure patients

心力衰竭已成为一个重大的公共卫生问题。在西半球，心力衰竭是最常见的发病和死亡原因之一。尽管符合指南的常规药物治疗和最近的治疗进展，关于心力衰竭患者的发病率和死亡率的总体预后仍然很差。越来越多的实验证据表明，炎症在心力衰竭的发病和维持中起着至关重要的作用。最近的临床数据表明，HFpEF的炎症活动性与疾病严重程度之间存在很强的相关性，慢性炎症和代谢紊乱与HFpEF之间也存在关联。因此，抗炎干预可能是治疗心力衰竭的一种很有前途的方法。然而，尽管炎症在心力衰竭中的作用的知识不断增加，炎症和心力衰竭的临床关联需要进一步解决。申请人正在哈佛大学布里格姆妇女医院（BWH）临床研究中心（CCI）提出一项研究策略，以破译炎症对心力衰竭严重程度和预后的贡献。为了研究炎症标志物与心力衰竭发病率、预后和亚组的临床关联，申请人将在心力衰竭患者中进行一项大规模纵向队列研究。因此，申请人将获得美国国立卫生研究院（NIH）最大的队列研究之一的机会。为了进一步验证从队列分析中获得的结果，申请人将在第二步中对大型多中心心力衰竭结局试验进行二次分析。作为关键的最后一步，申请人将设计并启动一项随机临床试验，根据之前的分析结果，评估心力衰竭患者群体的治疗性抗炎方法。这项研究旨在更好地了解炎症在心力衰竭中的作用，为开发创新的、个性化的抗炎疗法提供临床原则。第二目标是进一步提高申请人在临床研究方面的方法能力，为未来的合作建立科学网络，并了解国际临床研究中心的核心结构和操作标准。因此，申请人将参与临床试验的设计、实施和分析的所有阶段，以保证全面的培训。

Heart failure has emerged as a major public health issue. In the western hemisphere, heart failure is one of the most common causes of morbidity and mortality. Despite guideline-conform therapy with conventional drugs and recent therapeutic progress, the general prognosis regarding morbidity and mortality in patients with heart failure still remains poor. A variety of growing experimental evidence implicates that inflammation plays a critical role in the pathogenesis and maintenance of heart failure. Recent clinical data indicate a strong correlation between inflammatory activity and severity of disease in HFrEF as well as an association of chronic inflammatory and metabolic disorders with HFpEF. Thus, anti-inflammatory interventions might represent a promising therapeutic approach in heart failure. However, despite the rising knowledge of inflammatory contribution in heart failure, the clinical associations of inflammation and heart failure need to be further addressed. The applicant is proposing a research strategy to decipher the contribution of inflammation on severity and prognosis in heart failure at the Center for Clinical Investigation (CCI) at Brigham and Women’s Hospital (BWH) of the Harvard University. To address the clinical associations of inflammatory markers with incidence, prognosis and subgroups of heart failure, the applicant will perform a primary investigation in a large scaled longitudinal cohort study with heart failure patients. Therefore, the applicant will be provided access to one of the largest cohort studies of the National Institutes of Health (NIH). To further verify the obtained findings from the cohort analysis, the applicant will perform secondary analysis of large multicenter heart failure outcome trials in a second step. As a crucial final step, the applicant will design and initiate a randomised clinical trial evaluating therapeutic anti-inflammatory approaches in a collective of patients with heart failure based on findings of the previous analyses. The proposed investigations aim to contribute to a better understanding of the role of inflammation in heart failure, providing clinical principles for the development of innovative, personalized, anti-inflammatory therapies. Secondary aim of the fellowship is to further improve the applicant’s methodological competence concerning clinical research, to build a scientific network for future collaborations and to earn knowledge about core structures and operational standards in international clinical research centers. Consequently, the applicant will be involved in all stages of design, conduct and analysis of clinical trials to guarantee a full-comprehensive training.