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

点击翻译按钮获取中文摘要

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.