Circulating factors in heart failure:Biomarkers, markers of co-morbidities and disease factors

Heart failure (HF) is a clinical syndrome characterized by typical signs and symptoms caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intra-cardiac pressures at rest or during stress. The lifetime risk to develop HF at age 55 is 33% for men and 28% for women. In the Netherlands, every day more than 100 patients die of cardiovascular disease, and every year over 7500 patients die of HF. One of the key processes in the pathophysiology of HF is cardiac remodeling, a generally unfavorable process in which the myocardium is converted into a, mostly irreversible, changed structural and functional state. Circulating molecules, released during this process and also known as biomarkers, might aid physicians to better understand the pathophysiology of HF and to better treat and tailor therapy for specific patients. In this thesis, we investigate the utility of biomarkers in different clinical settings and whether biomarkers can provide insights in the interplay between different disease entities. We explore whether biomarkers could be used to identify subjects at low-risk for adverse events. Furthermore, we provide insight in the biological variation of biomarkers, to help clinicians to better interpret biomarkers levels over time. Biomarkers could also be used as a target for therapy. In a review article we discuss the possibilities of anti-galectin-3 therapy and the possible clinical consequences. Lastly, we demonstrate that biomarkers secreted by the failing heart have a direct effect on cancer development and growth. This interplay and possible other mechanisms involved are discussed within this thesis. Future studies need to further explore this interplay of the cardiac secretome with other organs and diseases