"Chronic heart failure (CHF) is a massive clinical, social and economic problem. Diabetes and obesity increase the risk of developing CHF. Cachexia is also an ominous sign. In 13 clinical and preclinical research projects, SICA-HF aims to investigate the impact of these co-morbidities in CHF patients at the clinical, vascular, cellular and molecular levels. SICA-HF will enrol >1600 patients with CHF, >300 patients with type 2 diabetes without CHF and >150 healthy control subjects. We will ensure that 50% of subjects are women and that group mean ages are similar. Clinical investigations using standardised protocols will focus on body composition, insulin resistance, exercise capacity, cardiopulmonary reflex patterns and peripheral blood flow. Subjects will be assessed at baseline, after 4-6 months, 16-18 months and at annual intervals thereafter. Outcome variables include morbidity and mortality and data on incidence and prevalence of type 2 diabetes, obesity and cachexia among CHF patients. A strength of this proposal is that clinical and preclinical researchers will study the same patients, as blood and tissue samples from patients being clinically evaluated will be sent to partner research laboratories. Such interaction is very rare in large-scale studies and allows integration of clinical and preclinical findings. The Central Blood and DNA Banks on the EU and the Russian side of the consortium permit validation of established and investigation of novel biomarkers. Pathophysiological pathways that are found to be important in the heart failure co-morbidity interaction will be further analysed mechanistically in in-vitro and in animal models. We aim to validate clinical study results in experimental settings towards the end of the project (year 3 & 4), particularly focusing on adipose tissue, skeletal muscle and (endothelial) progenitor cells. Our studies aim to enable developing tailored therapies for CHF patients with type 2 diabetes, obesity and cachexia."