Natriuretic Peptides and the Microcirkulation in Heart Failure Patients

Sammanfattning: The increased prevalence of chronic congestive heart failure (HF) is a tremendous challenge for society. In spite of effective medical treatment for acute HF, better pharmacological treatment for specific neurohormonal intervention and better diagnostic tools, e.g. biomarkers of natriuretic peptides, the morbidity and mortality due to this disease are still prominent. HF leads to vascular dysfunction in the general circulation but the interpretation of this is not clear. In our studies we have focussed on defining endothelial and smooth muscle dysfunction in the microvasculature of HF patients and correlating this dysfunction with the disease state. This thesis addresses studies of elderly patients with varying degrees of HF. We determined blood levels of homocysteine and the natriuretic peptide precursor, NT-proBNP which is released by the failing heart. We also investigated vasoreactive response of the cutaneous microcirculation to different stimuli using a non-invasive iontophoresis-Laser Doppler probe method. Paper I: We investigated the prognostic value of NT-proBNP for monitoring progression of HF. High blood levels (>5000) were found to indicate a poor prognosis of HF. Paper II: An open study,- in which we evaluated the function of the cutaneous peripheral circulation of patients with chronic HF. We found that vasoreactivity declines with increasing age and HF. Paper III: We evaluated vasoreactive responses in HF patients with homocysteinemi, before and 6 weeks after supplementary by B vitamin treatment. Homocysteine levels where then normalized and the cutaneous responses improved. Paper IV: A controlled study in which, we investigated the microcirculation in chronic HF patients with different degrees of HF. We saw that the degree of severity of congestive HF did not correlate with decrease in vasoreactive responses. Paper V: The effect of BNP in the microcirculation was studied in patients with severe congestive HF and compared to healthy, matched controls. The result shows that BNP has a significantly weaker vasodilation in HF patients and this is probably due to down regulation at the receptor-coupling level.