Page 15 - Biomarkers for risk stratification and guidance in heart failure

Chapter 1
Guided therapy of heart failure: Cardio-renal dilemma
HF and renal dysfunction often coincide,46,47 and the presence of renal dysfunction in HF is associated with worse outcome.48 In HF patients, worsening renal function over time has been associated with worse outcome,49 although reports are conflicting. Worsening renal function can be caused by ominous processes that are related to progression of HF like forward failure, venous congestion and activation of RAAS-system.50 On the contrary, worsening of renal function can also be caused by factors that are associated with favorable outcome like titration of evidence based HF medication like ACE-inhibitors, AT-2 antagonists and aldosterone receptor blockers.51-55 Therefore interpretation of change in renal function in HF patients is a challenging task.
Natriuretic peptides have shown to react upon HF treatment; NT-proBNP levels decrease after titration of evidence based HF medication.56-58 Furthermore, outpatient change in NT-proBNP has been related to outcome.45
In the setting of treating HF, clinicians may encounter conflicting prognostic information when evaluating changes in renal function and natriuretic peptides over time if they go in opposite directions. Thus, it is unclear if worsening renal function should get more attention than lowering (NT-pro)BNP levels and vice versa. This may be of particular importance early after hospital discharge when changes in medication are very common and risk for readmission or mortality is highest. Knowledge of both change in renal function and natriuretic peptide concentration may therefore help revealing part of the cardio-renal dilemma.
1.4 Outline of this thesis.
This thesis describes the potential use of biomarkers to manage patients with HF. Particular focus is placed on the role of NT-proBNP, which is the best-studied biomarker in such patients. Several new aspects are addressed to increase the utility and the clinical usefulness of biomarkers that help to not only better classify patients at risk, but also to guide further intervention in this fragile patient group. In order to achieve this aim, it was important to investigate which patients may benefit most and in what way comorbidities are influencing the response to therapy. One of the most important comorbidities in HF patients is renal dysfunction, which often limits the appropriate use of treatment in HF patients. Thus, additional focus is place on the importance of renal dysfunction as compared to severity of HF on the treatment response.
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