PhD ceremony Mr. F.P.J. Brouwers: New onset heart failure. Origin and manifestation

PhD ceremony: Mr. F.P.J. Brouwers

Dissertation: New onset heart failure. Origin and manifestation

Promotor(s): prof. W.H. van Gilst, prof. D.J. van Veldhuisen

Faculty: Medical Sciences

The first part of this thesis concerns the epidemiology, clinical characteristics and biomarkers of new onset heart failure, as well as heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). During the past decade, the prevalence and incidence of heart failure has stabilized, or slightly decreased. However, it should be noted that changes in HFrEF incidence may account for most of this decrease, while the incidence of HFpEF may have increased. Risk factors for both heart failure phenotypes are not well defined. This thesis provides clear evidence for a differential risk profile for HFpEF compared to HFrEF, which arises years before signs and symptoms due to either HFrEF or HFpEF become apparent. These results are further amplified by evaluating the prognostic value of multiple biomarkers for both subtypes of heart failure. An increased risk for heart failure was observed for several biomarkers, and in particular for HFrEF. In contrast, there was no clinically relevant association of biomarkers with new onset HFpEF. Finally, a heart failure risk model was created and included 21 commonly available variables. The predictive power for both heart failure syndromes was modest and therefore its clinical utility remains questionable. For HFpEF in particular, risk prediction will remain a significant challenge in daily clinical practice.

In the second part of this thesis, the aforementioned results are supported by several separate analyses, associating the prognostic value of single biomarkers with poor cardiovascular outcome. Urinary albumin excretion in particular has a powerful prognostic association with adverse cardiovascular outcome. In a sub-analysis, the Framingham Risk Score was shown to substantially underestimate the ten-year predicted risk for cardiovascular disease in subjects in the highest quintile of albuminuria (>50mg/24h). Finally, the novel biomarker mid-regional pro-adrenomedullin, expressed in endothelial cells, has been associated with poor cardiovascular outcome, especially in subjects below 70 years of age.