Publications & Posters

Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction

Tromp J, Khan MA, Klip IT, Meyer S, de Boer RA, Jaarsma T, Hillege H, van Veldhuisen DJ, van der Meer P and Voors AA

J Am Heart Assoc. 2017;6.




Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF.

Methods and Results

We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction ≥45%) measured at discharge after hospitalization for acute HF. The association between these markers and the occurrence of all‐cause mortality and/or HF‐related rehospitalizations at 18 months was compared between patients with HFrEF and HFpEF. Patients were 70.6±11.4 years old and 37.4% were female. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure. Levels of high‐sensitive C‐reactive protein were significantly higher in HFpEF, while levels of pro‐atrial‐type natriuretic peptide and N‐terminal pro‐brain natriuretic peptide were higher in HFrEF. Linear regression followed by network analyses revealed prominent inflammation and angiogenesis‐associated interactions in HFpEF and mainly cardiac stretch–associated interactions in HFrEF. The angiogenesis‐specific marker, neuropilin and the remodeling‐specific marker, osteopontin were predictive for all‐cause mortality and/or HF‐related rehospitalizations at 18 months in HFpEF, but not in HFrEF (P for interaction <0.05).


In HFpEF, inflammation and angiogenesis‐mediated interactions are predominantly observed, while stretch‐mediated interactions are found in HFrEF. The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HFpEF, but not in HFrEF.