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

Jasper Tromp, Mohsin A.F. Khan, IJsbrand T. Klip, Sven Meyer, Rudolf A. de Boer, Tiny Jaarsma, Hans Hillege, Dirk J. van Veldhuisen, Peter van der Meer, Adriaan A. Voors

Journal of the American Heart Association · 2017 · 246 citations · 29 references

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Abstract

Background Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure ( HF ) patients with a reduced ejection fraction ( HF r EF ) and a preserved ejection fraction ( HF p EF ). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HF r EF and HF p EF . 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% HF p EF , 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 HF r EF and HF p EF . Patients were 70.6±11.4 years old and 37.4% were female. Patients with HF p EF were older, more often female, and had a higher systolic blood pressure. Levels of high‐sensitive C‐reactive protein were significantly higher in HF p EF , while levels of pro‐atrial‐type natriuretic peptide and N‐terminal pro‐brain natriuretic peptide were higher in HF r EF . Linear regression followed by network analyses revealed prominent inflammation and angiogenesis‐associated interactions in HF p EF and mainly cardiac stretch–associated interactions in HF r EF . 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 HF p EF , but not in HF r EF ( P for interaction <0.05). Conclusions In HF p EF , inflammation and angiogenesis‐mediated interactions are predominantly observed, while stretch‐mediated interactions are found in HF r EF . The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HF p EF , but not in HF r EF .

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