Angs (Angiotensins) of the Alternative Renin-Angiotensin System Predict Outcome in Patients With Heart Failure and Preserved Ejection Fraction

Abstract

The renin-angiotensin system plays an important role in the development and progression of heart failure (HF). In addition to the classical renin-angiotensin pathway, an alternative pathway produces Angs (angiotensins), which counteract the negative effects of Ang II. We hypothesized that Ang profiling could provide insights into the pathogenesis and prognosis of HF with preserved ejection fraction. We aimed to investigate the effects of Angs on outcome in HF with preserved ejection fraction. Consecutive patients were included into a prospective single-center registry. Clinical, laboratory, and imaging parameters were assessed and serum samples were taken at baseline and measured by mass spectroscopy. Serum equilibrium levels were analyzed in regard to the combined clinical end point of cardiovascular death or HF hospitalization. In total, 155 patients were included during a median follow-up time of 22.5 (interquartile range, 4.0–61.0) months, 52 individuals (34%) reached the combined end point. We identified higher levels of Ang 1–7 and Ang 1–5 as predictors for poor outcome. After adjusting for potential confounding factors, Ang 1–5 remained predictive for poor outcome. In addition to Ang 1–7 and Ang 1–5, the novel ACE (angiotensin-converting enzyme) independent Ang composite marker [Ang 1–7+Ang 1–5] was shown to predict adverse events. We conclude that Angs of the alternative renin-angiotensin system seem to play a role in HF with preserved ejection fraction and are linked to outcome in patients with HF and preserved ejection fraction. Ang 1–5 and the alternative renin-angiotensin system composite marker [Ang 1–7+Ang 1–5] are independent predictors of outcome.