Age‐dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients

Abstract

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction ( HF p EF ), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood pressure and blood volume ( BV ) regulation. The present study sought to determine hemodynamic and endocrine responses to prolonged orthostatic stress in HF p EF patients. Central venous pressure ( CVP ) assessed via the internal jugular vein ( IJV ) aspect ratio with ultrasonography, arterial pressure and heart rate were determined at supine rest and during 2 hours of moderate (25–30°) head‐up tilt ( HUT ) in 18 stable HF p EF patients (71.2 ± 7.3 years), 14 elderly ( EC ), and 10 young ( YC ) healthy controls. Parallel endocrine measurements comprised main BV ‐regulating hormones: pro‐atrial natriuretic peptide, copeptin, aldosterone, and erythropoietin ( EPO ). At supine rest, the IJV aspect ratio was higher (>30%) in HF p EF patients compared with EC and YC , while mean arterial pressure was elevated in HF p EF patients (98.0 ± 13.1 mm Hg) and EC (95.6 ± 8.3 mm Hg) versus YC (87.3 ± 5.0 mm Hg) ( P < 0.05). HUT increased heart rate (+10%) and reduced the IJV aspect ratio (−52%), with similar hemodynamic effects in all groups ( P for interaction ≥ 0.322). The analysis of endocrine responses to HUT revealed a group×time interaction for circulating EPO , which was increased in YC (+10%) but remained unaltered in HF p EF patients and EC . The EPO response to a given reduction in CVP is similarly impaired in HF p EF patients and elderly controls, suggesting an age‐dependent dissociation of EPO production from hemodynamic regulation in the HF p EF condition.