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

• Published in: Physiological reports Vol. 7; no. 5; pp. e14021 - n/a
• Main Authors: Montero, David, Haider, Thomas, Barthelmes, Jens, Goetze, Jens P., Cantatore, Silviya, Lundby, Carsten, Sudano, Isabella, Ruschitzka, Frank, Flammer, Andreas J.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2019; John Wiley and Sons Inc
• Subjects: Adult; Age Factors; Aged; Ageing and Degeneration; Aldosterone; Atrial natriuretic peptide; Biomarkers - blood; Blood Pressure; Cardiovascular Conditions, Disorders and Treatments; Case-Control Studies; Central Venous Pressure; Congestive heart failure; Endocrinology and Metabolism; Erythropoietin; Erythropoietin - blood; Female; Geriatrics; heart failure; Heart Failure - blood; Heart Failure - diagnosis; Heart Failure - physiopathology; Heart rate; Humans; Jugular vein; Male; Middle Aged; Original Research; orthostatic tolerance; Patient Positioning; Physiology; Stroke Volume; Tilt-Table Test; Time Factors; Ultrasound; Up-Regulation; Ventricular Function, Left; Young Adult; United States > US; heart failure; Central venous pressure; orthostatic tolerance; erythropoietin
• ISSN: 2051-817X
• DOI: 10.14814/phy2.14021

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), 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 HFpEF 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 HFpEF 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 HFpEF patients compared with EC and YC, while mean arterial pressure was elevated in HFpEF 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 HFpEF patients and EC. The EPO response to a given reduction in CVP is similarly impaired in HFpEF patients and elderly controls, suggesting an age‐dependent dissociation of EPO production from hemodynamic regulation in the HFpEF condition. Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood volume regulation. The current study demonstrates that endocrine responses to reduced central venous pressure comprising increases in circulating erythropoietin (EPO) are impaired in HFpEF patients and age‐matched elderly individuals, suggesting that the hemodynamic regulation of EPO production is age‐dependent.