Abstract 15135: Bone Morphogenic Protein-2 is Increased in the Bone Marrow Plasma of Patients With Chronic Heart Failure and Correlates With the Disease Severity and Mortality
Background: Chronic heart failure with reduced EF (HFrEF) is associated with impaired bone marrow function. Bone morphogenetic protein-2 (BMP-2) supports osteogenesis as well as the development and maintenance of hematopoietic stem cell niche. The clinical role of BMP-2 in the progression of chronic heart failure has not been evaluated so far.
Methods and Results: BMP-2 was measured by ELISA in bone marrow plasma and peripheral blood of 237 patients (age: 61.4 ±12.2) with HFrEF, who were enrolled in the Frankfurt Bone Marrow-Derived Cell Therapy Registry, as well as in 50 healthy subjects (age 39.1±10.8). 54 patients died within a 5-year follow-up period.
BMP-2 bone marrow plasma levels were significantly increased in patients with HFrEF compared to healthy subjects (mean±SD: 47.78±34.6 vs 37.82±36.1, p=0.01). A similar trend was observed for peripheral blood BMP-2 levels (mean±SD: 12.02 ±15.9 vs 9.93±19.4, p=0.058). Furthermore, bone marrow derived BMP-2 levels were significantly increased in patients dying during follow-up (survivors vs. non-survivors, median, pg/mL: 37.26 vs 48.6, p=0.025). BMP-2 bone marrow plasma levels were closely correlated with peripheral BMP-2 levels (r=0.557, p<0.01). However, bone marrow levels were almost 5-times higher. Bone marrow BMP-2 plasma levels were significantly associated with age (r=0.35, p<0.001), NYHA class (r=0.26, p<0.001), NT-proBNP (r=0.28, p<0.001) and creatinine serum levels (r=0.46, p<0.001).
Increased BMP-2 bone marrow plasma levels were associated with a 1.5-fold increased risk for death (95%CI: 1.2 to 1.8, p<0.001). After adjustment for age, sex, LVEF and Seattle Heart Failure score, BMP-2 remained an independent predictor of death in patients with chronic heart failure.
Conclusions: These data for the first time demonstrate that bone marrow derived BMP-2 is increased in patients with chronic heart failure. Importantly, elevated bone marrow plasma levels of BMP-2 are independently associated with mortality in heart failure. These findings further support the link between the bone marrow and the failing heart and may provide insights into the functional consequences of chronic heart failure.
Author Disclosures: K. Sopova: None. B. von Jeinsen: None. L. Palapies: None. K. Stellos: None. F. Stephan: None. F. Seeger: None. S. Dimmeler: None. B. Assmus: None. A. Zeiher: None. T. Keller: None.
- © 2016 by American Heart Association, Inc.