Growth differentiation factor-15 is a useful prognostic marker in patients with heart failure with preserved ejection fraction.
BACKGROUND
Circulating growth differentiation factor 15 (GDF-15) levels correlate with heart mass and fibrosis; however, little is known about its value in predicting the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).


METHODS
We measured serum GDF-15 levels in 149 consecutive patients with left ventricular diastolic dysfunction (LVDD) and normal LV ejection fraction (>50%) and followed them for cardiovascular events. LVDD was defined according to the European Society of Cardiology guidelines.


RESULTS
The New York Heart Association functional class and circulating B-type natriuretic peptide (BNP) levels were significantly higher in the high-GDF-15 group (n = 75; greater than or equal to the median value [3694 pg/mL]) than in the low-GDF-15 group (n = 74). Patients were divided into HFpEF and LVDD groups according to the presence or absence of HF. Serum GDF-15 levels were significantly higher in the HFpEF group (n = 73) than in the LVDD group (n = 76) (median, 4215 [interquartile range, 3382-5287] vs 3091 [interquartile range, 2487-4217 pg/mL]; P < 0.0001). Kaplan-Meier curve analysis showed a significantly higher probability of cardiovascular events in the high-GDF-15 group than in the low-GDF-15 group for data of all patients (log-rank test P = 0.006) and data of patients in the HFpEF group only (P = 0.014). Multivariate Cox hazard analysis identified age (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.98; P = 0.008), atrial fibrillation (HR, 7.95; 95% CI, 1.98-31.85, P = 0.003), lnBNP (HR, 3.37; 95% CI, 1.73-6.55; P < 0.0001), and GDF-15 (ln[GDF-15]) (HR, 4.74; 95% CI, 1.26-17.88, P = 0.022) as independent predictors of primary end points.


CONCLUSIONS
GDF-15 is a potentially useful prognostic biomarker in patients with HFpEF.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: izumiya@kumamoto-u.ac.jp.
Yasuhiro
Y
Izumiya
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Shinsuke
S
Hanatani
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yuichi
Y
Kimura
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Seiji
S
Takashio
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Eiichiro
E
Yamamoto
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hiroaki
H
Kusaka
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Takanori
T
Tokitsu
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Taku
T
Rokutanda
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Satoshi
S
Araki
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Kenichi
K
Tsujita
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Tomoko
T
Tanaka
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Megumi
M
Yamamuro
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Sunao
S
Kojima
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Shinji
S
Tayama
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Koichi
K
Kaikita
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Seiji
S
Hokimoto
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hisao
H
Ogawa
D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology*; D015996:Survival Rate / Q000639:trends; D016277:Ventricular Function, Left / Q000502:physiology*
D015415:Biomarkers; D055436:Growth Differentiation Factor 15