HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.
BACKGROUND
Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1.


RESULTS
In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28-79), and HFrEF, 65 (29-101), vs controls, 27(14-35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF.


CONCLUSIONS
HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.
Department of Anesthesia and Intensive Care, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Stockholm, Karolinska Institutet, Sweden. Electronic address: ulrikaljungfaxen@gmail.com.
Ulrika Ljung
UL
Faxén
Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Camilla
C
Hage
Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.
Lina
L
Benson
Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Stanislava
S
Zabarovskaja
Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
Anna
A
Andreasson
Département de Cardiologie & CIC-IT U 804, Centre Hospitalier Universitaire de Rennes, France.
Erwan
E
Donal
Département de Cardiologie & CIC-IT U 804, Centre Hospitalier Universitaire de Rennes, France.
Jean-Claude
JC
Daubert
Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Cecilia
C
Linde
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
Kerstin
K
Brismar
Department of Medicine, Stockholm, Karolinska Institutet, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Lars H
LH
Lund
D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008660:Metabolism / Q000502:physiology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D013223:Statistics as Topic; D013318:Stroke Volume / Q000502:physiology; D013548:Sweden; D016277:Ventricular Function, Left / Q000502:physiology
D015415:Biomarkers; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
biomarker; heart failure with preserved ejection fraction; insulin-like growth factor 1; insulin-like growth factor binding protein 1