Prognostic Value of Insulin-Like Growth Factor-Binding Protein 7 in Patients with Heart Failure and Preserved Ejection Fraction.
BACKGROUND
The prognostic merit of insulin-like growth factor-binding protein 7 (IGFBP7) is unknown in heart failure and preserved ejection fraction (HFpEF).


RESULTS
Baseline IGFBP7 (BL-IGFBP7; n = 302) and 6-month change (Δ; n = 293) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years; secondary outcomes included HF events. Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age (R2= 0.13; P < .0001), amino-terminal pro-B-type NP (R2= 0.22; P < .0001), and estimated glomerular filtration rate (eGFR; R2= 0.14; P < .0001), but not with signs/symptoms of HFpEF. BL-IGFBP7 was significantly associated with the primary outcome (hazard ratio [HR] = 1.007 per ng/mL; P < .001), all-cause mortality (HR = 1.008 per ng/mL; P < .001), and HF events (HR = 1.007 per ng/mL; P < .001). IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro-B-type NP and eGFR but not all variables in the I-PRESERVE prediction model. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was significantly associated with decrease in eGFR in patients randomized to irbesartan (R2= 0.09; P = .002). ΔIGFBP7 was not independently associated with outcome.


CONCLUSIONS
Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events, but after multivariable adjustment this association was no longer present. Further studies of IGFBP7 are needed to elucidate its mechanism.


BACKGROUND
www.clinicaltrials.gov, NCT00095238.
Section of Cardiovascular Medicine, VA Connecticut, West Haven, Connecticut; Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut.
Parul U
PU
Gandhi
Western University of Health Sciences, Pomona, California.
Sheryl L
SL
Chow
Veterans Affairs Medical Center, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota.
Thomas S
TS
Rector
CCRE Therapeutics, Monash University, Melbourne, Australia.
Henry
H
Krum
Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts.
Hanna K
HK
Gaggin
British Heart Foundation Glasgow Cardiovascular Research Center, Glasgow, United Kingdom.
John J
JJ
McMurray
RHJ Department of Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, South Carolina.
Michael R
MR
Zile
Université Paris 6; Pitie Salpetriere Hospital, Paris, France.
Michel
M
Komajda
Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada.
Robert S
RS
McKelvie
Washington VAMC and Georgetown University, Washington, DC.
Peter E
PE
Carson
Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org.
James L
JL
Januzzi
Veterans Affairs Medical Center, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota.
Inder S
IS
Anand
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002423:Cause of Death / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D000077405:Irbesartan; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology*; D015996:Survival Rate / Q000639:trends; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D018969:Insulin-Like Growth Factor Binding Proteins; D013777:Tetrazoles; C102529:insulin-like growth factor binding protein-related protein 1; D000077405:Irbesartan
Heart failure; biomarkers; insulin-like growth factor-binding protein 7; preserved left ventricular function; prognosis