Abstract 14299: The Prognostic Value of Insulin-like Growth Factor-Binding Protein 7 in Patients With Heart Failure and Preserved Ejection Fraction: Results From Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) Trial
Introduction: Heart failure with preserved ejection fraction (HFpEF) is associated with considerable morbidity and mortality. Insulin-like growth factor-binding protein 7 (IGFBP7) is a cell cycle arrest biomarker associated with abnormal diastology and prognosis in HF with reduced EF (HFrEF). Its role in patients with HFpEF is unknown.
Hypothesis: IGFBP7 will be associated with adverse outcomes in HFpEF.
Methods: Baseline (BL) IGFBP7 (n=302; placebo=154, irbesartan=148) and 6 month change (Δ; n=293; placebo=147, irbesartan=146) were measured and correlated with clinical data, biomarkers, estimated glomerular filtration rate (eGFR), and the primary outcome of all-cause mortality (ACM) or cardiovascular hospitalization (CVH) in patients from the Irbesartan in HFpEF (I-PRESERVE) Trial; secondary outcomes included HF events.
Results: Median BL IGFBP7 concentration was 218 ng/mL, higher than previously seen in patients with HFrEF. BL IGFBP7 was correlated with age (R2=0.13; P<0.0001) and other prognostic variables including amino-terminal pro-B-type natriuretic peptide (NT-proBNP; R2=0.22; P<0.0001) and eGFR (R2=0.14; P<0.0001). BL IGFBP7 was associated with the primary outcome (hazard ratio [HR]=1.06 per 10 ng/mL; P<0.001), ACM (HR=1.08 per 10 ng/mL; P<0.001), and HF events (HR=1.07 per 10 ng/mL; P<0.001; Figure) and remained significant for all outcomes after adjustment for NT-proBNP and eGFR. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was not independently associated with outcomes but was associated with a decrease in eGFR in patients randomized to receive irbesartan (R2=0.09; P<0.002).
Conclusions: IGFBP7 is associated with adverse outcomes in HFpEF. Further studies are needed to identify the mechanistic link between IGFBP7, renal function, and outcomes in patients with HFpEF.
Author Disclosures: P.U. Gandhi: None. S.L. Chow: None. T.S. Rector: None. H. Krum: None. H.K. Gaggin: Research Grant; Modest; Roche Diagnostics. Consultant/Advisory Board; Modest; Critical Diagnostics, Roche Diagnostics, American Regent, Boston Heart Diagnostics. J.J. McMurray: None. M. Zile: None. M. Komajda: Speakers Bureau; Modest; Servier, MSD, Menarini, BMS, Astra Zeneca, Novartis, Sanofi, boehringer Ingelheim. Consultant/Advisory Board; Modest; servier, novartis, BMS. Speakers Bureau; Significant; significant, modest, modest, modest, modest, modest, modest, modest. Consultant/Advisory Board; Significant; significant, modest, modest. R.S. McKelvie: None. P.E. Carson: None. J.L. Januzzi: Research Grant; Significant; Siemens, Thermo Fisher, Provencio, Singulex. Consultant/Advisory Board; Modest; Critical Diagnostics, Sphingotec, Amgen. Consultant/Advisory Board; Significant; Roche Diagnostics, Novartis, Boehringer Ingelheim. I.S. Anand: None.
- © 2015 by American Heart Association, Inc.