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
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abstract
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 (R
2
=0.13; P<0.0001) and other prognostic variables including amino-terminal pro-B-type natriuretic peptide (NT-proBNP; R
2
=0.22; P<0.0001) and eGFR (R
2
=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 (R
2
=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.
