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.
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