Comparison of Prognostic Usefulness of Serum Insulin-Like Growth Factor-Binding Protein 7 in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction

Abstract

We aimed to characterize of the role of insulin-like growth factor-binding protein 7 (IGFBP-7) in heart failure (HF) pathophysiology. IGFBP-7 has been associated with cardiac hypertrophy and diastolic dysfunction in HF. In 86 patients with HF with a preserved ejection fraction (HFpEF) (ejection fraction [EF] ≥45%) and 79 with HF with a reduced ejection fraction (HFrEF), we assessed concentrations of serum IGFBP-7, correlations between serum IGFBP-7 and clinical data, diastolic function, and associations with outcome. IGFBP-7 was lower in HFpEF than HFrEF (102 vs 152 µg/L, p <0.001) and correlated with New York Heart Association class (HFpEF: r = 0.25, p = 0.020; HFrEF: r = 0.26, p = 0.022), N-terminal pro-brain natriuretic peptide (NT-proBNP) (HFpEF: r = 0.53, p <0.001; HFrEF: r = 0.50, p <0.001), and estimated glomerular filtration rate (eGFR) (HFpEF: r = -0.47, p <0.001; HFrEF: r = -0.45, p <0.001). In HFpEF, IGFBP-7 correlated with E/e' (r = 0.31, p = 0.012) and E/A ratio (r = 0.31, p = 0.011). In HFrEF, but not HFpEF, IGFBP-7 correlated with age (r = 0.29, p = 0.009) and atrial fibrillation (r = 0.34, p = 0.002). IGFBP-7 predicted the outcome in HFpEF (hazard ratio 4.19 [1.01 to 17.35], p = 0.048]) but not in HFrEF (0.72 [0.24 to 2.14], p = 0.554). In conclusion in HFrEF, IGFBP-7 was elevated and associated with HF severity but not prognostic, suggesting a marker of risk. In HFpEF, IGFBP-7 was less elevated but associated with markers of diastolic dysfunction, HF severity, and prognosis. IGFBP-7 may contribute to the progression of HFpEF possibly through inflammation and oxidative stress.

Echocardiographic assessment of insulin‐like growth factor binding protein‐7 and early identification of acute heart failure

“…Higher concentrations of IGFBP7 may result in premature ageing of the myocardium with consequent myocardial fibrosis 15 . Given the link between cardiac fibrosis, hypertrophy, and HF, several studies have demonstrated IGFBP7 as a novel biomarker of impaired myocardial relaxation in chronic HF with both reduced and preserved EF 9,15,29 . We found similar associations between IGFBP7 and measures of impaired relaxation; however the extent of association between higher IGFBP7 and other abnormalities of cardiac structure and function was greater in our subjects with more acute presentations.…”

“…biomarker of impaired myocardial relaxation in chronic HF with both reduced and preserved EF. 9,15,29 We found similar associations between IGFBP7 and measures of impaired relaxation; however the extent of association between higher IGFBP7 and other abnormalities of cardiac structure and function was greater in our subjects with more acute presentations. This might also imply acute expression of IGFBP7 in the setting of acute pressure and volume overload states.…”

“…In adjusted analyses, the association between LAVi and IGFBP7 remained robust, much as in prior studies 14,15 . Indexed LA volume has emerged as a prime imaging marker in HF given its very significant association with elevated LV end diastolic pressures with impaired myocardial relaxation 29,30,35 . Indeed, LAVi has been suggested as a marker of the severity and duration of diastolic dysfunction 30,35–37 .…”

“…14,15 Indexed LA volume has emerged as a prime imaging marker in HF given its very significant association with elevated LV end diastolic pressures with impaired myocardial relaxation. 29,30,35 Indeed, LAVi has been suggested as a marker of the severity and duration of diastolic dysfunction. 30,[35][36][37] Upregulation of several senescence-associated biomarkers in cardiac fibroblasts and atrial myocytes along with notable atrial fibrosis has been observed in atrial tissue extracts of atrial fibrillation patients, indicating tissue ageing associated with atrial enlargement.…”

Insulin-like growth factor-binding protein 7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation

“…Higher IGFBP-7 levels predicted adverse outcome events in CHF patients with preserved but not those with reduced ejection fraction (EF). 13 However, all these prior studies on IGFBP-7 were small, included selected patient populations, and had short follow-up. In addition, there are no data available in patients with AF.…”