Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction

Abstract

BackgroundInsulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF).MethodsSerum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77).ResultsIGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E’ ratio, and NT-proBNP levels (all P ≤ 0.02).ConclusionIn conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement.

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…Interestingly, IGFBP-7 was investigated in an HF mouse model in which IGFBP-7 expression and plasma levels were increased in relation to cardiac hypertrophy, which showed a link between IGFBP-7 and HF development [87]. IGFBP-7 levels were also elevated in serum of patients with both HFrEF and HFpEF [88][89][90], and levels in these patients were also associated with prognosis [88,89]. As a biomarker, IGFBP-7 may be interesting especially for the HFpEF population [90].…”

“…IGFBP-7 levels were also elevated in serum of patients with both HFrEF and HFpEF [88][89][90], and levels in these patients were also associated with prognosis [88,89]. As a biomarker, IGFBP-7 may be interesting especially for the HFpEF population [90]. First, IGFBP-7 has been associated with diastolic dysfunction, an important characteristic of HFpEF patients [88][89][90].…”

“…As a biomarker, IGFBP-7 may be interesting especially for the HFpEF population [90]. First, IGFBP-7 has been associated with diastolic dysfunction, an important characteristic of HFpEF patients [88][89][90]. Second, IGFBP-7 levels were associated with insulin resistance and metabolic syndrome risk [91], which were associated with HFpEF development by causing chronic low-grade inflammation [9].…”

“…Second, IGFBP-7 levels were associated with insulin resistance and metabolic syndrome risk [91], which were associated with HFpEF development by causing chronic low-grade inflammation [9]. It has been suggested that, in a multi-marker approach, IGFBP-7 levels can be used to link abnormalities in cardiac function and morphology to disturbances in the metabolic status of patients [90]. Further investigations will be needed to establish this association with HFpEF.…”

Novel Biomarkers of Subclinical Cardiac Dysfunction in the General Population

“…As IGF-1 levels decline with age, concentrations of IGFB-7 remain unchanged, offsetting the ratio with IGF-1 and are clinically associated with the diagnosis of diastolic HF [68]. Elevated IGF B-7/IGF-1 ratio was shown to be associated with multiple surrogate endpoints including elevated NT-proBNP and ST2, and correlated well with HF echocardiographic indices of transmitral E/A velocities, E/E′ ratio, left atrial volume index, and right ventricular systolic pressure [69, 70]. Prospective observational cohort studies evaluating incident HF related to IGF B-7 are lacking.…”