What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Heart failure with preserved ejection fraction (HFpEF) (n=300). Intervention: IGFBP-7/IGF-1 ratio vs. Controls (normal diastolic function). Primary outcome: IGFBP-7/IGF-1 ratio across patient groups (p=<0.001).

October 21, 2016Open Access

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

Q: What are the key findings of this study?

The IGFBP-7/IGF-1 ratio showed a significant graded increase from controls (0.43) to asymptomatic left ventricular diastolic dysfunction (0.48) to heart failure with preserved ejection fraction (0.68).

Key Result

The IGFBP-7/IGF-1 ratio showed a significant graded increase from controls (0.43) to asymptomatic left ventricular diastolic dysfunction (0.48) to heart failure with preserved ejection fraction (0.68).

Study Design

Type

Cross-Sectional (n=300)

Multicenter

Structured PICO

Does the IGFBP-7/IGF-1 ratio correlate with diastolic function and serve as a biomarker for HFpEF in patients referred for cardiac assessment?

Population

300 patients referred for elective coronary angiography and echocardiography, categorized into controls, asymptomatic left ventricular diastolic dysfunction, and HFpEF, to evaluate the IGF-1/IGFBP-7 axis.

Exposure

Measurement of serum IGF-1 and IGFBP-7 levels

Comparator

Controls with normal diastolic function and patients with asymptomatic left ventricular diastolic dysfunction (LVDD)

Outcome

Correlation of serum IGF-1, IGFBP-7, and IGFBP-7/IGF-1 ratio with diastolic function and diagnosis of HFpEFsurrogate

The IGFBP-7/IGF-1 ratio correlates with the severity of diastolic dysfunction and may serve as a novel biomarker for identifying patients with HFpEF.

Main Result

Absolute Event Rate: 0.68% vs 0.43%

p-value: p=<0.001

Limitations

Retrospective observational nature prohibits definitive determination of cause and effect relationships
Single-center experience with a relatively small number of subjects
Lack of longitudinal follow-up data to test associations between the IGFBP-7/IGF-1 axis and clinical outcomes
Study cohort referred for elective coronary angiography and echocardiography may not represent a general population
Other IGFBPs can also influence IGF-1 activity, so the ratio may not be a complete measure of IGF-1 activity

Abstract

BACKGROUND: Insulin-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). METHODS: Serum 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). RESULTS: IGFBP-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). CONCLUSION: In 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.

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