Insulin‐like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence

Bračun, Valentina; Essen, Bart van; Voors, Adriaan A.; Veldhuisen, Dirk J. van; Dickstein, Kenneth; Zannad, Faı̈ez; Metra, Marco; Anker, Stefan D.; Samani, Nilesh J.; Ponikowski, Piotr; Filippatos, Gerasimos; Cleland, John G.F.; Lang, Chim C.; Ng, Leong L.; Shi, Canxia; Wit, Sanne de; Msallem, Joseph P. About; Meijers, Wouter C.; Klip, IJsbrand T.; Meer, Peter van der; Boer, Rudolf A. de

doi:10.1002/ehf2.14120

Cited by 29 publications

(22 citation statements)

References 32 publications

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“…Although prognostic thresholds have been identified for NT-proBNP and hs-cTnT for predicting risk in T2D, those used for GDF-15 and IGFBP7 remain exploratory; to this point, we used the median concentration of IGFBP7 (122 ng/mL) as optimal. This threshold is closer to optimal values in studies of patients with HF [11][12][13] compared with the lower values seen in those with relatively less complicated T2D. 2 This points to the importance in the present study of providing more information on the optimal means of IGFBP7 measurement application in different patient populations.…”

Section: Discussionsupporting

confidence: 49%

“…Similarly, concentrations of GDF-15 and IGFBP7 were substantially higher than previously iden-tified prognostic values in the majority of participants with values closer to those in individuals with fully developed HF. [11][12][13] Table S3 shows the baseline distribution of dichotomized biomarker concentrations relative to treatment assignment.…”

Section: Biomarkers At Baselinementioning

confidence: 99%

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Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial

Januzzi,

Mohebi,

Liu

et al. 2023

Circulation

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BACKGROUND: People with type 2 diabetes and albuminuria are at an elevated risk for cardiac and renal events. The optimal biomarkers to aid disease prediction and to understand the benefits of sodium-glucose cotransporter-2 inhibition remain unclear. METHODS: Among 2627 study participants in the CREDENCE trial (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, growth differentiation factor-15, and IGFBP7 (insulin-like growth factor binding protein 7) were measured. The effect of canagliflozin on biomarker concentrations was evaluated. The prognostic potential of each biomarker on the primary outcome (a composite of end-stage kidney disease [dialysis, transplantation, or a sustained estimated glomerular filtration rate of <15 mL·min −1 ·1.73 m −2 ], doubling of the serum creatinine level, or renal death or cardiovascular death) was assessed. RESULTS: The median (quartiles 1 and 3) concentration of each biomarker was generally elevated: NT-proBNP, 180 ng/L (82, 442 ng/L); high-sensitivity cardiac troponin T, 19 ng/L (12, 29 ng/L); growth differentiation factor-15, 2595 ng/L (1852, 3775 ng/L); and IGFBP7, 121.8 ng/mL (105.4, 141.5 ng/mL). At 1 year, the biomarkers all rose by 6% to 29% in the placebo arm but only by 3% to 10% in the canagliflozin arm (all P <0.01 in multivariable linear mixed-effect models). Baseline concentrations of each biomarker were strongly predictive of cardiac and renal outcomes. When the biomarkers were analyzed together in a multimarker panel, individuals with high risk scores (hazard ratio [HR], 4.01 [95% CI, 2.52–6.35]) and moderate risk scores (HR, 2.39 [95% CI, 1.48–3.87]) showed a higher risk for the primary outcome compared with those with low risk scores. By 1 year, a 50% increase in NT-proBNP (HR, 1.11 [95% CI, 1.08–1.15]), high-sensitivity cardiac troponin T (HR, 1.86 [95% CI, 1.64–2.10]), growth differentiation factor-15 (HR, 1.45 [95% CI, 1.24–1.70]), and IGFBP7 (HR, 3.76 [95% CI, 2.54–5.56]) was associated with risk of the primary outcome. CONCLUSIONS: Multiple cardiorenal stress biomarkers are strongly prognostic in people with type 2 diabetes and albuminuria. Canagliflozin modestly reduced the longitudinal trajectory of rise in each biomarker. Change in the biomarker level in addition to the baseline level augments the primary outcome prediction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.

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Section: Discussionsupporting

confidence: 49%

Section: Biomarkers At Baselinementioning

confidence: 99%

Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial

Januzzi,

Mohebi,

Liu

et al. 2023

Circulation

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“…Mechanistic theories regarding IGFBP7's role in PAH are related to its effect on vasculogenesis and angiogenesis. Additionally, this protein has also been associated with cell proliferative and adhesive processes, senescence, and apoptosis 53,54 . The principal known action of IGFBP7, or PSF, is to stimulate prostacyclin (PGI2) production by endothelial cells, an action thought to be mediated primarily by the arachidonic acid cascade 55 .…”

Section: Discussionmentioning

confidence: 99%

Low‐affinity insulin‐like growth factor binding protein 7 and its association with pulmonary arterial hypertension severity and survival

Torres,

Lancaster,

Yang

et al. 2023

Pulm. circ.

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Insulin‐like growth factor (IGF) binding proteins (IGFBPs) are a family of growth factor modifiers, some of which are known to be independently associated with pulmonary arterial hypertension (PAH) survival. IGF factor binding protein 7 (IGFBP7) is a unique low‐affinity IGFBP that, independent of IGF, stimulates prostacyclin production. This study proposed to establish associations between IGFBP7 and PAH severity and survival, using enrollment and longitudinal samples. Serum IGFBP7 levels were significantly elevated in patients with PAH compared to controls. After adjusting for age and sex, logarithmic increases in IGFBP7 were associated with a 20 m shorter six‐minute walk distance (6MWD; p < 0.001), a 2−3 mmHg higher mean right atrial pressure (p < 0.001 and 0.02), and a higher likelihood of a greater REVEAL 2.0 risk category placement (p < 0.001). Kaplan−Meier analysis demonstrated significantly decreased survival with IGFBP7 above the median and Cox multivariable analysis adjusted for age and sex, demonstrated higher serum IGFBP7 was an independent predictor of survival. Though the exact mechanism is still unknown, given IGFBP7's role as a prostacyclin stimulant, it has potential use as a therapeutic target for disease modulation.

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“…According to the results of this clinical study, IGFPB7 presents as an independent and robust prognostic biomarker in patients with HFpEF and HFrEF. Shortly, IGFBP7 pathways are supposedly involved in different stages of immune system regulation, linking HF to senescence pathways 64 …”

Section: Preclinical and Translational Investigationsmentioning

confidence: 99%

“…Shortly, IGFBP7 pathways are supposedly involved in different stages of immune system regulation, linking HF to senescence pathways. 64 The acute phase of a coxsackievirus 3 (CVB3)-induced myocarditis involves direct toxic cardiac effects and the systemic activation of the immune system, including the cardiosplenic axis. In their model study in mice, Pappritz et al tested whether the anti-inflammatory drug colchicine can improve experimental CVB3-induced myocarditis.…”

Section: Preclinical and Translational Investigationsmentioning

confidence: 99%

A year in heart failure: updates of clinical and preclinical findings

et al. 2023

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We witnessed major advances in the management of heart failure (HF) in 2022. Results of recent clinical and preclinical investigations aid preventive strategies, diagnostic efforts, and therapeutic interventions, and collectively, they hold promises for a more effective HF care for the near future. Accordingly, currently available information extends the 2021 European Society of Cardiology guidelines and provides a solid background for the introduction of improved clinical approaches in the number of HF‐related cases. Elaboration on the relationships between epidemiological data and risk factors lead to better understanding of the pathophysiology of HF with reduced ejection fraction and HF with preserved ejection fraction. The clinical consequences of valvular dysfunctions are increasingly interpreted not only in their haemodynamic consequences but also in association with their pathogenetic factors and modern corrective treatment possibilities. The influence of coronavirus disease 2019 pandemic on the clinical care of HF appeared to be less intense in 2022 than before; hence, this period allowed to refine coronavirus disease 2019 management options for HF patients. Moreover, cardio‐oncology emerges as a new subdiscipline providing significant improvements in clinical outcomes for oncology patients. Furthermore, the introduction of state‐of‐the‐art molecular biologic methods, multi‐omic approaches forecast improved phenotyping and precision medicine for HF. All above aspects are addressed in this article that highlights a selection of papers published in ESC Heart Failure in 2022.

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Insulin‐like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence

Abstract: Insulin-like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence

Cited by 29 publications

References 32 publications

Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial

Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial

Low‐affinity insulin‐like growth factor binding protein 7 and its association with pulmonary arterial hypertension severity and survival

A year in heart failure: updates of clinical and preclinical findings

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