IGFBP-4 Fragments as Markers of Cardiovascular Mortality in Type 1 Diabetes Patients With and Without Nephropathy

Hjortebjerg, Rikke; Tarnow, Lise; Jorsal, Anders; Parving, Hans-Henrik; Rossing, Peter; Bjerre, Mette; Frystyk, Jan

doi:10.1210/jc.2015-2196

Cited by 34 publications

(48 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth mentioning that in neither this nor previous studies did we find an association between the NT-or CT-IGFBP-4 fragments and LVEF, peak TnI, location and complexity of the culprit lesion, symptom-toballoon time, or the use of statins and antiplatelet agents, such as glycoprotein IIb/IIIa and cyclooxygenase inhibitors. 5,12 Although our findings are interesting and potentially clinically relevant, the specific mechanisms in STEMI patients are elusive and warrant further investigation. Furthermore, we acknowledge that the value and utility of biomarkers in STEMI patients is limited compared with other CVDs.…”

Section: Discussionmentioning

confidence: 89%

“…Biomarkers that mirror the degree and severity of the plaque burden are especially interesting because they may also be useful in syndromes such as unstable angina pectoris, in which peak TnI and creatinine kinase–MB levels are not elevated and ECG changes are often lacking or inconclusive. The rationale for the use of IGFBP‐4 fragments as biomarkers for cardiac risk assessment is based on the assumption that PAPP‐A is actively involved in the development of atherosclerosis . It has been suggested, however, that IGF‐1 and PAPP‐A may instead be cardioprotective and increase as a compensatory mechanism attempting to limit plaque progression and overall atherosclerotic burden .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin‐Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST‐Segment Elevation Myocardial Infarction

Hjortebjerg

Lindberg

Pedersen

et al. 2017

JAHA

Self Cite

View full text Add to dashboard Cite

BackgroundFragments of insulin‐like growth factor binding protein 4 (IGFBP‐4) are potential new biomarkers for cardiac risk assessment. The fragments are generated on specific cleavage by pregnancy‐associated plasma protein‐A, which exerts proatherogenic activity. This study investigated the prognostic value of IGFBP‐4 fragments in patients with ST‐segment elevation myocardial infarction.Methods and ResultsWe prospectively included 656 patients with ST‐segment elevation myocardial infarction treated with percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn before percutaneous coronary intervention, and levels of intact IGFBP‐4 and N‐terminal and C‐terminal IGFBP‐4 fragments were measured by specific assays. End points were 5‐year all‐cause and cardiovascular mortality and the combined end point of major adverse cardiac events. Prognostic potential was evaluated on top of a clinical model in terms of discrimination, calibration, and reclassification analysis. During follow‐up, 166 patients experienced a major adverse cardiac event and 136 patients died, of whom 69 died from cardiovascular causes. Both IGFBP‐4 fragments were associated with all end points (P<0.001). After multivariable adjustments, both N‐terminal and C‐terminal IGFBP‐4 fragment levels remained associated with all end points, including cardiovascular mortality with hazard ratios per doubling in protein concentration of 2.54 (95% CI 1.59–4.07; P<0.001) and 2.07 (95% CI 1.41–3.04; P<0.001), respectively. Incorporation of IGFBP‐4 fragments into a clinical model with 15 risk factors improved C‐statistics and model calibration and provided incremental prognostic contribution, as assessed by net reclassification improvement and integrated discrimination improvement.Conclusions IGFBP‐4 fragments are associated with increased risk of all‐cause mortality, cardiovascular mortality, and major adverse cardiac events in patients with ST‐segment elevation myocardial infarction.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Insulin‐Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST‐Segment Elevation Myocardial Infarction

Hjortebjerg

Lindberg

Pedersen

et al. 2017

JAHA

Self Cite

View full text Add to dashboard Cite

show abstract

“…After collection, the lithium‐heparin plasma samples were aliquoted and stored at −80 °C until analysis. Long‐term stability of IGFBP‐4 fragments at −80 °C was previously demonstrated . For the purposes of this study, lithium‐heparin plasma samples of 156 patients were randomly selected.…”

Section: Methodsmentioning

confidence: 99%

CT‐IGFBP‐4 as a novel prognostic biomarker in acute heart failure

et al. 2020

View full text Add to dashboard Cite

Aims Insulin-like growth factor binding protein-4 (IGFBP-4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment-elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy-terminal fragment of IGFBP-4 (CT-IGFBP-4) for all-cause mortality in emergency room patients with acute heart failure (AHF). Methods and results CT-IGFBP-4, N-terminal pro brain natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) were measured at admission from the lithium-heparin plasma of 156 patients with AHF. All-cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan-Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT-IGFBP-4, NT-proBNP, CRP, and their combinations. During 1 year of follow-up, 52 (33.3%) patients died. CT-IGFBP-4 only weakly correlated with NT-proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT-IGFBP-4 for the prediction of all-cause mortality (0.727) was significantly higher than that of NT-proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT-IGFBP-4, NT-proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P < 0.01 for all). The addition of CT-IGFBP-4 to a clinical prediction model that included age, gender, systolic blood pressure, creatinine, and sodium levels, as well as the history of previous heart failure, coronary artery disease, and hypertension significantly improved the mortality risk prediction (ROC AUC 0.774 vs. 0.699, P = 0.025). Cox hazard analysis indicated that elevated CT-IGFBP-4 was independently associated with 1 year mortality (hazard ratio 3.26, P = 0.0008) after adjustment for age, gender, history of previous heart failure, coronary artery disease, hypertension, chronic kidney failure, history of diabetes, heart rate, haemoglobin, plasma sodium, NT-proBNP, CRP, cystatin C, and elevated cardiac troponin I or T. Patients with increased levels of either two or three of the biomarkers CT-IGFBP-4, NT-proBNP, and CRP had significantly higher mortality risk (adjusted hazard ratio 10.04, P < 0.0001) than patients with increased levels of one or none of the biomarkers. Conclusions CT-IGFBP-4 was independently associated with all-cause mortality in patients with AHF. Compared with single biomarkers, the combination of CT-IGFBP-4, NT-proBNP, and CRP improved the prediction of all-cause mortality in patients with AHF.Clinical prediction model included age, gender, systolic blood pressure on admission, creatinine, sodium, previous history of HF, hypertension, and coronary artery disease. P < 0.001 for all ROC curves compared with 0.5 curves. CRP, C-reactive protein; NT-proBNP, N terminal pro brain natriur...

show abstract

“…IGFBP4 was only reported in one study to be significantly increased in prepubertal T1DM children (47). More recently, higher IGFBP4 fragment levels was reported to be associated with cardiovascular mortality rates in T1DM patients, which made it a potential prognostic biomarker (63). Decreased IGFBP6 was reported to be related with diabetic retinopathy in both T1DM and T2DM (54).…”

Section: Igfbps As Biomarkers In Autoimmune Diseasesmentioning

confidence: 99%

Insulin-Like Growth Factor Binding Proteins in Autoimmune Diseases

Ding

2018

Front. Endocrinol.

View full text Add to dashboard Cite

Insulin-like growth factor binding proteins (IGFBPs) are a family of proteins binding to Insulin-like growth factors (IGFs), generally including IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, and IGFBP6. The biological functions of IGFBPs can be classified as IGFs-dependent actions and IGFs-independent effects. In this review, we will discuss the structure and function of various IGFBPs, particularly IGFBPs as potential emerging biomarkers and therapeutic targets in various autoimmune diseases, and the possible mechanisms by which IGFBPs act on the pathogenesis of autoimmune diseases.

show abstract

IGFBP-4 Fragments as Markers of Cardiovascular Mortality in Type 1 Diabetes Patients With and Without Nephropathy

Abstract: High IGFBP-4 fragment levels were associated with increased all-cause and cardiovascular mortality rates in T1D patients with and without diabetic nephropathy.

Cited by 34 publications

References 35 publications

Insulin‐Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST‐Segment Elevation Myocardial Infarction

Insulin‐Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST‐Segment Elevation Myocardial Infarction

CT‐IGFBP‐4 as a novel prognostic biomarker in acute heart failure

Insulin-Like Growth Factor Binding Proteins in Autoimmune Diseases

Contact Info

Product

Resources

About