Diagnostic utility of BNP, corin and furin as biomarkers for cardiovascular complications in type 2 diabetes mellitus patients

Fathy, Shadia A.; Hamid, Fatma F. Abdel; Zabut, Baker M.; Jamee, Amal; Ali, Mohamed A.; Mustafa, Ayman M Abu

doi:10.3109/1354750x.2015.1093032

Cited by 33 publications

(29 citation statements)

References 39 publications

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“…We identified an elevation of furin several years before the onset of DM. Furthermore, furin levels remained elevated in overt DM, which is in agreement with a recent study where patients with DM had a tendency to higher furin plasma levels compared to healthy subjects [18]. Furthermore, the aforementioned study established that a strong increase in plasma furin concentration occurred in patients with both overt DM and cardiovascular disease compared to controls.…”

Section: Discussionsupporting

confidence: 91%

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Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

et al. 2018

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BackgroundDiabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality.ObjectivesTo test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality.MethodsOvernight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population‐based prospective Malmö Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3–21.7 years follow‐up.ResultsAn association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (|0.11| ≤ β ≤ |0.31|, P < 0.001). Plasma furin (hazard ratio [HR] per one standard deviation increment of furin) was predictive of future diabetes mellitus (727 events; HR = 1.24, CI = 1.14–1.36, P < 0.001) after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive treatment, alcohol intake and fasting plasma level of glucose, insulin and lipoproteins cholesterol. Furin was also independently related to the risk of all‐cause mortality (1229 events; HR = 1.12, CI = 1.05–1.19, P = 0.001) after full multivariable adjustment.ConclusionIndividuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality.

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Section: Discussionsupporting

confidence: 91%

“…Furthermore, it is established that furin is partially shed from most cells [17]. Plasma furin concentration has also recently been measured in healthy individuals in two small studies [9,18]. Here, we were able to measure furin levels in the circulation in a large number of individuals from a middleaged general population.…”

Section: Discussionmentioning

confidence: 84%

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

et al. 2018

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“…In addition, NT-proBNP has been shown to be a marker of heart failure; therefore, cardiac insufficiency was excluded from the inclusion criteria, in order to reduce its impact on NT-proBNP concentrations. Numerous previous studies have reported that patients with ACS and cardiac insufficiency (Killip grading, grade 2) had a high mortality rate (13,(23)(24)(25). As compared with the GRACE scores of such indicators as Killip grading and cardiac enzymes, NT-proBNP was demonstrated to be an independent risk factor of ACS in the present study.…”

Section: Discussionsupporting

confidence: 52%

Establishment of a hybrid risk model to predict major cardiac adverse events in patients with non-ST-elevation acute coronary syndromes

Zhang

Liu

2016

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to generate a hybrid risk model for the prediction of major cardiac adverse events (MACE) in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), by combining the Global Registry of Acute Coronary Events (GRACE) scoring system and the plasma concentration of N-terminal of the prohormone brain natriuretic peptide (lgNT-proBNP). A total of 640 patients with NSTE-ACS were randomly divided into either the model-establishing group (409 patients) or the prediction model group (231 patients). The clinical endpoint event was MACE, including cardiogenic death, myocardial infarction and heart failure-induced readmission. Among the 409 patients in the model-establishing group, 26 (6.6%) experienced MACE. The hybrid risk model was calculated using the following equation: Hybrid risk model = GRACE score + 20 x logarithm (lg) NT-proBNP + 15, in which the area under the receiver operating curves (ROCs) for the GRACE score and lgNT-proBNP were 0.807 and 0.798, respectively. From the equation, the area under the ROC for the hybrid risk model was 0.843; thus suggesting that the hybrid risk model may be better able to predict the occurrence of MACE compared with either of its components alone. Following re-stratification, 6% of patients in the hybrid risk model were re-grouped. A total of 15 patients in the prediction model group experienced MACE (6.5%). The areas under the ROCs for the hybrid risk model and the GRACE scores for the prediction model group were 0.762 and 0.748, respectively. The results of the present study suggested that the lgNT-proBNP and GRACE score-established hybrid risk model may improve the accuracy by which MACE are predicted.

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“…Till now limited information on the association of plasma furin and cardiovascular events after acute myocardial infarction is present. A small study has found that furin is a better predictor compared with BNP and corin for CV outcomes in type 2 diabetes patients [16]. But whether in MI patients this relationship still exists is unknown.…”

Section: Introductionmentioning

confidence: 99%

The Association Between Plasma Furin and Cardiovascular Events After Acute Myocardial Infarction

Liu

et al. 2020

Preprint

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Background: Furin is the key enzyme to cleave pro-BNP, and plays a critical role in the cardiovascular system through its involvement in the lipid metabolism, blood pressure and formation of atheromatous plaques. NT-proBNP and recently corin, which is also a key enzyme to cleave pro-BNP, have been approved as predictors of prognosis after acute myocardial infarction (AMI). We here conducted this prospective cohort study to investigate the relationship between plasma furin and the prognosis outcome in patients after AMI. Methods: We enrolled 1100 AMI patients and measured their plasma furin concentration. The primary endpoint was the major adverse cardiac events (MACE), a composite of cardiovascular (CV) death, non-fatal myocardial infarction or non-fatal stroke. The association of plasma furin concentration with AMI outcomes was explored by using Kaplan–Meier curve and multivariate Cox regression analysis. Results: Our results showed that slight increase of mean cTNT in patients with higher furin concentration (P=0.016). Over a median follow-up of 31 months, multivariate Cox regression analysis suggested that plasma furin was not associated with MACE (HR: 1.01; 95% CI: 0.93-1.06; P=0.807) after adjustment for potential conventional risk factors. However, plasma furin was associated with non-fatal MI (HR: 1.09; 95% CI: 1.01-1.17; P=0.022) after fully adjustment. Subgroup analysis indicated no relationship between plasma furin and MACE in different subgroup populations.Conclusions: Our study demonstrated that plasma furin was not associated with risk of MACE and may not be used as a predictor of poor prognosis after AMI. But higher levels of plasma furin may be associated with higher risk of non-fatal MI, future studies are needed to verify this.

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Diagnostic utility of BNP, corin and furin as biomarkers for cardiovascular complications in type 2 diabetes mellitus patients

Abstract: Furin may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment in T2DM patients.

Cited by 33 publications

References 39 publications

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality

Establishment of a hybrid risk model to predict major cardiac adverse events in patients with non-ST-elevation acute coronary syndromes

The Association Between Plasma Furin and Cardiovascular Events After Acute Myocardial Infarction

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