Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease

Alexander J. Kula; Ronit Katz; Leila R. Zelnick; Elsayed Soliman; Alan Go; Michael Shlipak; Rajat Deo; Bonnie Ky; Ian Deboer; Amanda Anderson; Rob Christenson; Stephen L. Seliger; Chris Defilippi; Harold I. Feldman; Myles Wolf; John Kusek; Tariq Shafi; Jiang He; Nisha Bansal

doi:10.1093/ndt/gfaa296

Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease

Alexander J. Kula^*, Ronit Katz, Leila R. Zelnick, Elsayed Soliman, Alan Go, Michael Shlipak, Rajat Deo, Bonnie Ky, Ian Deboer, Amanda Anderson, Rob Christenson, Stephen L. Seliger, Chris Defilippi, Harold I. Feldman, Myles Wolf, John Kusek, Tariq Shafi, Jiang He, Nisha Bansal

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. Methods: We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. Results: In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. Conclusions: hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.

Original language	English (US)
Pages (from-to)	2282-2289
Number of pages	8
Journal	Nephrology Dialysis Transplantation
Volume	36
Issue number	12
DOIs	https://doi.org/10.1093/ndt/gfaa296
State	Published - Dec 1 2021

Funding

Funding for the CRIC Study was obtained under a cooperative agreement from the NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963 and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania (Clinical and Translational Science Award NIH/NCATS UL1TR000003), Johns Hopkins University (UL1 TR-000424), University of Maryland (GCRC M01 RR- 16500), Clinical and Translational Science Collaborative of Cleveland, National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (UL1TR000439), Michigan Institute for Clinical and Health Research (UL1TR000433), University of Illinois at Chicago (CTSA UL1RR029879), Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases (P20 GM109036), Kaiser Permanente (NIH/NCRR UCSF-CTSI UL1 RR-024131), NIDDK (R01KD103612) and Seattle Children's Hospital/University of Washington (NIH T32DK997662).

Keywords

Cardiac biomarkers
Cardiovascular disease
Chronic kidney disease
Myocardial conduction

ASJC Scopus subject areas

Nephrology
Transplantation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ndt/gfaa296

Cite this

Kula, A. J., Katz, R., Zelnick, L. R., Soliman, E., Go, A., Shlipak, M., Deo, R., Ky, B., Deboer, I., Anderson, A., Christenson, R., Seliger, S. L., Defilippi, C., Feldman, H. I., Wolf, M., Kusek, J., Shafi, T., He, J., & Bansal, N. (2021). Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease. Nephrology Dialysis Transplantation, 36(12), 2282-2289. https://doi.org/10.1093/ndt/gfaa296

@article{ee2a95396a7b4db6835d03592867fa40,

title = "Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease",

abstract = "Background: Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. Methods: We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. Results: In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. Conclusions: hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.",

keywords = "Cardiac biomarkers, Cardiovascular disease, Chronic kidney disease, Myocardial conduction",

author = "Kula, {Alexander J.} and Ronit Katz and Zelnick, {Leila R.} and Elsayed Soliman and Alan Go and Michael Shlipak and Rajat Deo and Bonnie Ky and Ian Deboer and Amanda Anderson and Rob Christenson and Seliger, {Stephen L.} and Chris Defilippi and Feldman, {Harold I.} and Myles Wolf and John Kusek and Tariq Shafi and Jiang He and Nisha Bansal",

note = "Funding Information: Funding for the CRIC Study was obtained under a cooperative agreement from the NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963 and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania (Clinical and Translational Science Award NIH/NCATS UL1TR000003), Johns Hopkins University (UL1 TR-000424), University of Maryland (GCRC M01 RR- 16500), Clinical and Translational Science Collaborative of Cleveland, National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (UL1TR000439), Michigan Institute for Clinical and Health Research (UL1TR000433), University of Illinois at Chicago (CTSA UL1RR029879), Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases (P20 GM109036), Kaiser Permanente (NIH/NCRR UCSF-CTSI UL1 RR-024131), NIDDK (R01KD103612) and Seattle Children's Hospital/University of Washington (NIH T32DK997662). Publisher Copyright: {\textcopyright} 2020 The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.",

year = "2021",

month = dec,

day = "1",

doi = "10.1093/ndt/gfaa296",

language = "English (US)",

volume = "36",

pages = "2282--2289",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "12",

}

Kula, AJ, Katz, R, Zelnick, LR, Soliman, E, Go, A, Shlipak, M, Deo, R, Ky, B, Deboer, I, Anderson, A, Christenson, R, Seliger, SL, Defilippi, C, Feldman, HI, Wolf, M, Kusek, J, Shafi, T, He, J & Bansal, N 2021, 'Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease', Nephrology Dialysis Transplantation, vol. 36, no. 12, pp. 2282-2289. https://doi.org/10.1093/ndt/gfaa296

TY - JOUR

T1 - Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease

AU - Kula, Alexander J.

AU - Katz, Ronit

AU - Zelnick, Leila R.

AU - Soliman, Elsayed

AU - Go, Alan

AU - Shlipak, Michael

AU - Deo, Rajat

AU - Ky, Bonnie

AU - Deboer, Ian

AU - Anderson, Amanda

AU - Christenson, Rob

AU - Seliger, Stephen L.

AU - Defilippi, Chris

AU - Feldman, Harold I.

AU - Wolf, Myles

AU - Kusek, John

AU - Shafi, Tariq

AU - He, Jiang

AU - Bansal, Nisha

N1 - Funding Information: Funding for the CRIC Study was obtained under a cooperative agreement from the NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963 and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania (Clinical and Translational Science Award NIH/NCATS UL1TR000003), Johns Hopkins University (UL1 TR-000424), University of Maryland (GCRC M01 RR- 16500), Clinical and Translational Science Collaborative of Cleveland, National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (UL1TR000439), Michigan Institute for Clinical and Health Research (UL1TR000433), University of Illinois at Chicago (CTSA UL1RR029879), Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases (P20 GM109036), Kaiser Permanente (NIH/NCRR UCSF-CTSI UL1 RR-024131), NIDDK (R01KD103612) and Seattle Children's Hospital/University of Washington (NIH T32DK997662). Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Background: Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. Methods: We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. Results: In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. Conclusions: hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.

AB - Background: Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. Methods: We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. Results: In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. Conclusions: hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.

KW - Cardiac biomarkers

KW - Cardiovascular disease

KW - Chronic kidney disease

KW - Myocardial conduction

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DO - 10.1093/ndt/gfaa296

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AN - SCOPUS:85110116612

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SP - 2282

EP - 2289

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 12

ER -

Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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