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

Alexander J Kula¹, Ronit Katz², Leila R Zelnick², Elsayed Soliman³, Alan Go⁴, Michael Shlipak⁵, Rajat Deo⁶, Bonnie Ky⁶, Ian DeBoer², Amanda Anderson⁷, Rob Christenson⁸, Stephen L Seliger⁸, Chris Defilippi⁹, Harold I Feldman^{6

10}, Myles Wolf¹¹, John Kusek¹², Tariq Shafi¹³, Jiang He⁷, Nisha Bansal²

Affiliations

¹ Division of Pediatric Nephrology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
² Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA, USA.
³ Department of Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
⁴ Division of Research, Kaiser Permanente Northern California, San Francisco, CA, USA.
⁵ Department of General Internal Medicine, San Francisco VA Medical Center, San Francisco, CA, USA.
⁶ Departments of Medicine and Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Translational Science Institute School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
⁸ Department of Medicine, University of Maryland School of Medicine, Baltimore, LA, USA.
⁹ Inova Heart and Vascular Institute, Falls Church, VA, USA.
¹⁰ Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Department of Medicine, School of Medicine, Duke University, Durham, NC, USA.
¹² National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
¹³ Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.

PMID: 33367652
PMCID: PMC8826765
DOI: 10.1093/ndt/gfaa296

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

Alexander J Kula et al. Nephrol Dial Transplant. 2021.

. 2021 Dec 2;36(12):2282-2289.

doi: 10.1093/ndt/gfaa296.

Authors

Affiliations

¹ Division of Pediatric Nephrology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
² Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA, USA.
³ Department of Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
⁴ Division of Research, Kaiser Permanente Northern California, San Francisco, CA, USA.
⁵ Department of General Internal Medicine, San Francisco VA Medical Center, San Francisco, CA, USA.
⁶ Departments of Medicine and Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Translational Science Institute School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
⁸ Department of Medicine, University of Maryland School of Medicine, Baltimore, LA, USA.
⁹ Inova Heart and Vascular Institute, Falls Church, VA, USA.
¹⁰ Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹¹ Department of Medicine, School of Medicine, Duke University, Durham, NC, USA.
¹² National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
¹³ Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.

PMID: 33367652
PMCID: PMC8826765
DOI: 10.1093/ndt/gfaa296

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.

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Figures

**FIGURE 1**
Mean ECG interval length by biomarker quartile. ^*P < 0.05 for linear trend.

**FIGURE 2**
Forest plots for ECG outcomes by biomarker, stratified by β-blocker usage. Adjusted models controlled for age, race/ethnicity, sex, eGFR, urinary albumin:creatinine ratio, diabetes, history of MI/revascularization, history of CHF, history of stroke, number of antihypertensives and systolic blood pressure.

See this image and copyright information in PMC

References

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

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

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