Hypertension-driven cardiac remodeling in feline CKD: diagnostic utility of cTnI/creatinine and NT-proBNP/ creatinine ratios

Abstract

The objective of this study was to evaluate cardiac remodeling and the diagnostic utility of cardiac biomarkers, cardiac troponin I (cTnI) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), in cats with chronic kidney disease (CKD), with or without systemic hypertension. The study population included 11 healthy controls, 11 normotensive cats with chronic kidney disease (CKD), and 16 hypertensive cats with CKD. All cats underwent a comprehensive evaluation including blood pressure measurement, serum biochemistry, biomarker analysis, and echocardiographic assessment. CKD cats exhibited significantly elevated serum concentrations of cTnI and NT-proBNP compared to the control group, with hypertensive cats demonstrating the highest levels of these markers (P<0.001). Of notable significance is the finding that only the hypertensive CKD group demonstrated significantly elevated biomarker-to-creatinine ratios, supporting the presence of true myocardial injury rather than impaired renal clearance alone. Echocardiographic assessment revealed increased left atrial to aortic root (LA/Ao) ratios, left ventricular posterior wall thickness in diastole (LVPWd), and interventricular septal thickness in diastole (IVSd) in hypertensive CKD cats, indicating structural cardiac remodeling. Elevated serum urea and phosphorus levels in cats with CKD may also contribute to these myocardial alterations. These findings suggest that cats with hypertensive CKD experience actual myocardial injury, which is reflected in structural changes and biomarker ratios, while cats with normotensive CKD show milder and less definitive alterations. The incorporation of biomarker-to-creatinine ratios with echocardiography has the potential to enhance the early detection of subclinical cardiac injury in hypertensive CKD cats, thereby supporting the timely implementation of cardio-protective strategies.

Keywords

• Cardiac biomarkers
• Cardiac remodeling
• Chronic kidney disease
• Echocardiography
• Systemic hypertension

References

1. Acierno MJ, Brown S, Coleman AE, et al (2018): ACVIM consensus statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med, 32, 1803-1822.
2. Antman E, Bassand JP, Klein W, et al (2000): Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: the Joint European Society of Cardiology/American College of Cardiology Committee. J Am Coll Cardiol, 36, 959-969.
3. Apple FS, Murakami MM, Pearce LA, et al (2002): Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation, 106, 2941-2945.
4. Benmachiche M, Marques-Vidal P, Waeber G, et al (2018): In-hospital mortality is associated with high NT-proBNP level. PLoS One, 13, e0207118.
5. Bijsmans E, Jepson R, Wheeler C, et al (2017): Plasma N‐terminal probrain natriuretic peptide, vascular endothelial growth factor, and cardiac troponin I as novel biomarkers of hypertensive disease and target organ damage in cats. J Vet Intern Med, 31, 650-660.
6. Borgeat K, Connolly D, Fuentes VL (2015): Cardiac biomarkers in cats. J Vet Cardiol, 17, S74-S86.
7. Boyd L, Langston C, Thompson K, et al (2008): Survival in cats with naturally occurring chronic kidney disease (2000–2002). J Vet Intern Med, 22, 1111-1117.
8. Chue CD, Edwards NC, Moody WE, et al (2012): Serum phosphate is associated with left ventricular mass in patients with chronic kidney disease: a cardiac magnetic resonance study. Heart, 98, 219-224.

9. Coleman AE, Brown SA (2020): Hypertension and the heart and vasculature. 187-215. In: Hypertension in the Dog and Cat. Springer International Publishing, Cham.
10. D’Marco L, Bellasi A, Raggi P (2015): Cardiovascular biomarkers in chronic kidney disease: state of current research and clinical applicability. Dis Markers, 2015, 586569.
11. De Albuquerque Suassuna PG, Sanders-Pinheiro H, De Paula RB (2018): Uremic cardiomyopathy: a new piece in the chronic kidney disease-mineral and bone disorder puzzle. Front Med, 5, 206.
12. Flora Z, Tang PK, Smith K, et al (2025): Cardiac pathology associated with hypertension and chronic kidney disease in aged cats. J Comp Pathol, 216, 40-49.
13. Foley RN, Parfrey PS, Sarnak MJ (1998): Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis, 32, S112-S119.
14. Freda BJ, Tang WW, Van Lente F, et al (2002): Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol, 40, 2065-2071.
15. Go AS, Chertow GM, Fan D, et al (2004): Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med, 351, 1296-1305.
16. Gutiérrez OM, Januzzi JL, Isakova T, et al (2009): Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation, 119, 2545-2552.
17. Hemdon WE, Kittleson MD, Sanderson K, et al (2002): Cardiac troponin I in feline hypertrophic cardiomyopathy. J Vet Intern Med, 16, 558-564.
18. Hertzsch S, Roos A, Wess G (2019): Evaluation of a sensitive cardiac troponin I assay as a screening test for the diagnosis of hypertrophic cardiomyopathy in cats. J Vet Intern Med, 33, 1242-1250.
19. Hori Y, Yamano S, Iwanaga K, et al (2008): Evaluation of plasma C‐terminal atrial natriuretic peptide in healthy cats and cats with heart disease. J Vet Intern Med, 22, 135-139.
20. Hsu A, Kittleson MD, Paling A (2009): Investigation into the use of plasma NT-proBNP concentration to screen for feline hypertrophic cardiomyopathy. J Vet Cardiol, 11, S63-S70.
21. Kaesler N, Babler A, Floege J, et al (2020): Cardiac remodeling in chronic kidney disease. Toxins (Basel), 12, 161.
22. Kato T, Niizuma S, Inuzuka Y, et al (2010): Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circ Heart Fail, 3, 420-430.
23. Lalor SM, Connolly DJ, Elliott J, et al (2009): Plasma concentrations of natriuretic peptides in normal cats and normotensive and hypertensive cats with chronic kidney disease. J Vet Cardiol, 11, S71-S79.
24. Langhorn R, Willesen J (2016): Cardiac troponins in dogs and cats. J Vet Intern Med., 30, 36-50.
25. Law JP, Pickup L, Pavlovic D, et al (2023): Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations. J Hum Hypertens, 37, 1-19.
26. Polzin DJ (2011): Chronic kidney disease in small animals. Vet Clin Small Anim Pract, 41, 15-30.
27. Pouchelon J, Atkins C, Bussadori C, et al (2015): Cardiovascular–renal axis disorders in the domestic dog and cat: a veterinary consensus statement. J Small Animal Pract, 56, 537-552.
28. Tagore R, Ling LH, Yang H, et al (2008): Natriuretic peptides in chronic kidney disease. Clin J Am Soc Nephrol, 3, 1644-1651.
29. van Hoek I, Hodgkiss Geere H, Bode EF, et al (2020): Associations among echocardiography, cardiac biomarkers, insulin metabolism, morphology, and inflammation in cats with asymptomatic hypertrophic cardiomyopathy. J Vet Intern Med, 34, 591-599.
30. Wang AYM, Lai KN (2008): Use of cardiac biomarkers in end-stage renal disease. J Am Soc Nephrol, 19, 1643-1652.
31. Wess G, Daisenberger P, Mahling M, et al (2011): Utility of measuring plasma N‐terminal pro‐brain natriuretic peptide in detecting hypertrophic cardiomyopathy and differentiating grades of severity in cats. Vet Clin Pathol, 40, 237-244.
32. Yasue H, Yoshimura M, Sumida H, et al (1994): Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation, 90, 195-203.
33. Zoccali C, Mark PB, Sarafidis P, et al (2023): Diagnosis of cardiovascular disease in patients with chronic kidney disease. Nat Rev Nephrol, 19, 733-746.