Relationships between NT-proBNP and Obesity, Glucose and Lipid Profiles in Dogs with Chronic Mitral Valve Insufficiency

이첨판 패쇄부전증에 이환된 개에서 NT-proBNP농도, 비만, 당 관련 인자 및 지방 관련인자간에 상관관계에 대한 연구

  • Lee, Seung-Gon (Choong-Hyun Animal Medical Center) ;
  • Nam, Hyo-Seung (Section of Small Animal Internal Medicine, School of Veterinary Medicine and Institute of Veterinary Medicine, Kangwon National University) ;
  • Hyun, Chang-Baig (Section of Small Animal Internal Medicine, School of Veterinary Medicine and Institute of Veterinary Medicine, Kangwon National University)
  • Accepted : 2012.08.16
  • Published : 2012.08.30

Abstract

In humans, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was shown to be inversely related to obesity; in addition, its association with contributing factors for obesity such as insulin, lipids, and glucose profiles has been demonstrated in the literature. However, this association between NT-proBNP and the severity of obesity has not been investigated in veterinary medicine. Our study hypothesis is that plasma levels of NT-proBNP may be related to body condition score (BCS) and contributing factors to obesity in dogs with heart diseases. To achieve our study goal, we collected blood samples from 73 client-owned dogs of small breeds at different stages of heart failure due to chronic mitral valvular insufficiency (CMVI). Fasting glucose concentrations, lipid profiles (i.e., total triglycerides [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]), fructosamine, insulin and NT-proBNP concentrations were measured. The insulin/glucose ratio was also determined. NT-proBNP showed not only a significant correlation with the severity of CMVI related heart failure but also an inverse relationship to body condition scores (BCS), insulin plasma levels and fructosamine concentrations. We found the presence of an inverse relationship between plasma levels of NT-proBNP and the severity of obesity. In addition, NT-proBNP was associated with lower levels of contributing factors to obesity such as fructosamine and insulin, creating a possible link between the obesity and NT-proBNP in dogs with heart disease. This is also the first report demonstrating an inverse association between obesity and NT-proBNP in dogs with heart failure.

사람에 연구에 따르면 심부전 진단에 널리 사용되는 NT-proBNP농도는 비만, 비만 관련인자들과 밀접한 상관 관계가 있는 것으로 알려져 있다. 그러나 이러한 상관관계는 아직까지 수의분야에서는 입증된 바가 없다. 따라서 본 연구에서는 다양한 정도의 이첨판 패쇄부전증(CMVI)에 이환된 73마리 개 집단에서 NT-proBNP와 비만 및 비만 관련인자들간의 상호관계를 조사하였다. 절식시 혈당 농도, 지방관련 인자(i.e., total triglycerides [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]), fructosamine, insulin 및 NT-proBNP 농도를 측정하였다. Insulin/glucose ratio 역시 계산하였다. NT-proBNP 농도는 CMVI에 의한 심부전의 정도에 따라 농도변화가 관찰되었으며, body condition scores (BCS), insulin 및 fructosamine 농도와도 관련이 있었다. 또한 본 연구를 통해 비만과 혈중 NT-proBNP농도 간에 상관관계 역시 확인되었다. 또한 NT-proBNP농도는 비만과 관련 있는 인자인 fructosamine과 insulin농도와도 관련이 있었다. 본 연구는 개에서 NT-proBNP농도와 비만 정도와 상관관계를 입증한 첫 보고이다.

Keywords

References

  1. Atkins C, Bonagura J, Ettinger S, Fox P, Gordon S, Haggstrom J, Hamlin R, Keene B, Luis-Fuentes V, Stepien R. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. J Vet Intern Med 2009; 23: 1142-1150. https://doi.org/10.1111/j.1939-1676.2009.0392.x
  2. Bailhache E, Nguyen P, Krempf M, Siliart B, Magot T, Ouguerram K. Lipoproteins abnormalities in obese insulinresistant dogs. Metabolism 2003; 52: 559-564. https://doi.org/10.1053/meta.2003.50110
  3. Bayes-Genis A, DeFilippi C, Januzzi JL, Jr. Understanding amino-terminal pro-B-type natriuretic peptide in obesity. Am J Cardiol 2008; 101: 89-94. https://doi.org/10.1016/j.amjcard.2007.07.079
  4. Boswood A. Biomarkers in cardiovascular disease: beyond natriuretic peptides. J Vet Cardiol 2009; 11 Suppl 1: S23-32.
  5. Boswood A, Dukes-McEwan J, Loureiro J, James RA, Martin M, Stafford-Johnson M, Smith P, Little C, Attree S. The diagnostic accuracy of different natriuretic peptides in the investigation of canine cardiac disease. J Small Anim Pract 2008; 49: 26-32.
  6. Chetboul V, Serres F, Tissier R, Lefebvre HP, Sampedrano CC, Gouni V, Poujol L, Hawa G, Pouchelon JL. Association of plasma N-terminal pro-B-type natriuretic peptide concentration with mitral regurgitation severity and outcome in dogs with asymptomatic degenerative mitral valve disease. J Vet Intern Med 2009; 23: 984-994. https://doi.org/10.1111/j.1939-1676.2009.0347.x
  7. Das SR, Drazner MH, Dries DL, Vega GL, Stanek HG, Abdullah SM, Canham RM, Chung AK, Leonard D, Wians FH Jr, de Lemos JA. Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation 2005; 112: 2163-2168. https://doi.org/10.1161/CIRCULATIONAHA.105.555573
  8. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497. https://doi.org/10.1001/jama.285.19.2486
  9. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109: 433-438. https://doi.org/10.1161/01.CIR.0000111245.75752.C6
  10. Guyard-Dangremont V, Desrumaux C, Gambert P, Lallemant C, Lagrost L. Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. Relation to atherogenesis susceptibility. Comp Biochem Physiol B Biochem Mol Biol 1998; 120: 517-525. https://doi.org/10.1016/S0305-0491(98)10038-X
  11. Hess RS. Insulin resistance in dogs. Vet Clin North Am Small Anim Pract 2010; 40: 309-316. https://doi.org/10.1016/j.cvsm.2009.12.001
  12. Jensen MD, Haymond MW, Gerich JE, Cryer PE, Miles JM. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. J Clin Invest 1987; 79: 207-213. https://doi.org/10.1172/JCI112785
  13. Kalra PR, Tigas S. Regulation of lipolysis: natriuretic peptides and the development of cachexia. Int J Cardiol 2002; 85: 125-132. https://doi.org/10.1016/S0167-5273(02)00241-3
  14. Kanda H, Kita Y, Okamura T, Kadowaki T, Yoshida Y, Nakamura Y, Ueshima H. What factors are associated with high plasma B-type natriuretic peptide levels in a general Japanese population J Hum Hypertens 2005; 19: 165-172. https://doi.org/10.1038/sj.jhh.1001792
  15. Laflamme D. Development and validation of a body condition score system for dogs. Canine Pract 1997; 22: 12-15.
  16. Li WY, Chiu FC, Chien YF, Lin JW, Hwang JJ. Association of amino-terminal pro-brain natriuretic peptide with metabolic syndrome. Intern Med 2011; 50: 1143-1147. https://doi.org/10.2169/internalmedicine.50.4765
  17. Maldonado EN, Casanave EB, Aveldano MI. Major plasma lipids and fatty acids in four HDL mammals. Comp Biochem Physiol A Mol Integr Physiol 2002; 132: 297-303. https://doi.org/10.1016/S1095-6433(02)00031-4
  18. Maldonado EN, Romero JR, Ochoa B, Aveldaño MI. Lipid and fatty acid composition of canine lipoproteins. Comp Biochem Physiol B Biochem Mol Biol 2001; 128: 719-729. https://doi.org/10.1016/S1096-4959(00)00366-3
  19. Moonarmart W, Boswood A, Luis Fuentes V, Brodbelt D, Souttar K, Elliott J. N-terminal pro B-type natriuretic peptide and left ventricular diameter independently predict mortality in dogs with mitral valve disease. J Small Anim Pract 2010; 51: 84-96. https://doi.org/10.1111/j.1748-5827.2009.00889.x
  20. Moro C, Polak J, Richterova B, Sengenès C, Pelikanova T, Galitzky J, Stich V, Lafontan M, Berlan M. Differential regulation of atrial natriuretic peptide- and adrenergic receptordependent lipolytic pathways in human adipose tissue. Metabolism 2005; 54: 122-131. https://doi.org/10.1016/j.metabol.2004.07.020
  21. Oyama MA, Fox PR, Rush JE, Rozanski EA, Lesser M. Clinical utility of serum N-terminal pro-B-type natriuretic peptide concentration for identifying cardiac disease in dogs and assessing disease severity. J Am Vet Med Assoc 2008; 232: 1496-1503. https://doi.org/10.2460/javma.232.10.1496
  22. Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, Borch-Johnsen K, Ibsen H, Jorgensen T, Hildebrandt P. N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome. Hypertension 2005; 46: 660-666. https://doi.org/10.1161/01.HYP.0000179575.13739.72
  23. Oyama MA, Singletary GE. The use of NT-proBNP assay in the management of canine patients with heart disease. Vet Clin North Am Small AnimPract 2010; 40: 545-558. https://doi.org/10.1016/j.cvsm.2010.03.004
  24. Potter LR. Natriuretic peptide metabolism, clearance and degradation. FEBS J 2011; 278: 1808-1817. https://doi.org/10.1111/j.1742-4658.2011.08082.x
  25. Puavilai W, Laorugpongse D, Deerochanawong C, Muthapongthavorn N, Srilert P. The accuracy in using modified Friedewald equation to calculate LDL from non-fast triglyceride: a pilot study. J Med Assoc Thai 2009; 92: 182-187.
  26. Sarzani R, Dessì-Fulgheri P, Paci VM, Espinosa E, Rappelli A. Expression of natriuretic peptide receptors in human adipose and other tissues. J Endocrinol Invest 1996; 19: 581-585.
  27. Scott-Moncrieff JC. Insulin resistance in cats. Vet Clin North Am Small Anim Pract 2010; 40: 241-257. https://doi.org/10.1016/j.cvsm.2009.10.007
  28. Serres F, Pouchelon JL, Poujol L, Lefebvre HP, Trumel C, Daste T, Sampedrano CC, Gouni V, Tissier R, Hawa G, Chetboul V. Plasma N-terminal pro-B-type natriuretic peptide concentration helps to predict survival in dogs with symptomatic degenerative mitral valve disease regardless of and in combination with the initial clinical status at admission. J Vet Cardiol 2009; 11: 103-121. https://doi.org/10.1016/j.jvc.2009.07.001
  29. Sengenes C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. Faseb J 2000; 14: 1345-1351. https://doi.org/10.1096/fj.14.10.1345
  30. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BC, Ciullo M. Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome. J Intern Med 2010; 268: 338-347. https://doi.org/10.1111/j.1365-2796.2010.02255.x
  31. Takemura N, Toda N, Miyagawa Y, Asano K, Tejima K, Kanno N, Arisawa K, Kurita T, Nunokawa K, Hirakawa A, Tanaka S, Hirose H. Evaluation of plasma N-terminal probrain natriuretic peptide (NT-proBNP) concentrations in dogs with mitral valve insufficiency. J Vet Med Sci 2009; 71: 925- https://doi.org/10.1292/jvms.71.925
  32. Tarnow I, Olsen LH, Kvart C, Hoglund K, Moesgaard SG, Kamstrup TS, Pedersen HD, Haggstrom J.Predictive value of natriuretic peptides in dogs with mitral valve disease. Vet J 2009; 180: 195-201. https://doi.org/10.1016/j.tvjl.2007.12.026
  33. Veiga AP, Price CA, de Oliveira ST, Dos Santos AP, Campos R, Barbosa PR, Gonzalez FH. Association of canine obesity with reduced serum levels of C-reactive protein. J Vet Diagn Invest 2008; 20: 224-228. https://doi.org/10.1177/104063870802000214
  34. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS. Impact of obesity on plasma natriuretic peptide levels. Circulation 2004; 109: 594-600. https://doi.org/10.1161/01.CIR.0000112582.16683.EA
  35. Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PW, Sutherland P, Omland T, Vasan RS. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. Am J Cardiol 2002; 90: 254-258. https://doi.org/10.1016/S0002-9149(02)02464-5
  36. Xenoulis PG, Levinski MD, Suchodolski JS, Steiner JM. Association of hypertriglyceridemia with insulin resistance in healthy Miniature Schnauzers. J Am Vet Med Assoc 2011; 238: 1011-1016. https://doi.org/10.2460/javma.238.8.1011