Journal of Cardiovascular Imaging

Korean Society of Echocardiography (한국심초음파학회)
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The Combined Impact of Neutrophil-to-Lymphocyte Ratio and Type 2 Diabetic Mellitus on Significant Coronary Artery Disease and Carotid Artery Atherosclerosis

  • Kim, Bong-Joon (Division of Cardiology, Department of Internal Medicine, Convergence Medicine & Exercise Science Research Institute, Kosin University School of Medicine) ;
  • Cho, Sang-Hoon (Department of Statistics and Actuarial Science, Soongsil University) ;
  • Cho, Kyoung-Im (Division of Cardiology, Department of Internal Medicine, Convergence Medicine & Exercise Science Research Institute, Kosin University School of Medicine) ;
  • Kim, Hyun-Su (Division of Cardiology, Department of Internal Medicine, Convergence Medicine & Exercise Science Research Institute, Kosin University School of Medicine) ;
  • Heo, Jung-Ho (Division of Cardiology, Department of Internal Medicine, Convergence Medicine & Exercise Science Research Institute, Kosin University School of Medicine) ;
  • Cha, Tae-Joon (Division of Cardiology, Department of Internal Medicine, Convergence Medicine & Exercise Science Research Institute, Kosin University School of Medicine)
  • Received : 2015.11.10
  • Accepted : 2016.05.10
  • Published : 2016.06.27
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Abstract

Background: Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a new important inflammatory marker for predicting cardiovascular events. This study aimed to evaluate the combined impact of NLR and type 2 diabetes mellitus (T2DM) on significant coronary artery disease (CAD) and carotid artery atherosclerosis. Methods: This study includes a total of 828 patients evaluated by coronary angiography and carotid ultrasonography. Significant CAD was defined as at least one vessel with stenosis greater than 50%. We employed logistic regression models to investigate the association of NLR and T2DM with significant CAD. The goodness-of-fit and discriminability of the models were assessed by the loglikelihood ratio test and C-index, respectively. Also, we investigated the clinical relevance of the categorized NLR that classifies patients into three risk groups (low, intermediate, high). Results: According to logistic regression analysis, both NLR [adjusted odds ratio (OR) 1.31, p < 0.001] and T2DM (adjusted OR 2.46, p = 0.006) were independent risk factors of significant CAD. The addition of NLR and T2DM into a logistic regression model including conventional cardiovascular risk factors significantly improved the goodness-of-fit (p < 0.001) and the discriminability of the model (p = 0.004). Also, T2DM patients assigned into the high risk group (NLR > 2) showed the greater prevalence of significant CAD and carotid artery atherosclerosis compared with patients without T2DM or type 2 diabetic patients assigned into the low risk group ($NLR{\leq}1$). Conclusion: Our results suggest that type 2 diabetic patients with high inflammatory state would be more vulnerable to significant CAD and carotid artery atherosclerosis.

Keywords

Acknowledgement

Supported by : Kosin University College of Medicine

References

  1. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340:115-26. https://doi.org/10.1056/NEJM199901143400207
  2. Libby P. What have we learned about the biology of atherosclerosis? The role of inflammation. Am J Cardiol 2001;88(7B):3J-6J.
  3. Lee GK, Lee LC, Chong E, Lee CH, Teo SG, Chia BL, Poh KK. The long-term predictive value of the neutrophil-to-lymphocyte ratio in type 2 diabetic patients presenting with acute myocardial infarction. QJM 2012;105: 1075-82. https://doi.org/10.1093/qjmed/hcs123
  4. Lou M, Luo P, Tang R, Peng Y, Yu S, Huang W, He L. Relationship between neutrophil-lymphocyte ratio and insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMC Endocr Disord 2015;15:9. https://doi.org/10.1186/s12902-015-0002-9
  5. Kaya H, Ertac F, Soydinc MS. Association between neutrophil to lymphocyte ratio and severity of coronary artery disease. Clin Appl Thromb Hemost 2014;20:221. https://doi.org/10.1177/1076029613499821
  6. Acet H, Ertas F, Akil MA, Oylumlu M, Polat N, Yildiz A, Bilik MZ, Yuksel M, Kaya Z, Ulgen MS. New inflammatory predictors for nonvalvular atrial fibrillation: echocardiographic epicardial fat thickness and neutrophil to lymphocyte ratio. Int J Cardiovasc Imaging 2014;30:81-9.
  7. Park BJ, Shim JY, Lee HR, Lee JH, Jung DH, Kim HB, Na HY, Lee YJ. Relationship of neutrophil-lymphocyte ratio with arterial stiffness and coronary calcium score. Clin Chim Acta 2011;412:925-9. https://doi.org/10.1016/j.cca.2011.01.021
  8. Kim JA, Choi CJ, Yum KS. Cut-off values of visceral fat area and waist circumference: diagnostic criteria for abdominal obesity in a Korean population. J Korean Med Sci 2006;21:1048-53. https://doi.org/10.3346/jkms.2006.21.6.1048
  9. Vermeersch SJ, Rietzschel ER, De Buyzere ML, Van Bortel LM, D'Asseler Y, Gillebert TC, Verdonck PR, Segers P. Validation of a new automated IMT measurement algorithm. J Hum Hypertens 2007;21:976-8. https://doi.org/10.1038/sj.jhh.1002251
  10. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Hernandez Hernandez R, Jaff M, Kownator S, Naqvi T, Prati P, Rundek T, Sitzer M, Schminke U, Tardif JC, Taylor A, Vicaut E, Woo KS. Mannheim carotid intimamedia thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis 2012;34:290-6. https://doi.org/10.1159/000343145
  11. Choi JO, Shin MS, Kim MJ, Jung HO, Park JR, Sohn IS, Kim H, Park SM, Yoo NJ, Choi JH, Kim HK, Cho GY, Lee MR, Park JS, Shim CY, Kim DH, Shin DH, Shin GJ, Shin SH, Kim KH, Park JH, Lee SY, Kim WS, Park SW. Normal echocardiographic measurements in a Korean population study: part I. Cardiac chamber and great artery evaluation. J Cardiovasc Ultrasound 2015;23:158-72. https://doi.org/10.4250/jcu.2015.23.3.158
  12. Kim HS, Cho KI. Association of carotid artery parameters of atherosclerosis in coronary artery disease. J Cardiovasc Ultrasound 2013;21:72-80. https://doi.org/10.4250/jcu.2013.21.2.72
  13. Gnasso A, Carallo C, Irace C, Spagnuolo V, De Novara G, Mattioli PL, Pujia A. Association between intima-media thickness and wall shear stress in common carotid arteries in healthy male subjects. Circulation 1996;94:3257-62. https://doi.org/10.1161/01.CIR.94.12.3257
  14. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837-45. https://doi.org/10.2307/2531595
  15. Vinh-Hung V, Verkooijen HM, Fioretta G, Neyroud-Caspar I, Rapiti E, Vlastos G, Deglise C, Usel M, Lutz JM, Bouchardy C. Lymph node ratio as an alternative to pN staging in node-positive breast cancer. J Clin Oncol 2009;27:1062-8. https://doi.org/10.1200/JCO.2008.18.6965
  16. Pitsavos C, Tampourlou M, Panagiotakos DB, Skoumas Y, Chrysohoou C, Nomikos T, Stefanadis C. Association between low-grade systemic inflammation and type 2 diabetes mellitus among men and women from the ATTICA study. Rev Diabet Stud 2007;4:98-104. https://doi.org/10.1900/RDS.2007.4.98
  17. Dalla Vestra M, Mussap M, Gallina P, Bruseghin M, Cernigoi AM, Saller A, Plebani M, Fioretto P. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol 2005;16 Suppl 1:S78-82. https://doi.org/10.1681/ASN.2004110961
  18. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116:1793-801. https://doi.org/10.1172/JCI29069
  19. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821-30. https://doi.org/10.1172/JCI200319451
  20. Rajwani A, Cubbon RM, Wheatcroft SB. Cell-specific insulin resistance: implications for atherosclerosis. Diabetes Metab Res Rev 2012;28:627-34. https://doi.org/10.1002/dmrr.2336
  21. Sunbul M, Gerin F, Durmus E, Kivrak T, Sari I, Tigen K, Cincin A. Neutrophil to lymphocyte and platelet to lymphocyte ratio in patients with dipper versus non-dipper hypertension. Clin Exp Hypertens 2014;36: 217-21. https://doi.org/10.3109/10641963.2013.804547
  22. Okyay GU, Inal S, Onec K, Er RE, Pasaoglu O, Pasaoglu H, Derici U, Erten Y. Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with chronic kidney disease. Ren Fail 2013;35:29-36. https://doi.org/10.3109/0886022X.2012.734429
  23. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol 2008; 102:653-7. https://doi.org/10.1016/j.amjcard.2008.05.006
  24. Cho KI, Ann SH, Singh GB, Her AY, Shin ES. Combined usefulness of the platelet-to-lymphocyte ratio and the neutrophil-to-lymphocyte ratio in predicting the long-term adverse events in patients who have undergone percutaneous coronary intervention with a drug-eluting stent. PLoS One 2015;10: e0133934. https://doi.org/10.1371/journal.pone.0133934
  25. Verdoia M, Schaffer A, Barbieri L, Aimaretti G, Marino P, Sinigaglia F, Suryapranata H, De Luca G; Novara Atherosclerosis Study Group (NAS). Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease. Diabetes Metab 2015;41:304-11. https://doi.org/10.1016/j.diabet.2015.01.001
  26. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999;340:14-22. https://doi.org/10.1056/NEJM199901073400103
  27. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol 1997; 146:483-94. https://doi.org/10.1093/oxfordjournals.aje.a009302
  28. Naqvi TZ, Lee MS. Carotid intima-media thickness and plaque in cardiovascular risk assessment. JACC Cardiovasc Imaging 2014;7:1025-38. https://doi.org/10.1016/j.jcmg.2013.11.014
  29. Asakura T, Karino T. Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries. Circ Res 1990;66:1045-66. https://doi.org/10.1161/01.RES.66.4.1045
  30. Thomson SP, McMahon LJ, Nugent CA. Endogenous cortisol: a regulator of the number of lymphocytes in peripheral blood. Clin Immunol Immunopathol 1980;17:506-14. https://doi.org/10.1016/0090-1229(80)90146-4
  31. Naruko T, Ueda M, Haze K, van der Wal AC, van der Loos CM, Itoh A, Komatsu R, Ikura Y, Ogami M, Shimada Y, Ehara S, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation 2002;106:2894-900. https://doi.org/10.1161/01.CIR.0000042674.89762.20
  32. Chapman CM, Beilby JP, McQuillan BM, Thompson PL, Hung J. Monocyte count, but not C-reactive protein or interleukin-6, is an independent risk marker for subclinical carotid atherosclerosis. Stroke 2004;35:1619-24. https://doi.org/10.1161/01.STR.0000130857.19423.ad
  33. Raitakari M, Mansikkaniemi K, Marniemi J, Viikari JS, Raitakari OT. Distribution and determinants of serum high-sensitive C-reactive protein in a population of young adults: The Cardiovascular Risk in Young Finns Study. J Intern Med 2005;258:428-34. https://doi.org/10.1111/j.1365-2796.2005.01563.x

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