Yonsei Medical Journal

Yonsei Univ College Medicine (연세대학교의과대학)
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Impact of Insulin Resistance on Acetylcholine-Induced Coronary Artery Spasm in Non-Diabetic Patients

  • Kang, Kwan Woo (Department of Medicine, Korea University College of Medicine) ;
  • Choi, Byoung Geol (Research Institute of Health Sciences, Korea University College of Health Science) ;
  • Rha, Seung-Woon (Cardiovascular Center, Korea University Guro Hospital)
  • Received : 2018.05.09
  • Accepted : 2018.07.29
  • Published : 2018.11.01
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Abstract

Purpose: Coronary artery spasm (CAS) and diabetes mellitus (DM) are implicated in endothelial dysfunction, and insulin resistance (IR) is a major etiological cause of type 2 DM. However, the association between CAS and IR in non-diabetic individuals has not been elucidated. The aim of the present study was to evaluate the impact of IR on CAS in patients without DM. Materials and Methods: A total of 330 eligible patients without DM and coronary artery disease who underwent acetylcholine (Ach) provocation test were enrolled in this study. Inclusion criteria included both hemoglobin A1c <6.0% and fasting glucose level <110 mg/dL without type 2 DM. Patients were divided into quartile groups according the level of homeostasis model assessment of insulin resistance (HOMA-IR): 1Q (n=82; HOMA-IR<1.35), 2Q (n=82; $1.35{\leq}HOMA-IR<1.93$), 3Q (n=83; $1.93{\leq}HOMA-IR<2.73$), and 4Q (n=83; $HOMA-IR{\geq}2.73$). Results: In the present study, the higher HOMA-IR group (3Q and 4Q) was older and had higher body mass index, fasting blood glucose, serum insulin, hemoglobin A1c, total cholesterol, and triglyceride levels than the lower HOMA-IR group (1Q). Also, poor IR (3Q and 4Q) was considerably associated with frequent CAS. Compared with Q1, the hazard ratios for Q3 and Q4 were 3.55 (95% CI: 1.79-7.03, p<0.001) and 2.12 (95% CI: 1.07-4.21, p=0.031), respectively, after adjustment of baseline risk confounders. Also, diffuse spasm and accompanying chest pain during Ach test were more strongly associated with IR patients with CAS. Conclusion: HOMA-IR was significantly negatively correlated with reference diameter measured after nitroglycerin and significantly positively correlated with diffuse spasm and chest pain.

Keywords

References

  1. Kugiyama K, Ohgushi M, Motoyama T, Sugiyama S, Ogawa H, Yoshimura M, et al. Nitric oxide-mediated flow-dependent dilation is impaired in coronary arteries in patients with coronary spastic angina. J Am Coll Cardiol 1997;30:920-6. https://doi.org/10.1016/S0735-1097(97)00236-2
  2. Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y. Coronary artery spasm--clinical features, diagnosis, pathogenesis, and treatment. J Cardiol 2008;51:2-17. https://doi.org/10.1016/j.jjcc.2008.01.001
  3. Stern S, Bayes de Luna A. Coronary artery spasm: a 2009 update. Circulation 2009;119:2531-4. https://doi.org/10.1161/CIRCULATIONAHA.108.843474
  4. Lanza GA, Careri G, Crea F. Mechanisms of coronary artery spasm. Circulation 2011;124:1774-82. https://doi.org/10.1161/CIRCULATIONAHA.111.037283
  5. Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U. Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study. J Am Coll Cardiol 2008;52:523-7. https://doi.org/10.1016/j.jacc.2008.04.050
  6. Laporte F, Moulin F, Brembilla-Perrot B. Sudden death caused by atypical variant angina. Arch Cardiovasc Dis 2011;104:480-1. https://doi.org/10.1016/j.acvd.2011.01.012
  7. Diabetes mellitus: a major risk factor for cardiovascular disease. A joint editorial statement by the American Diabetes Association; The National Heart, Lung, and Blood Institute; The Juvenile Diabetes Foundation International; The National Institute of Diabetes and Digestive and Kidney Diseases; and The American Heart Association. Circulation 1999;100:1132-3. https://doi.org/10.1161/01.CIR.100.10.1132
  8. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2013;36 Suppl 1:S67-74. https://doi.org/10.2337/dc13-S067
  9. Li YJ, Hyun MH, Rha SW, Chen KY, Jin Z, Dang Q, et al. Diabetes mellitus is not a risk factor for coronary artery spasm as assessed by an intracoronary acetylcholine provocation test: angiographic and clinical characteristics of 986 patients. J Invasive Cardiol 2014;26:234-9.
  10. Choi BG, Park SH, Rha SW, Ahn J, Choi SY, Byun JK, et al. Threeyear follow-up of patients with acetylcholine-induced coronary artery spasm combined with insignificant coronary stenosis. Int J Cardiol 2017;238:66-71. https://doi.org/10.1016/j.ijcard.2017.03.081
  11. Choi BG, Jeon SY, Rha SW, Park SH, Shim MS, Choi SY, et al. Impact of renin-angiotensin system inhibitors on long-term clinical outcomes of patients with coronary artery spasm. J Am Heart Assoc 2016;5:e003217.
  12. Choi BG, Rha SW, Park T, Choi SY, Byun JK, Shim MS, et al. Impact of cigarette smoking: a 3-year clinical outcome of vasospastic angina patients. Korean Circ J 2016;46:632-8. https://doi.org/10.4070/kcj.2016.46.5.632
  13. Choi BG, Park SH, Rha SW, Park JY, Choi SY, Park Y, et al. Five-year clinical outcomes in patients with significant coronary artery spasm: a propensity score-matched analysis. Int J Cardiol 2015;184:533-9. https://doi.org/10.1016/j.ijcard.2015.02.021
  14. Im SI, Rha SW, Choi BG, Choi SY, Kim SW, Na JO, et al. Angiographic and clinical characteristics according to intracoronary acetylcholine dose in patients with myocardial bridge. Cardiology 2013;125:250-7. https://doi.org/10.1159/000351181
  15. Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv 2004;59:141-54. https://doi.org/10.1097/01.OGX.0000109523.25076.E2
  16. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14:173-94.
  17. Petersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A 2007;104:12587-94. https://doi.org/10.1073/pnas.0705408104
  18. JCS Joint Working Group. Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008): digest version. Circ J 2010;74:1745-62. https://doi.org/10.1253/circj.CJ-10-74-0802
  19. Muniyappa R, Montagnani M, Koh KK, Quon MJ. Cardiovascular actions of insulin. Endocr Rev 2007;28:463-91. https://doi.org/10.1210/er.2007-0006
  20. Baron AD. Hemodynamic actions of insulin. Am J Physiol 1994;267(2 Pt 1):E187-202.
  21. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996;97:2601-10. https://doi.org/10.1172/JCI118709
  22. Lee CH, Shih AZ, Woo YC, Fong CH, Leung OY, Janus E, et al. Optimal cut-offs of homeostasis model assessment of insulin resistance (HOMA-IR) to identify dysglycemia and type 2 diabetes mellitus: a 15-year prospective study in Chinese. PLoS One 2016;11:e0163424. https://doi.org/10.1371/journal.pone.0163424
  23. Arcaro G, Cretti A, Balzano S, Lechi A, Muggeo M, Bonora E, et al. Insulin causes endothelial dysfunction in humans: sites and mechanisms. Circulation 2002;105:576-82. https://doi.org/10.1161/hc0502.103333
  24. DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 2010;53:1270-87. https://doi.org/10.1007/s00125-010-1684-1
  25. Potenza MA, Addabbo F, Montagnani M. Vascular actions of insulin with implications for endothelial dysfunction. Am J Physiol Endocrinol Metab 2009;297:E568-77. https://doi.org/10.1152/ajpendo.00297.2009
  26. Nakagomi A, Saiki Y, Kosugi M, Kohashi K, Yoshikawa Y, Yamane Y, et al. Effect of insulin resistance associated with compensatory hyperinsulinemia on the long-term prognosis in patients with vasospastic angina. Int J Cardiol 2013;167:2222-7. https://doi.org/10.1016/j.ijcard.2012.06.016
  27. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403. https://doi.org/10.1056/NEJMoa012512
  28. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-50. https://doi.org/10.1056/NEJM200105033441801
  29. Rha SW, Choi BG, Seo HS, Park SH, Park JY, Chen KY, et al. Impact of statin use on development of new-onset diabetes mellitus in Asian population. Am J Cardiol 2016;117:382-7. https://doi.org/10.1016/j.amjcard.2015.11.009

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