Post-challenge insulin concentration is useful for differentiating between coronary artery disease and cardiac syndrome X in subjects without known diabetes mellitus

Kae-Woei Liang, Wayne H-H Sheu, Wen-Jane Lee, Wen-Lieng Lee, Hung-Chih Pan, I-Te Lee, Jun-Sing Wang, Kae-Woei Liang, Wayne H-H Sheu, Wen-Jane Lee, Wen-Lieng Lee, Hung-Chih Pan, I-Te Lee, Jun-Sing Wang

Abstract

Background: Cardiac syndrome X (CSX) is characterized by angina pectoris but with patent coronary arteries. Our previous study demonstrated that subjects with CSX had a higher fasting insulin-resistance (IR) than the controls. However, few studies have investigated the degree of IR, including oral glucose tolerance test (OGTT)-derived indices and profiles of metabolic abnormalities between CSX and coronary artery disease (CAD).

Methods: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus (DM) underwent coronary angiogram (CAG) for angina pectoris and also agreed to receive OGTT and glycated hemoglobin (HbA1C) evaluations for screening abnormal glucose regulation and IR.

Results: CAD group had more subjects with metabolically unhealthy obesity (52.4 vs. 31.5%, p < 0.001) than the CSX group. The CAD group had higher OGTT 2 h glucose and insulin (both p < 0.005) while fasting glucose, insulin and HOMA-IR were similar to those of CSX subjects. In the binary regression analysis, OGTT 2 h insulin and being metabolic unhealthy were significantly different between the CAD and CSX groups, but there were no significant differences in Matsuda index, fasting glucose, insulin, HOMA-IR, or HbA1C.

Conclusions: Post challenge OGTT 2 h insulin and being metabolic unhealthy were useful parameters in differentiating between CAD and CSX in subjects without known DM but suffered from angina pectoris and underwent CAG. Different degrees of IR and metabolic abnormalities might be implicated in the pathogenesis of micro vs. macro vascular coronary diseases. Trial registration NCT01198730 at https://clinicaltrials.gov, Registered Sep. 8, 2010.

Keywords: Cardiac syndrome X (CSX); Coronary artery disease (CAD); Insulin resistance (IR); Metabolic health; Oral glucose tolerance test (OGTT).

Figures

Fig. 1
Fig. 1
Flow chart of the study enrollment protocol. CAD: coronary artery disease; CAG: coronary angiogram; CSX: cardiac syndrome X DM: diabetes mellitus; HbA1C: glycated hemoglobin; LV: left ventricle; OGTT: oral glucose tolerance test; PCI: percutaneous coronary intervention

References

    1. Beltrame JF. Advances in understanding the mechanisms of angina pectoris in cardiac syndrome X. Eur Heart J. 2005;26(10):946–948. doi: 10.1093/eurheartj/ehi242.
    1. Vermeltfoort IA, Raijmakers PG, Riphagen II, Odekerken DA, Kuijper AF, Zwijnenburg A, Teule GJ. Definitions and incidence of cardiac syndrome X: review and analysis of clinical data. Clin Res Cardiol. 2010;99(8):475–481. doi: 10.1007/s00392-010-0159-1.
    1. Cannon RO., 3rd Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms. J Am Coll Cardiol. 2009;54(10):877–885. doi: 10.1016/j.jacc.2009.03.080.
    1. Singh M, Singh S, Arora R, Khosla S. Cardiac syndrome X: current concepts. Int J Cardiol. 2010;142(2):113–119. doi: 10.1016/j.ijcard.2009.11.021.
    1. Huang SS, Huang PH, Leu HB, Wu TC, Lin SJ, Chen JW. Serum bilirubin predicts long-term clinical outcomes in patients with cardiac syndrome X. Heart. 2010;96(15):1227–1232. doi: 10.1136/hrt.2009.192393.
    1. Liang KW, Lee WJ, Lee WL, Liao YC, Wang KY, Lee IT, Wang JS, Sheu WH. Circulating adipokines and insulin resistance in subjects with combined cardiac and metabolic syndrome X. Diabetol Metab Syndr. 2015;7:83. doi: 10.1186/s13098-015-0078-4.
    1. Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH. Hyperinsulinaemia and microvascular angina (“syndrome X”) Lancet. 1991;337(8739):456–457. doi: 10.1016/0140-6736(91)93408-2.
    1. Swan JW, Walton C, Godsland IF, Crook D, Oliver MF, Stevenson JC. Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men. Br Heart J. 1994;71(1):41–44. doi: 10.1136/hrt.71.1.41.
    1. Piatti P, Fragasso G, Monti LD, Caumo A, Van Phan C, Valsecchi G, Costa S, Fochesato E, Pozza G, Pontiroli AE, Chierchia S. Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls. J Am Coll Cardiol. 1999;34(5):1452–1460. doi: 10.1016/S0735-1097(99)00379-4.
    1. Botker HE, Moller N, Ovesen P, Mengel A, Schmitz O, Orskov H, Bagger JP. Insulin resistance in microvascular angina (syndrome X) Lancet. 1993;342(8864):136–140. doi: 10.1016/0140-6736(93)91344-L.
    1. Jadhav ST, Ferrell WR, Petrie JR, Scherbakova O, Greer IA, Cobbe SM, Sattar N. Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X. Am J Cardiol. 2006;97(12):1727–1731. doi: 10.1016/j.amjcard.2005.12.069.
    1. Liao YC, Liang KW, Lee WJ, Lee WL, Lee IT, Wang JS, Ting CT, Sheu WH. Leptin to adiponectin ratio as a useful predictor for cardiac syndrome X. Biomarkers. 2013;18(1):44–50. doi: 10.3109/1354750X.2012.730550.
    1. Hinnouho GM, Czernichow S, Dugravot A, Nabi H, Brunner EJ, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study. Eur Heart J. 2015;36(9):551–559. doi: 10.1093/eurheartj/ehu123.
    1. Lakka HM, Lakka TA, Tuomilehto J, Salonen JT. Abdominal obesity is associated with increased risk of acute coronary events in men. Eur Heart J. 2002;23(9):706–713. doi: 10.1053/euhj.2001.2889.
    1. Bressler P, Bailey SR, Matsuda M, DeFronzo RA. Insulin resistance and coronary artery disease. Diabetologia. 1996;39(11):1345–1350. doi: 10.1007/s001250050581.
    1. Zethelius B, Lithell H, Hales CN, Berne C. Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease. A population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp. Diabetologia. 2005;48(5):862–867. doi: 10.1007/s00125-005-1711-9.
    1. Chauhan A, Foote J, Petch MC, Schofield PM. Hyperinsulinemia, coronary artery disease and syndrome X. J Am Coll Cardiol. 1994;23(2):364–368. doi: 10.1016/0735-1097(94)90421-9.
    1. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Stahle E, Feldman TE, van den Brand M, Bass EJ, Van Dyck N, Leadley K, Dawkins KD, Mohr FW. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–972. doi: 10.1056/NEJMoa0804626.
    1. Chang Y, Kim BK, Yun KE, Cho J, Zhang Y, Rampal S, Zhao D, Jung HS, Choi Y, Ahn J, Lima JA, Shin H, Guallar E, Ryu S. Metabolically-healthy obesity and coronary artery calcification. J Am Coll Cardiol. 2014;63(24):2679–2686. doi: 10.1016/j.jacc.2014.03.042.
    1. (2002) 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) final report. Circulation 106(25):3143-3421.
    1. Stefan N, Haring HU, Hu FB, Schulze MB. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013;1(2):152–162. doi: 10.1016/S2213-8587(13)70062-7.
    1. Reilly MP, Wolfe ML, Rhodes T, Girman C, Mehta N, Rader DJ. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation. 2004;110(7):803–809. doi: 10.1161/01.CIR.0000138740.84883.9C.
    1. Soyama A, Nishikawa T, Ishizuka T, Ito H, Saito J, Yagi K, Saito Y. Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in each type of impaired glucose tolerance in man. Endocr J. 2005;52(2):229–236. doi: 10.1507/endocrj.52.229.
    1. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–1470. doi: 10.2337/diacare.22.9.1462.
    1. (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33 (Suppl 1):S62-69.
    1. Wang JS, Lee IT, Lee WJ, Lin SY, Fu CP, Lee WL, Liang KW, Sheu WH. Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography. Clin Chem Lab Med. 2015;53(9):1441–1449. doi: 10.1515/cclm-2014-0860.
    1. Wang JS, Lee IT, Lee WJ, Lin SY, Fu CP, Ting CT, Lee WL, Liang KW, Sheu WH. Performance of HbA1c and fasting plasma glucose in screening for diabetes in patients undergoing coronary angiography. Diabetes Care. 2013;36(5):1138–1140. doi: 10.2337/dc12-1434.
    1. Mossmann M, Wainstein MV, Goncalves SC, Wainstein RV, Gravina GL, Sangalli M, Veadrigo F, Matte R, Reich R, Costa FG, Bertoluci MC. HOMA-IR is associated with significant angiographic coronary artery disease in non-diabetic, non-obese individuals: a cross-sectional study. Diabetol Metab Syndr. 2015;7:100. doi: 10.1186/s13098-015-0085-5.
    1. Kim HK, Lee SK, Suh CJ, Yoon HJ, Lee KY, Park HY, Kang MH. Postchallenge hyperglycemia but not hyperinsulinemia is associated with angiographically documented coronary atherosclerosis in Korean subjects. Diabetes Res Clin Pract. 2003;59(2):129–136. doi: 10.1016/S0168-8227(02)00199-7.
    1. Gast KB, Tjeerdema N, Stijnen T, Smit JW, Dekkers OM. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS ONE. 2012;7(12):e52036. doi: 10.1371/journal.pone.0052036.
    1. Laakso M. Insulin resistance and coronary heart disease. Curr Opin Lipidol. 1996;7(4):217–226. doi: 10.1097/00041433-199608000-00008.
    1. Wang CC, Gurevich I, Draznin B. Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways. Diabetes. 2003;52(10):2562–2569. doi: 10.2337/diabetes.52.10.2562.
    1. Borai A, Livingstone C, Ferns GA. The biochemical assessment of insulin resistance. Ann Clin Biochem. 2007;44(Pt 4):324–342. doi: 10.1258/000456307780945778.
    1. Celik T, Ozturk C, Balta S, Demirkol S, Iyisoy A. Coronary microvascular dysfunction in patients with cardiac syndrome X: ongoing debate. Int J Cardiol. 2016;218:233–234. doi: 10.1016/j.ijcard.2016.05.050.
    1. Demirkol S, Balta S, Kucuk U, Celik T, Arslan Z, Olgun Kucuk H, Unlu M, Cagdas Yuksel U, Samedli S, Yokusoglu M, Iyisoy A, Kursaklioglu H. Association between microvascular angina and erectile dsyfunction. Int J Impot Res. 2014;26(4):124–127. doi: 10.1038/ijir.2013.49.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi