Abd El Meguid, K., Abd El Aziem, M., Elanwar, R., Abd El Aleem, H., Mahmoud, H. (2025). Predictors of Coronary Micro-Vascular Dysfunction in Patients without Myocardial Disease and Obstructive Atherosclerosis. test, 6(1), 64-82. doi: 10.21608/ejmr.2023.223586.1423
Khaled Refaat Abd El Meguid; Mahmoud Hassan Abd El Aziem; Rehab Elanwar; Hanan Hosny Abd El Aleem; Hesham Boshra Mahmoud. "Predictors of Coronary Micro-Vascular Dysfunction in Patients without Myocardial Disease and Obstructive Atherosclerosis". test, 6, 1, 2025, 64-82. doi: 10.21608/ejmr.2023.223586.1423
Abd El Meguid, K., Abd El Aziem, M., Elanwar, R., Abd El Aleem, H., Mahmoud, H. (2025). 'Predictors of Coronary Micro-Vascular Dysfunction in Patients without Myocardial Disease and Obstructive Atherosclerosis', test, 6(1), pp. 64-82. doi: 10.21608/ejmr.2023.223586.1423
Abd El Meguid, K., Abd El Aziem, M., Elanwar, R., Abd El Aleem, H., Mahmoud, H. Predictors of Coronary Micro-Vascular Dysfunction in Patients without Myocardial Disease and Obstructive Atherosclerosis. test, 2025; 6(1): 64-82. doi: 10.21608/ejmr.2023.223586.1423

Predictors of Coronary Micro-Vascular Dysfunction in Patients without Myocardial Disease and Obstructive Atherosclerosis

Egyptian Journal of Medical Research
Volume 6, Issue 1, January 2025, Pages 64-82    PDF (705.37 K)
Document Type: Original Article
DOI: 10.21608/ejmr.2023.223586.1423
Authors
Khaled Refaat Abd El Meguid1; Mahmoud Hassan Abd El Aziem* 1; Rehab Elanwar2; Hanan Hosny Abd El Aleem3; Hesham Boshra Mahmoud1
1Cardiology department, Faculty of Medicine, Beni-Suef University
2Neurophysiology department, Faculty of Medicine, Beni-Suef University
3Neurophysiology Department, Faculty of Medicine, Beni-Suef University
Abstract
Background The importance of microvascular dysfunction in a number of CV disease presentations has been shown by the growing use of invasive and non-invasive coronary and peripheral microvascular evaluation tools. Parallel to this, it has become clear through a deeper knowledge of the molecular processes underlying microvascular dysfunction that the microvascular phenotype is closely controlled by heightened levels of systemic inflammation. The purpose of this research is to identify several factors that may serve as reliable screening tests for microvascular dysfunction. The aim of this study is to determine different clinical, laboratory, echo, and autonomic functions parameters that related to micro-vascular dysfunction as a screening test. Methods: This study was conducted in Beni-Suef university Hospital in the period from October 2020 to June 2022. A total of 152 participants were included in the trial, 76 of them had angina-like chest discomfort, responded well to exercise stress tests, and were shown to have no major stenosis of their coronary arteries on coronary angiography, all while being free of any other particular cardiac illness. Results: In this study, CRP, HDL, LDL, Cholesterol, and triglyceride were higher significantly in cases than controls. Also, the mean latency in upper and lower limb higher significantly in cases than controls. Additionally, there is a significantly higher amplitude of the upper limb in cases than controls. R-R internal variation (RRIV) parameters during rest and during breathing were significantly higher in cases than in controls patients. Results showed that significant roles of latency in lower limb and resting RRIV in prediction of Coronary Micro-Vascular Dysfunction in Patients without Myocardial Disease and Obstructive Atherosclerosis. Results detected that the only autonomic function that found to increase the probability of Coronary Micro-Vascular Dysfunction was the latency in lower limb, presence of Diabetes in addition to the increase of LDL. Conclusion: The well-researched and appropriately standardized established functional tests of the cardiovascular autonomic nerve system are provided here. They often make it possible to evaluate the cardiovascular autonomic nerve system using simple methods. A more precise diagnosis of the risk of micro-vascular dysfunction may be made by frequent testing for autonomic functioning abnormalities.
Keywords
Ischemic Heart Disease; Atherosclerosis; autonomic function
References
 

  1. Ford, T. J., Rocchiccioli, P., Good, R., McEntegart, M., Eteiba, H., Watkins, S., ... & Berry, C. (2018). Systemic microvascular dysfunction in microvascular and vasospastic angina. European heart journal, 39(46), 4086-4097.‏
  2. Rizzoni, D., Palombo, C., Porteri, E., Muiesan, M. L., Kozàkovà, M., La Canna, G., ... & Rosei, E. A. (2003). Relationships between coronary flow vasodilator capacity and small artery remodelling in hypertensive patients. Journal of hypertension, 21(3), 625-631.‏
  3. Rammos, C., Hendgen-Cotta, U. B., Sobierajski, J., Bernard, A., Kelm, M., & Rassaf, T. (2014). Dietary nitrate reverses vascular dysfunction in older adults with moderately increased cardiovascular risk. Journal of the American College of Cardiology, 63(15), 1584-1585.
  4. ‏ Leonardi, R. A., Townsend, J. C., Patel, C. A., Wolf, B. J., Todoran, T. M., Fernandes, V. L., ... & Powers, E. R. (2013). Left ventricular end-diastolic pressure affects measurement of fractional flow reserve. Cardiovascular Revascularization Medicine, 14(4), 218-222.‏
  5. Verma, A., & Solomon, S. D. (2009). Diastolic dysfunction as a link between hypertension and heart failure. Medical Clinics of North America, 93(3), 647-664.‏
  6. Camici, P. G., d'Amati, G., & Rimoldi, O. J. N. R. C. (2015). Coronary microvascular dysfunction: mechanisms and functional assessment. 12(1), 48-62.
  7. American Diabetes Association. (2010). Standards of medical care in diabetes—2010. Diabetes care, 33(Suppl 1), S11.‏
  8. Cardoso, C. R. L., Leite, N. C., Moram, C. B. M., & Salles, G. F. (2018). Long-term visit-to-visit glycemic variability as predictor of micro-and macrovascular complications in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study. Cardiovascular diabetology, 17(1), 1-16.‏
  9. Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., ... & Desormais, I. (2018). 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European heart journal, 39(33), 3021-3104.‏
  10. Takashio, S., Yamamuro, M., Izumiya, Y., Sugiyama, S., Kojima, S., Yamamoto, E., ... & Ogawa, H. (2013). Coronary microvascular dysfunction and diastolic load correlate with cardiac troponin T release measured by a highly sensitive assay in patients with nonischemic heart failure. Journal of the American College of Cardiology, 62(7), 632-640.‏
  11. Galderisi, M., Lancellotti, P., Donal, E., Cardim, N., Edvardsen, T., Habib, G., ... & Popescu, B. A. (2014). European multicentre validation study of the accuracy of E/e′ ratio in estimating invasive left ventricular filling pressure: EURO-FILLING study. European Heart Journal–Cardiovascular Imaging, 15(7), 810-816.
  12. ‏ Ishimori, M. L., Martin, R., Berman, D. S., Goykhman, P., Shaw, L. J., Shufelt, C., ... & Bairey Merz, C. N. (2011). Myocardial ischemia in the absence of obstructive coronary artery disease in systemic lupus erythematosus. JACC: Cardiovascular Imaging, 4(1), 27-33.‏
  13. Recio-Mayoral A, Rimoldi OE, Camici PG, Kaski JC. (2013). Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease. JACC Cardiovasc Imaging. 6:660-7.
  14. Ortega, F. B., Lavie, C. J., & Blair, S. N. (2016). Obesity and cardiovascular disease. Circulation research, 118(11), 1752-1770.‏
  15. Heymsfield, S. B., & Wadden, T. A. (2017). Mechanisms, pathophysiology, and management of obesity. New England Journal of Medicine, 376(3), 254-266.‏
  16. Roth GA, Abate D, Abate KH, et al. (2018). Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 392:1736–88.
  17. Kaski JC, Crea F, Gersh BJ, Camici PG. (2018). Reappraisal of ischemic heart disease: fundamental role of coronary microvascular dysfunction in the pathogenesis of angina pectoris. 138(14), 1463-1480.
  18. Ford, T.J., Ong P., Sechtem U., Beltrame J. et al. (2020). Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease Why, How, and When. J Am Coll Cardiol Intv.13(16):1847–1864.
  19. Kenkre TS, Malhotra P, Johnson BD, et al. (2017). Tenyear mortality in the WISE study (Women’s Ischemia Syndrome Evaluation). Circ Cardiovasc Qual Outcomes. 10:e003863.
  20. Knuuti J, Wijns W, Saraste A, et al. (2020). 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 41: 407–77.
  21. Ong P.; Camici, P.G.; Beltrame, J.F.; Crea, F.; Shimokawa, H.; Sechtem, U.; Kaski, J.C.; Bairey Merz, C.N. (2018). International standardization of diagnostic criteria for microvascular angina. Int. J. Cardiol. 250, 16–20.
  22. Pepine C.J.; Ferdinand, K.C.; Shaw, L.J.; Light-McGroary, K.A.; Shah, R.U.; Gulati, M.; Duvernoy, C.; Walsh, M.N.; Bairey Merz, C.N.; Committee, A.C.i.W. (2015). Emergence of Nonobstructive Coronary Artery Disease: A Woman’s Problem and Need for Change in Definition on Angiography. J. Am. Coll. Cardiol. 66, 1918–1933.
  23. Brainin, P.; Frestad, D.; Prescott, E. (2018). The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease: A systematic review and meta-analysis. Int. J. Cardiol. 254, 1–9.
  24. Hoef, T.P.V.d.; Lavieren, M.A.V.; Damman, P.; Delewi, R. et al. (2014). Physiological Basis and Long-Term Clinical Outcome of Discordance Between Fractional Flow Reserve and Coronary Flow Velocity Reserve in Coronary Stenoses of Intermediate Severity. Circ. Cardiovasc. Interv. 7, 301–311.
  25. Meng-Yu, W.; Chia-Jung, L.; Ming-Feng, H.; Pei-Yi, C. (2017). New Insights into the Role of Inflammation in the Pathogenesis of Atherosclerosis. Int. J. Mol. Sci. 18, 2034
  26. Libby P, Ridker PM, Hansson GKLeducq Transatlantic Network on Atherothrombosis. (2009). Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 54: 2129-38.
  27. Arroyo-Espliguero R, Mollichelli N, Avanzas P, et al. (2003). Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X. Eur Heart J. 24:2006-11.
  28. Cosín-Sales, J., Pizzi, C., Brown, S., & Kaski, J. C. (2003). C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms. Journal of the American College of Cardiology, 41(9), 1468-1474.‏
  29. Kaufmann PA, Gnecchi-Ruscone T, Sch¨afers KP, Lüscher TF, Camici PG. (2000). Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol. 36:103-9.
  30. Mangiacapra F, De Bruyne B, Peace AJ, Melikian N, Wijns W, Barbato E. (2012). High cholesterol levels are associated with coronary microvascular dysfunction. J Cardiovasc Med. 13:439-42.
  31. Wei, J., Cheng, S., & Merz, C. N. B. J. J. (2019). Coronary microvascular dysfunction causing cardiac ischemia in women. 322(23), 2334-2335.
  32. Lindemann, H.; Petrovic, I.; Hill, S.; Athanasiadis, A.; Mahrholdt, H.; Schaufele, T.; Klingel, K.; Sechtem, U.; Ong, P. (2018). Biopsy-confirmed endothelial cell activation in patients with coronary microvascular dysfunction. Coron. Artery Dis. 29, 216–222.
  33. Tsimikas S, Willerson JT, Ridker PM. (2006). C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol. 47:C19-31.
  34. Kapa S, Venkatachalam KL, Asirvatham SJ (2010). The autonomic nervous system in cardiac electrophysiology an elegant interaction and emerging concepts. Cardiol Rev 18: 275-284.
  35. Ogunlade O, Ayoka AO, Akintomide A, Akomolafe RO, Akinsomisoye OS, et al. (2015). Non-Invasive Assessment of Cardiac Autonomic Functions in Healthy Young Adults in Ile-Ife, South-Western Nigeria. Int J Clin Cardiol 2:036.
  36. Low PA, Tomalia VA, Park KJ (2013). Autonomic function tests: some clinical applications. J Clin Neurol 9: 1-8.
  37. Novak P. (2017). Electrochemical skin conductance: a systematic review. Clin Auton Res. 15:193–13.
  38. Ziemssen T and Siepmann T (2019). The Investigation of the Cardiovascular and Sudomotor Autonomic Nervous System—A Review. Front. Neurol. 10:53.
  39. Mehta PK, Nelson M, Thomson L, Friedman J, Hayes S, Hermel D, Slomka P, Swift A, Wei J, Cook-Wiens G, Sayari S, Irwin MR, Krantz D, Travin M, Berman D, Bairey Merz CN. (2016). Abnormal cardiac sympathetic activity detected by 123-I-meta-iodobenzylguanidine imaging in women with signs and symptoms of ischemia and no obstructive coronary artery disease. J Am Coll Cardiol.  67(13_S):1619.
  40. Muller MD, Gao Z, McQuillan PM, Leuenberger UA, Sinoway LI. (2014). Coronary responses to cold air inhalation following afferent and efferent blockade. Am J Physiol Heart Circ Physiol. 307:H228–35.
  41. Williams DP, Koenig J, Carnevali L, Sgoifo A, JarczokMN, Sternberg EM et al. (2019). Heart rate variability and inflammation: a meta-analysis of human studies. Brain Behav Immun. 80:219–26.
  42. Hu SG, Wang L, Ou YG, Ji P, Yu P, Wang P, et al. (2016). The effect of electroacupuncture on the cardiopulmonary function and the quality of life for patients with coronary heart disease. Chin J Rehab Med. 31(12):1318–23.
  43. Wilkowska A, Rynkiewicz A, Wdowczyk J, Landowski J, Cubała WJ. (2019). Heart rate variability and incidence of depression during the first six months following first myocardial infarction. Neuropsychiatr Dis Treat. 15:1951–6.
  44. Vaccarino V, Badimon L, Bremner JD, Cenko E, Cubedo J, Dorobantu M, et al. (2020). Depression and coronary heart disease: 2018 position paper of the ESC working group on coronary pathophysiology and microcirculation. Eur Heart J. 41:1687–96.
  45. Godo, S., Suda, A., Takahashi, J., Yasuda, S., & Shimokawa, H. (2021). Coronary microvascular dysfunction. Arteriosclerosis, thrombosis, and vascular biology, 41(5), 1625-163.
Statistics
Article View: 121
PDF Download: 18