Prediction of cardiovascular complications in microvascular angina: pathogenesis, risk markers, and stratification
https://doi.org/10.38109/2225-1685-2026-2-68-75
Abstract
A review of modern Russian and foreign literature on the problem of impaired coronary blood flow reserve as a manifestation of microvascular dysfunction has been conducted. When searching for information on this issue, materials from the following databases were used: RSCI, Best Evidence, Scopus, Elsevier, PubMed, Clinical Evidence, Cochrane Library. Microvascular angina (MVA) is a clinically significant form of ischemic heart disease characterized by myocardial ischemia in the absence of obstructive epicardial coronary artery lesions. This review summarizes key pathophysiological mechanisms contributing to cardiovascular complications in patients with MVA, highlights modern biomarkers and imaging methods used for risk stratification and prognosis, and discusses therapeutic individualization and future directions in clinical monitoring.
About the Authors
Lyudmila D. Khidirova
Novosibirsk State Medical University; Novosibirsk Clinical Cardiology Dispensary
Russian Federation
Russian Federation
Lyudmila D. Khidirova, Dr. of Scien. (Med.), Professor, Department of Pharmacology, Clinical Pharmacology, and Evidence-Based Medicine; cardiologist,
52, Krasny Prospekt, Novosibirsk, 630091;
6, Zalesskogo St., Bldg. 8, Novosibirsk, 630047.
Nurzhan Sulaimanov
Novosibirsk Clinical Cardiology Dispensary
Russian Federation
Russian Federation
Nurzhan Sulaimanov, Physician, Department of X-ray Surgical Diagnostic and Treatment Methods,
6, Zalesskogo St., Bldg. 8, Novosibirsk, 630047.
Alena A. Lykova
Novosibirsk Clinical Cardiology Dispensary
Russian Federation
Russian Federation
Alena A. Lykova, Cardiologist,
6, Zalesskogo St., Bldg. 8, Novosibirsk, 630047.
References
1. Stable ischemic heart disease. Clinical guidelines. RKO, 2020 (in Russ.)
2. Gmurov D.V., Parfenteva M.A., Semenova Y.V. Coronary heart disease. Colloquium-Journal. 2020;29(81):32-37. (in Russ.) https://doi.org/10.24411/2520-6990-2020-12227
3. Enikeev D.A., Hisamov E.N., Nurgaleeva E.A. et al. Fundamentals of pathophysiology. Typical pathological processes: textbook. Ufa: GBOU VPO BSMU of the Ministry of Health of Russia, 2015; 113 p. (in Russ.)
4. Mazur E.S., Mazur V.V., Rabinovich R.M. et al. On the Causes of Angina Pectoris in Patients With Pulmonary Embolism. Kardiologiia. 2020;60(1):28-34. (in Russ.) https://doi.org/10.18087/cardio.2020.1.n729
5. Machula A.V., Kopteva K. V., Maltseva A. N. and others. Reserve of coronary blood flow in patients with chronic heart failure with preserved left ventricular ejection fraction. Russian Journal of Cardiology. 2022;27(2):4743. (in Russ.) https://doi.org/10.15829/1560-4071-2022-4743
6. D’Amario D, Migliaro S, Borovac JA, et al. Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction. Front Physiol. 2019;10:1347. https://doi.org/10.3389/fphys.2019.01347
7. Taqueti VR, Di Carli MF. Clinical significance of noninvasive coronary flow reserve assessment in patients with ischemic heart disease. Curr Opin Cardiol. 2016;31(6):662-9. https://doi.org/10.1097/HCO.0000000000000339
8. Khabibullina M.M., Bazhenova O.V., Shamilov M.D. Review of modern research on microvascular angina. Doctor, 2024;(2):64-69. (in Russ.) https://doi.org/10.29296/25877305-2024-02-12
9. Driessen RS, Raijmakers PG, Stuijfzand WJ, Knaapen P. Myocardial perfusion imaging with PET. Int J Cardiovasc Imaging. 2017;33:1021-31. https://doi.org/10.1007/s10554-017-1084-4
10. Nagueh S.F., Smiseth O.A., Appleton C.P. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016;17:1321-60. https://doi.org/10.1016/j.echo.2016.01.011
11. Austen WG, Edwards JE, Frye RL, et al. A reporting system on patients evaluated for coronary artery disease. Circulation. 1975;51:5-40. https://doi.org/10.1161/01.cir.51.4.5
12. Murthy VL, Naya M, Taqueti VR, et al. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation. 2014;129:2518-27. https://doi.org/10.1161/CIRCULATIONAHA.113.008507
13. Mileva N, Nagumo S, Mizukami T, et al. Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta‐Analysis. J Am Heart Assoc. 2022;11:e023207. https://doi.org/10.1161/JAHA.121.023207
14. Chinov G.N., Rukhmaleva V.A., Gladysheva Yu.K. et al. Characteristic features of coronary artery lesions in patients with stable angina pectoris. Topical issues of modern medical science and healthcare: collection of articles of the V International (75 All-Russian) Scientific and Practical Conference. 2020;1:418-23. (in Russ.)
15. Guliyeva S. V., Khalilov V. G. Pathobiochemical changes in tissues during ischemia. Problems of modern science and education. 2016; 26(68):16-9 (in Russ.)
16. Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., et al.; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. https://doi.org/10.1056/NEJMoa1707914
17. Shimokawa H, Suda A, Takahashi J, et al. Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group. Eur Heart J. 2021;42(44):4592-600. https://doi.org/10.1093/eurheartj/ehab282
18. Arkhipova L.V., Gurevich M.A. Features of primary microvascular angina. Medical alphabet. 2017;1(13):12-15. (In Russ.)
19. Schroder J., Michelsen M.M., Mygind N.D., et al. Coronary flow velocity reserve predicts adverse prognosis in women with angina and no obstructive coronary artery disease: results from the iPOWER study. Eur Heart J. 2021;42(3):228-39. https://doi.org/10.1093/eurheartj/ehaa944
20. Soboleva G.N., Fedulov V.K., Samko A.N., Levitsky I.V., Rogoza A.N., Balakhonova T.V., Karpov Yu.A. Prognostic significance of coronary and brachial artery endothelial dysfunction, traditional risk factors in the development of cardiovascular complications in patients with microvascular angina. Russian Journal of Cardiology 2017;22(3):54-58. (In Russ.) https://doi.org/10.15829/1560-4071-2017-3-54-58
21. Kato S, Fukui K, Kodama S, et al. Cardiovascular magnetic resonance assessment of coronary flow reserve improves risk stratification in heart failure with preserved ejection fraction. J Cardiovasc Magn Reson. 2021;23:112. https://doi.org/10.1186/s12968-021-00807-3
22. Filali Y, Kesäniemi A, Ukkola O. Soluble ST2, a biomarker of fibrosis, is associated with multiple risk factors, chronic diseases and total mortality in the OPERA study. Scand J Clin Lab Invest. 2021;81(4):324- 31. https://doi.org/10.1080/00365513.2021.1904518
23. Tagliamonte E, Rigo F, Cirillo T, Astarita C, Quaranta G, Marinelli U et al. Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease. Echocardiography. 2015 Mar; 32(3):516-21. https://doi.org/10.1111/echo.12674
24. Zavadovsky KV, Mochula AV, Boshchenko AA, et al. Absolute myocardial blood flows derived by dynamic CZT scan vs invasive fractional flow reserve: correlation and accuracy. J Nucl Cardiol. 2021;28(1):249-59. https://doi.org/10.1007/s12350-019-01678-z
25. Kopyeva K.V., Maltseva A.N., Mochula A.V., Grakova E.V., Zavadovsky K.V. Adverse cardiovascular events in patients with coronary microvascular dysfunction: results of a 12-month follow-up with a control group. Russian Journal of Cardiology. 2023;28(3):5269. (In Russ.) https://doi.org/10.15829/1560-4071-2023-5269
26. Ouellette M., Löffler A.I., Beller G.A., Workman V.K., Holland E., Bourque J.M. Clinical characteristics, sex differences, and outcomes in patients with normal or near normal coronary arteries, non obstructive or obstructive coronary artery disease. Journal of American Heart Association. 2018 May 2;7(10):e007965. https://doi.org/10.1161/JAHA.117.007965
27. Kopyeva K.V., Grakova E.V., Maltseva A.N., Mochula A.V., Gusakova A.M., Soldatenko M.V., Kovalenko G.V., Kolmakova A.M., Aptekar V.D., Pushnikova E.Yu., Zavadovsky K.V. Coronary microvascular dysfunction: the importance of markers of sympathetic activity and autonomic imbalance. Russian Journal of Cardiology. 2025;30(7):6335. (In Russ.) https://doi.org/10.15829/1560-4071-2025-6335
28. Acien P., Acien M. Coronary microvascular dysfunction and estrogen receptor signaling. Maturitas. 2020;135:42-48. https://doi.org/10.1016/j.maturitas.2019.11.003
29. Sucato V., Corrado E., Manno G., et al. Biomarkers of Coronary Microvascular Dysfunction in Patients With Microvascular Angina: A Narrative Review. Angiology. 2022;73(5):395-406. https://doi.org/10.1177/00033197211034267
30. Rahman H., Demir O., Ryan M., et al. Circulating Biomarkers in Coronary Microvascular Dysfunction. J Am Heart Assoc. 2023;12(14):e029341. https://doi.org/10.1161/JAHA.122.029341
31. Kim B.J., Jo E.A., Im S.I., et al. Heart rate recovery and blood pressure response during exercise testing in patients with microvascular angina. Clin Hypertens. 2019;25:40-45. https://doi.org/10.1186/s40885-019-0108-x
32. Munteanu M. Pathophysiology of Coronary Microcirculation Dysfunction. Bulletin of the Academy of Sciences of Moldova. Medical Sciences. 2025;81(1):61-70. https://doi.org/10.52692/1857-0011.2025.1-81.08
33. Chepurnenko S.A. Cardiac syndrome X: possibilities of therapy. Bulletinof modern Clinical Medicine. 2017;10(6):71-74. (In Russ.)
34. Wu M., Villano A., Russo G., Di Franco A., Stazi A., Lauria C., Sestito A., Lanza G.A., Crea F. Poor tolerance and limited effects of isosorbide-5-mononitrate in microvascular angina. Cardiology. 2015;130(4):201-206. https://doi.org/10.1159/000370027
35. Trisvetova E.L. Coronary Microvascular Dysfunction: Epidemiology, Clinical Presentation, Diagnosis and Treatment. Rational Pharmacotherapy in Cardiology. 2023;19(2):186-196. (In Russ.) https://doi.org/10.20996/1819-6446-2023-04-02
36. Rehan R, Yong A, Ng M, Weaver J, Puranik R. Coronary microvascular dysfunction: A review of recent progress and clinical implications. Front Cardiovasc Med. 2023 Jan 26;10:1111721. https://doi.org/10.3389/fcvm.2023.1111721
37. Lanza G.A., De Vita A., Kaski J.C. ‘Primary’ microvascular angina: clinical characteristics, pathogenesis and management. Journal of Interventional Cardiology. 2018;13(3):108-111. https://doi.org/10.15420/icr.2018.15.2
38. Usenko E.V., Tereshina O.V., Ryabova E.N., Shchukin Yu.V., Trusov Yu.A. Microvascular angina: definition, clinical manifestations, diagnosis and Cardiology: News, Opinions, Training. 2018;6(2):48- 54. (In Russ.) https://doi.org/10.24411/2309-1908-2018-12006
39. Muszyński P., Pawluczuk E., Pasławska M., Kowalczuk M., Kozakiewicz J., Sot-Muszyńska N., Kożuch M., Dobrzycki S. Gender differences in the prevalence of classical and nonclassical risk factors and treatment of chronic coronary syndrome. J Clin Med. 2023, November 26;12(23):7320. https://doi.org/10.3390/JCM12237320
40. Kravchenko M.A., Khidirova L.D. Microvascular angina pectoris: pathophysiology of decreased coronary reserve. Archive of Internal Medicine. 2026;16(2):96-103. (In Russ.) https://doi.org/10.20514/2226-6704-2026-16-2-96-103
41. Brainin P., Frestad D., Prescott E. 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. 2018;254:1-9. https://doi.org/10.1016/j.ijcard.2017.10.052
42. Pelletier R., Khan N.A., Cox J., et al. Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young? J Am Coll Cardiol. 2016;67(2):127-35. https://doi.org/10.1016/j.jacc.2015.10.067
43. Dedov II. Personalized Medicine. Annals of the Russian Academy of Medical Sciences. 2019;74(1):61-70. (In Russ.) https://doi.org/10.15690/vramn1108
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For citations:
Khidirova L.D., Sulaimanov N., Lykova A.A. Prediction of cardiovascular complications in microvascular angina: pathogenesis, risk markers, and stratification. Eurasian heart journal. 2026;(2):68-75. (In Russ.) https://doi.org/10.38109/2225-1685-2026-2-68-75
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