Mechanisms of ectopic calcification of the coronary arteries: role of genetic factors, inflammation and carbohydraten metabolism disorders

The issues of ectopic coronary artery calcification (ECC) attract the attention of researchers. Calcium deposition in atherosclerotic plaques poses the problem of choosing a revascularization method for cardiovascular surgeons, namely, choosing an anastomosis fixation point when performing aortocoronary bypass grafting (ACB). Patients with ectopic calcium deposits in the coronary vessels are most often defined as a group of very high cardiovascular risk, in this regard, the use of drugs capable of influencing the formation of calcinates in the coronary arteries is actively discussed. In most publications, the authors discuss the mechanisms of formation and the search for markers of coronary calcification. Opinions that CAC is the final stage of the atherosclerotic process are divided. Currently, a number of researchers consider the process of CAC formation as active with the involvement of inflammatory mechanisms. Evidence of this is an increase in the content of proinflammatory cytokines and C-reactive protein. Active systemic inflammation against the background of atherosclerotic lesions of the arterial walls leads to the development of fibrosis and calcification of the intercellular substance of the arterial wall. Publications available to date show that the development of CAC may be due to genetic predisposition, but genetic markers have not yet been clearly defined, so their search can help to uncover the mechanisms of ectopic calcification. The review presents literature data on the study of the mechanisms of CAC.

1. G.B. Mayorov, S.K. Kurbanov, E.E. Vlasova et al. The problem of calcification in coronary heart disease: issues of diagnosis, prognosis, and treatment choice. Cardiological Bulletin. 2018. 4. 4-10.

2. E.N. Kachurina, A.N. Kokov, A.I. Kareeva, et al. Assessment of the prevalence of coronary calcification in people living in Western Siberia (according to the ESSE-RF study). Complex problems of cardiovascular diseases. 2018. 4. 33-40. DOI: 10.17802/2306-1278-2018-7-4-33-40

3. O.L. Barbarash, M.V. Zykov, O.N. Khryachkova et al. Pathogenetic mechanisms of comorbidity formation in coronary heart disease: atherocalcinosis, renal dysfunction, and bone mineral disorders. Nauka, 2019. 228 p. ISBN 978-5-02-038842-0.

4. Quantification of coronary artery calcium ultrafast computed tomography. A. Agatston, W. Janowitz., F. Hildner F. et al. DOI: 10.1016/0735-1097(90)90282-t. J Am Coll Cardiol. 1990. №15. P. 827-33.

5. Assessment of coronary artery lesions in men with osteopenic syndrome and coronary heart disease. A.N. Kokov, E.B. Malyuta, V.L. Masenko et al. Therapeutic archive. 2014. Volume 86, No. 3. P. 65-70.

6. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) TRIALS. P.Généreux, M.V. Madhavan, G.S. Mintz et al. - DOI:10.1016/j.jacc.2014.01.034 J Am Coll Cardiol. 2014. V.6. P. 1845-5184.

7. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. G.S. Mintz, J.J. Popma, A.D. Pichard et al. DOI: 10.1161/01.cir.91.7.1959. Circulation. 1995. V. 91. P. 1959-1965.

8. Detection of intralesional calcium by intracoronary ultrasound depends on the histologic pattern. GJ Friedrich, NY Moes, VA Mühlberger et al. DOI: 10.1016/0002-8703(94)90614-9. Am Heart J. 1994. V. 128, № 3. P. 435-441.

9. A new optical coherence tomography-based calcium scoring system to predict stent underexpansion. A. Fujino, GS Mintz, M. Matsumura et al. DOI: 10.4244/EIJ-D-17-00962. Euro Intervention. 2018. V. 13. P. 2182-2189.

10. Prognostic implications of coronary calcification in patients with obstructive coronary artery disease treated by percutaneous coronary intervention: a patient-level pooled analysis of 7 contemporary stent trials. CV Bourantas, YJ Zhang, S. Garg et al. DOI: 10.1136/heartjnl-2013-305180 Heart. 2014. V.100. P. 1158-1164.

11. Usefulness of rotational atherectomy in preventing polymer damage of everolimus-eluting stent in calcified coronary artery. N. Kuriyama, Y. Kobayashi, M. Yamaguchi. DOI: 10.1016/j.jcin.2010.11.017. J Am Coll Cardiol Intv. 2011. №4. P. 588-589.

12. Impact of severity of coronary artery calcification on clinical events in patients undergoing coronary artery bypass grafting (from the Acute Catheterization and Urgent Intervention Triage Strategy trial). K. Ertelk, P. Généreux, GS Mintz et al. DOI: 10.1016/j.amjcard.2013.07.038. Am. J. Cardiol. 2013.V. 112. P. 1730-1737.

13. Incidence, location, magnitude, and clinical correlates of saphenous vein graft calcification: an intravascular ultrasound and angiographic study. M.T. Castagna, G.S. Mintz, P. Ohlmann et al DOI: 10.1161/01.CIR.0000157160.69812.55. Circulation. 2005. V. 111, №9. P. 1148-1152.

14. Assessment of the role of polymorphic variants of the IL-6 and IL-10 genes as a risk factor for the development of restenosis in patients after implantation of drug-eluting stents. K.B. Timizheva, A.V. Aghajanyan. L.V. Tskholrebova and [others]. - DOI: 10.22363/2313-0245-2021-21-1-48-54. Bulletin of RUDN University. Series: Medicine. 2021. Volume 25. P. 48-54.

15. Replication of genetic association studies in aortic stenosis inadults. N. Gaudreault, V. Ducharme, M. Lamontagne et al DOI: 10.1016/j.amjcard.2011.06.050. Am. J. Cardiol. 2011. V. 108, №9. P. 1305-1310.

16. Rajamannan NM. Osteocardiology. Cardiac bone formation. Springer. 2018. V. 110 p ISBN 978-3-319-64994-8.

17. Biological secondary contributors to osteoporosis in fractured patients, is an early systematic assay relevant? PE Cailleaux, D. Biau, L. Philippe et al. 86(6):777-781. doi: 10.1016/j.jbspin.2019.03.009. Joint Bone Spine. – 2019.

18. Potential role for osteocalcin in the development of atherosclerosis and blood vessel disease Nutrients. Tacey A., Qaradakhi T., Brennan-Speranza T. et al. DOI: 10.3390/nu10101426. Nutrients. 2018. V.10, №10. P. 1426.

19. Diabetic macroangiopathy. A.F. Verbovoy, A.V. Pashentseva, N.I. Verbovaya. DOI: 10.26442/00403660.2019.10.000109. Therapeutic archive. 2019. No. 10. With. 138-143.

20. Hemoglobin a1c and the progression of coronary artery calcification among adults without diabetes. Carson AP, Steffes MW, Carr JJ, et al. DOI: 10.2337/dc14-0360. Diabetes Care. 2015. V. 38. P. 66-71.

21. Dyslipidemia, Diabetes and Atherosclerosis: Role of Inflammation and ROS-Redox-Sensitive Factors. E. Hasheminasabgorji, JC Jha. DOI: 10.3390/biomedicines9111602. Biomedicines. 2021.V. 9, № 11. P. 1602.

22. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. AP Burke, FD Kolodgie, A. Zieske et al DOI: 10.1161/01.ATV.0000131783.74034.97. Arterioscler Thromb Vasc Biol. 2004. V. 24. P. 1266-1271.