Analysis of associations of rs2305948 genotypes of KDR (VEGFR2) gene, collateral coronary blood flow degree and statin treatment dose intensity with long-term prognosis in patients with myocardial infarction
https://doi.org/10.52727/2078-256X-2025-21-1-49-59
Abstract
The aim of the study was to analyze the associations of rs2305948 KDR (VEGFR2) genotypes, the state of collateral coronary blood flow, as well as the intensity of statin therapy with the development of structural and functional remodeling of the left ventricle and the onset of ischemic cardiovascular events during long-term observation in patients with myocardial infarction (MI). Material and methods. The prospective observational study included 51 patients with acute MI with ST-segment elevation. All patients underwent coronary angiography and angioplasty with stenting of the coronary arteries, as well as echocardiography and laboratory diagnostics with biomarker assessment at the hospital stage and over time (36 months). Also, the rs2305948 genotypes of the KDR (VEGFR2) gene were determined using real-time polymerase chain reaction. Two groups were allocated for further observation: 1 – with poor coronary collaterals (n = 25), 2 – with good coronary collaterals (n = 26). The duration of outpatient observation and treatment of both groups of patients with registration of ischemic cardiovascular events after MI was 108 months. Results and discussion. In group 1, compared with group 2, there was a higher incidence of severe left ventricular structural and functional remodeling (LVSFR) over 36 months (p = 0.0380), the combined end point (CEP) over 108 months (p = 0.0001), carriage of genotypes C/T and T/T rs2305948 KDR (VEGFR2) (p = 0.0002), as well as the size of the acute and past MI zone (according to the value of the LV local contractility impairment index) (p = 0.0107 and p = 0.0443, respectively); at the post-infarction stage – all echocardiographic parameters of LVSFR (p < 0.05). According to the logistic regression analysis, the development of LVSFR was directly affected by hypertension (p = 0.037) and inversely by the presence of good coronary collaterals in the MI zone (p = 0.024); the onset of CEP was directly determined by the comorbidity index (p = 0.041) and inversely by the presence of good coronary collaterals (p < 0.0001), as well as long-term treatment with high doses of statins (p = 0.043). Conclusions. The development of LVSFR and the onset of CEP are associated with the rs2305948 genotypes of KDR (VEGFR2), the status of coronary collaterals, the size of the MI zone, as well as long-term use of high-dose statin therapy in post-infarction patients.
Keywords
About the Authors
A. S. VorobyovRussian Federation
Anton S. Vorobyov, candidate of medical sciences, associate professor of the department of cardiology
1, Lenin ave., Surgut, 628400
175/1, Boris Bogatkov st., Novosibirsk, 630089
69/1, Lenin ave., Surgut, 628400
G. I. Lifshits
Russian Federation
Galina I. Lifshits, doctor of medical sciences, head of the laboratory of personalized medicine, associate professor
8, Academician Lavrentiev ave., Novosibirsk, 630090
I. A. Urvantseva
Russian Federation
Irina A. Urvantseva, candidate of medical sciences, head of the department of cardiology, chief physician
1, Lenin ave., Surgut, 628400
69/1, Lenin ave., Surgut, 628400
M. Yu. Donnikov
Russian Federation
Maxim Yu. Donnikov, candidate of medical sciences, senior researcher
1, Lenin ave., Surgut, 628400
L. V. Kovalenko
Russian Federation
Lyudmila V. Kovalenko, doctor of medical sciences, professor, head of the department of general pathology and pathophysiology, director of the Medical Institute
1, Lenin ave., Surgut, 628400
E. M. Zelenskaya
Russian Federation
Elena M. Zelenskaya, junior researcher at the laboratory of personalized medicine, graduate student of the department of cardiology
1, Lenin ave., Surgut, 628400
8, Academician Lavrentiev ave., Novosibirsk, 630090
I. D. Astrakhantseva
Russian Federation
Irina D. Astrakhantseva, candidate of medical sciences, head of organizational and methodological department
1, Lenin ave., Surgut, 628400
69/1, Lenin ave., Surgut, 628400
I. V. Markov
Russian Federation
Igor V. Markov, researcher of the laboratory of emergency therapy
175/1, Boris Bogatkov st., Novosibirsk, 630089
K. Yu. Nikolaev
Russian Federation
Konstantin Yu. Nikolaev, doctor of medical sciences, chief researcher of the laboratory of emergency therapy, professor of the department of cardiology
1, Lenin ave., Surgut, 628400
69/1, Lenin ave., Surgut, 628400
References
1. Traupe T., Gloekler S., de Marchi S.F., Werner G.S., Seiler C. Assessment of the human coronary collateral circulation. Circulation, 2010; 122 (12): 1210–1220. doi: 10.1161/CIRCULATIONAHA.109.930651
2. Seiler C. Assessment and impact of the human coronary collateral circulation on myocardial ischemia and outcome. Circ. Cardiovasc. Interv., 2013; 6 (6): 719–728. doi: 10.1161/CIRCINTERVENTIONS.113.000555
3. Stoller M., Seiler C. Salient features of the coronary collateral circulation and its clinical relevance. Swiss Med. Wkly, 2015; 145: w14154. doi: 10.4414/smw.2015.14154
4. Meier P., Schirmer S.H., Lansky A.J., Timmis A., Pitt B., Seiler C. The collateral circulation of the heart. BMC Med., 2013; 11: 143. doi: 10.1186/1741-7015-11-143
5. Reichek N., Kodali V. Visualizing myocardial salvage: new methods, new insights. JACC Cardiovasc. Imaging., 2010; 3 (5): 501–503. doi: 10.1016/j.jcmg.2010.01.006
6. Kim E.K., Choi J.H., Song Y.B., Hahn J.Y., Chang S.A., Park S.J., Lee S.C., Choi S.H., Choe Y.H., Park S.W., Gwon H.C. A protective role of early collateral blood flow in patients with ST-segment elevation myocardial infarction. Am. Heart. J., 2016; 17 1(1): 56–63. doi: 10.1016/j.ahj.2015.10.016
7. Elsman P., van Hof A.W., de Boer M.J., Hoorntje J.C., Suryapranata H., Dambrink J.H., Zijlstra F.; Zwolle Myocardial Infarction Study Group. Role of collateral circulation in the acute phase of STsegment-elevation myocardial infarction treated with primary coronary intervention. Eur. Heart. J., 2004; 25 (10): 854–858. doi: 10.1016/j.ehj.2004.03.005
8. Ortiz-Pérez J.T., Lee D.C., Meyers S.N., Davidson C.J., Bonow R.O., Wu E. Determinants of myocardial salvage during acute myocardial infarction: evaluation with a combined angiographic and CMR myocardial salvage index. JACC Cardiovasc. Imaging, 2010; 3 (5): 491–500. doi: 10.1016/j.jcmg.2010.02.004
9. Steg P.G., Kerner A., Mancini G.B., Reynolds H.R., Carvalho A.C., Fridrich V., White H.D., Forman S.A., Lamas G.A., Hochman J.S., Buller C.E.; OAT Investigators. Impact of collateral flow to the occluded infarct-related artery on clinical outcomes in patients with recent myocardial infarction: a report from the randomized occluded artery trial. Circulation, 2010; 121 (25): 2724–2730. doi: 10.1161/CIRCULATIONAHA.109.933200
10. Florek K., Mendyka D., Gomułka K. Vascular endothelial growth factor (VEGF) and its role in the cardiovascular system. Biomedicines, 2024; 12 (5): 1055. doi: 10.3390/biomedicines12051055
11. Vorobyov A.S., Lifshits G.I., Zelenskaya E.M., Nikolaev K.Yu. Associations of VEGFR2 rs2305948 polymorphism with long-term prognosis of myocardial infarction. Ateroscleroz, 2024; 20 (2): 92–99. (In Russ.) doi: 10.52727/2078-256Х-2024-20-2-92-99
12. Kirdeev A., Burkin K., Vorobev A., Zbirovskaya E., Lifshits G., Nikolaev K., Zelenskaya E., Donnikov M., Kovalenko L., Urvantseva I., Poptsova M. Machine learning models for predicting risks of MACEs for myocardial infarction patients with different VEGFR2 genotypes. Front. Med. (Lausanne), 2024; 11:1452239. doi: 10.3389/fmed.2024.1452239
13. Kozlova E.V., Starostin I.V., Bulkina O.S., Lopukhova V.V., Karpov Yu.A. Clinical significance of collateral coronary blood flow in patients with coronary heart disease. Doctor.Ru, 2016; 11 (128): 17–22. (In Russ.)
14. Flachskampf F.A., Schmid M., Rost С., Achenbach S., Demaria A.N., Daniel W.G. Cardiac imaging after myocardial infarction. Eur. Heart. J., 2011; 32 (3): 272–283. https://doi.org/10.1093/eurheartj/ehq446.
15. Alsanjari O., Chouari T., Williams T., Myat A., Sambu N., Blows L., Cockburn J., de Belder A., Hildick-Smith D. Angiographically visible coronary artery collateral circulation improves prognosis in patients presenting with acute ST segment-elevation myocardial infarction. Catheter Cardiovasc. Interv., 2020; 96 (3): 528–533. doi: 10.1002/ccd.28532
16. Allahwala U.K., Nour D., Alsanjari O., Bhatia K., Nagaraja V., Khatri J.J., Cockburn J., Hildick-Smith D., Sakata Y., Ward M., Weaver J.C., Bhindi R. Prognostic implications of the rapid recruitment of coronary collaterals during ST elevation myocardial infarction (STEMI): a meta-analysis of over 14,000 patients. J. Thromb. Thrombolysis, 2021; 51 (4): 1005–1016. doi: 10.1007/s11239-020-02282-6
17. Meier P., Hemingway H., Lansky A.J., Knapp G., Pitt B., Seiler C. The impact of the coronary collateral circulation on mortality: a meta-analysis. Eur. Heart. J., 2012; 33 (5): 614–621. doi: 10.1093/eurheartj/ehr308
18. Zhou Y., Zhu X., Cui H., Shi J., Yuan G., Shi S., Hu Y. The role of the VEGF family in coronary heart disease. Front. Cardiovasc. Med., 2021; 8: 738325. doi: 10.3389/fcvm.2021.738325
19. Medvedeva M.V. Associations of rs2305948 and rs1870377 polymorphic variants of the vascular endothelial growth factor receptor type 2 (KDR) gene with the risk of coronary heart disease. Research Results in Biomedicine, 2021; 7 (1): 32–43 (In Russ.) doi: 10.18413/2658-6533-2020-7-1-0-3
20. Wang L., Ge H., Peng L., Wang B. A meta-analysis of the relationship between VEGFR2 polymorphisms and atherosclerotic cardiovascular diseases. Clin. Cardiol., 2019; 42 (10): 860–865. doi: 10.1002/clc.23233
21. Buysschaert I., Schmidt T., Roncal C., Carmeliet P., Lambrechts D. Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. J. Cell. Mol. Med., 2008; 12 (6B): 2533–2551. doi: 10.1111/j.1582-4934.2008.00515.x
22. Astrakhantseva I.D., Urvantseva I.A., Vorobyev A.S., Nikolaev K.Yu. Pathophysiological and clinical aspects of high-dose atorvastatin cardioptotection in patients with acute coronary syndrome. Ateroscleroz, 2018; 14 (3): 78–83. (In Russ.) doi: 10.15372/ATER20180312
Review
For citations:
Vorobyov A.S., Lifshits G.I., Urvantseva I.A., Donnikov M.Yu., Kovalenko L.V., Zelenskaya E.M., Astrakhantseva I.D., Markov I.V., Nikolaev K.Yu. Analysis of associations of rs2305948 genotypes of KDR (VEGFR2) gene, collateral coronary blood flow degree and statin treatment dose intensity with long-term prognosis in patients with myocardial infarction. Ateroscleroz. 2025;21(1):49-59. (In Russ.) https://doi.org/10.52727/2078-256X-2025-21-1-49-59