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

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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.

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