Galina Israilevna Lifshits

Machine learning (ML) models integrating genetic and clinical data show promise for personalizing antiplatelet therapy after myocardial infarction (MI). This study aimed to develop an ML model using clinical features and CYP2C19 genotype to predict long-term major adverse cardiac events (MACEs) and guide P2Y12 inhibitor selection. In a prospective observational study of 218 patients with MI undergoing percutaneous coronary intervention, with up to 9-year follow-up for MACEs, we trained and evaluated multiple models incorporating clinical, genetic, and angiographic variables. Uplift modeling principles were applied to assess treatment heterogeneity, and feature importance was analyzed using Shapley Additive Explanations (SHAP). The optimal model (CatBoost with SHAP-based feature selection) achieved an area under the receiver operating characteristic curve of 0.721. Discrimination remained stable under bootstrap resampling and across both infarction presentations. Key prognostic predictors included age, comorbidity index, number of significant coronary lesions, P2Y12 inhibitor type, stent type, and CYP2C19 loss-of-function/gain-of-function variants. Notably, CYP2C19 variants were significant MACE predictors, while drug-eluting stents and ticagrelor were associated with lower predicted long-term risk. These findings suggest that an ML framework incorporating CYP2C19 genotype can stratify long-term MACE risk. This data-driven approach points to the prognostic utility of genetic testing and supports the potential role of ticagrelor, particularly in genetically defined high-risk patients with MI, for optimizing secondary prevention.

Aim. To identify independent genetic and non-genetic predictors of hypertension (HTN) and rank their contribution to disease progression, as well as to identify potential new mechanisms that may influence the hypertension development. Material and methods. This cross-sectional observational study included 610 patients, including 142 with HTN. All participants completed a questionnaire, blood pressure (BP) measurements, biometric measurements, and molecular genetic testing. HTN predictors were identified using logistic regression models. Using singlefactor models, individual HTN predictors were determined. A multivariate logistic regression model was created using covariates with a significance level of pResults. A mathematical model was constructed using non-genetic and genetic markers to assess the risk of HTN, better classifying individuals with a low genetic risk for HTN. Genetic predictors were more significant for optimal calculations of HTN probability in the logistic regression model, while non-genetic traits were not included in the final model. Possible mechanisms that may lead to HTN, based on the identified genetic predictors, are considered. In addition, the concept of the contribution of a protective combination of genetic variants is also explored. Conclusion. A logistic regression model based on molecular genetic testing results is optimal for identifying individuals with a low HTN risk. Thus, for patients with a low genetic risk, lifestyle factors are more significant, and lifestyle modification is especially important for them to prevent HTN.

Aim of the study was to evaluate the effect of ticagrelor treatment in combination with high-dose statins on the relative risk of ischemic cardiovascular events during long-term follow-up in patients with myocardial infarction (MI) carrying different genotypes of rs2305948 VEGFR2. Material and methods. The study included 218 patients with acute MI, including 23 % women , average age 58 [52; 64] years. After the initial examination and preparation in the hospital emergency department, patients underwent coronary angiography followed by percutaneous coronary intervention or coronary artery bypass grafting. Two groups were identified for further observation in accordance with the therapy mode: 1 – individuals who received treatment with ticagrelor (12 months) and high-dose statins (≥ 12 months) after MI (n = 48, 22 %), 2 – individuals who took other drug combinations of statins in low or high doses in combination with various platelet P2Y12 receptor inhibitors – clopidogrel or ticagrelor (n = 170, 78 %). All 218 patients underwent genotyping (C/C, C/T, T/T) rs2305948 VEGFR2 using real-time polymerase chain reaction. The duration of outpatient observation of these patients was 9 years (2015–2024) after MI. Results. It was established that in the first group, in 48 individuals, along with 6 (13 %) identified heterozygous (C/T) genotypes of rs2305948 VEGFR2, 42 (87 %) cases with the homozygous genotype C/C were also identified, and in the second group, in 170 individuals, along with 70 (41 %) heterozygous C/T and homozygous T/T genotypes, 100 (59 %) cases with the homozygous genotype C/C rs2305948 VEGFR2 were identified (χ2 = 13.56, p < 0.001). In patients with MI in the first group, who received treatment with ticagrelor in combination with high-dose statins, there was a lower incidence of cardiovascular death (p = 0.024), recurrent acute coronary syndrome (p = 0.011), repeat myocardial revascularization (p = 0.025) and a combined end point (CEP) (p < 0.001) than among patients in group 2 who received other drug combinations of statins in high or low doses and P2Y12 platelet inhibitors. In a multivariate analysis using binary logistic regression, the Charlson comorbidity index increased the relative risk of CEP by 2.2 times (p < 0.001), the C/T and T/T rs2305948 VEGFR2 genotypes increased by 2.1 times (p = 0.023), and baseline three-vessel coronary disease increased by 2.3 times (p = 0.001). At the same time, treatment with ticagrelor in combination with high-dose statins reduced the risk of CEP by 72 % (p = 0.005), achieving low-density lipoprotein cholesterol level less than 1.4 mmol/l within 3 years after MI by 54 % (p = 0.044), and the use of drug-eluting stents by 45 % (trend, p = 0.093). Conclusions. In long-term follow-up (9 years) in patients with MI, the relative risk of ischemic cardiovascular events is directly determined by the C/T and T/T rs2305948 VEGFR2 genotypes, severe comorbidity, and baseline three-vessel coronary disease. The relative risk of ischemic events is inversely determined by treatment with ticagrelor in combination with high-dose statins and achievement of target low-density lipoprotein cholesterol level after MI.

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.

Recently, the role of metabolic syndrome (MS) has become crucial. There is a tendency for this disease to increase not only in the Russian Federation and throughout the world. According to World Health Organization data for 2022, approximately 60% of the European population is overweight or obese. The United States and Russia have the largest numbers of obese individuals. MS often occurs in developed countries, mainly in the adult population, and is a comorbid pathology. MS increases the risk of future disability and mortality. Despite the environmental factors that increase the risk of MS, genetic factors are also involved in the development of this pathology. The genes involved in the development of MS: MC4R, LEP, LEPR, PCSK1, ADCY3, POMC, and MRAP2, were identified. These genes and MRAP2 were identified and involved in the leptin-melanocortin signaling pathway, namely, they regulate energy metabolism, which, when a mutation occurs, leads to nonsyndromic monogenic obesity. MS is a multifactorial pathological condition that includes four independent sub-syndromes: obesity or overweight, hypertension, dyslipidemia, and insulin resistance. This article describes the features of genes contributing to the development of MS as well as the clinical features of the MS course.

Aim. To develop a non-invasive method for diagnosing reflux esophagitis in patients with comorbid pathology: HP associated chronic gastritis and atopic dermatitis. Materials and methods. Two groups of children were examined: 60 had AtD and HP+CG and 30 had HP+CG without At D. Risk factors were selected on the basis of clinical, anamnestic, laboratory, and instrumental data, a decision tree was created as well. Conclusion. The conducted research allowed us to develop a plausible non-invasive method for diagnosing reflux esophagitis in children with AtD and HP+CG. Every risk factor (female gender, complaints of bitterness in the mouth, heartburn, abdominal pain, increased fat mass according to impedanceometry and increased level of zonulin in feces) is estimated as 1 point; the sum of points 5 and more indicates the presence of reflux esophagitis with a probability of 94.1% (invention application № 2024139936 from 26.12.2024).

The aim of the study is to evaluate cardiac fatty acid binding protein as a prognostic biomarker for the occurrence of severe post-infarction structural and functional remodeling of the left ventricular myocardium and heart failure with clinical manifestations in patients with acute myocardial infarction during long-term follow-up. Material and methods. The study included 95 patients with acute myocardial infarction and ST-segment elevation (mean age 56.8 ± 9.8 years). Upon admission to the emergency room, all patients underwent clinical and laboratory studies to determine cardiac fatty acid binding protein (cFABP) and high-sensitivity troponin T (hs-TnT). At the end of the long-term follow-up (Me = 36 months), the patients were examined for clinically evident heart failure (NYHA functional class II and higher), high-sensitivity C-reactive protein (hsCRP) was determined in the blood, and echocardiography was performed. According to the echocardiography data, the presence and severity of structural and functional remodeling of the left ventricle myocardium (SFR LV) were established. Results. It was determined that the presence of clinically evident heart failure is directly associated with age, the Charlton comorbidity index, cFABP ≥10 ng/ml upon admission to the hospital and has a direct tendency to be associated with hs-TnT upon admission to the hospital. The presence of severe structural and functional remodeling of the left ventricle myocardium is directly associated with age, obesity, creatinine, cFABP ≥ 10 ng/ml and hs-TnT upon admission to hospital, and there is also a direct tendency towards an association with age. It was revealed that hs-TnT upon admission to hospital is directly associated with hsCRP ≥ 2 mg/l at the end of long-term followup. Conclusions. the presence of cFABP ≥ 10 ng/ml in the blood of patients with acute myocardial infarction upon admission to hospital is associated with an increase in the probability of developing clinically evident heart failure during long-term follow-up by 4.27 times, and severe structural and functional remodeling of the left ventricle myocardium is 3.07 times more likely, which is due to the size of the infarction lesion and the subsequent development of myocardial fibrosis.

HighlightsThe complex role of the brain natriuretic peptide in the pathogenesis of arterial hypertension, as well as the successful use of the N-terminal fragment of the prohormone brain-type natriuretic peptide as a biomarker of cardiovascular diseases determine the relevance of this work. Aim. To study the association between brain natriuretic peptide levels (NT-proBNP) and markers of the severity of resistant arterial hypertension.Methods. The study included 40 patients with diagnosed resistant arterial hypertension (RAH) and 30 patients with AH. All patients underwent clinical examination and measurement of NT-proBNP levels before and after receiving standard antihypertensive therapy.Results. Before receiving standardized antihypertensive therapy (AHT), NT-proBNP levels in the group of patients with RAH and in the group of patients with non-resistant hypertension did not differ significantly (p = 0.48), but systolic BP was statistically significantly higher (p = 0.039) in the group of patients with RAH. RAH revealed a direct association between NT-proBNP and sodium (r = 0,38; p = 0.01), as well as a direct association between NT-proBNP and body mass index (r = 0,32; p = 0.02). Factor analysis revealed a relationship between NT-proBNP and age (p < 0.01), as well as a direct relationship between NT-proBNP and potassium (r = 0,29; p = 0.04). After receiving standardized AHT, NT-proBNP levels decreased in the RAH group and in the non-resistant AH group (p = 0.03; p = 0.0001), but the decrease was less pronounced in the RAH group. NT-proBNP levels after standardized AHT in the RAH group were higher (p < 0.0001) compared to the non-resistant AH group, and relatively high NT-proBNP levels were directly associated with the presence of RAH (p = 0.0025).Conclusion. The results of the study indicate the presence of an association between NT-proBNP levels and resistant arterial hypertension. Supposedly, this association determines the uncontrolled course of resistant arterial hypertension – desensitization of receptors that regulate vascular tone, lipid metabolism disorders and natriuresis dysfunction.

Histamine intolerance is a disorder associated with impaired ability to absorb ingested histamine. Histaminosis occurs in 1-3% of the population. This condition was described at the beginning of the 21st century. This article provides an overview of histamine intolerance, mainly devoted to clinical manifestations, diagnosis and treatment.

Currently, natriuretic peptides (including brain natriuretic peptide (BNP)) are widely used in clinical practice as biomarkers for various cardiovascular diseases. Study of the structure and function of NPPA-NPPB locus can help to better identify patients at risk of future cardiovascular diseases, in particular heart failure.