Aim. To analyze and compare the clinical, echocardiographic characteristics and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels depending on the central cardiometabolic risk factors, with a focus on obesity, in patients with heart failure (HF) with mid-range ejection fraction (HFmrEF).Material and methods. The study included 111 patients with old myocardial infarction and HFmrEF (men, 100%; mean age, 60 years) predominantly of NYHA class II. Echocardiography and blood sampling for NT-proBNP were performed with sinus rhythm. Left atrial volume (LAV) and left ventricular mass (LVM) were indexed to body surface area (BSA) and height raised to a power.Results. Type 2 diabetes, overweight and obesity were diagnosed in 25%, 19%, 38% of cases, respectively, and were associated with greater changes in the morphologic and functional left ventricular parameters. There were no intergroup differences among patients with and without obesity in the LAV and LVM indexed to BSA. However, in patients with a body mass index (BMI) ≥30 kg/m2, the LAV indexed to height squared and LVM indexed to height2,7 were higher (p<0,05 for all). In 11% of obese patients, there were no changes in the criterion LAV or LVM values indexed to BSA, but the values indexed to height raised to a power exceeded the standard values. In 20% of patients with clinical manifestations of stable HFmrEF and structural and functional echocardiographic criteria, NT-proBNP were ≤125 pg/ml. An inverse correlation was found between NT-proBNP and BMI (r=-0,29; p=0,008), and lower values of myocardial stress marker were observed in obese patients (p=0,048).Conclusion. Considering the high incidence of obesity in patients with HFmrEF and its ability to reduce NT-proBNP, an algorithm modification is required for diagnosing HFmrEF as follows: focus on clinical and personalized echocardiography data, taking into account the obesity and, possibly, indexing the threshold natriuretic peptide values in patients with BMI ≥30 kg/m2. The issues of indexation of echocardiographic parameters depending on morphometric parameters in obese patients today remain open, predetermining the limitations in diagnosis of heart failure with left ventricular ejection fraction >40%. This requires the search for optimal standardization and the development of a unified methodological approach.
Objective Comparative analysis of structural and functional specific features of the heart in patients with toxic cardiomyopathy (TCMP) with a low left ventricular ejection fraction (LVEF) and severe, chronic heart failure (CHF) and in patients with idiopathic dilated cardiomyopathy (DCMP) and similar LVEF and CHF severity.Materials and Methods This observational, single-site study included 15 patients with TCMP (12 of them received treatment including anthracycline antibiotics and 3 patients received targeted therapies) and 26 patients with idiopathic DCMP. Data of echocardiography were compared for patients with TCMP and DCMP with comparably low LVEF of <40 %.Results In patients with severe heart damage associated with antitumor therapy with low LVEF, volumetric and linear indexes of left and right ventricles and the left atrium (left atrial volume index (LAVI), 33.7 (21.5–36.9) ml / m2; right ventricular end-diastolic dimension (RVDd), 2.49 (1.77–3.53) cm; and end-diastolic volume index (EDVI), 78.0 (58.7–90.0) ml / m2) were considerably less than in the DCMP group (LAVI, 67.1 (51.1–85.0) ml / m2; RVDd, 4.05 (3.6–4.4) cm; and EDVI, 117.85 (100.6–138.5) ml / m2, p<0.0001). Furthermore, LV wall thickness and pulmonary artery systolic pressure did not differ in these groups. Both in men and women with TCMP, LAVI and EDVI were significantly less than in men and women with DCMP.Conclusion The study showed significant differences in parameters of cardiac remodeling. In TCMP patients as distinct from DCMP patients, despite a pronounced decrease in LVEF, LV dilatation was absent or LV volumetric parameters were moderately increased with a more severe somatic status.
Objective. To analyze pathogenetic mechanisms underlying the development of endometrial hyperplasia in women of reproductive age. Patients and methods. We have examined 143 women of reproductive age with endometrial hyperplasia (EH). Study participants were divided into three groups: Group I included EH patients without atypia; Group II included patients with atypical hyperplasia of the endometrium; Group III (control group) comprised 56 women with abnormal uterine bleeding, in whom we excluded adenomyosis, uterine fibroids, endometrial hyperplasia, endometrial cancer, and iatrogenic causes of uterine bleeding. Genomic DNA was isolated using phenol-chloroform extraction. Real-time polymerase chain reaction (RT-PCR) was used to detect microRNA-210, -18a, -221, and -222. The detection of tumor pyruvate kinase M2 was performed using the ScheBo® Tumor M2-PK kit designed for quantitative assessment of this metabolic cancer marker in plasma and endometrial tissue samples. Results. Significant risk factors triggering the pathogenetic mechanism of EH development in reproductive age include extragenital disorders (obesity, thyroid diseases, diseases of the urinary system, hypertension) and gynecological diseases (pelvic inflammatory diseases, adenomyosis, benign breast dysplasia, uterine fibroids). Alterations affecting estrogen receptors lead to changes in microRNA messengers, which, in turn, affect target genes and cause changes in the adaptive abilities of the cell. Expression of pyruvate kinase M2 in this chain confirms proapoptotic changes in the cell and the risk of its atypia. Conclusion. The pathogenesis of EH is based on the following factors: polymorphism of the ERS1 and PRG genes, increased expression of miRNA-210, -18a, and -222, decreased expression of miRNA-221, and overexpression of pyruvate kinase M2. Key words: endometrial hyperplasia, miRNA, pyruvate kinase M2, progesterone receptors, estrogen receptors
Purpose To study the impact of genetic variants rs1739843, rs2290149 and rs10838692 in HSPB7 and MADD genes on myocardial remodeling in the patients with postinfarction cardiosclerosis. Methods and Results. The study included 252 men aged 30-65 y.o., who had MI more than 1 year ago. All patients had Q-MI of the anterior wall of the LV. Echocardiography was performed by the standard method (Vivid S6, GE, USA). Arterial hypertension (AH) was registered in more than 60% patients. Myocardial revascularization (CABG/PCI) was performed in more than in 50% of cases. Among 252 cases studies 156 patients had HFrEF (II–IV NYHA) LVEF (Sim)<40% (№1 group) and 96 patients had no clinical signs of HF and LVEF (Sim)>55% (№2 group). The groups were comparable in the AH prevalence and age. Patients all groups were on optimal drug therapy. Polymorphic genetic variants were studies using real-time-PCR. Eccentric types of LV remodeling prevailed in group 1 and concentric types of LV remodeling prevailed in group 2 (p < 0.001). The presence AH combined with CC genotype of rs1739843 in HSPB7 gene and TT genotype of rs2290149 in MADD and simultaneous carriage of the CC genotype of rs1739843 HSPB7 were associated with the presence of non-dilated ventricle (LV volume index ≤75 mL/m2) and relative wall thickness (RWT) >0.42 independently to LV mass index (p = 0.03). The T allele of rs1739843 HSPB7 (p = 0.006) and a combination of T allele of rs1739843 HSPB7 with the TT genotype of rs2290149 of the MADD gene were associated with the presence of dilated ventricles (p = 0.009) with LV hypertrophy (LV mass index >115 g/m2) independently to RWT. Conclusion Our preliminary data demonstrate that the genotype of HSPB7 (rs1739843) can modulated the association of AH and MADD rs2290149 with markers of ventricular hypertrophy and predispose to various types of post-MI remodeling of LV.
Резюме Актуальность. Изучение генетических фенотипов ХСН и поиск маркеров, ассоциированных с исходами заболевания может способствовать более полному пониманию патофизиологии ХСН и наметить мишени для терапевтических воздействий. Цель исследования. Изучить взаимосвязь клинико-инструментальных и генетических факторов, включающих полиморфные варианты генов HSPB7 (rs1739843), FRMD4B (rs6787362), rs10519210 локуса 15q22 и MADD (rs10838692, rs2290149) с выживаемостью пациентов с постинфарктным кардиосклерозом и ХСН. Материалы и методы. В исследование включено 506 мужчин в возрасте 55,4±13,5лет с перенесенным более 3 месяцев назад ИМ. Основную группу составили 260 пациентов с СН-нФВ (ХСН I-IV ФК, с ФВЛЖ (Simpson) <40%), референтную-246 пациентов без клиники ХСН с ФВЛЖ (Simpson)>55%. Контрольную группу составили 257 здоровых донора, сопоставимых по полу и возрасту. Проспективное наблюдение осуществляли посредством телефонного контакта. Результаты. Аллель Т и ТТ генотип полиморфного варианта rs2290149 гена MADD были ассоциированы с развитием ИБС и ПИКС (р 1,2 < 0,005). Наибольшая встречаемость аллеля Т обоих полиморфных вариантов rs2290149 и rs10838692 гена MADD наблюдалась у пациентов с СН-нФВ (р 1,2 < 0,0001). СС генотип полиморфизмов (rs2290149, rs10838692) гена MADD ассоциирован с протективным эффектом в отношении ИБС с ПИКС и, возможно, АГ, встречающейся у ≥68% больных и выступающей как конкурирующая по отношению ИБС патология. Генотип СС полиморфного варианта rs1739843 гена HSPB7 был ассоциирован с более низкой 3-х годичной смертностью у пациентов с ИБС независимо от ФВЛЖ и клинических проявлений ХСН (p< 0,05). Заключение. Полученные данные подтверждают необходимость дальнейшего генетического анализа более широкой популяции пациентов ХСН ишемической этиологии. Ключевые слова: постинфарктный кардиосклероз, хроническая сердечная недостаточноть, полиморфные варианты, прогноз.
Prevalence of proliferative processes is very high nowadays. Moreover, such processes easily transform into malignant ones. However, pathogenesis of endometrial hyperplasia (EH) is not fully understood. Imbalance of estrogen and progesterone, as well as estrogen and progesterone receptors is the reason for hyperplastic process onset in hormone-dependent tissues. Currently, there are no markers that could serve as objective predictors for EH development. It is unclear, whether EH transforms into cancer or spontaneously improves. The purpose of the study is to determine prevalence of ESR1 and PRG polymorphism in women of reproductive age with endometrial hyperplasia. Materials and Methods. Trial subjects (n=143) were divided into three groups: Group 1 consisted of 53 patients with glandular and glandular-cystic EH without atypia; Group 2 contained 34 patients with atypical EH; Group 3 was the control group. Polymerase chain reaction of DNA synthesis was used to conduct molecular and genetic loci study. Statistical analysis of the data obtained was performed with SAS JMP 11 and Statistica 10. Results. Mutant CC-allele of PvuII ESR1 polymorphism was found in every fourth woman with glandular endometrial hyperplasia and in every third patient with atypical endometrial hyperplasia. Prevalence of GG genotype of XbaI ESR1 polymorphism did not have any statistically significant differences in comparison with the control group. Mutant TT-allele of Val660Leu PRG polymorphism in glandular endometrial hyperplasia was 1.8 times more common in experimental groups than in the control one. Homozygous AA-genotype of 331G/A PRG polymorphism was not identified in women with endometrial hyperplasia. Conclusion. In endometrial hyperplasia, prevalence of mutant CC-allele of PvuII C/T ESR1 polymorphism leads to a decrease in ERa sensitivity, whereas prevalence of mutant TT-allele of Val660Leu PRG polymorphism leads to impaired sensitivity and a decrease in the biosynthesis rate of progesterone receptors. EH etiology and pathogenesis in women of reproductive age still remains the subject for future scientific research. Keywords: estrogen receptors, progesterone receptors, glandular endometrial hyperplasia, atypical endometrial hyperplasia. Актуальность проблемы пролиферативных процессов связана с высокой частотой распространения и высоким риском их трансформации в злокачественный процесс. В настоящее время до конца не изучен патогенез гиперплазии эндометрия (ГЭ). Причиной формирования гиперпластического процесса в гормонально-зависимых тканях может быть дисбаланс эстрогенов и прогестерона, а также эстрогеновых и прогестероновых рецепторов. В настоящее время отсутствуют маркеры, которые могли бы служить объективными предикторами развития ГЭ в направлении трансформации в рак или, наоборот, спонтанной ее регрессии. Цель исследования. Определить частоту встречаемости полиморфизмов генов ESR1 и PRG у пациенток репродуктивного возраста с различными вариантами гиперплазии эндометрия. Материалы и методы. Все обследованные женщины (143 чел.) были поделены на три группы: I группу составили 53 пациентки с железистой и железисто-кистозной ГЭ без атипии; II группу – 34 пациентки с атипической гиперплазией эндометрия; III группа стала контрольной. Молекулярно-генетическое исследование локусов проведено методом полимеразной цепной реакции синтеза ДНК. Статистический анализ полученных данных выполнен в программах SAS JMP 11 и Statistica 10. Результаты. Мутантный аллель СС полиморфизма PvuII гена ESR1 обнаружен у каждой четвертой женщины с железистой гиперплазией эндометрия и у каждой третей пациентки с атипической гиперплазией эндометрия. Частота встречаемости генотипа GG полиморфизма XbaI гена ESR1 в сравнении с группой контроля не имела статистически значимых различий. Мутантный аллель ТТ полиморфизма Val660Leu гена PRG при железистой гиперплазии эндометрия встречался в 1,8 раза чаще, чем в группе контроля. Гомозиготный генотип АА полиморфизма 331G/A гена PRG у женщин с гиперплазией эндометрия выявлен не был. Выводы. При гиперплазии эндометрия преобладание мутантного аллеля CC полиморфизма PvuII C/T гена ESR1 приводит к снижению чувствительности ERa, а преобладание мутантного аллеля TT полиморфизма Val660Leu гена PRG – к нарушению чувствительности и снижению скорости биосинтеза прогестероновых рецепторов. Предметом исследований по-прежнему остается концепция этиологии и патогенеза ГЭ у женщин репродуктивного возраста, что требует дальнейшего научного поиска. Ключевые слова: эстрогеновые рецепторы, прогестероновые рецепторы, железистая гиперплазия эндометрия, атипическая гиперплазия эндометрия.
Aim. To study the prevalence of RBM20 gene polymorphisms and their relationship with the structural and functional left atrial (LA) characteristics in patients with coronary artery disease and heart failure with reduced ejection fraction (HFrEF).Material and methods. The study included 138 men aged 55,8±6,6 years with prior myocardial infarction ³12 months ago and HFrEF (class II-IV heart failure, left ventricular ejection fraction (Simpson’s methods), 25,1±7,2%). The control group consisted of 384 healthy donors. Genotyping of two RBM20 polymorphic variants (rs942077 and rs35141404) was performed by real-time polymerase chain reaction.Results. The prevalence of RBM20 polymorphisms did not differ in the HFrEF cohort and the control group. The GA rs35141404 genotype was more common among patients with a less pronounced increase in LA volume index (LAVI) (p=0,034). The minor A allele rs35141404 was associated with a protective effect on severe LA remodeling. However, this association did not reach the level of significance.Conclusion. For the rs942077 and rs35141404 polymorphic variants of the RBM20 gene, no significant associations were found with the LA size and atrial fibrillation presence in patients with HFrEF and old myocardial infarction. There was a tendency towards the association of the A allele and the GA rs35141404 genotype with a protective effect on LA remodeling. The data obtained confirm the need for further search for genotype-phenotype relationships of a wider population of patients with heart failure and coronary artery disease.
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