Growth differentiation factor 15 and the risk of cardiovascular events in patients with atrial fibrillation after elective percutaneous coronary intervention

Aim. To study the predictive value of growth differentiation factor 15 (GDF-15) in patients with atrial fibrillation (AF) after elective percutaneous coronary intervention (PCI).Material and methods. The study included 150 patients (men, 69,3%) with AF receiving direct oral anticoagulants in combination with two (89,3%) or one antiplatelet agent (10,7%) after elective PCI. Median age was 71,0 [interquartile range, 66,0; 77,0] years. The median follow-up was 11,5 months [interquartile range, 8,0; 12,0]. The efficacy endpoint was the sum of cardiovascular events (CVEs), including cardiovascular death, ischemic stroke, venous thromboembolism, peripheral arterial thrombosis, acute coronary syndrome, and the need for emergency PCI. The safety endpoint was considered to be BARC type 2-5 bleeding. Prior to PCI, blood plasma samples were taken from patients to determine GDF-15 and D-dimer by enzyme immunoassay.Results. The incidence of CVEs was 16%. The incidence of BARC type 2-5 bleeding was 24,7%. The median GDF-15 level was 1270,0 pg/ml [953,0; 1778,0]. According to multiple regression, the GDF-15 level is associated with D-dimer (t=3,20; p=0,0018), diabetes (t=3,97; p=0,0001) and SYNTAX score II (t=4,77; p<0,0001). In patients with single-vessel coronary artery disease, the GDF-15 level was significantly lower than in patients with three-vessel disease (p=0,0119). According to the ROC analysis, a GDF-15 >1191 pg/ml (p=0,0076) increases the likelihood of CVE (area under the curve, 0,647; confidence interval (CI), 0,5650,723). According to Kaplan-Meier survival curves, significant differences were found in terms of absence of CVEs during the follow-up period between the groups of patients with a GDF-15 >1191 and those with GDF-15 <1191 pg/ml (76% vs 94%, p=0,0032; relative risk, 4,36; CI 1,50-7,48). The relationship of GDF-15 level with BARC type 2-5 bleeding was not revealed.Conclusion. GDF-15 is a novel marker of CVE in AF patients after elective PCI

Маркеры повреждения эндотелия, активации гемостаза и неоангиогенеза у больных активным раком и мультифокальным атеросклерозом: общие черты и особенности

Introduction. Thrombotic complications (TC) in different vascular systems dictate the fate of high-risk patients. In cardiological practice, patients with advanced atherosclerotic vascular disease (MFA) represent the most vulnerable group. Malignant neoplasm (MN) is one of the most significant risk factors for developing TCs, especially in the context of antineoplastic therapy. The presence of significant differences in the mechanisms of thrombogenesis in malignant neoplasms and atherosclerosis determines the appropriateness of a comparative study of markers of coagulation activation and endothelial damage in order to identify common features and differences specific to each pathology. Aim. To examine markers of coagulation activation and growth factors in active cancer and advanced atherosclerotic vascular disease, to identify their common features and differences specific to each pathology.  Materials and methods. A total of 22 patients with MN (Group 1) and 58 patients with MFA (Group 2) were enrolled in the study. The assessed biomarkers included: von Willebrand factor (VWF), D-dimer, growth differentiation factor-15 (GDF-15) and vascular endothelial growth factor A (VEGF-A).  Results. Patients with MN had an increased likelihood of disease progression within 6 months at D-dimer level > 1121 ng/mL (OR = 10.5; 95% CI 1.4–81.0, p = 0.014) or VWF > 189% (OR 10.5, 95% CI 1.36–81.0, p = 0.014); the likelihood of death within two years of follow-up at D-dimer level > 1121 ng/mL (OR = 7.0; 95% CI 0.97–50.57, p = 0.04), or VWF > 203% (OR = 10, 5, 95% CI 1.36–81.06, p = 0.014). In patients with MFA, the likelihood of prognosis determining events within one-year of follow-up was determined by increased levels of VWF > 157% (OR = 9.2, 95% CI 1.02–82.8, p = 0.048) and GDF-15 > 1548 pg/ml (OR = 5.7; 95% CI 1.09–29.5, p = 0.04).  Conclusions. Endothelial damage and coagulation activation are more pronounced in patients with MN than in patients with MFA. In patients with malignant neoplasms, the outcomes were associated with D-dimer and VWF levels, and in patients with MFA – with VWF and GDF-15 levels.Введение. Тромботические осложнения (ТО) в различных сосудистых бассейнах определяют судьбу больных высокого риска. В кардиологической практике наиболее уязвимая группа – больные с распространенным атеросклеротическим поражением (МФА). Злокачественное новообразование (ЗНО) является одним из наиболее значимых факторов риска ТО, особенно в условиях медикаментозного противоопухолевого лечения. Наличие существенных различий в механизмах тромбообразования при ЗНО и атеросклерозе определяет целесообразность проведения сравнительного исследования маркеров активации свертывания крови и повреждения эндотелия для выявления общих признаков и особенностей, характерных для каждой патологии.Цель. Изучить маркеры активации свертывания крови и факторы роста при активном раке и распространенном атеросклеротическом поражении, найти их общие черты и особенности, характерные для каждой патологии.  Материалы и методы. В исследование было включено 22 пациента с ЗНО (группа 1) и 58 больных с МФА (группа 2). Определялись биомаркеры: фактор фон Виллебранда (ФВ), Д-димер, фактор дифференцировки роста-15 (GDF-15) и фактор роста эндотелия сосудов А (VEGF-A).  Результаты. У пациентов с ЗНО повышается вероятность прогрессирования заболевания в течение 6 мес. при уровне Д-димера > 1121нг/мл (ОШ = 10,5; 95% ДИ 1,4–81,0, p = 0,014), или ФВ > 189% (ОШ 10,5; 95% ДИ 1,36–81,0, p = 0,014); вероятность смерти за два года наблюдения при уровне Д-димера > 1121нг/мл (ОШ = 7,0; 95% ДИ 0,97–50,57, р = 0,04), или ФВ > 203% (ОШ = 10,5; 95% ДИ 1,36–81,06, р = 0,014). У больных МФА вероятность развития прогноз-определяющих событий за год наблюдения определяется повышением уровней ФВ > 157% (ОШ = 9,2, 95% ДИ 1,02–82,8, р = 0,048) и GDF-15 > 1548 пг/мл (ОШ = 5,7; 95%ДИ 1,09–29,5, р = 0,04).  Выводы. У больных ЗНО повреждение эндотелия и активация свертывания крови выражены в большей степени, чем у пациентов с МФА. Связь с исходами у больных ЗНО была обнаружена с уровнями Д-димера и ФВ, а у больных с МФА – ФВ и GDF-15

FACTORS ASSOCIATED WITH D-DIMER ELEVATION IN PATIENTS WITH VENOUS THROMBOEMBOLIC EVENTS

Aim. To study the factors associated with elevated D-dimer levels in patients with acute venous thromboembolic events (VTEE). material and methods. The study included 111 patients (76 men and 35 women aged 18–76 years) with a first or repeat episode of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the last 2 months. The majority of the patients (n=80) received unfractionated heparin (UFH) for at least 5 days, followed by warfarin (international normalized ratio (INR) control at least once a month; target INR 2,0–3,0). Some patients (n=31) received therapeutic doses of enoxaparin (1 mg/kg subcutaneously, every 12 hours) for at least 30 days, followed by warfarin treatment. D-dimer levels (norm <0,5 mkg/ml) were measured by the latex agglutination method, with the use of “STA LIATEST >® D-DI” reagents (Diagnostica Stago). Results. D-dimer levels varied from 0,02 to 9,96 mkg/ml (median 1,05 mkg/ml, interquartile range 0,49–1,99 mkg/ml) and exceeded the upper norm limit in 74% of the patients. There was a positive association between D-dimer levels and thrombus “size” (r=0,304; p<0,001), and a negative association between D-dimer levels and >< 0,001), and a negative association between D-dimer levels and thrombus “age” (r=-0,418; p<0,001). Predictors of D-dimer elevation were identified among 150 demographic, anthropometric, anamnestic, clinical, laboratory, genetic, or ultrasound parameters and VTEE risk factors. The results of the multivariate stepwise regression analysis demonstrated that female gender, chronic heart failure (CHF), VTEE symptom duration ><28 days, and thrombus “size” >< 0,001). Predictors of D-dimer elevation were identified among 150 demographic, anthropometric, anamnestic, clinical, laboratory, genetic, or ultrasound parameters and VTEE risk factors. The results of the multivariate stepwise regression analysis demonstrated that female gender, chronic heart failure (CHF), VTEE symptom duration <28 days, and thrombus “size” >< 28 days, and thrombus “size” < 6 points were independent predictors of D-dimer elevation in the acute period of DVT/PE. Conclusion. D-dimer levels, measured 32 (23–44) days after the development of DVT/PE symptoms, were elevated in 74% of the patients. D-dimer elevation in the acute period of VTEE was associated with female gender, CHF, “age” and “size” of the thrombus