Гепсидин и его связь с воспалением у больных с анемией хронических заболеваний на фоне ХСН в пожилом и старческом возрасте Ключевые слова: хроническая сердечная недостаточность, анемия хронических заболеваний, гепсидин, пожилой и старческий возраст

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Резюме Цель: провести сравнительный анализ анемии хронических заболеваний (АХЗ) и железодефицитной анемии (ЖДА) у больных ХСН пожилого и старческого возраста по показателям феррокинетики и воспаления, а также исследование связей между ними. Материал и методы. Обследованы 65 пациентов с ИБС: 35 с ХСН и АХЗ; 10 пациентов с ХСН и ЖДА и 20 пациентов без ХСН, АХЗ и ЖДА, составивших контрольную группу (КГ). Результаты. Выявлено, что у больных ХСН с ЖДА имеется истинный дефицит железа, тогда как у 54 % больных ХСН с АХЗ-функциональный дефицит железа, а у 46 %-отсутствие дефицита железа. У больных ХСН с АХЗ выявлены весьма значимые относительно пациентов ХСН с ЖДА уровни острофазовых белков-ферритина и гепсидина, а также-С-реактивного белка (СРБ) и интерлейкина-6 (ИЛ-6), при этом между ИЛ-6 и ферритином, ИЛ-6 и СРБ, СРБ и гепсидином выявлены значимые положительные связи. У больных ХСН с ЖДА уровни острофазовых белков-ферритина и гепсидина, а также СРБ и ИЛ-6-низкие, а связи между ИЛ-6 и ферритином, ИЛ-6 и СРБ, СРБ и гепсидином незначимы. Выявлено, что уровни эритропоэтина значимо повышены как у больных ХСН с АХЗ, так и у больных ХСН с ЖДА относительно пациентов контрольной группы, при этом значимых различий между ними не выявлено.

The review of the current literature presents data on chronic disease anemia (CDA), a topical problem of internal medicine belonging to the group of iron-deficient anemia and taking its name from the inflammatory process behind its pathogenesis. It is also called inflammation anemia or cytokine-mediated anemia. This condition is of primary importance in connection with associated, according to recent epidemiological studies , with high prevalence of CDA that impairs quality of life, aggravates prognosis, and increases mortality. Mechanisms of CDA development are discussed with special reference to three trigger factors, viz. cytokines, erythropoietin, and the recently discovered protein hepcidin. The latter has attracted especially much attention in the past years. Iron-containing medications being inefficient in the patients with CDA, other modern approaches to their treatment designed to directly influence the pathophysiological processes behind the disease are considered with special emphasis laid on the enhancement of ferroportin activity and reduction of hepcidin synthesis.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The reported study was funded by Russian Foundation for Basic Research (RFBR) project number 19-315-90034 Background. Nowadays gastric cancer is one of the leading causes of world cancer mortality. Modern chemotherapy (CT) significantly improves survival and quality of life among these patients. Unfortunately, anticancer drugs induce some biomolecular disorders, which influence endothelial dysfunction and microcirculation lesions, subsequently leading to vasculo- and cardiotoxicity. The aim To study the dynamics of endothelial dysfunction’s (ED) biomarkers (endothelin-1 (ET-1), von Willebrand factor (VWF)) in patients with gastric cancer before and after CT. Material and methods The study included 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage II - IV, who have been treated by CT including platinum compound (oxaliplatin, cisplatin) and fluoropyrimidine group (5-fluorouracil, capecitabine) and are proven to be cardiovasculotoxic. All patients underwent blood tests, computer nailfold capillaroscopy and finger photoplethysmography (non-invasive assessment of vascular wall stiffness and endothelial function), electrocardiography (ECG), 24-hour ECG, echocardiography before CT and within a month after the last course. Results The median patients’ age was 64 ± 13 years; 68% were male; 52% had a prior cardiac illness: arterial hypertension (n = 12, 48%), coronary artery disease (n = 7, 28%), chronic heart failure (n = 3, 12%). The data obtained showed that ET-1 median levels were below normal values and did not change during CT: 0,95pg/ml (0,6;1,4) vs. 0,94pg/ml (0,7;1,4), р<0,9 (N = 1–3pg/ml), before and after CT respectively. The level of VWF remained within normal ranges and did not significantly differ in cancer patients before and after treatment 0,75IU/ml (0,7;0,9) vs. 0,8IU/ml (0,74;0,9), р<0,6 (N = 0,5–1,5IU/ml). Even before CT, endothelial dysfunction was detected, which significantly worsened after the treatment (occlusion index (IO) before and after CT 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p < 0.0002, respectively). During data analysis, significant correlations were found: between ET-1 level and IO (r = 0.554, p = 0,006), ET-1 and percentage of capillary recovery (r= -0.7, p = 0,029) [both parameters characterize functional abnormalities of the microvasculature], ET-1 and the quantity of supraventricular extrasystoles (r=-0.48, p = 0,032). Conclusion In this study, the dynamics of ED biomarkers in patients with gastric cancer were studied. Even though reliable changes were not proven for the assessed molecular parameters ET-1 and VWF during CT (supposing depletion of endothelin system, small patient cohort), the above parameters may be used for identifying early signs of close and long-term cardio/vasculotoxicity due to significant positive correlations with microvasculature lesions. Further bigger trials for identification of other accurate and effective laboratory methods of detecting early features of vasculotoxicity are required.