Leukocyte and platelet markers of blood in the dynamics of the hospital period in patients with acute myocardial infarction: the ability to predict the development of long-term adverse events

The aim – to create a new method of assessing the development of long-term complications in STEMI patients by studying blood cell composition and its adaptation to practical application in general clinical practice.Materials and methods. The study was involved 148 patients with acute myocardial infarction (AMI) who was admitted from January 2014 to June 2020 to the intensive care unit. Some patients were evaluated retrospectively and were in group 1 (n=92). Group 2 – 56 patients, who were studied prospectively. The groups of patients did not differ in clinical and anamnestic characteristics and treatment. The study provided an annual observation period. The endpoint in group 1 was: death, stroke, exacerbation of coronary heart disease – including the need for revascularization, the developement or decompensation for heart failure, which led to hospitalization (in addition, group 2 was analyzed for onset of cardiac death).Results and discussion. There complex indicators were built, based on the analysis of the clinical profile and dynamics of laboratory parameters in patients with the onset of the endpoint – a modified leukocyte index (mLI), which contains the values ​​of the number and percentage of granulocytes, lymphocytes and monocytes on days 1, 3 and 10 of STEMI and leukocyte-platelet index (mLPI), which additionally includes indicators of platelet inhomogeneity in size (PDWc and P-LCR). These indices with their limit values ​​(mLI > 140 units and mLPI > 242 units) were more informative in predicting distant cardiovascular events than other laboratory markers (including neutrophil-leukocyte ratio, NLR). In a prospective study branch (group 2), the mLI and mLPI indicators also turned out to be more informative than other markers (in particular, the NLR indicator) in determining the propensity to occur as a combined endpoint (area under the curve 0.71 for both; p>0.0001), so and death (areas under the curve 0.78 and 0.84, respectively; p>0.0001). Based on the data obtained, a computer algorithm has been created that simplifies the risk assessment in AMI patients using the developed indicators.Conclusions. Created leukocyte and leukocyte-platelet indices are highly informative in predicting the risk of complications in patients within a year after AMI.

The effectiveness of a fixed double combination (bisoprolol, perindopril) in patients with stable coronary artery disease and arterial hypertension different degrees

The aim – to evaluate the hypotensive and antianginal efficacy of a fixed double combination (bisoprolol, perindopril) in patients with coronary artery disease (CAD) and concomitant hypertension.Materials and methods. The study involved 170 cardiologists from various regions of Ukraine. Each researcher selected 15 consecutive outpatients with coronary heart disease who came for a regular visit. Inclusion criteria: age over 18 years old, blood pressure (BP) above 140/90 mm Hg, heart rate (HR) above 60 bpm, bisoprolol as part of antihypertensive therapy in the last ≥ 3 months. The study included two visits. At each visit, the patient’s objective status was assessed; an individual questionnaire with office systolic and diastolic blood pressure, heart rate, ECG data, clinical manifestations of CAD, risk factors, lifestyle features, concomitant diseases, current therapy was filled out. Medication adherence was also evaluated, the therapy was corrected if necessary and the presence of side effects and adverse events was registered. We analyzed the levels of BP and HR at the beginning and at the end of the study, the percentage of achievement of the recommended levels of these indicators, the antianginal efficacy of treatment and adherence to therapy in patients with CAD and different degrees of hypertension after 4 weeks of treatment.Results and discussion. 2785 patient questionnaires were provided by doctors, 1747 patients were included in substudy. The mean age of the patients was 60.9±10.2 years old, men – 57.1 %, women – 42.9 %. The diagnosis of coronary artery disease was based on: chest pain – 554 (31.7 %), a history of documented myocardial infarction – 935 (53.5 %), coronary ventriculography – 536 (30.7 %), revascularization (CABG/stenting) – 344 (19.8 %) patients. The use of a fixed combination of previously taken drugs (perindopril, bisoprolol) for 4 weeks allows to reduce heart rate and blood pressure effectively (HR ≤ 70 bpm reached 84.9 % of patients, BP ≤ 140/90 mm Hg – 86.9 %), to reduce the number of angina attacks (from 4.48, 4.5 and 4.7 per week at the beginning of the study to 2.4; 2.9 and 2.3 per week in patients with 1, 2 and 3 degrees of hypertension, respectively) and the need for nitroglycerin from from 4.5; 4.9 and 5.9 tab per week up to 2.4; 2.9 and 2.3 tab per week. The most significant absolute decrease of BP and HR was in patients with a more severe degree of hypertension (decrease systolic BP was – 40.8 mm Hg, diastolic BP – 21.4 mm Hg, HR – 21.8 bpm).Conclusions. The study demonstrated that the use of the fixed combination of bisoprolol and perindopril in patients with coronary artery disease and concomitant hypertension (different degrees) helps to improve treatment efficacy, to achieve recommended levels of blood pressure and heart rate, also has a significant antianginal effect (reliable decrease of the number of angina attacks and the need to take nitroglycerin) and increases adherence to therapy.

Effect of multicomponent therapy on left ventricular diastolic function in resistant hypertension patients

The aim – to determine prognostic factors of improving left ventricular diastolic function (LV DF) in resistant hypertension (RH) patients (pts) treated with multicomponent antihypertensive therapy during three years.Materials and methods. 102 patients with true RH were included. Patients received triple fixed combination (blocker of the renin-angiotensin-aldosterone system / calcium antagonist / diuretic), to which has been added a fourth drug (spironolactone, eplerenone, moxonidine, torasemide or nebivolol). The state of LV DF was studied at the beginning and at the end of the study. Office and 24-h ambulatory blood pressure (BP) measurements, echocardiography, clinical characteristics, neurohumoral and proinflammatory status were assessed.Results and discussion. Impairment LV DF was detected in 75.5 % of pts. The first degree of LV diastolic dysfunction (DD) was observed in 63.7 %. The patients were divided into 2 groups: the first group included persons without initial impairment of LV DF (n=25), the second – pts with LV DD (n=77). Patients with LV DD were older, had a longer duration of hypertension, higher body mass index, 24-h urinary albumin excretion, office BP and 24-h ambulatory BP, more often (in 2 times) disorders of circadian BP rhythm and concomitant diabetes mellitus (DM). Left ventricular DD in 100 % of cases was associated with severe LV hypertrophy (LVH), increased plasma concentration of inflammatory proteins (CRP, fibrinogen), cytokines (IL-6, TNF-α), increased activity of leukocyte elastase, macrophage matrix metalloproteinase-12. The concentration in the blood of aldosterone, active renin, 24-h urinary excretion of metanephrines did not differ between the groups.Conclusions. Improvement and stabilization of LV DF occurred in parallel with regression of LVH (normalization of LVMI in 35.1 % of pts and significant decrease of LVMI in 64.9 %) against the background of decrease of BP and in the proportion of pts with disturbed circadian BP rhythm. The independent factors of the E/E’ ratio were the initial plasma concentrations of aldosterone (β=0.556; р=0.0001), glucose (β=0.366; р=0.0001), active renin (β=–0.223; р=0.004), 24-h urinary albumin excretion (β=0.188; р=0.016), age (β=0,192; р=0,023). The odds of an improvement in LV DF increased by 3.7 times, if the patient with RH had no DM, LVH regression occurred.

Clinical and demographic characteristics, management of patients with type 2 diabetes mellitus and vascular complications: analysis of the Ukrainian cohort of the DISCOVER Global Registry

The aim – to describe baseline data of the Ukraine cohort of DISCOVER Global Registry (DGR) with real-world insights on current treatment practices, complications, and associated clinical outcomes in people with type 2 diabetes mellitus (T2DM).Materials and methods. This healthcare provider-led prospective registry involves non‑interventional data collection from adults (aged ≥ 18 years) with T2DM receiving standard medical care as part of routine clinical practice per their treating physician’s discretion.Results and discussion. The initial data of 353 people with T2DM, who were included in the Ukrainian cohort of the DGR Register, were analyzed. The mean (±standard deviation) age of the study population was 58.85±10.02 years with female predominance (64 % [n=226]). The mean T2DM duration was 10.27±12.15 years with a mean glycated hemoglobin (HbA1c) level of 8.62±1.89 %. Only one-fifth (20.5 %, n=59) of the patients had glycemic control (HbA1c < 7.0 %). Among those with any complication, 73.8 % had microvascular and 79.3 % had cardiovascular complications. Retinopathy and heart failure were the most common microvascular and cardiovascular complications, respectively. Overall, 88 % of the patients were taking any antidiabetic therapy; of these, 27.3 % received insulin (monotherapy: n=28; combination therapy: n=57). As oral antidiabetic drugs (OAD), 32.2 % and 12.9 % received metformin and sulphonylurea monotherapies, respectively; minor proportions received newer OAD monotherapy (sodium-glucose co-transporter-2 inhibitors [4.8 %] and dipeptidyl peptidase-4 inhibitor [1 %]).Conclusions. Baseline data from the Ukraine cohort of DGR reveals poor glycemic control, with a higher mean HbA1c and proportion of patients with micro- and cardiovascular complications than that of the global cohort. The landscape of therapeutic agents displayed marked diversities in the management strategies. Robust real-world data from the DGR can help understand the gaps in care of T2DM patients and lights the need of the formulation of region-specific holistic therapeutic strategies to optimize glycemic control and improving clinical patients’ outcomes.

Predictors of 5-year survival in patients with chronic heart failure and reduced left ventricular ejection fraction depending on the presence of type 2 diabetes mellitus

The aim – to determine the predictors of 5-year survival of patients with CHF and reduced LV EF depending on the presence of type 2 diabetes mellitus.Materials and methods. 490 case histories of patients in the period from 2011 to 2018 with CHF, 40–80 years of age (median – 64 years), II–IV NYHA functional class, LVEF ≤ 40 % were analyzed. For the analysis of all patients with CHF and reduced LV EF were divided into two groups: Group I included 338 (69 %) patients without diabetes mellitus type 2, group II consisted of 152 (31 %) patients diagnosed with diabetes mellitus type 2. To measure the values ​​of the independent predictors, we calculated the value of the odds ratio (OR) with a 95 % confidence interval. To determine predictors of mortality/survival of the studied patients, was calculated the Хі-square criterion. Additionally, we calculated the estimate of the frequency difference between the groups, the odds ratio, the confidence interval for the odds ratio, the Pearson correlation coefficient r, for all the calculated characteristics we determined the probability of error of the first kind p. As a result, we formed a final table of indicators-predictors of mortality/survival of patients with CHF with reduced LV EF with and without diabetes mellitus type 2 for which there is a statistical relationship between mortality / survival and the studied indicator.Results and discussion. In patients without diabetes, many indicators are associated with the prognosis of long-term survival. These include hemodynamic parameters (heart rate, the left atrium size (LV) and indexed left ventricular (LV) volumes, LV myocardial mass index, right ventricular size (RV) and LV ejection fraction, renal function parameters (microalbuminuria (UIA), glomerular filtration rate (GFR), urea nitrogen), systemic inflammatory marker (C-reactive protein (CRP)), markers of systemic oxidative stress (myeloperoxidase, citrulline, uric acid) and antioxidant defence – SOD, as well as the N-terminal fragment of the precursor of natriuretic peptide (NT-proBNP), flow-dependent vasodilatory response (FDVR), high-density lipoprotein cholesterol (HDL), insulin and the relative content of lymphocytes in the blood. Patients with diabetes had significantly fewer such predictors: in addition to parameters of intracardiac hemodynamics and heart modeling, other significant predictors of 5-year survival were daily UIA level, CRP, SOD, HDL, insulin and the lymphocyte level.Conclusions. Quantitative predictors of poor 5-year survival prognosis among patients with CHF and reduced LV EF with and without concomitant diabetes mellitus type 2 are parameters of heart remodeling, LV systolic function-EF, UIA level, antioxidant stress marker (SOD), HDL level, blood lymphocytes and the level of circulating insulin. Patients without diabetes are characterized by a wider range of poor long-term survival predictors, which include indicators of renal nitrogen function, markers of systemic oxidative stress (myeloperoxidase, citrulline, uric acid), flow-dependent vasodilatory response and circulating NT-proBNP. The determined quantitative predictors can be used in algorithms of individual prediction of the course of CHF and reduced LV EF, which should be created separately for patients with and without concomitant diabetes mellitus type 2

Diagnostic value of right heart and pulmonary artery catheterization in patients with suspected pulmonary hypertension. Part 2. Invasive study of parameters of hemodynamics and oxygen transport

The aim – evaluate the parameters of pulmonary and systemic hemodynamics obtained in patients with various forms of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Ukraine.Materials and methods. The study included 195 patients: IPAH was in 68 patients; PAH associated with connective tissue diseases (CTD) – in 21 patients; PAH associated with HIV infection – in 4 patients; PAH associated with portal hypertension (PH) – in 4 patients; PAH associated with congenital heart disease – in 25 patients; CTEPH – in 51 patients, pulmonary hypertension (PH) associated with left heart disease (LHC) – in 5 patients and 17 patients who were excluded from the diagnosis of PH. From 2014 to 2019, these patients underwent 220 procedures of right heart catheterization (RHC) in accordance with current European Guidelines. Also, all patients underwent echocardiographic examination and determined the gas composition of blood and indicators of acid-base balance using the ABL 735 analyzer, calculated the parameters of the affinity of hemoglobin to oxygen (p50).Results and discussion. The lowest level of arterial blood oxygen saturation was in the group of patients with PH due to LHD – 88.9 % (p<0.05); in other groups it averaged 94–97 %. The oxygen content in arterial blood was the lowest in the group of patients with PH due to LHD – 15.7 ml/L (p<0.05); in other groups this indicator was equal to 17.4–18.7 ml/L. The lowest oxygen saturation of mixed venous blood (SvO2) was in the PAH group associated with HIV – 58 % (p<0.05), and close to critical (< 65 %) SvO2 level was observed in the IPAH group – 66.3 %. CTEPH – 66.0 %. The highest level of this indicator was in the PAH group associated with portal hypertension – 81.1 %. The arterio-venous difference was highest in the PAH associated with HIV group – 5.6 ml/L, and the smallest in the PAH associated with PH group – 2 ml/L. On the other hand, the oxyhemoglobin dissociation curve was almost normal in all groups, except for the group of patients with PAH associated with portal hypertension.Conclusions. The most severe disorders of hemodynamics and oxygen transport were observed in the group of PAH patients associated with HIV compared with other forms of PAH and CTEPH. The IPAH and CTEPH groups were similar in terms of hemodynamics, despite a different pathophysiological mechanism. In the group of patients with PAH associated with CTD, the results of the RHC were slightly better than in the group of patients with IPAH, reflecting that the hemodynamic component is not the leading one for prognosis in these patients. Also, the performance of the right ventricle was significantly higher in patients with PAH compared with the group without PH.

COVID-19-associated myocarditis: single center experience of pathogenetic treatment

The aim – to evaluate the effectiveness of glucocorticoid therapy in patients with myocarditis with reduced left ventricular ejection fraction that developed after COVID-19 infection.Materials and methods. The results of glucocorticoid therapy in 32 patients aged (35.2±2.3) years with acute myocarditis after COVID-19 infection and left ventricular ejection fraction < 40 % are presented. All patients were prescribed a 3-month course of methylprednisolone at a daily dose of 0.25 mg/kg, followed by a gradual dose reduction of 1 mg per week until complete withdrawal 6 months after the start of treatment.Results and discussion. The analysis of the results of the examinations was performed in the 1st month from the onset of myocarditis to the appointment of glucocorticoids and after 6 months of observation. Six months later, the end-diastolic volume index decreased by 18.5 %, the left ventricular ejection fraction increased by 23.8 %, and the longitudinal global systolic straine increased by 39.8 %. On cardiac MRI, the number of left ventricular segments affected by inflammatory changes decreased from 6.22±0.77 to 2.89±0.45 segments, and the number of segments with fibrotic changes did not change significantly. After 6 months of treatment, there was a significant decrease in the concentrations of proinflammatory cytokines and cardiospecific antibodies.Conclusions. The use of a 6-month course of glucocorticoid therapy in patients with myocarditis that developed after COVID-19 infection improved the contractility of the left ventricle against the background of a significant reduction in inflammatory lesions of the left ventricle and reduced concentrations of proinflammatory cytokines and cardiospecific antibodies.

Influence fixed combination therapy on arterial stiffness and erectile function in patients with arterial hypertension

The aim – to evaluate the therapeutic efficacy and dynamics of arterial stiffness using сardio-ankle vascular index (CAVI), as well as the dynamics of erectile function in men of the generic fixed triple combination of valsartan/amlodipine/hydrochlorothiazide and a double fixed combination of valsartan/amlodipine in the treatment of patients with arterial hypertension II–III degree. Materials and methods. The study included patients with moderate and severe arterial hypertension without diabetes. Patients were divided into 2 groups by the method of envelopes of 25 each. The first group (n=25) was assigned a fixed triple combination of tablets valsartan/amlodipine/hydrochlorothiazide. The drug was administered 1 tablet (160 mg of valsartan/5 mg of amlodipine/12.5 mg of hydrochlorothiazide) once a day in the morning for 1 month. Patients in the second group (n=25) received a similar scheme of a double fixed combination of the drug valsartan/amlodipine. The drug was administered 1 tablet (160 mg of valsartan/5 mg of amlodipine) once a day in the morning for 1 month. If necessary, the target level of office blood pressure was less than 140/90 mm Hg, the dose was titrated to a daily dose of 320/10/12.5 mg (valsartan/amlodipine/hydrochlorothiazide) on a fixed triple combination and up to 320/10 mg (valsartan/amlodipine) on a fixed double combination. After 3 months of treatment there was control of therapy.Results and discussion. The study included 50 patients with moderate and severe hypertension. The average age of patients was 54.9±1.8 (25–75) years. The average BMI is 31.2±0.7 kg/m2. The average of the office of SBP and DBP at the beginning of the study were 161.7±1.8 mm Hg and 98.5±1.4 mm Hg in accordance. The office heart rate is 70.7±1.4 bpm. The decrease in the office blood pressure (SBP/DBP) was 35/19 mm Hg (р<0,05) on the double combination and 42/26 mm Hg (р<0,05) on the triple combination. Achieving target BP measurement in the office was 90.9 % – in the double combination and 95.7 % – in triple combination. In the dual combination group, withdrawal was observed in 3 (6 %) patients, in the triple combination group, withdrawal was observed in 4 (8 %) patients. There was a tendency to decrease the stiffness of the arterial wall in terms of cardio-vascular index CAVI, but there was no significant difference. CAVI right on dual therapy up to 8.68±0.57 units and after treatment 8.30±0.55 units. CAVI on the left on double therapy to 8.49±1.49 units and after treatment 8.17±1.49 units. CAVI right on triple therapy up to 8.86±0.39 units and after treatment 8.50±0.40 units from CAVI on the left in a triple combination up to 8.09±0.53 units and after treatment 8.27±0.36 units (p>0.05 for all values). No significant change in erectile function in men was detected during treatment.Conclusion. The dual (valsartan/amlodipine) and triple (valsartan/amlodipine/hydrochlorothiazide) fixed combination showed high antihypertensive efficacy, did not adversely affect metabolic disorders and erectile function in men, and inhibited the progression of stiffness.

Comparative characteristics of the state of the immune system in patients with coronary artery disease with stable angina pectoris and acute coronary syndrome

The aim – to assess the relationship between the state of the immune system and the development of acute coronary syndrome in patients with IHD.Materials and methods. The first group consisted of 64 patients with ST-segment elevation acute coronary syndrome, mean age 54 (49–64) years; the second group – 223 patients with coronary artery disease with stable exertional angina, FC II–III, mean age 56 (49–63) years; the third group – 47 patients with acute coronary syndrome without ST segment elevation, mean age 61 (52–65) years. The material for the immunological study was peripheral venous blood. To determine the parameters of cellular and humoral innate and adaptive immunity in blood serum and supernatants of mononuclear cells, enzyme immunoassay was used.Results and discussion. In patients with coronary artery disease with acute coronary syndrome with ST segment elevation compared with patients with coronary artery disease with stable angina pectoris, the levels of indicators of the immune status in the blood were: CRP – 9.3 (5.3–12.0) versus 4.8 (2.4–8.1) mg/L (p=0.0001), sICAM – 785 (690–830) versus 565 (406–744) ng/ml (p=0.0001), IL-10 in blood mononuclear cells – 48 (1–228) versus 194 (21–758) pg/ml (p=0.0007), circulating immune complexes – 90 (70–108) versus 76 (54–105) od. (p=0.045), lymphocytes with apoptosis (CD95) – 16 (9–27) versus 11 (8–17) % (p=0.029), spontaneous oxygen-dependent metabolism of monocytes – 16 (12–21) versus 13 (9–17) (p=0.001). The levels of indicators of the immune system in the blood in patients with coronary artery disease with acute coronary syndrome with ST segment elevation compared with patients with coronary artery disease with acute coronary syndrome without ST segment elevation were: T-helpers – 37 (32–41) versus 42 (37–48) % (p=0.0006) (R=–0.33; p=0.0005), reaction of lymphocyte blast transformation to nonspecific antigen – 38 (32–47) versus 50 (42–61) % (p=0.0004) (R=–0.37; p=0.0003).Conclusions. The development of acute coronary syndrome is directly combined with increased activity of the immune system, as evidenced by the high production of proinflammatory CRP, IL-8, sICAM with a low level of anti-inflammatory IL-10, a pronounced humoral adaptive immune response (in terms of antibodies to the myocardium and vascular tissues, CD40, circulating immune complexes) and active functional state of monocytes (according to cNCT test, functional reserve, phagocytosis) in patients with coronary artery disease with acute coronary syndrome, regardless of the position of the ST segment in comparison with patients with stable coronary artery disease. Elevated levels of antibodies to the myocardium in patients with stable coronary heart disease indicate moderate myocardial damage due to temporary ischemia in angina attacks, even with a stable course of the disease. In patients with acute coronary syndrome, high levels of antibodies to the myocardium indicate myocardial damage due to increased ischemia in plaque destabilization much earlier than the clinical manifestations of acute coronary syndrome. In acute coronary syndrome with ST-segment elevation, compared with ACS patients without ST-segment elevation, activation of neutrophils and suppression of the activity of adaptive T-cell immunity is noted (by the level of T-helpers, sCD40L, blast transformation of lymphocytes, γ-interferon in mononuclear cells, apoptosis of lymphocytes).

General analysis of clinical and laboratory characteristics of the Ukrainian familial hypercholesterolemia registry

The aim – to evaluate clinical and laboratory characteristics of patients of the Ukrainian familial hypercholesterolemia registry taking into account gender differences.Materials and methods. 231 patients with familial hypercholesterolemia were included to the Ukrainian Familial Hypercholesterolemia Registry: 8 children (under 18 years of age) and 223 adult patients (68 men (30.5 %), mean age 43.4±1.3 and 155 women) 69.5 %) – 45.5±1.0 years) with familial hypercholesterolemia verified according to the DLCN criteria. General clinical, laboratory, instrumental examinations and genetic testing were performed.Results and discussion. In the general registry among the patients with familial hypercholesterolemia in the setting of early manifestation of atherosclerosis the male patients with familial hypercholesterolemia were more likely to have coronary artery disease, premature coronary artery disease, cerebral and peripheral atherosclerosis, xanthoma, hypertriglyceridemia, diabetes mellitus, smoking and a history of MI, which caused a higher DLCN score (9.3 points in men against 7.8 points in women, p<0,05). Female patients with familial hypercholesterolemia had a higher percentage of obesity and hypertension, which corresponds to the main gender trends of the Ukrainian population study.Conclusions. Since 2017, for the first time in Ukraine, the register of patients with familial hypercholesterolemia has been initiated. In December 2019 the most severe form – homozygous familial hypercholesterolemia – was first included in the list of orphan diseases by the Order of the Ministry of Health of Ukraine. According to the analysis of the data of the Ukrainian familial hypercholesterolemia registry, this pathology is diagnosed rather late and insufficiently in Ukraine. In patients with familial hypercholesterolemia, against the background of an earlier manifestation of atherosclerotic lesions, gender features of the cardiovascular risk factors profile, which are characteristic of the entire adult population of Ukraine, are preserved. The lower severity of familial hypercholesterolemia clinical manifestations in women according to the general Ukrainian familial hypercholesterolemia registry may be due to the predominance of heterozygous forms in the registry and inclusion of women of reproductive age against the background of preserved antiatherogenic effects of estrogen to the registry.