ACUTE CORONARY SYNDROME
Aim: to assess relation ofhigh functional activity ofplatelets to prognosis ofunfavorable cardiovascular events in patients with Acute Coronary Syndrome (ACS).
Materials. The study was based on the data of a single center ACS registry conducted in the Central Clinical Hospital of the Presidential Affairs Department of Russian Federation. Of 529 included patients in 425 without contraindications to double antiplatelet therapy we carried out analysis of dependence of 30 days level of unfavorable events on parameters of functional activity of platelets.
Results. High on-treatment platelet reactivity (HTPR) was found to be associated with 3.5 increase of mortality in the group of patients with high cardiovascular risk. Logistic model of prognosis of unfavorable events based on multifactorial analysis of data from patients with measured platelet aggregation included chronic kidney disease, type of myocardial infarction, and degree ofplatelet aggregation >45%. C -statistic was equal to 0.77. We also present in this paper discussion of problems related to studying approaches to individualization of anti-aggregation therapy in real clinical practice and problems of organization ofsimilar studies.
Conclusion. The study showed that patients with ACS increased platelet aggregation, as well as chronic kidney disease and type 2 MI are associated with a 30 day prognosis of adverse events.
Purpose: to study distribution of genes of the coagulation system, unfavorable in relation to the risk of thrombosis, and their influence on serum parameters ofthe hemostasis system in patients with nonobstructive coronary atherosclerosis (NCA) and acute coronary syndrome (ACS).
Materials and methods. We included in this nonrandomized open study patients with ACS older than 18 years with intact coronary arteries or confirmed at coronary angiography stenosis <50%. Genotypes of these patients were analyzed by 8 polymorphic variants of the hemostatic system genes which previously were found to be associated with the thrombophilia risk: F2 (20210 G>A) rs1799963, F5 (1691 G>A) rs6025, F7 (10976G>A) rs6046, F13 (163 G>T) rs5985, F1 (-455G>A) rs1800790, GP Ia - Ila (807C>t) rs1126643, GP Ilb-IIIa (1565 T>C) rs5918, PAI-I (-6755G>4G) rs1799889. Activities of protein C, Von Willebrand factor, plasminogen, and antithrombin III were also determined.
Results. Of 913 patients with ACS in 30 (3.3%) with mean age 54±11 years we detected NCA. Acute myocardial infarction (AMI) was diagnosed in 24 (80%), unstable angina - in 6 (20%) patients. Only in 1 patient we found no carriage of thrombosis associated genotypes. The frequency of occurrence of the heterozygous genotype of the factor V gene was 1 (3%). Heterozygous genotype of the factor XIII was registered significantly more often in patients with present atherosclerotic lesion compared with those with intact coronary arteries. Mean activity of protein C was 103% [90; 110], antithrombin III - 96% [88; 103], Von Willebrand factor - 137% [114; 162], plasminogen - 109% [102; 112]. At admission lowering of antithrombin III and protein C activities was detected in 4 cases (13%). In dynamics level of these parameters was restored. Elevation of Von Willebrand factor activity at admission was detected in 14 cases (14%) and remained elevated one year after the index event. There was no association between of fibrinogen level, protein C activity, rs1800790 and rs6025 gene polymorphisms, respectively. One-year mortality was 7% (n=2). For one year occurred 1 AIM recurrence (3%), heart failure developed in 15 patients (50%), 11 patients (37%) were repetitively hospitalized due to all causes. No association was revealed between activity of studied blood serum markers and 1 -year outcomes (death, re-AIM, rehospitalization).
Conclusion. Among ACS patients 3.3% had NCA, what corresponded to the literature data. Carriage of at least 1 polymorphic variant of 8 thrombosis associated genes of the coagulation system was found in 97 % of patients with ACS and NCA. Distribution of these variants was like that in the European population and in patients with AIM at the background of stenosing atherosclerosis. Level of serum markers did not depend on distribution of polymorphic variants of the coagulation system genes, and presence of atherosclerotic coronary artery lesions. There was no association between hospital and long-term outcomes and distribution of polymorphic variants of thrombosis associated coagulation system genes, as well as levels of blood serum markers.
ISCHEMIC HEART DISEASE
Aim: to compare diagnostic accuracy of exercise treadmill testing and stress echocardiography in the diagnosis of stable coronary artery disease (CAD) in patients aged >70 years.
Materials and methods. The study included 390 patients aged >70 years with suspected stable ischemic heart disease, who underwent elective coronary artery angiography (CAG). Exercise treadmill testing (ETT) according to the modified Bruce protocol was carried out in 189 patients (48 %), bicycle stress echocardiography - in 179 patients (46 %). Initially we determined the prevalence of angiographically significant CAD according to the gender and chest pain character, and identified persons in whom stress testing was appropriate. After that diagnostic accuracy of both tests was evaluated in patients with atypical angina and non-anginal chest pain.
Results. Among 72 patients with atypical angina and non-anginal pain who underwent ETT and had unequivocal results, 38 (53 %) had obstructive CAD. ETT for detection of obstructive CAD had sensitivity 79 %, specificity 82 %, positive likelihood ratio (LR+) 4.4, and negative likelihood ratio (LR-) 0.3. Positive result increased probability of obstructive CAD from 53 % to 83 %, negative result reduced probability of obstructive CAD to 25 %. Among 111 patients with atypical angina and non-anginal pain who underwent stress echocardiography and had unequivocal results, 69 (62 %) had obstructive CAD. Sensitivity, specificity, LR+, and LR- of stress echocardiography were equal to 89 %, 95 %, 17.8, and 0.1, respectively. Positive result increased probability of obstructive CAD from 62 % to 95 %, negative result reduced probability of obstructive CAD to 16 %.
Conclusion: bicycle stress echocardiography was found to be more accurate than ETT to rule in or rule out obstructive CAD in patients aged ≥ 70 years with atypical angina and non-anginal pain.
ARTERIAL HYPERTENSION
Finding the best options for combined antihypertensive therapy is one of the main tasks to be solved for achieving target blood pressure (BP) and, accordingly, reduction of the risk of complications in patients with arterial hypertension (AH).
Purpose of this study was to evaluate the effectiveness of the perindopril arginine/amlodipine fixed combination in patients with 1-2 degree hypertension not achieving BP control on previous therapy with sartan-containing free combinations.
Materials and methods. In the multicenter open uncontrolled observational program AVANGARD 203 doctors in 53 cities of the Russian Federation included 658 patients who had not achieved target BP on therapy with two drugs, one of which was sartan (sartan with diuretic, calcium antagonist, β-blocker, or moxonidine in 49%, 33%, 17%, and 1% of cases, respectively). This therapy was replaced with a fixed combination of perindopril arginine/amlodipine. Duration of observation was 3 months.
Results. On therapy with perindopril arginine/amlodipine, BP decreased 159.9±8.5/92.1±7.4 to 125.8±7.1/77.4±5.5 mm Hg. Target BP <140/90 mm Hg was achieved in 93.5% of patients (office measurement); target BP <135/85 mm Hg - in 83.5% of patients (home measurement). Mean 24-hour BP variability decreased from 4.4±2.9/3.0±2.0 to 3.0±2.2/2.2±1.7 mm Hg (p<0.01). Number of patients complaining of headache decreased by 2.9 times, dizziness - by 2.8 times, fatigue - by 2.3 times, irritability - by 3.0 times, sleep disturbances - by 2.3 times, dyspnea - by 3.8 times, palpitations - by 2.7 times, angina pectoris attacks - by 4.6 times. Dose of perindopril arginine/amlodipine was 10/5 mg in 36.6%, and 10/10 mg in 28.3% of cases, respectively. Number ofparticipants who dropped out ofthe study prematurely was 11 (1.6%) (1 because of adverse event). Adverse events were observed in 4 more patients (2 [0.14%] - edema of lower extremities, and 2 [0.14%] -cough), but they did not require the withdrawal of therapy.
Conclusion. In case of ineffective combination therapy containing sartans, transfer of patients to a fixed combination of perindopril and amlodipine should be considered.
ATHEROSCLEROSIS
Purpose: to study relationship of lipoprotein(a) [Lp(a)], indicators of systemic inflammation and humoral immunity with severity of atherosclerotic involvement of various vascular beds in women.
Materials and methods. We included in this study 148 women aged 69±11 years with results of instrumental investigation of coronary, carotid arteries, and arteries of lower extremities. According to results of coronary angiography and ultrasound study patients were distributed into two groups: with stenosing atherosclerosis (those with hemodynamically significant [>50%] atherosclerotic lesions in any of these vascular beds, n=108), and control (those without hemodynamically significant stenoses, n=40). In dependence of extent of atherosclerotic involvement patients with stenosing atherosclerosis were divided into subgroups: with lesions in one vascular bed (subgroup 1, n=44) and with lesions in two and more vascular beds (subgroup 2, n=64). All patients with stenosing atherosclerosis and 78% of control patients took statins. In all patients we measured lipid spectrum, Lp(a) concentration, C-reactive protein (CRP). Preparations of oxidized lipoproteins [oxLp(a)] were obtained by Cu2+-induced free radical oxidation at 37 °С for 3 hours. Titer of autoantibodies to Lp(a), LDL and their oxidized modifications was determined by enzyme-linked immunosorbent assay (ELISA). Concentration of low-density lipoprotein cholesterol corrected on cholesterol in Lp(a) (LDLCh corr) was calculated by Dahlen modification of Friedewald formula.
Results. Stenosing atherosclerosis was diagnosed in 60 of 74 women (80%) with Lp(a) concentration above median - 33 mg/dl (in 38 multifical). Increase of blood serum Lp(a) concentration was associated with presence of isolated as well as multifocal atherosclerosis according to unifactorial, multifactorial, and logistic analysis, irrespective of other factors of risk and indicators of inflammation. According to results of logistic regression analysis increase of Lp(a) concentration by 1 mg/dl was associated with 1 % elevation of probability of appearance and development of multifocal atherosclerosis in women. Low level of class IgM autoantibodies to Lp(a) was linked with detection of stenosing atherosclerosis in any of 3 vascular beds (1st vs. 4th quartile of IgM autoantibodies concentration - OR 7.6., 95%CI 1.9-29.4; р=0.004) and had diagnostic significance. Indicators of systemic inflammation such as CRP and circulating immune complexes were high and had diagnostic significance for detection of multifocal atherosclerosis in studied women. However none of indicators was predictor of appearance of stenosing atherosclerosis according to data of logistic regression analysis.
Conclusion. Elevated concentration of Lp(a) is an independent predictor of risk of development stenosing atherosclerosis in various vascular beds and appearance of multifocal irrespective of other risk factors, indicators of systemic inflammation, and factors of humoral immunity in women. Markers of inflammation, as well as IgM autoantibodies against Lp(a) have diagnostic value for detection of patients stenosing lesions ib one or several vascular beds.
MISCELLANEOUS
Purpose: to perform comparative morphological analysis of causes of dysfunction of epoxy-treated, xenoaortic and xenopericardial, tissues heart valves.
Materials and methods. We included in this study 475 patients with mitral valve disease who have undergone heart valve replacement with tissue valve: (“KemCor”, n=211 [group 1]; “PeriCor”, n=126 [group 2]; and “UniLine”, n=138 [group 3]). Degenerative changes in 26 tissue valves (n=9 “KemCor”, n=11 “PeriCor”, and n=6 “UniLine”) explanted from the mitral position during the repeat replacement were evaluated macroscopically for the presence of calcifications, perforations, leaflet tears and ruptures, pannus, and leaflet fusion to the stent frame. Analysis of survival, freedom from dysfunction and reoperation of the studied tissue heart valves was performed for the period from January 1, 1995 to March 01, 2017.
Results: Pannus overgrowth on the stent struts with extension onto the leaflets was seen on 53.8% of explanted tissue valves. “KemCor” and “PeriCor” tissue valves demonstrated over 70% rate of adhesion formation at the commissure, and in 93% of these cases there were leaflet ruptures at the commissure. Signs of calcification of different grades had 57.6% of specimens. Over 50% of “PeriCor” and “UniLine” tissue valve specimens had calcification at the stent frame. Calcified pannus was noted in 35% of all studied tissue heart valves. Interestingly, dysfunction in 53.3% of the studied tissue heart valves with detected calcification was not associated with calcific deposits. The 6-year actuarial survival for groups I, II and III was 73.5, 66.1 and 87.6%, respectively (group I vs. group II, p=0.6; group II vs. group III - p<0.05; group I vs. group III - p<0.05). The actuarial freedom from reoperation was 81.9%, 75.0% and 94.2%, respectively (pI-II>0.05; pII-III<0.05; pI-III<0.05). The actuarial freedom from dysfunction was 79.6%, 75.0%, and 94.2%, respectively (pI-II>0.05; pII-III<0.05; pI-III<0.05).
Conclusion. The structure of dysfunctions of the studied tissue heart valves was represented by primary tissue failure, calcification and pannus growth. Specific design of the “UniLine” valve allowed to prevent the formation of adhesions between leaflets and the frame in the commissure buttress area, and as a result leaflet rupture from the stent struts. Xenopericardial “UniLine” tissue valves turned out to be superior to xenoaortic “KemCor” and “PeriCor” tissue valves in terms of survival, freedom from reoperations and dysfunction within the 6-year follow-up.
REVIEWS
Ischemic heart disease (IHD) and chronic heart failure (CHF) belong to leading causes of death among patients with cardiovascular diseases (CVD). Modern medical approaches to the treatment of patients with CHF do not always provide a significant improvement in the quality of life, a decrease in the frequency of CHF exacerbations and hospitalizations, and an improvement of the long-term prognosis. According to the neurohumoral theory of IHD and CHF development, the blockade of the sympathoadrenal system with β-adrenoblockers (β-AB) is pathogenetically substantiated, and preparations of this group are recommended as one of the main classes of drugs for the treatment of patients with CHF. However, selection of heart rhythm slowing therapy in patients with CHF of ischemic genesis is often difficult due to the development of undesirable side effects of β-AB, intolerance and/or due to the presence of contraindications for their use. Randomized studies have shown that prescribing a combination of β-AB and If-channel blocker ivabradine for heart rate (HR) reduction or solely ivabradine when use of β-AB is impossible in complex CHF therapy, improves the left ventricle (LV) diastolic function, reducing mortality from CHF decompensation. However, the prognostic significance of the use of ivabradine in patients with CHF with preserved left ventricular ejection fraction of ischemic genesis with heart rate higher than 70 beats/min receiving maximum tolerated doses of β-AB remains not fully investigated.
CLINICAL SEMINARS
Atrial fibrillation (AF) and cognitive dysfunction - common states with similar risk factors. Recently significant scientific epidemiological data has been received in favor of independence of effect of AF on possibility of development of cognitive dysfunction. In this review we present problems of prevalence, pathogenesis, and diagnostics of various variants of cognitive disorders at the background of AF, as well as methods of their prevention and tactics of anticoagulant therapy in the presence of cognitive disturbances.
Coronary artery disease is the most clinically significant manifestation of atherosclerosis and the main cause of morbidity and mortality around the world. Atherogenesis is a complex process, involving various types of cells and regulatory molecules. MicroRNA molecules were discovered at the end of the 20th century, and nowadays are the important regulators of several pathophysiological processes of atherogenesis. The review examines data on the participation of various microRNAs in the development of atherosclerosis and its main clinical manifestations and discusses the possibility of using microRNAs as diagnostic markers for these diseases.
In 2017 the Endocrine Society issued the Scientific Statement “Screening for Endocrine Hypertension" This document was developed by experts from different medical institutions of USA, Europe and Australia. Herein we present the main provisions of this Statement in the form of brief algorithm for the clinicians’ actions for timely detection of secondary endocrine hypertension and rational referral of the patient for confirmational testing.
The full text of the Scientific Statement in English is contained in the article. Young WF Jr., Calhoun DA, Lenders JW, Stowasser M, Textor SC. Screening for Endocrine Hypertension: An Endocrine Society Scientific Statement. Endocrine Reviews. 2017; 38 (2):103-122.
URL: https://academic.oup.com/edrv/article/38/2/103/3104343
ISSN 2412-5660 (Online)