CLINICAL MEDICINE NEWS
ORIGINAL ARTICLES
Aim. To identify associations of polyphenols consumption in general, as well as their classes with the risk of dyslipidemia in the population of Novosibirsk aged 45-69.
Material and methods. In 2003-2005, in the frames of the HAPIEE international project “Determinants of cardiovascular diseases in Eastern Europe: a multicenter cohort study” the population sample aged 45-69 (9360 people, 4266 men and 5094 women, average age - 57.6 years) was examined in Novosibirsk. For the analysis of nutrition, a Food Frequency Questionnaire (FFQ) was used (141 product names). The content of polyphenolic compounds and their classes was evaluated using the European database Phenol-Explorer 3.6. The eating habits of the population and typically consumed foods were taken into account. The determination of total cholesterol and HDL cholesterol levels were carried out by enzymatic method. Hypercholesterolemia was diagnosed with cholesterol level greater than 5.0 mmol/l (190 mg/dL). Levels of HDL cholesterol <1.0 mmol/l in men and <1.2 mmol/l in women were considered as high-density lipoprotein hypocholesterolemia (hypoHDL-C). The concentration of low-density lipoprotein cholesterol was calculated with the Friedewald formula (1972). HyperLDL-C was diagnosed if level of LDL cholesterol was <3.0 mmol / l.
Results. The chance of developing of hypercholesterolemia in the quartile with the highest consumption of “other polyphenols” was 20% less (OR 1.2 confidence interval (CI 1.01-0.14), p = 0.033), phenolic acids by 20% (OR 1.2 (CI 1.01-1.42), p = 0.04) and stilbenes by 37% (OR 1.37 (CI 1.15-1.64), p = 0.001) less than in the quartile of low consumption. The risk of developing hypoHDL-C was lower in the quartile of high polyphenols consumption in general by 18% (OR 1.18 (CI 1.002-1.4), p = 0.051), phenolic acids by 32% (OR 1.32 (CI 1.11-1.57), p = 0.001) and the groups of “other polyphenols” by 20% (OR 1.2 (CI 1.01-1.41), p = 0.04). The chance of hyperLDL-C in the high quartile of consumption of “other polyphenols” decreased by 16% (OR 1.16 (CI 1.002-1.355), p = 0.049) and lignans - by 33% (OR 1.33 (CI 1.14-1, 56), p <0.001) compared with low consumption.
Conclusion. Thus, the consumption of polyphenols in general and in classes (phenolic acids, stilbenes, and “other polyphenols”) decreased the risk of dyslipidemia in Siberian population.
Aim. To study the effectiveness of 1-year exercise training (ET) after acute myocardial infarction (AMI) during outpatient cardiac rehabilitation in patients with different body mass index (BMI).
Material and methods. The study included 312 patients after AMI, who were randomized into four groups depending on BMI: patients who used ET program with BMI <30 kg/m2 (group 1 (n=78)) and BMI >30 kg/m2 (group 2 (n=78)); patients who did not use ET program with BMI <30 kg/m2 (group 3 (n=78)) and BMI >30 kg/m2 (group 4 (n=78)). ET of moderate intensity (60% of the threshold value) was carried out 3 times a week for a year.
Results. In patients with obesity, ET was associated with decrease of blood pressure by 3,3/3,6% (p<0,01 for each) and BMI by 7,7% (p<0,001), while there was an increase by 4,2/3,6% (p<0,05 for each) and 2,1% (p<0,05), respectively, in obese patients without ET. In patients without obesity, ET was associated only with BMI decrease by 3,3% (p<0,01), while in patients without obesity and ET it did not change. Daily physical activity after ET increased regardless of BMI, and without ET it decreased in obese patients. ET was associated with the increase of duration and intensity of training in non-obese patients by 39,2% (p<0,001) and 47,1% (p<0,001), respectively; in obese patients — by 23,8% (p<0,001) and 26,5% (p <0,001), respectively. In control groups it has not changed. After ET with any BMI, the levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) decreased, and the high-density lipoprotein-cholesterol (HDL-C) increased. In the control groups, the concentration of TG increased, and with obesity there was also an increase in LDL-C and a decrease in HDL-C. Against the background of ET, the fibrinogen values decreased with any BMI, in contrast to the control groups. After 1-year ET number of cardiovascular events (CVE) significantly decreased in nonobese patients by 37,5% (p<0,05) and in obese ones by 28,6% (p<0,05).
Conclusion. Long-term aerobic ET in patients with any BMI reduced cardiovascular risk factors and the risk of CVE. At the same time, with concomitant obesity, the maximum effect of cardiac rehabilitation was not achieved, which confirms the importance of controlling BMI in patients after AMI.
METHODS OF STUDY
Aim. To analyze the association of parameters characterizing the degree of arterial stiffness and echocardiographic criteria for cardiac remodeling in patients with abdominal obesity.
Material and methods. The study included 194 patients (men aged 46 to 55 years (49,0±2,3 years)), without hypertension (24-hour average blood pressure (BP) 117,5±5,5/73,0±4,1 mmHg), diabetes and cardiovascular diseases, with abdominal obesity (waist circumference >94 cm, body mass index 31,3±3,5 kg/m2). Lipids and glucose concentrations were evaluated, and glomerular filtration rate was estimated using the CKD-EPI equation. We conducted 24-hour monitoring of blood pressure and arterial stiffness parameters (aortic pulse wave velocity (PWV), augmentation index (AIx) and systolic BP in the aorta), and echocardiography.
Results. Left ventricular (LV) hypertrophy was detected in 14 (7,2%) patients, LV diastolic dysfunction — in 36 (18,6%) patients. The correlation of the average aortic PWV and the AIx with the LV mass index and the left atrial volume was shown. Patients with a high aortic PWV exceeding the 75th percentile of distribution (8,2 m/s) were characterized by a higher incidence of hypertrophy (18,8% vs 4,9%,
p<0,01) and LV diastolic dysfunction (50,0% vs 12,3%, p<0,001). Patients with/with-out LV hypertrophy and diastolic dysfunction were characterized by higher values of average 24-hour aortic PWV, AIx and systolic BP in the aorta. According to the regression analysis, the predictors of LV diastolic dysfunction were age, waist circumference, aortic PWV, and AIx.
Conclusion. The relationship of parameters characterizing the degree of arterial stiffness, primarily, aortic PWV and echocardiographic parameters of the structural and functional cardiac remodeling in obese patients was revealed. Patients with a high aortic PWV (>8,2 m/s for men aged 46-55 years) are characterized by a higher prevalence of LV hypertrophy and diastolic dysfunction, as well as left atrial dilatation. This association is probably a reflection of one of the many pathogenesis links of HF and supraventricular cardiac arrhythmias in obese patients.
Aim. To assess the prospects of using quantitative contrast-enhanced ultrasound perfusion imaging of atherosclerotic carotid sinus plaques.
Material and methods. The study included 5 men and 1 woman (59-76 years old, median 72) with symptomatic coronary sinus atherosclerosis. The inclusion criterion was history of ischemic stroke due to internal carotid artery lesion (NASCET >60%). We performed contrast-enhanced ultrasound perfusion imaging of the carotid arteries, endarterectomy, studying pathomorphology of the removed plaque with the calculation of the neovascular density and the total number of neovessels with a diameter <40 μm. Neovascularization was assessed by quantitative contrast-enhanced ultrasound 20 seconds after the 1 ml infusion of Sonovia (Bracco, Italy) and subsequent application of the flash. The analysis of dynamics of ultrasonic signal intensity in the atherosclerotic plaque was carried out by creating the curves of the ultrasonic signal intensity (dB)/time (s) over 3 segments of the cross section of the internal carotid artery long axis. The automatic calculation of the intensity dynamics took into account the parameter values in the studied areas within 20 s after the flash. The calculated coefficients (A, B, β) of the exponential equation for 3 atherosclerotic segments were recorded.
Results. Perfusion and neovascularization were assessed in 27 segments of atherosclerotic plaques. The correlation relationships between the ultrasonic parameters of plaque perfusion and the severity of neovascularization were assessed according to the histological data. Significant correlations of the exponential curve coefficient β and histological parameters characterizing the prevalence of “young” vessels (<40 microns) in the atherosclerotic plaque were revealed. Spearman’s R for the density of neovessels was 0,54; for the number of neovessels with a diameter <40 μm. —0,66 (p<0,01).
Conclusion. Diagnosis of atherosclerotic plaque neovascularization becomes possible to quantify, assessing not only the presence of neovascular vessels, but also the perfusion intensity. The novel approach replaces the qualitative and semi-quantitative method for calculating the number of carotid plaques neovessels in vivo.
Aim. To study the parameters of beta-adrenergic reactivity of membrane (p-ARM) of erythrocytes in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and single-vessel CAD.
Material and methods. The study included 40 patients with MI (experimental group — 19 patients; control group — 21 patients). Three patients (15,7%) with diagnosed acute myocarditis were excluded from the analysis. Levels of β -ARM were determined upon admission, on the 2nd, 4th and 7th day after MI. The normal range of β -ARM were <20 CU.
Results. In a significant proportion of patients, p-ARM values were two times higher than normal values. The median β -ARM in the experimental group at admission was 41,7 (29,0;61,5) CU, on the day 1 — 48,6 (38,5;57,3) CU, day 4 — 49,4 (39,0;63,3) CU, day 7 — 53,5 (35,2;67,7) CU. In the control group, the median p-ARM at admission was 52,5 (25,4;64,5) CU, day 1 — 51,6 (28,3;56,9) CU, day 4 — 48,5 (34,9;61,2) CU, day 7 — 45,1 (32,2;68,9) CU. Static analysis of p-ARM at all followup periods did not show differences between the groups by median level (p>0,05). The curves of β -ARM median changes show its multidirectional dynamics in the studied groups. During the hospitalization, in the group of patients with MINOCA there was a downward trend in β -ARM. In the control group, there was a tendency to increase of β -ARM. A statistically significant correlation of β -ARM with the ejection fraction (r=0,83, p=0,0007) and a moderate correlation between the p-ARM level on the 4th day and GRACE risk (r=0,55, p=0,03) in patients of the control group were revealed.
Conclusion. β-ARM values in patients with MINOCA were doubled, and this increase was comparable to levels in patients with obstructive CAD. During the hospitalization, the β -ARM levels did not significantly change, despite the use of beta-blockers.
GUIDELINES FOR THE PRACTITIONER
Aim. To assess the effect of dual antiplatelet therapy (DAPT) including acetylsali-cylic acid and P2Y12 receptor blockers ticagrelor and clopidogrel in patients with acute coronary syndrome (ACS) with interventional and conservative management on the targets of the national cardiovascular program: 1) cardiovascular mortality, 2) myocardial infarction mortality.
Material and methods. The patients were divided into two cohorts: with the invasive or conservative management used. Patients after ACS followed by percutaneous coronary intervention (PCI) were included in the invasive management cohort, while patients without PCI constituted the conservative management cohort. To determine the effect of DAPT with ticagrelor and clopidogrel on mortality and th ncidence of cardiovascular events in the above cohorts, two sub-analyzes of PLATO study were used: in a subgroup of invasive management patients and in a subgroup of conservative management patients. Based on mortality rates, depending on the management strategy, the number of deaths that can be prevented by using ticagre-lor instead of clopidogrel was calculated. Then we calculated the proportion of national cardiovascular program targets that could be achieved in 2020 by using DAPT with ticagrelor instead of clopidogrel.
Results. The 1-year use of DAPT with ticagrelor for the management of ACS in accordance with clinical guidelines will allow (compared with clopidogrel):
• to prevent an additional 7199 cardiovascular deaths per year, which will ensure achievement of 25% target for reducing mortality from CVD in Russian Federation in 2020;
• to prevent an additional 1278 deaths from recurrent myocardial infarction, which will ensure achievement of 63% target for reducing mortality from myocardial infarction in the Russian Federation in 2020.
Aim. To compare the effects of 3-month therapy with a fixed-dose combination of an angiotensin-converting enzyme inhibitor (perindopril) and a thiazide-like diuretic (indapamide) in genetically heterogeneous subgroups of patients with hypertension (HTN) for assessing the prospects of using genetic testing for choosing the antihypertensive treatment regimen.
Material and methods. Forty-one patients with grade 1-2 HTN with insufficient effectiveness of previous antihypertensive therapy and 20 healthy individuals were examined to compare the prevalence of gene polymorphism in the Rostov Oblast. Patients with HTN underwent standard diagnostic tests, as well as a molecular genetic test to determine the most clinically significant polymorphic genes involved in the pathogenesis of HTN.
Results. A relationship was found between the clinical and morphofunctional characteristics of HTN in patients with polymorphisms of AGT, AGTR2, CYP11B2, GNB3, and NOS3 -786 genes, of which 3 polymorphic genes (AGT, AGTR2, CYP11B2) encode the activity of the angiotensin-converting enzyme. The effectiveness of using a combination of renin-angiotensin-aldosterone system inhibitor agent with a thiazide-like diuretic as an initial antihypertensive therapy was evaluated.
An analysis showed that fixed-dose combination of perindopril (10,0) and indapamide (2,5) (Noliprel A Bi-forte) in genetically heterogeneous subgroups of HTN patients displays a more pronounced antihypertensive and organ-protective effects in individuals with the mutant allele 704C of AGT T704C polymorphism. A significant decrease in blood pressure was demonstrated according to standard 24-hour monitoring (p<0,05). A significant decrease in the left ventricular mass index (p=0,0001), as well as a significant increase in the ratio of peak mitral flow velocity in early and late diastole (VE/VA) (p=0,0024) were showed. There was a positive effect of therapy on arterial stiffness parameters: a decrease of the pulse wave velocity (p=0,0035), vascular age (p=0,00002) and reflection index (Ri) (p=0,000001), compared with noncarriers of mutant allele 704C of AGT gene.
Conclusion. The results obtained indicate the promise of using genetic approaches to develop a personalized drug treatment strategy for HTN patients in order to increase its effectiveness.
Aim. To study the characteristics of direct oral anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease (COPD) and atrial fibrillation. To show the efficacy of idarucizumab in complex therapy of severe gastrointestinal bleeding caused by dabigatran.
Material and methods. The single-center prospective observational study included 150 patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants. Of these patients, 75 had heart failure in combination with COPD (experimental group) and 75 — HF without comorbidities (comparison group). Groups were formed by propensity score matching. Sex, age, bleeding risk by HAS-BLED score were covariates. HF was diagnosed in accordance with the criteria applied by Russian Federal clinical guidelines. COPD was diagnosed according to GOLD 2011-2020 criteria. Frequency of all bleeding, major bleeding, bleeding into critical organs were evaluated. Follow-up period was 14 (12; 16) months. Cox regression method was used to determine relationships.
Results. Annual rate of major bleeding in group of HF and COPD was higher (Hazard ratio (HR) 3,0, 95% confidence interval (CI) 1,1-6,2, р=0,02), regardless of which anticoagulant was used. Gastrointestinal bleeding occurs in 7 (9,3%) and 2 (2,7%) patients (HR 3,5, 95% CI 1,1-7,3, р=0,05). In subjects with comorbidity, major and gastrointestinal bleeding were associated with partial pressure of arterial oxygen (HR 0,89, 95% CI 0,55-0,95 and HR 0,88, 95% CI 0,50-0,98 respectively), serum NT-pro-BNP (HR 1,10, 95% CI 1,05-2,14 and HR 1,14, 95% CI 0,07-4,28, respectively) and chemokine ligand 18 (HR 1,15, 95% CI 1,11-5,75 and HR 1,13, 95% CI 1,09-4,50). A case of successful use of idarucizumab for reversal of dabigatran anticoagulant effect in the patient with severe bleeding from esophageal erosion, nonvalvular AF, HF and COPD was reported. Coagulation was restored within 4 hours, which allowed to stop bleeding conservatively and antishock measures were effective.
Conclusion. Anticoagulation therapy in patients with AF and comorbidity of HF and COPD is associated with additional risk of major bleeding, especially gastrointestinal. Possibility to reverse the anticoagulant effect is an important argument when choosing an anticoagulant for these patients.
OPINION ON THE ISSUE
Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.
CLINICAL AND INVESTIGATIVE MEDICINE
Aim. Catheter ablation (CA) is an effective approach for rhythm control in atrial fibrillation (AF), however antiarrhythmic therapy (AAT) remains important. There is a lack of data about long-term AAT use after CA. This study evaluates AAT after CA for AF.
Material and methods. In 2012-2016, EURObservational Research Programme of Atrial Fibrillation Ablation Long-Term (EORP AFA L-T) registry was conducted, which included 476 Russian patients (57,1% — men; mean age — 57,1±8,7 years). The follow-up after CA was 12 months (available in 81,9% of patients). The use of AAT was evaluated prior to hospitalization, during hospitalization for CA, as well as at 3, 6 and 12 months of follow-up.
Results. Prior to CA, 439 (92,2%) patients received AAT During CA, 459 (96,4%) patients were treated with AAT. After CA, AAT was used by 463 (97,3%), 370 (94,8%), and 307 (78,7%) patients at 3, 6 and 12 months of follow-up, respectively. There was no arrhythmia recurrence in 187 (47,9%) subjects. Among these patients, 40 (21,4%) received class IC or III AAT. The peak of AAT use was found for class IC agents within 3 months after CA (P<0,05), while for other drugs this trend was not observed. There were no factors associated with AAT usage in patients without arrhythmia recurrence after CA. A positive correlation of arrhythmia non-recurrence with a minimum number of previously used antiarrhythmic agents was revealed (RR=0,85; 95% CI 0,73-0,98; P=0,03).
Conclusion. The frequency of AAT use after AF ablation is significantly reduced. However, there is a cohort of patients without documented arrhythmia recurrence still receiving AAT, which requires special attention of physicians. There were no clinical predictors of continued AAT in subjects without arrhythmia recurrence.
CLINICAL CASES
History of heart transplantation in combination with immunosuppressive therapy and acute viral respiratory infection overlay makes the patient difficult to manage. In case of COVID-19, the setting is complicated by unknown pathogenesis, including its effect on blood, coagulation system, and lung tissue. Current case report discusses the 60-year-old patient with a COVID-19 infection occurred in the immediate postoperative period after heart transplantation.
Right atrial myxoma is one of the rare diseases in cardiology practice. It is accompanied by an unclear clinical picture, and in most cases is asymptomatic and is an incidental finding. The article is devoted to the clinical observation of primary cardiac tumor and the difficulties of its differential diagnosis.
Patient T, 58 years old, was hospitalized in a respiratory medicine center with complaints of cough with viscous sputum, weakness, fatigue, loss of appetite, shortness of breath on exertion, weight loss and sweating at night. The preliminary diagnosis was an exacerbation of chronic bronchitis. Then a space-occupying mass in the right atrium was revealed. Computed tomography imaging identified a bilateral pulmonary embolism. In the cardiac surgery department, surgical removal of the right atrial myxoma was performed.
The diagnosis of right atrial myxoma was established by echocardiography, confirmed macroscopically during surgery, and then by histological verification.
REVIEW
The review presents an analysis of publications on use of machine learning (ML) to assess the pretest probability of obstructive and non-obstructive coronary artery disease (CAD). Data on the high prevalence of non-obstructive CAD among patients referred for coronary angiography are presented, which served as a reason for the development of ML-based models for pretest assessment of coronary anatomy. The use of modern modeling technologies has great potential in verification of obstructive and non-obstructive CAD. It is emphasized that the improvement of prognostic models and their practical implementation is an important element of medical decision making and should be carried out with interdisciplinary cooperation of clinicians and information technology specialists.
Formation of atherosclerotic plaque in the coronary arteries is complex and multifactorial process, depending not only on conventional risk factors for cardiovascular diseases, but also on the features of local hemodynamics. Atherosclerotic plaques often form in the bifurcation area, where blood flow is uneven. In these settings, parietal shear stress becomes a key factor in the development, spread and progression of atherosclerotic plaque. In addition, a number of factors, such as the individual geometry of bifurcation, coronary stenting, and implantation technique can significantly affect the shear stress values, thus, affect the pathophysiology of coronary atherosclerosis.
EXPERT CONSENSUS
Relationships and Activities. The Council of Experts was supported by AstraZeneca.
CLINICAL GUIDELINES
The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)
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