Unresolved issues of increasing physical activity after myocardial infarction

The review presents the results of studies on the problems of increasing the efficiency of rational  physical  activity  within the concept of comprehensive secondary  prevention of myocardial  infarction. The aspects of insufficient adherence of specialists and patients to rehabilitation methods were discussed; possible safe exercise modes after infarction and available monitoring methods were given. We also described the potential characteristics of physical training, taking into account the initial clinical severity  and completeness of revascularization after myocardial infarction. In addition, the need for socio-economic,  as well as informational support of the state and healthcare system has been updated

Intensification of lipid-lowering therapy in very high-risk patients: potential of combination with PCSK9 inhibitors

Aim. To assess the efficacy and safety of 6-month combined lipid-lowering therapy with a PCSK9 inhibitor in patients with very high cardiovascular risk (CVR).Material and methods. This prospective, open-label, single-center exploratory research study with active treatment included 5 outpatients with very high CVR. So, 80% of patients had prior coronary artery disease, 20% peripheral arterial disease, and 60% old myocardial infarction. The key inclusion criterion was the failure to achieve the target low-density lipoprotein cholesterol (LDL-C) <1,4 mmol/l with high-intensity statin monotherapy at the maximal tolerated doses or combination therapy with ezetimibe. On a regular basis, all included patients took atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day, or pitavastatin 2-4 mg/day. In addition, 2 patients received a statin in combination with ezetimibe 10 mg/day. Patients were followed up for 6 months as follows: every 2 weeks, with a lipid profile monitoring, subcutaneous injections of alirocumab at a dose of 150 mg/ml were performed. Additionally, clinical and laboratory indicators of the safety of therapy were evaluated.Results. After 6 months, with the combined lipid-lowering therapy with alirocumab, a decrease in median LDL-C from 4,3 (4,11-4,67) to 1,27 (1,06-1,47) (p=0,001) mmol/l, total cholesterol from 6,1 (6-7) to 3,7 (3,5-3,9) (p=0,018) mmol/l, atherogenic index from 3,2 (3-3,26) to 0,8% (0,8-1,5) (p=0,001). There was no significant decrease in median triglycerides and an increase in median high-density lipoprotein cholesterol. Six-month lipid-lowering therapy with a PCSK9 inhibitor had no adverse events and made it possible to achieve a maximum decrease in LDL-C by an average of 75,4% already by 4 months of treatment in actual clinical practice.Conclusion. Six-month combined lipid-lowering therapy with alirocumab 150 mg subcutaneously every 2 weeks in very high-risk patients allows the majority of patients to achieve target LDL-C values

Polymorphism of inflammatory system genes in the pathogenesis of rheumatic heart disease

Aim. To assess the contribution of polymorphic variants of inflammatory response genes to the predisposition to rheumatic heart disease.Material and methods. Using real-time polymerase chain reaction, we analyzed the prevalence of 18 polymorphic variants of 8 genes involved in the inflammatory process in 251 patients with rheumatic heart disease and 300 healthy donors.Results. We found that homozygous TT genotypes of rs1800871 (IL10) (p=0,02) and TT rs1800872 (IL10) polymorphisms (p=0,027), as well as TT genotypes of CRP gene (rs1205) (p=0,015) and GG genotypes of rs375947 (IL12RB) (p=0,037) are "risky" and associated with the development of rheumatic heart disease.Conclusion. Associations of polymorphic variants rs1800871 and rs1800872 of the IL10 gene, rs1205 of the CRP gene, and rs375947 of the IL12RB gene can be an important link in the pathogenesis of rheumatic heart disease and can later be used as biological markers for a personalized assessment of the disease risk

Quantification of the initial levels of calciprotein particles as a screening marker of mineral homeostasis in patients with cardiovascular disease and in patients with chronic kidney disease

Aim. To evaluate the initial concentration of calciprotein particles (CPPs), which are scavengers of excessive calcium and phosphate, in patients with cardiovascular disease and in patients with chronic kidney disease as compared with the healthy volunteers.Material and methods. The study included 308 individuals as follows: 1) 88 participants of the PURE study without hemodynamically relevant carotid athero scle rosis and symptomatic coronary atherosclerosis; 2) 88 patients with cere brovascular disease (CVD) who required carotid endarterectomy; 3) 88 pa tients with coronary artery disease (CAD) who required percutaneous coronary intervention or coronary artery bypass graft surgery; 4) 63 patients with stage 5 chronic kidney disease (CKD). We measured following mineral homeostasis parameters: total and ionized calcium, phosphate, total protein, albumin, and fetuin-A. Then, we determined a baseline serum CPP concentration by flow cytometry using a fluorescent-labeled bisphosphonate OsteoSense 680EX. Results. In comparison with other patients, healthy volunteers had the highest serum CPP concentration (249 CPPs/µL), indicating the retained ability to compensate mineral homeostasis disturbances by aggregation of excessive calcium and pho sphate with acidic proteins (mineral chaperones). Reduced serum CPP concentration in patients with CVD (170 CPPs/µL), CAD (139 CPPs/µL), and stage 5 CKD (193-203 CPPs/µL) showed impaired aggregation of excessive serum calcium and phosphate, which was also reflected by an increased level of blood ionized calcium.Conclusion. Patients with CVD, CAD, and stage 5 CKD have lower serum CPP concentration than healthy individuals. In combination with elevated ionized calcium and reduced albumin, this suggests the depletion of calcium binding buffers in the serum of patients with cardiovascular and renal diseases

PCSK9 inhibitors for in-hospital treatment of patients with acute coronary syndrome and severe lipid metabolism disorders

Aim. To assess the efficacy and safety of PCSK9 inhibitor alirocumab as part of a combination lipid-lowering therapy in patients with acute coronary syndrome (ACS).Material and methods. This prospective, open-label, single-center activetreatment study included 13 patients hospitalized due to ACS. The main inclusion criterion was nonachievement of target low-density lipoprotein cholesterol (LDL-C) values (<1,4 mmol/L) with high-intensity statin therapy prior to ACS. During the first 30 days after ACS, all patients received therapy with atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day in combination with alirocumab 150 mg/ml (Praluent) administered by subcutaneous injection. Lipid and biochemical profiles were monitored. The first injection of the PCSK9 inhibitor was performed on days 3-5 of hospitalization, the second — after 2 weeks.Results. On admission, the median LDL-C was 4,3 [3,5;5,3] mmol/L. A day after administration, there was a decrease in LDL-C by 41,9% (median 2,5 [1,8;3,2] mmol/L; p=0,001) without a negative effect on high-density lipoproteins (HDL-C) (median 1,2 [0,8;1,4] mmol/L; p=0,270). Before the next injection, LDL-C decreased by another 8% (median 2,3 [1,1;4,1] mmol/L). A day after the second injection, a decrease in LDL-C from the baseline values was 69,8% (median 1,3 [0,7;1,5] mmol/L; p=0,010). Strengthening lipid-lowering therapy with a PCSK9 inhibitor within 30 days after ACS did not lead to clinical and biochemical deterioration.Conclusion. The use of subcutaneous 150-mg injections of alirocumab 2 times a week 30 days after ACS in patients who did not reach target LDL-C values with statin therapy, leads to a 69% decrease in LDL-C from baseline values and is safe

EVALUATION OF THE CALCIUM-PHOSPHOR HOMEOSTASIS AND PROINFLAMMATORY STATUS OF RECIPIENTS WITH CALCIUM DEGENERATION OF CARDIAC VALVES PROSTHESES

Aim. To study calcium-phosphor homeostasis and proinflammatory status of the cardiac valves bioprostheses (BP) recipients related to their interference with calcium degeneration of biomaterials.Material and methods. A retrospective assessment was performed of the calcium-phosphor metabolism and markers of non-specific inflammatory response in recipients of BP in mitral position: with histologically confirmed calcification — group I (n=22) and with normal morphology and prosthesis function — group II (n=48).Results. In patients with BP degeneration, comparing to the recipients of biological prostheses with normal function at the background of moderate hypovitaminosis D (34,0 [21,0; 49,4] versus 40 [27,2; 54,0] pmol/L, р>0,05), osteoprotegerine deficiency (82,5 [44,2; 115,4] versus 113,5 [65,7; 191,3] pg/ml, р>0,05) and osteopontine (4,5 [3,3; 7,7] versus 5,2 [4,1; 7,2] ng/ml, р>0,05) there was statistically significant decrease of the bone isoenzyme of alkaline phosphatase (17,1 [12,2; 21,4] versus 22,3 [15,5; 30,5] E/L, р=0,01), and significant decrease of IL-8 (9,74 [9,19; 10,09] pg/ml versus 13,17 [9,72; 23,1] pg/ml, р=0,045) with general increase of proinflammatory serum markers activity.Conclusion. Into the group of probable predictors determining the tempos of BP calcification, the following could be included: specifics of recipient metabolic status defined by the activity of bone resorption processes, and local and systemic inflammation

Relationship between bone remodeling markers, bone mineral density, and severity of coronary atherosclerosis in men with stable coronary heart disease

The development of atherosclerosis is a complex multifactorial process, in which the markers of bone formation and resorption play an important role and which is closely related to the calcification of the vessel intima and fibrous plaques.Objective: to assess the relationship between bone remodeling markers (cathepsin K, C-terminal telopeptide of type I collagen (CTX-I) and osteopontin), bone mineral density (BMD), and severity of coronary atherosclerosis in men with stable coronary heart disease (CHD).Patients and methods. The investigation enrolled 102 male patients with verified stable CHD. Coronary angiographic and densitometric findings and blood cathepsin K, osteopontin, and CTX-I concentrations were assessed.Results.The concentration of cathepsin K and CTX-I was significantly higher and that of osteopontin was significantly lower in patients with CHD than in men without CHD. There was no association of the level of bone remodeling markers with the type of coronary artery lesion and the severity of coronary atherosclerosis. Cathepsin K concentrations in patients with a high SYNTAX score of coronary atherosclerosis were shown to be 5.5 times lower in the presence of osteopenic syndrome (OPS) than in those with the similar severity of atherosclerosis and normal BMD. Analysis of osteopontin and CTX-I levels from the standpoint of the presence of OPS suggests that there are no differences in relation to both the type of coronary vessel lesion and its severity. Conclusion. Current data suggest that there are common mechanisms for the development of two socially significant conditions: atherosclerosis and osteoporosis (OP). The phenomenon of concomitant development of these diseases has been studied mainly in postmenopausal women. Today, however, OP is also increasingly found in men, associating with more severe manifestations of coronary atherosclerosis than in patients with no signs of osteopenia

The relationship of biochemical markers of bone metabolism, osteopenic syndrome and coronary atherosclerosis in men with stable coronary heart disease

Aim: To assess the levels of bone metabolism markers in patients with stable coronary artery disease according to the severity of osteoporosis, coronary atherosclerosis and coronary artery calcification. Material and Methods: 112 males with angiographically verified stable coronary artery disease with an average age of 59.8 (55; 70) years were included in the study. All the patients underwent coronary angiography, multislice computed tomography (MSCT) and densitometry. The levels of mineral metabolism markers were measured by enzyme-linked immunosorbent assay. The allocation of comparison groupswas based on the severity of coronary atherosclerosis (the Syntax Score), the degree of coronary artery calcification (the Agatston score), the presence and absence of osteopenic syndrome defined by the femoral neck T-score in accordance with the guidelines of the International Society for Clinical Densitometry (ISCD, 2007). Results: Osteopenic syndrome has been reported in 90 (80.4 %) patients: 34 (30.4 %) patients with signs of osteoporosis, and 56 (50 %) with osteopenia. A significant decrease in cathepsin K and an increase inosteocalcinhave been found in the group with radiographically verified osteopenic syndrome compared to the group with normal bone mineral density (BMD). The assessment of coronary artery disease severity reported that multivessel coronary artery disease and severe lesions were more commonly found in patients with osteopenic syndrome. Moreover, this group of patients had more pronounced calcification compared with patients with normal BMD. Patients with severe coronary atherosclerosis had the lowest cathepsin K levels. Severe coronary artery calcification was significantly associated with lower levels of cathepsin K and osteoprotegerin, elevated alkaline phosphatase and parathyroid hormone levels. Conclusion: A significant association between osteopenic syndrome and severe coronary atherosclerosis and calcification has been found in males with stable coronary artery disease. Biochemical markers of bone metabolism were more likely associated with the calcification of the existing vascular lesions than with the development of coronary atherosclerosis. The findings of the study suggest that the most significant markers are cathepsin K whichsignificantly reduced in all cases, i. e. in patients with osteopenic syndrome, severe atherosclerosis and severe coronary calcification, and osteocalcin which elevated levels are associated with decreased BMD