Aim. To study the structure of cardiovascular disease (CVD) and prevalence of comorbidity, the needs for diagnostics and treatment methods in out-patient practice of cardiologists and therapeutists.

Material and methods. The study involved polyclinic-based cardiologists and therapeutists from 5 subjects of the Russian Federation. During 3 consecutive days, the doctors enrolled male and female patients aged over 18 years, with one or several CVD and/or congenital valve pathology (CVP). Individual registration forms (IRFs), completed for each patient, were mailed to A.N. Bakulev Research Center for Cardiovascular Surgery. All data were centrally processed. Out of 6312 scanned IRFs, 3982 were selected (63,1 %; 95 % CI 61,9–64,3) and analyzed as one sample and by 3 nosological groups: coronary heart disease (CHD), CVP, acquired valve pathology.

Results. Among out-patients, combined pathology (CVD and comorbidity) was widely prevalent. The combination of CHD and arterial hypertension (AH) was observed in 34 %, of CHD, AH and other CVD – in 28 %. The most prevalent comorbidities were diabetes mellitus (19 %) and chronic obstructive pulmonary disease (9 %). Comorbidity prevalence was associated with the main diagnosis and age. Leading reasons for seeking medical help were disease exacerbation and need for prescription during remission period (59 %). According to doctors’ opinion, the main indication for diagnostic procedures was “controlling the patient’s status”. At present, methodology of assessing the need for surgical and endovascular interventions among CVD patients is not standardised. In most out-patients (71,7 %), main income source is social subsidies. It could be expected that even in the future, federal budget subsidies will dominate in the payments for high-technology medical service.

Conclusion. The study results reflect social and clinical characteristics of CVD and CVP patients, as well as primary healthcare doctors’ views on the need for diagnostic and therapeutic interventions.

Aim. To investigate the association between serum homocysteine, lipoprotein(a) (Lp(a)) and coronary atherosclerosis in young and middle-aged men.

Material and methods. The study included 40 men aged 29-58 years (mean age 43,8±6,2 years), with coronary heart disease (CHD) verified by coronary angiography. The control group (CG) included 27 CHD-free men. In all participants, concentrations of homocysteine, Lp(a), total cholesterol (TCH), triglycerides (TG), high-density lipoprotein CH (HDL-CH) were assessed. Low-density lipoprotein CH (LDL-CH) level was calculated using Friedewald formula.

Results. Concentrations of homocysteine, Lp(a), TCH, and LDL-CH were significantly higher in CHD patients than in CG individuals: 12,4±5,8 and 10,0±2,9 micromol/l (p<0,05); 37±40 and 13±11 mg/dl (p<0,01); 6,4±1,3 and 5,6±1,0 mmol/l (p<0,01); 4,4±1,2 and 3,4±0,9 mmol/l (p<0,001), respectively. No significant inter-group differences in TG and HDL-CH levels were observed. In multiple regression analysis, coronary atherosclerosis presence and severity was independently associated with Lp(a), but not with homocysteine level. There was a positive correlation between Lp(a) and homocysteine concentrations.

Conclusion. In young and middle-aged men, coronary atherosclerosis was associated with increased Lp(a) level, being unassociated with homocysteine concentration.

Aim. To assess effectiveness and safety of stem cell auto-transplantation (SCT) into renal and vertebral arteries among patients with renovascular hypertension (RVH) lasting over 10 years.

Material and methods. Seventy-eight patients were randomized into main (MG, n=26) and placebo groups (PG, n=52). Primary end-point was systolic blood pressure (SBP) level. Secondary end-points included: restenosis incidence; glomerular filtration rate (GFR); effective renal plasma flow (ERPF); creatinine level and microalbuminuria (MAU); quality of life (QoL); renal biopsy and immuno-hystochemical assay data; renal vessel calcification; cerebral metabolism level.

Results. Restenosis at 12 months was observed in 17% of both MG and CG patients; repeated revascularization was needed in 8%. Stenting resulted in average BP decrease from 181/107 to 142/93 mm Hg; after 6 weeks, no patient achieved target BP levels. After SCT into both renal arteries, BP normalization was achieved in 61% of MG participants. Only 23% of regenerated renal tissue originated from transplanted SC (trans-differentiation), the rest originated from local tissues (de-differentiation). After 50-55 weeks, in 37-39% of the patients Stage I AH was observed. At 6-8 weeks after SCT into both vertebral arteries, cerebral metabolism increased, and BP normalized, reducing from 138/90 to 119/69 mm Hg.

Conclusion. SCT plays an important role in renal artery thrombosis prevention and RVH control. Renal and vertebral artery SCT solves the problems of nephron destruction and renal tissue fibrosis, atherosclerosis treatment and harmful cerebral influences. Remaining problems include target organ damage and genetic defects.

Aim. To assess microcirculatory (MC) function in patients with arterial hypertension (AH), AH and metabolic syndrome (MS), AH, MS and Type 2 diabetes mellitus (DM-2).

Material and methods. In total, 96 patients with Stage I-II AH and 26 healthy individuals were examined. All patients were divided into three groups: Group I (no clinical or laboratory evidence for MS and DM-2), Group II (MS), Group III (MS and DM-2). In all participants, lipid profile and forearm skin MC (laser Doppler flowmetry method) were assessed.

Results. Combination of AH and MS or DM-2 was associated with progressive MC deterioration (increased vasoconstriction, activated passive mechanisms of MC tonus regulation, reduced blood flow effectiveness due to non-capillary bypass, decreased tissue perfusion reserve, prevalent congestive and static MC types).

Conclusion. Modern methods of MC assessment in clinical practice provide additional objective information about disease severity and prognosis, which is especially important for patients with MS and DM-2.

Aim. To assess the long-term results of coronary artery stenting (CAS) with drug-eluting stents (DES) in patients with coronary heart disease (CHD) and Type 2 diabetes mellitus (DM-2).

Material and methods. CAS results were analyzed for 99 male and female CHD patients with angina and DM-2. In total, 78 sirolimus-eluting stents were implanted in 53 patients, and 57 non-DES were implanted in 46 individuals. In both groups, lethality and complication incidence were assessed, including the rates of recurrent angina, myocardial infarction, coronary artery bypass graft surgery, repeated endovascular intervention (EI) in the first 12 months after coronary angioplasty and in 2,5 years after EI.

Results. DES usage reduced 12-month incidence of severe cardiovascular events (CVE) from 28,9% to 9,4%, and recurrent angina incidence – from 37,8% to 17%. Decrease in severe CVE rates was explained by reduction in repeated CA angioplasty – from 22% to 5,7%. In DES group, reduced long-term incidence was observed for severe CVE – from 40% to 18,9% and recurrent angina – from 44,4% to 22,6%.

Conclusion. Endovascular myocardial revascularization with DES reduced 12-month risk of severe CVE and recurrent angina in patients with CHD and DM-2. This positive tendency remained for at least 2,5 years after coronary angioplasty.

Aim. To study the links between four polymorphisms of three antioxidant enzymes (catalase, paraoxonase, endothelial NO synthase) and restenosis risk after coronary artery stenting (CAS).
Material and methods. The study included male patients with coronary heart disease (CHD), stable angina and angiographically verified stenosis of one or two main CA ≥70%, after intracoronary CAS with non-eluting stents and control coronary angiography 6 months later. Angiographical stenosis was determined as local reduction in CA diameter ≥50%. In all participants, -262 C/T polymorphism of CAT gene, L55M and Q192R polymorphisms of PON gene, and E298D polymorphism of eNOS gene were identified.
Results. The study included 101 patients, and restenosis was diagnosed in 44%. E298D polymorphism of eNOS gene was associated with stent restenosis. In D allele carriers, restenosis risk was higher (p=0,008). The combination of LM/QQ genotypes for L55M and Q192R polymorphisms of PON gene was twice as prevalent in restenosis  group: 41% vs. 21% (p=0,044).
Conclusion. Genotyping on E298D polymorphism of eNOS gene and L55M and Q192R polymorphisms of PON gene could be used for post-CAS restenosis risk stratification in Russian patients.

Aim. To assess the dynamics of an inflammatory marker, C-reactive protein (CRP), and lipid profile during 3-month high- and low-dose atorvastatin therapy (40 mg/d and 10 mg/d) in patients with rheumatoid arthritis (RA) or coronary heart disease (CHD) and moderate hyperlipidemia (HLP).
Material and methods. The study included 64 male and female patients: 40 with CHD and 24 with RA, aged 45-60 years, with moderate HLP and positive CRP reaction. Atorvastatin therapy effectiveness was assessed by decrease in CRP, total cholesterol (TCH) and low-density lipoprotein CH (LDL-CH) levels, comparing to baseline concentrations.
Results. During high- and low-dose atorvastatin therapy, 84% and 44% of CHD patients, respectively, achieved target LDL-CH levels (< 2,6 mmol/l). Among RA patients, these figures were 67% and 50%, respectively. Triglycerides and high-density lipoprotein CH dynamics was insignificant in each group. Maximal reduction in CRP level was observed among CHD patients with initially elevated CRP concentration and RA patients receiving high-dose atorvastatin therapy (reduction by 20% and 65%, respectively); in all the other subgroups, CRP dynamics was insignificant.
Conclusion. Statins reduced CRP concentration in RA patients more effectively than in CHD individuals, possibly, due to initially higher CRP levels among the former.

Aim. To study the effects of simvastatin (20 mg/d) on cardiac hemodynamics and chronic heart failure (CHF) clinical course in elderly patients.
Material and methods. The study included 180 elderly patients (mean age 80,8±5,8 years) with Functional Class (FC) II-III CHF, left ventricular (LV) systolic and diastolic dysfunction. All participants were divided into 2 equally sized groups, receiving standard CHF treatment, or standard treatment plus simvastatin (20 mg/d). The follow-up period lasted for 12 months, with intermediate control assessment after 3 months of the treatment. Clinical status, Doppler echocardiography, lipid profile parameters, and tumor necrosis factor-alpha (TNF-alpha) level were controlled. End-points included CHF death or any acute vascular event.
Results. Starting from the first month of the treatment, there was a significant difference in end-point number (р=0,028), CHF FC (p<0,001), angina FC (р<0,0001) and TNF-alpha level (p<0,05). Simvastatin therapy was not associated with reduced LV pump function.

Aim. To study the effects of eNOS gene polymorphisms (Glu298Asp and VNTR intron 4) on endothelial dysfunction (ED) development, chronic heart failure (CHF) severity and progression in patients with coronary heart disease (CHD) and arterial hypertension (AH).
Material and methods. In total, 165 CHF patients were examined (121 men, 44 women; mean age 56,7±5,3 years). Vasomotor endothelial function was evaluated by ultrasound method in reactive hyperemia and nitroglycerin tests. Genotypes were identified by polymerase chain reaction-restriction fragment-length polymorphism analysis. The control group consisted of 114 persons (54 men, 60 women; mean age 53,2±4,9 years).
Results. Glu/Glu genotype of Glu298Asp polymorphic loci was identified in CHF patients significantly more often than in controls (p<0,05), and Glu/Asp genotype was significantly more prevalent in controls (p<0,01). Glu/ Glu genotype prevalence in patients with Functional Class (FC) I (NYHA) was significantly lower than in those with FC II or FC III-IV (p<0,05). Moreover, Glu/Glu genotype was more prevalent in patients with unfavourable CHF clinical course than in those with more favourable CHF course (75,7% and 43,2%, respectively; p<0,05). This genotype was also more prevalent in patients with left ventricular ejection fraction <50%, but the difference was not statistically significant. Flow-induced dilatation of brachial artery was significantly lower in patients with Glu/Glu genotype than in those with Asp298 allele (р<0,01). Distribution of alleles and genotypes of another eNOS gene polymorphism (VNTR intron 4) was similar in CHF patients and controls.
Conclusion. Alleles of eNOS gene Glu298Asp polymorphism were associated with CHF development risk and CHF clinical course features, as well as with vasomotor ED development.

Aim. To investigate the effects of an anti-ischemic medication trimetazidine on Са2+ ion metabolism in human leukocyte and monocyte precursors – HL-60 promyelocytes.
Material and methods. HL-60 cells were cultivated in vitro. Changes in intracellular free Са2+ ion concentration were registered with fluorescent Са2+ probes Fura-2. Results. For the first time it was demonstrated for differentiated and non-differentiated HL-60 cells that an antianginal agent trimetazidine suppressed the activity of plasmatic membrane store operated Са2+ channels (SOC channels). Importantly, trimetazidine did not cause Са2+ ion release from the stores and did not open SOC channels, in contrast to other SOC channel inhibitors, e.g., miconazole. In open SOC channels, trimetazidine and miconazole targeted the same binding areas.
Conclusion. The results obtained demonstrate additional trimetazidine effects, linked to selective SOC channel blockade. It provides new potential explanations for trimetazidine effects on electro-inert cells (e.g. blood phagocytes) and its effects in myocardial ischemia.

Aim. To study testosterone undecanoate effects on some modifiable cardiovascular risk factors in men with metabolic syndrome (MS).
Material and methods. Androgen status screening (anthropometry, total and free testosterone level measurement) was performed in 35-75-year-old men with cardiovascular disease (CVD). In 50 MS patients, a double-blind, randomized, placebo-controlled trial of testosterone undecanoate was performed, focusing on hypogonadism clinics, erectile function (EF), quality of life (QoL), lipid profile (LP), inflammatory markers: C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6).
Results. In men with CVD, clinical and laboratory androgen deficiency was observed in 67,8%, more often in those with visceral obesity. By Week 30 of testosterone treatment, androgen deficiency became less manifested clinically; EF, QoL, and LP also improved. Baseline levels of inflammatory markers pointed to elevated CVD risk. Testosterone undecanoate therapy was associated with significant, 2-fold reduction in CRP concentration, and 1.2-fold decrease in TNF-alpha and IL-6 levels.
Conclusion. In men with CVD, hypogonadism was widely prevalent; testosterone level was age-independent in combined pathology. Testosterone level normalization facilitated improvements in LP and QoL. Testosterone undecanoate therapy was safe and well-tolerated.

HYVET Study was aimed at assessing the effects of indapamide SR (1,5 mg/d), as monotherapy or combined with an ACE inhibitor perindopril (2-4 mg/d), compared to placebo, on the risk of stroke and other cardiovascular events in arterial hypertension patients aged over 80 years. Active indapamide SR therapy significantly reduced the risk of fatal and non-fatal stroke by 30%, fatal and non-fatal heart failure – by 64%, fatal stroke – by 39%, allcause mortality – by 21%, with additional reduction in the risk of cardiovascular and non-cardiovascular mortality, coronary heart disease and chronic heart failure mortality.

The review is devoted to diagnostics and differential treatment issues in elderly patients  with stable angina. Therapeutic potential of modern antianginal and other cardiovascular agents is presented. Clinical aspects of pharmaceutical therapy in coronary heart disease patients are emphasized. Surgery potential in elderly patients is also discussed.

The article is focused on postprandial hyperglycemia role in cardiovascular event (CVE) development. Modern views on postprandial hyperglycemia pathogenetic mechanisms, its effects on type 2 diabetes mellitus progression and CVE are presented. Postprandial hyperglycemia control with an alpha-glucosidase inhibitor acarbose is discussed, and data are presented on acarbose influence on physical fitness and atherogenic metabolic factors in patients with coronary heart disease and impaired carbohydrate metabolism.

Modern concept of arterial hypertension (AH) combined therapy is based on using agents with various pharmacotherapeutic mechanisms of action. Despite the impressive number of clinical trials conducted, the real-life basis for combined therapy is mostly clinician’s empirical experience. Computer program and database PASS (Prediction of Activity Spectra of Substances; website http://www.ibmc.msk.ru/PASS) gives an opportunity to predict potential activity spectra for specific chemical structures. PASS could be used for assessment of: a) main pharmaco-therapeutic effects; b) biochemical mechanisms underlying these effects; c) possible adverse (toxic) effects. Using this approach for some antihypertensives (lisinopril, amlodipine, trandolapril, etc.) provided information on medication action spectra and cellular-biochemical mechanisms. Reliable prognostic data were obtained for additional, unstudied before, pharmaco-therapeutic effects. These vasodilatation-independent effects are linked to chemical structure specifics. PASS program provides clinicians with unique information on potential medication polymodality and adverse effects in treating AH and its complications.

The review is devoted to the problem of arterial hypertension (AH) combined with obesity. Pharmaceutical and non-pharmaceutical methods for weight reduction, as well as their effects on blood pressure (BP), are emphasised. Sibutramine safety in AH and obesity management is analysed. The most effective regimens of antihypertensive therapy combined with pharmaceutical weight reduction are discussed.

Endothelial dysfunction (ED) amplifies the effects of vascular risk factors (RF), and is directly linked to pathogenetic mechanisms of atherosclerosis and its complications. To clarify ED prognostic role, a review of relevant studies was performed. ED interrelation with various clinical outcomes of cardiovascular disease (CVD) was demonstrated. At the moment, the main method of 5-10-year CVD risk assessment in CVD patients and asymptomatic individuals is evaluation of total mortality risk. ED could be an independent marker of atherosclerosis, including its subclinica course, and a predictor of various CVD events. Endothelium may link various RF and their damaging effect on vascular wall. Future studies will confirm whether endothelial function assessment could be used for dynamic follow-up of CVD patients, as a measure of prevention effectiveness.