EDITORIAL
The paper presents the results of an analytical study on the complex problem of preventive counselling in patients with multifactorial chronic non-communicable diseases (CNCD). Based on the extensive experience of the author and the major external sources of evidence, the conceptual principles of preventive counselling are presented for people with CNCD or CNCD risk factors (RFs), according to individual personality traits and behavioural specifics. The key requirements for the development of preventive counselling algorithms focusing on major behavioural RFs are identified, which opens a new perspective in the CNCD prevention.
CORONARY HEART DISEASE
Aim. To study the effects of a β-adrenoblocker (β-AB) metoprolol (Mp) and its combination with trimetazidine (Tmd) on glucose tolerance and insulin sensitivity in patients with angina pectoris.
Material and methods. In total, 28 men aged 46-68 years, with Functional Class (FC) II-III stable angina, positive exercise stress test (EST), and no prior β-AB therapy were examined. Individual Mp doses were selected based on the paired EST results. For one month, the Mp dose of 50 or 100 mg/d was administered twice a day; for the next month, participants received Mp and Tmd (70 mg/d). A standard glucose tolerance test (GTT) was performed at baseline and at the end of one-month periods of Mp or Mp + Tmd treatment. Carbohydrate metabolism disturbances were diagnosed according to the WHO criteria (1999). Insulin resistance (IR) was assessed by HOMA2-IR parameter, and tissue insulin sensitivity by ISI0,120 parameter.
Results. After one month of Mp treatment, a decrease in fasting glucose levels was observed (p=0,025). At the same time, the GTT results demonstrated increased glucose levels 2 hours after glucose load, compared to baseline (p=0,049). Tissue insulin sensitivity (ISI0,120) showed some reduction (p=0,14), while the number of patients with impaired glucose tolerance (IGT) increased from 4 to 8 (p=0,006). The levels of fasting and post-load glycemia after one month of the combination therapy with Mp and Tmd were similar to those after the Mp treatment. Insulin levels at 2 hours after glucose load were higher than those observed after the Mp therapy (p=0,045). Compared to baseline, HOMA2-IR values increased, and IDI0,120 values decreased (p=0,036). The IDI0,120 dynamics suggested a reduction in insulin sensitivity for both treatment regimens. IGT was registered in 10 patients.
Conclusion. In angina patients, impaired glucose control was observed as early as 1 month after the start of Mp treatment. This early impairment could be diagnosed by GTT. Although the combination therapy with Mp and Tmd did not prevent this impairment, but provided a greater antiischemic effect and, therefore, was clinically appropriate
Aim. To assess the association between ω-3 index of erythrocytes and demographic, electrophysiological, and echocardiographic (EchoCG) predictors of sudden cardiac death (SCD) in patients with coronary heart disease (CHD) and ventricular arrhythmias (VA).
Material and methods. The study included 25 patients with a verified diagnosis of CHD and VA. Gas chromatography method was used to measure the content (%) of eicosapentaenoic (EPA) and docosahexaenoic (DHA) polyunsaturated fatty acids (PUFA) in peripheral blood erythrocytes, with the calculation of a summary (EPA + DHA) ω-3 index. All participants underwent 24-hour electrocardiography (ECG) monitoring, with the assessment of maximal, minimal, and mean heart rate (HR), heart rate variability (HRV) parameters (SDNN and pNN50), heart rate turbulence (TO and TS), microvolt T wave alternans (mTWA), and the number of ventricular extrasystoles (VE) and transient and persistent ventricular tachycardia (VT) episodes. All patients also underwent EchoCG.
Results. In examined patients, the values of ω-3 index of erythrocytes varied from 1,12% to 6,4% (mean 3,74%, 95% CI 2,02-4,38%). There was a weak correlation between ω-3 index or EPA levels (%) and the HRV parameter of pNN50. In addition, ω-3 index or DHA levels (%) negatively correlated with the daily VE number. The 5:00 AM value of mTWA (II lead, update factor 1/8) weakly correlated withω-3 index and DHA levels. There was a moderate positive correlation between E/A ratio and omega-3 index, or EPA and DHA levels.
Conclusion. Patients with CHD and VA were characterised by low ω-3 index values and high (56%) or moderate (44%) levels of cardiovascular risk. The values of ω-3 index positively correlated with the daily VE number and negatively correlated with E/A ratio and pNN50 parameter of HRV.
STRUCTURAL AND FUNCTIONAL VASCULAR PATHOLOGY
Aim. To compare the effects of Mildronate and hormone replacement therapy (HRT) with estradiol (1 mg) and drospirenone, DSPR (2 mg) on circadian blood pressure (BP) profile, arterial structure and function, and vascular stiffness parameters in women with early postmenopause and climacteric syndrome (CS).
Material and methods. The study included 94 women with early postmenopause and CS, who provided written informed consent to participate and were divided into two groups. Group I included 36 women receiving Mildronate (500 mg twice a day), while Group II included 28 women who were administered, according to clinical indications, HRT (1 mg 17β-estradiol and 2 mg DRSP once a day). The control group (CG) included 30 women who did not receive either Mildronate or DRSP. At baseline and 16 weeks later, all participants underwent the assessment of blood biochemistry; intima-media thickness (IMT) of common carotid artery (CCA); endothelium-dependent vasodilatation (EDVD) of brachial artery (BA); antithrombogenic activity of vascular wall; aortal pulse wave velocity (aPWV); arterial stiffness; and 24-hour BP monitoring (BPM).
Results. The study demonstrated positive effects of Mildronate therapy and HRT (1 mg 17β-estradiol and 2 mg DRSP) on metabolic status, circadian dynamics and variability (Var) of BP, and arterial structure and function. The largest positive changes in blood lipid profile were observed in Group I and II patients. By the end of the study, these patients demonstrated significantly decreased levels of systolic and diastolic BP and reduced BP Var, particularly in Group II. Mildronate therapy, but not HRT, was associated with normalisation of vascular wall antiaggregant potential. Group II demonstrated a significant reduction in CCA IMT levels, with a similar tendency in Group I. In both groups, the degree of endothelial dysfunction (ED) decreased, which was manifested in increased BA EDVD, decreased aPWV, and reduced arterial stiffness and was more pronounced in Group II.
Conclusion. In menopausal women with CS, the effects of Mildronate and HRT on metabolic, structural, and functional disturbances were similar. Therefore, Mildronate therapy could be a new method of correction of these systemic disturbances.
TREATMENT
Aim. To assess the impact of automatic telephone survey with a differentiated reminder text, as well as of the survey combination with the self-control dairy, on the compliance with lipid-lowering and antihypertensive therapy and on therapy effectiveness during the longterm ambulatory follow-up.
Material and methods. The study included 604 patients: 323 individuals with high or very high cardiovascular risk levels by SCORE scale and 281 participants with coronary heart disease (CHD). The patients were divided into two groups, according to their agreement to participate in the automatic telephone reminder survey (“Survey” and “Refusal”). All participants were also given a self-control diary. At baseline and one year later, the patients underwent general clinical examination, office blood pressure (BP) measurement, blood biochemistry assessment, and the measurement of therapy compliance (Morisky-Green test), anxiety, and depression levels (HADS scale).
Results. The reduction in diastolic BP levels was significantly larger in the Survey group (p=0,04). This group also demonstrated a significantly larger decrease in the levels of total cholesterol (TCH) (p=0,0003) and low-density lipoprotein cholesterol (LDL-CH) (p=0,001), as well as a significantly larger increase in the levels of high-density lipoprotein cholesterol (HDL-CH) (p=0,04). The therapy compliance, assessed by the Morisky-Green test, improved in both groups; however, among CHD patients, a significant improvement was observed only in the Survey group (p<0,00001). The percentage of patients submitting their self-control diaries was higher for the Survey group (p<0,0001).
Conclusion. The automatic telephone reminder method provides an opportunity to significantly increase the therapy compliance.
Aim. To study the effects of hormone replacement therapy (HRT) with a combination of estradiol and drospirenone on cardiometabolic risk levels and subclinical vascular pathology among women in early postmenopause.
Material and methods. In total, 84 women in early postmenopause, who had given informed consent and underwent a standard examination, were divided into two groups: Group I (with gynaecologist-confirmed indications for HRT with Angeliq (1 mg 17 β-estradiol and 2 mg drospirenone)) and Group II (no HRT). All participants underwent the assessment of metabolic parameters, visceral obesity, intima-media thickness (IMT) of common carotid arteries (CCA), arterial stiffness, and microcirculation (MC) status at baseline and 12 months later.
Results. HRT demonstrated beneficial effects on autonomic regulation, lipid metabolism, CCA IMT, and arterial stiffness. It was also associated with a reduction in visceral obesity, some antihypertensive effect, and an increase in the MC dilatation reserve in postmenopausal women.
Conclusion. Low-dose combined hormone therapy with drospirenone and estradiol could be recommended to a specific clinical group of women in early postmenopause.
DIABETES
Aim. To investigate potential gender differences in the association between plasma fibrinolytic activity (FLA) and atherosclerotic pathology in elderly people.
Material and methods. This analysis was performed as a part of the prospective population-based cohort study “Stress, Ageing, and Health in Russia”. The study included randomly selected Moscow residents of both genders and age of ≥55 years (n=1863; 889 men and 974 women). Based on the levels of blood FLA (time of spontaneous lysis of euglobin blood fraction, or euglobin lysis time, ELT), all participants were divided into three groups: with normofibrinolysis (ELT 180-260 minutes), hypofibrinolysis (ELT >260 minutes), and hyperfibrinolysis (ELT <180 minutes).
Results. In this cohort of elderly Muscovites, the association between FLA and the presence of cardiovascular disease (CVD) or Type 2 diabetes mellitus (DM-2) differed in men and women. The link between hypofibrinolysis, atherogenic changes in lipid profile, or high fasting levels of insulin and arterial hypertension (AH), myocardial infarction (MI), or DM-2 was present only in men. In women, either reduced or increased FLA was not related to DM-2. Men with hyperfibrinolysis demonstrated lower odds of AH and DM-2, while women with hyperfibrinolysis had lower odds of AH, coronary heart disease, or angina.
Conclusion. In elderly people, high FLA appears to provide protection against atherothrombotic pathology, regardless of gender. Low FLA was associated with higher odds of CVD and DM-2 in men only.
Aim. To study the dynamics of left ventricular (LV) structure and function, as well as vasomotor activity of arterial endothelium, in patients with Type 2 diabetes mellitus (DM-2) and diastolic heart failure (DHF) who are treated with an angiotensin II receptor antagonist olmesartan.
Material and methods. The study included 56 patients (26 men and 30 women; mean age 58,2±5,3 years) with NYHA Functional Class I-II chronic heart failure (CHF), diastolic LV dysfunction (abnormal relaxation), and LV ejection fraction (EF) >50%. Other inclusion criteria were DM-2 duration <15 years and per os glucoselowering treatment.
Results. The major pathogenetic mechanisms of LV diastolic dysfunction and endothelial dysfunction in DM-2 are linked to the development of central sympathetic hyperactivation and activation of the tissue reninangiotensin system.
Conclusion. After 30 weeks of olmesartan therapy, LV structure and geometry, LV diastolic function, and vasomotor activity of arterial endothelium had improved, which was expected to reduce the risk of myocardial ischemia.
ЭПИДЕМИОЛОГИЯ И ПРОФИЛАКТИКА
Background. The elevation of blood pressure (BP) affects the development of vascular inflammation. At the same time, it has been suggested that inflammation itself could be an independent risk factor (RF) of arterial hypertension (AH) development.
Aim. To investigate whether the association between increased levels of C-reactive protein (CRP) and AH is independent from classical RFs.
Material and methods. The data were obtained during a crosssectional survey of 1876 Muscovites (47,9% men) aged ≥55 years, who participated in the prospective study “Stress, Ageing, and Health in Russia”. In all participants, socio-demographic characteristics, health behaviours, parameters of anthropometry and rest electrocardiography (ECG) were assessed. The levels of BP and blood lipids were also measured. The outcome variable was an increase in CRP levels (>3 mg/l). Statistical methods included logistic regression; the risk estimates were presented as odds ratios (OR) and 95% confidence intervals (CI).
Results. There was a positive link between AH and CRP levels of >3 mg/l. After adjustment for age and sex, OR of increased CRP levels in hypertensive participants vs. their AH-free peers was 1,688 (95% CI 1,323-2,154; p=0,0001). In the final model (adjustment for age, sex, educational level, smoking, alcohol consumption, abdominal obesity, high atherogenicity index, and coronary heart disease, CHD), this effect remained statistically significant (OR 1,450; 95% CI 1,127-1,864; p=0,004).
Conclusion. In elderly Muscovites, a positive association between increased CRP levels and the elevation of BP was independent from RFs and CHD.
CLINICAL TRIALS AND REGISTRIES
The high prevalence of persistent dyslipidemia in primary and specialized care patients treated with statins justifies the need to identify its reasons and develop the recommendations on the treatment optimization. At present, Russian studies focusing on the achievement of target lipid levels remain scarce, which emphasizes the importance of the problem and its further investigation.
Aim. Cross-sectional epidemiological study which assessed the prevalence of persistent dyslipidemia in statin-treated patients and analysed the predictors of the achievement of target lipid levels.
Material and methods. The lipid profile parameters were analysed in 1586 statin-treated out-patients with varied levels of cardiovascular risk, taking into account the type of lipid-lowering therapy and its doses. The assessment of the cardiovascular event (CVE) risk and the definition of target levels of low-density lipoprotein cholesterol (LDL–CH), as well as normal levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL–CH), was based on the clinical recommendations by the European Society of Cardiology (ESC 2007) and by the European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS 2011).
Results. The analysis based on the ESC 2007 recommendations has demonstrated that the target levels of LDL–CH (<2,5 mmol/l for high-risk patients) were not achieved in 53,5% of the participants. The elevation of LDL–CH levels could be isolated or combined with the HDL–CH decrease and/or the TG increase. Low levels of HDL–CH were observed in 32,3% of the patients, while high TG levels were registered in 55,6% of the participants. The achievement of target LDL–CH levels was predicted by the higher-dose statin therapy (odds ratio 0,44). The analysis based on the ESC/EAS 2011 recommendations has shown that the prevalence of target LDL–CH levels was 12,2% in very high-risk patients (<1,8 mmol/l), 30,3% in high-risk patients (<2,5 mmol/l), and 53,4% in moderate-risk patients (<3,0 mol/l).
Conclusion. Over a half of the statin-treated patients failed to achieve target levels of LDL–CH. The lowest prevalence of target LDL–CH levels was observed in very high-risk and high-risk patients. The predictors of target LDL–CH level achievement included moderate cardiovascular risk and higher-dose statin therapy. The obtained results suggest that the correction of persistent dyslipidemia in statin-treated patients could be achieved via increasing the satin dose and combining lipid-lowering medications.
Aim. Using the prospective Registry data, to assess the effects of conventional and specific therapy on the clinical course and survival of the patients with pulmonary arterial hypertension (PAH).
Material and methods. The study included 124 patients (mean age 38,2±13,7 years; 34 men and 78 women): 31 with idiopathic PAH (IPAH), 52 with Eisenmenger syndrome, 17 with inoperable chronic thromboembolic pulmonary hypertension, 9 with PAH and corrected congenital heart disease, 6 with PAH and systemic scleroderma, and 6 with PAH and HIV infection.
Results. The cumulative one-year and three-year survival rates were 94% and 75%, respectively. Irrespective of the absence of right heart catheterisation and vasoreactive testing, 42,7% of the patients were treated with calcium antagonists. PAH-specific therapy was administered to 40,3% of the participants (64,5% and 21% of those with IPAH and Eisenmenger syndrome, respectively). PAH-specific therapy was associated with an increase in survival time.
Conclusion. In PAH patients, the prognosis is linked to early administration of specific monotherapy and possible combination therapy. Developing a national registry of pulmonary hypertension will facilitate the assessment of the real-world demand for specific therapy and the related costs.
OPINION ON A PROBLEM
The wide prevalence (82%) of coronary heart disease (CHD) in combination with arterial hypertension (AH), as well as its initiating role in the development of fatal complications, such as myocardial infarction (MI) or heart failure, emphasise the need for the choice of optimal ACE inhibitors with organ-protective characteristics. This paper presents a literature review on the effectiveness of a SH-containing ACE inhibitor zofenopril in patients with CHD and AH, in terms of its anti-anginal and antihypertensive activity. The authors summarise the results of the international SMILE studies which included patients after acute MI. It was demonstrated that zofenopril therapy is associated with reduced combined incidence of cardiovascular death or cardiovascular hospitalisation, and is also safe in the acute post-MI period. In patients with preserved left ventricular function, zofenopril reduced the incidence of angina attacks and arrhythmias of coronary genesis, as well as improved exercise capacity. A clinical case of zofenopril therapy, as a part of a complex treatment regimen, is also presented.
REVIEWS
The authors discuss major structural and functional vascular changes accompanying ageing, the mechanisms of their development, and potential methods of their correction.
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