This paper presents the results of the pharmaco-epidemiological study of arterial hypertension (AH) in Russia (PIFAGOR III). The survey included both doctors (961 questionnaires) and patients with AH (3030 questionnaires) from 38 Russian cities. The pharmacological therapy analysis demonstrated that the most widely prescribed classes of antihypertensives are ACE inhibitors, beta-adrenoblockers, diuretics, and calcium antagonists. Angiotensin II receptor antagonists are prescribed more often, while “old” drugs with central mechanism of antihypertensive action become less popular. Detailed analysis was performed for each class of antihypertensive agents. In particular, the majority of the patients taking ACE inhibitors receive enalapril (44%). The most popular agents among beta-blockers are bisoprolol (41%) and metoprolol (31,9%), among calcium antagonists – amlodipine (53%), and among diuretics – indapamide (67%). The frequency of original medication prescription was 46% and 39%, based on the survey data for doctors and patients, respectively. An increase was observed in the proportion of AH patients receiving long-term (79%) and combined (74%) antihypertensive therapy. Average number of antihypertensive drugs taken by a patient with AH increased from 1,72 in 2002 to 2,22. Target blood pressure levels (<140/90 mm Hg) were achieved in 69%. Patients’ awareness of AH and its complications, as well as patients’ motivation and therapy compliance, has also increased. In 58% of the patients, the monthly cost of AH medications is under 5000 roubles.

In total, 43 patients with essential arterial hypertension (EAH) and 34 patients with isolated systolic arterial hypertension (ISAH) underwent echocardiography, Doppler echocardiography (Hewlet-Pacard Sonos 100, USA), and pulse wave velocity (PWV) assessment (Complier-2, France). All participants were divided into two groups: Group I – with concentric left ventricular hypertrophy (LVH): 27 (62,8%) EAH patients and 12 (35,3%) ISAH patients; and Group II – with eccentric LVH: 16 (37,2%) EAH patients and 22 (64,7%) ISAH patients. In EAH and ISAH, respectively, the most prevalent geometric LV models were concentric and eccentric LVH. Left atrium diameter and right ventricular (RV) outflow tract size were increased in all Group II patients. PWV was increased in both EAH and ISAH patients, to a greater extent among the latter. There was a positive correlation between systolic blood pressure, PWV and LVH parameters. In addition, there was a negative correlation between PWV and relative wall thickness (RWT). Diastolic LV function was impaired in all participants, while Group II patients demonstrated systolic LV dysfunction and diastolic RV dysfunction. LV myocardial mass index was inversely associated with E/A peak ratio. The study described the features of cardiovascular remodelling in EAH and ISAH. Typical structural and functional parameters of heart adaptation to increased workload were specified. The patients at high risk of congestive heart failure were identified.

The study was aimed at assessing the reactivity of cerebral vessels in patients with essential arterial hypertension (EAH) and different stages of blood pressure elevation. In 100 EAH patients, aged 30-60 years, cerebral blood flow parameters were assessed by transcranial Doppler ultrasound and capnometry at rest and during ventilation tests. The parameters of cerebral blood flow auto-regulation (CBFA) were calculated. The hemodynamic response to hyper- and hypoventilation was disturbed in 50 EAH patients (48,6%). Reduced blood vessel reactivity and functional CBFA reserve were explained by a decrease in vasodilatation reserve. The severity of CBFA disturbances positively correlated with EAH stage. The authors suggest that EAH stage could be a risk factor in the development of hemodynamic deficiency of cerebral blood flow.

In total, 86 patients with hypertrophic cardiomyopathy (HCMP), aged 21-88 years, were examined. All participants were divided into two groups: Group I – patients without signs and symptoms of chronic heart failure (CHF); Group II – patients with Stage IIB CHF. There are three pathophysiological mechanisms of CHF development in HCMP: – concentric left ventricular (LV) hypertrophy with minimal LV chamber size, diastolic LF dysfunction and systolic right ventricular (RV) dysfunction; – LV remodelling and dilatation, systolic LV dysfunction; – persistent atrial fibrillation. The HCMP clinical course, characterized by congestive heart failure and fatal outcome, was more prevalent in women. In our patients, LV outflow obstruction did not affect CHF development.

Endothelial dysfunction is one of the earliest stages in atherosclerosis development among patients with diabetes mellitus (DM). At the moment, cardiovascular disease (coronary atherosclerosis complications and coronary heart disease, CHD) is the leading cause of disability and mortality in patients with Type 2 DM (DM-2). This justifies the need for а thorough pathogenetic investigation of diabetic microangiopathy, endothelial function, and endothelial dysfunction role in the development of CHD in DM-2 patients. The study included 35 patients with CHD and DM-2; 35 patients with DM-2 and no CHD; 15 healthy volunteers, comparable by age and sex with DM-2 patients (control group). Endothelium-dependent vasodilatation, anti-thrombogenic activity of vascular wall, and hemostasis parameters were assessed in all participants. In patients with CHD and DM-2, functional endothelial activity was substantially decreased, including such parameters as flow-dependent vasodilatation, anti-coagulant, anti-aggregant, and anti-fibrinolytic activity. These disturbances were progressing over the clinical course of the disease and directly correlated with the disease severity.

Anti-ischemic effects of high-dose cardiac cytoprotector Mexicor (0,014 g/kg/d, 0,019 g/kg/d) were examined in rabbits with experimental myocardial infarction. In addition, anti-ischemic activity of Mexicor (0,4 g/d) was assessed in patients with acute coronary syndrome (ACS). It has been demonstrated that Mexicor reduced the size of infarction area and decreased the ratio “necrosis area / ischemia area”, compared to the control animals. In ACS patients, Mexicor facilitated faster recovery of left ventricular diastolic function, and also decreased blood levels of NT-proBNP.

Chronic heart failure (CHF) is a complex clinical syndrome, which can result in structural and/or functional cardiac disturbances, decreased ventricular pump function, and inadequate cardiac ejection. This study was aimed at investigating microcirculation features in CHF patients, as well as evaluating the effects of treatment with ACE inhibitors, diuretics, and anti-aggregants on microcirculation parameters (assessed by computerized nailfold capillaroscopy) among patients with normal and low ejection fraction (EF). The study included 58 participants: 20 healthy volunteers without cardiovascular disease (mean age 52,6±6,6 years; mean EF 63,1±4,5%); 36 patients with coronary heart disease (CHD) and myocardial infarction, arterial hypertension, and CHF in anamnesis; and 2 patients with dilated cardiomyopathy. All patients were divided into two groups, by EF values. Group I included 22 individuals (12 men, 10 women; mean age 63,2±9,4 years) with EF >52%. Group II included 16 people (11 men, 5 women; mean age 62,9±8,5 years) with EF <52%. The patients received enalapril (20 mg/d), acetylsalicylic acid (125 mg/d), and furosemide (40 mg twice a week). Microcirculation parameters (perivascular zone area, capillary blood flow velocity, arterial, intermediate, and venous diameters, and “sludge” phenomenon) were assessed at baseline and after 2 weeks of the treatment. The study results demonstrated the potential of non-invasive computerized nailfold capillaroscopy for microcirculation assessment in CHF patients. This method allowed the authors to identify the microcirculation features typical for CHF: 1) increased perivascular zone area, compared to healthy controls; 2) increased ratio “venous diameter / arterial diameter”; 3) reduced capillary blood flow velocity; 4) and “sludge” phenomenon.

The aim of the study was to assess the effectiveness of Accupro (Quinapril; 40 mg/d), as monotherapy and basis medication of combined therapy, in the treatment of arterial hypertension (AH) among patients with metabolic syndrome (MS). After 8 weeks of Accupro monotherapy (40 mg/d), target levels of blood pressure (BP) were achieved in 68% of the patients. BP normalization correlated with endothelial function improvement. Accupro therapy (40 mg/d) was also well tolerated. Accupro (40 mg/d) could be recommended as an effective and safe basis medication for combined antihypertensive therapy in patients with AH and MS.

The study was aimed at the investigation of “test” (6 days) and longer-term (8 weeks) acarbose treatment effects on plasma uric acid (UA) concentration in patients with metabolic syndrome (MS). Material and methods. In total, 33 men with MS and carbohydrate metabolism disturbances were administered 6-day “test” acarbose therapy. At baseline and 7 days later, saccharose tolerance test was performed, with the measurement of venous plasma levels of fasting UA, fasting fructose, glucose (fasting, 60 and 120 minutes after saccharose load), and insulin (fasting and 120 minutes after the load). 4 weeks later, 20 patients were administered 8-week acarbose therapy, with standard gradual dose increase. At baseline and after the treatment, venous plasma concentrations of UA and fructose were measured. Results. Hyperfructosemia was observed in 100% of the patients, with mean plasma fructose concentration of 0,82±0,97 mmol/l. Hyperuricemia was observed in 51,5% (n=17), with mean plasma UA concentration of 413,2±86,5 mmol/l. Six-week acarbose therapy resulted in a significant decrease of UA levels (p=0,0015) and fructose levels (p=0,049), as well as in postprandial levels of glucose (p=0,03) and insulin (p=0,013). Eight-week acarbose therapy was associated with mean decrease of plasma UA concentration by 5,8% (p=0,04), but no significant changes in fasting plasma levels of fructose (p>0,05).

The study was aimed at assessing the incidence of sudden cardiac death (SCD) in patients with coronary heart disease (CHD) and evaluating the quality of SCD diagnostics and statistical registration in medical institutions (MI). In the population of 285736 patients with CHD (76,4% aged 18 years or older; 46% men), the incidence of SCD cases registered in MIs was compared to the study algorithm-based incidence of SCD. The latter was as high as 156 per 100 000 in men and 72 per 100 000 in women, which was 2,3 and 2,8 times higher, respectively, than the MI-registered levels (р<0,001). MI-based diagnostics and/or registration missed 55,6% and 66,5% of the SCD cases in men and women with CHD, respectively. The two main explanations were inadequate diagnostic search at death cause identification (45,4%) and mistakes made at completing medical documents (55,6%). Therefore, every second SCD case in men with CHD and two-thirds of SCD cases in women with CHD are not identified by MIs, which results in under-estimation of SCD incidence.

The patients with arterial hypertension (AH) and diabetes mellitus (DM) are at high risk of cardiovascular events. The modern pharmacotherapy potential in patients with AH and DM is reviewed. The evidence base for various antihypertensive classes in cardiovascular event prevention among these patients is analysed.

The aim of this longitudinal, open-label, comparative, multi-centre study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine. Hypertensive patients aged 40 years or older were treated with lercanidipine (10 mg daily) after 7–10 days washout period. The duration of the study was 6 months. Blood pressure (BP) was measured every 4 weeks (JNC 6th report). In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT). In the study population of 467 patients, BP decreased from 154,4/95,3 mmHg at baseline to 134,8/80,7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% – an angiotensin-converting enzyme inhibitor, and 6% – doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation) MMSE scores improved from 32,35 (2,59) to 33,25 (2,36) (p<0,0001). Patients with good BP control scored significantly better than those with inadequate BP control (p<0,05), which was already observed at the first month. Conclusion: The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be associated with a decrease in BP.

The significance of β-blockers in the treatment of cardiovascular diseases is well established. The effect of vasodilating β-blockers on endothelial function and prothrombotic state has not been investigated. The study comprised 550 consecutive patients with uncomplicated essential hypertension. They were treated with celiprolol, carvedilol or nebivolol monotherapy (171, 179, and 200 patients, respectively), achieving comparable blood pressure reduction. Plasma levels of fibrinogen and homocysteine and serum levels of plasminogen activator inhibitor-1 (PAI-1) were obtained before and 6 months after initiation of treatment. The three drugs differentiated in regard to homocysteine (p<0,00001) and fibrinogen level changes (p=0,00003), but not (p=NS) in PAI-1 change. In smokers, differentiation was found in all three parameters (p=0,0002, p=0,001, and p=0,006 for fibrinogen, PAI-1, and homocysteine, respectively), but in non-smokers differentiation was found only in homocysteine change (p=0,00003). In smokers, fibrinogen, PAI-1, and homocysteine were reduced more (p=0,002, p=0,0009, and p<0,0001, respectively) than in non-smokers in the whole study cohort. The effect of nebivolol was more prominent in smokers than non-smokers in reducing all three parameters (p=0,0001, p=0,003, and p=0,003, respectively), whereas in celiprolol and carvedilol-treated groups, differentiation between smokers and non-smokers was significant (p=0,00003 and p=0,01, respectively) only in homocysteine level change. In hypertensive smokers, nebivolol resulted in a significant decrease of plasma PAI-1, fibrinogen, and homocysteine. Celiprolol also significantly affected these parameters but to a lesser degree, whereas carvedilol had no significant favourable action. In non-smokers, homocysteine was reduced significantly by nebivolol. We conclude that smoking status should be a determinant of antihypertensive treatment choice.

Olmesartan medoxomil is a new angiotensin II receptor blocker. In this randomized, double-blind, placebo-controlled study, the efficacy and safety of olmesartan medoxomil was assessed in 334 patients with moderate to severe essential hypertension. Patients were randomized to receive placebo; 5, 20, or 80 mg olmesartan medoxomil q.d.; or 2,5, 10, or 40 mg olmesartan medoxomil b.i.d. Ambulatory and cuff blood pressure were measured prior to and after 8 weeks of treatment. Treatment with olmesartan medoxomil resulted in a significant placebo-adjusted reduction of mean 24-hour ambulatory diastolic blood pressure of 9,6 mm Hg, 12,2 mm Hg, and 10,6 mm Hg in the 5-, 20-, and 80-mg q.d. groups, respectively. Corresponding reductions in mean ambulatory systolic blood pressure were 14,5 mm Hg, 16,5 mm Hg, and 15,4 mm Hg. Similar reductions of diastolic and systolic blood pressure were seen with b.i.d. dosing. The diastolic trough-to-peak ratios of the q.d. doses of olmesartan medoxomil ranged from 57% to 70%, indicating 24-hour effectiveness. The safety profile of olmesartan medoxomil was similar to that of placebo. Olmesartan medoxomil appears to be a safe and effective once-a-day treatment for hypertension.

Nicorandil has cardioprotective effects in the ischemic myocardium, mimicking ischemic preconditioning, and is thus expected to improve the prognosis of ischemic heart disease (IHD). As part of the Japanese Coronary Artery Disease (JCAD) Study, a multi-centre collaborative prospective observational study of a large cohort of coronary artery disease patients, the effect of nicorandil on outcome was examined. In total, 2,558 patients with nicorandil treatment and controls subjected to propensity score matching were eligible among 13,812 patients registered in the JCAD study. The mean follow-up interval was 2,7 years. The primary endpoint, death from all causes, was significantly lower, by 35% (hazard ratio 0,65, p=0,0008), in the nicorandil group than in the control group. There were also significant reductions in secondary endpoints, including cardiac death (56%), fatal myocardial infarction (56%), cerebral or vascular death (71%), and congestive heart failure (33%) in the nicorandil group, with no excess of deaths from other non-cardiovascular causes. Treatment with nicorandil reduced the number of deaths from all causes to a similar extent with or without treatment with sulfonylureas. The reduction in cardiovascular death with nicorandil was large in patients with IHD, which has important implications for treatment.