Subclinical target organ damage in subjects with different components of metabolic syndrome.

BACKGROUND: To assess the association of metabolic syndrome (MS) and its components with target organ damage in a follow-up study of relatively healthy bank employers. METHODS: Out of 1600 random samples of office workers in Saint Petersburg (Russia), a group of 383 participants with at least one component of MS and without cardiovascular complications was selected (mean age 46.6 ± 9.0 years, 214 females (64.6%)). Follow-up visit was performed in 331 subjects. Target organ damage (TOD) was assessed by echocardiography, carotid ultrasound, applanational tonometry, brachial-ankle index, and urine albumin excretion measurements. Anthropometry, vital signs, and biochemistry were performed according to standard protocols. RESULTS: Presence of MS was not associated with higher probability of TOD. Multiple linear regression revealed significant association of all markers of TOD with older age. Hypertension was a significant predictor of left ventricular hypertrophy (LVH), increased arterial stiffness, and early signs of carotid atherosclerosis in logistic regression adjusted for age and gender. During follow-up, proportion of patients with LVH significantly decreased (from 46.7% to 32.9%, р = 0.003) and prevalence of patients with IMT > 0.09 сm increased (from 24.5% to 44.1%, p < 0.001) accompanying by significant declining of office blood pressure (BP) and total cholesterol. CONCLUSIONS: MS per se is not related to increased probability to TOD. Hypertension, female gender, and older age are main determinants of subclinical changes. After 2-years follow-up, significant LVH and renal damage regression was observed probably owing to BP reduction. Alternatively, early signs of carotid atherosclerosis increase with aging despite decreasing of the prevalence of hypercholesterolemia.

Remote vs. local ischaemic preconditioning in the rat heart: infarct limitation, suppression of ischaemic arrhythmia and the role of reactive oxygen species.

The unmet clinical need for myocardial salvage during ischaemia-reperfusion injury requires the development of new techniques for myocardial protection. In this study the protective effect of different local ischaemic preconditioning (LIPC) and remote ischaemic preconditioning (RIPC) protocols was compared in the rat model of myocardial ischaemia-reperfusion, using infarct size and ischaemic tachyarrhythmias as end-points. In addition, the hypothesis that there is involvement of reactive oxygen species (ROS) in the protective signalling by RIPC was tested, again in comparison with LIPC. The animals were subjected to 30-min coronary occlusion and 90-min reperfusion. RIPC protocol included either transient infrarenal aortic occlusion (for 5, 15 and 30 min followed by 15-min reperfusion) or 15-min mesenteric artery occlusion with 15-min reperfusion. Ventricular tachyarrhythmias during test ischaemia were quantified according to Lambeth Conventions. It was found that the infarct-limiting effect of RIPC critically depends on the duration of a single episode of remote ischaemia, which fails to protect the heart from infarction when it is too short or, instead, too prolonged. It was also shown that RIPC is ineffective in reducing the incidence and severity of ischaemia-induced ventricular tachyarrhythmias. According to our data, the infarct-limiting effect of LIPC could be partially eliminated by the administration of ROS scavenger N-2-mercaptopropionylglycine (90 mg/kg), whereas the same effect of RIPC seems to be independent of ROS signalling.

New technique of local ischemic preconditioning induction without repetitive aortic cross-clamping in cardiac surgery.

BACKGROUND: Several studies have demonstrated that local ischemic preconditioning can reduce myocardial ischemia-reperfusion injury in cardiac surgery patients; however, preconditioning has not become a standard cardioprotective intervention, primarily because of the increased risk of atheroembolism during repetitive aortic cross-clamping. In the present study, we aimed to describe and validate a novel technique of preconditioning induction. METHODS: Patients undergoing coronary artery bypass grafting (12 women and 78 men; mean age, 56 ± 11 years) were randomized into 3 groups: (1) Controls (n = 30), (2) Perfusion (n = 30), and (3) Preconditioning (n = 30). All patients were operated under cardiopulmonary bypass using normothermic blood cardioplegia. Preconditioning was induced by subjecting the hemodynamically unloaded heart to 2 cycles of 3 min of ischemia and 3 min of reperfusion with normokalemic blood prior to cardioplegia. In the Perfusion group, the heart perfusion remained unaffected for 12 min. Troponin I (TnI) levels were analyzed before surgery, and 12, 24, 48 h, and 7 days after surgery. The secondary endpoints included the cardiac index, plasma natriuretic peptide level, and postoperative use of inotropes. RESULTS: Preconditioning resulted in a significant reduction in the TnI level on the 7th postoperative day only (0.10 ± 0.05 and 0.33 ± 0.88 ng/ml in Preconditioning and Perfusion groups, respectively, P < 0.05). In addition, cardiac index was significantly higher in the Preconditioning group than in the Control and Perfusion groups just after weaning from cardiopulmonary bypass. The number of patients requiring inotropic support with ≥ 2 agents after surgery was significantly lower in the Preconditioning and Perfusion group than in the Control group (P < 0.05). No complications of the procedure were recorded in the Preconditioning group. CONCLUSIONS: The preconditioning procedure described can be performed safely in cardiac surgery patients. The application of this technique of preconditioning was associated with certain benefits, including improved left ventricular function after weaning from cardiopulmonary bypass and a reduced need for inotropic support. However, the infarct-limiting effect of preconditioning in the early postoperative period was not evident. The procedure does not involve repetitive aortic cross-clamping, thus avoiding possible embolic complications.

Prevalence of metabolic syndrome components in a population of bank employees from St. Petersburg, Russia.

BACKGROUND: The aim of this study was to assess prevalence of metabolic syndrome and its components according to different criteria in the population of bank employees in St. Petersburg, Russia. METHODS: A total of 1,600 office workers were screened at their working places from the Sberbank state bank in St. Petersburg. All subjects were interviewed by a special questionnaire that included personal data, smoking status, physical activity, alcohol consumption, and medical history. Anthropometry measurements, vital signs, and fasting blood samples were obtained. Serum lipids and plasma glucose were measured. RESULTS: In all, 1,561 responders were included in the final analysis. Hypertension (HTN) was observed in 35.2% of subjects (64% in males and 25.4% in females), abdominal obesity (AO) according to Internation Diabetes Federation (IDF) criteria in 45.6% (51.5% in males and 44.0% in females), high triglyceride levels in 28.4%, low high-density lipoprotein cholesterol (HDL-C) levels in 23.9%, and elevated fasting glucose over 5.6 mmol/L in 28.4% of subjects. AO associated with HTN was observed in 24.3%. Metabolic syndrome according to IDF criteria was diagnosed in 21.5% (17.9% in females and 34.6% in males, P<0.01), and according to Adult Treatment Panel III (ATP III) (2005) criteria in 18.8% of subjects (16.2% in females and 28.4% in males, P<0.01). The correlation between criteria was ρ(S)=0.79. Low physical activity, smoking, and alcohol abuse were associated with metabolic syndrome. CONCLUSIONS: Metabolic syndrome and its distinct components were very prevalent in Russian bank office workers. AO was most prevalent component for females with metabolic syndrome, whereas HTN was most prevalent for males. Coexistence of HTN and AO was the most frequent coupling of metabolic syndrome components. Unhealthy lifestyle characterized the selected group and was associated with metabolic syndrome, especially low physical activity.

Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity.

The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.

Prospective study of the changes in left ventricular mass and geometry patterns in hypertensive patients During 5 years of follow-up.

BACKGROUND: Left ventricular hypertrophy (LVH), as well as the geometry pattern of the left ventricle, is believed to be an independent risk factor for hypertension. The present study investigated the changes in left ventricular mass, diastolic function and geometry in hypertensive patients in a prospective 5-year follow-up in conjunction with an evaluation of the regularity and effectiveness of treatment. METHODS AND RESULTS: One hundred hypertensive patients older than 18 years were examined according to the study protocol, which included registration of weight, height, vital signs, and echocardiography. After 5 years a repeat examination was performed. Patients were divided into 3 groups according to blood pressure (BP) control: group 1 (n=32), no regular medication; group 2 (n=44), regular treatment but no target BP levels; group 3 (n=14), regular effective treatment. In group 1 an increase in LVH and worsening of diastolic function were observed; in group 2 LVH and isovolumetric relaxation time remained unchanged, while the early peak velocity/atrial peak velocity ratio decreased; in group 3 there was a significant decrease in LVH. The geometry pattern only changed in 21 (23%) patients. CONCLUSIONS: LVH can be successfully reversed in only hypertensive with adequate BP control. The remodeling pattern appears to be a stable characteristic of the patient and transformation of one pattern into another is infrequent.

Lack of association of G-protein subunit gene C825T polymorphism with left ventricular hypertrophy in essential hypertension.

BACKGROUND: The aim of the present study was to determine if there is an association of G-protein b3 subunit (GNB3) gene polymorphisms and left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) in a St. Petersburg population. MATERIAL/METHODS: We examined 135 patients (mean age 48 +/- 7 yrs) with mild to moderate EH recruited from the general population of an outpatient hypertension clinic. Left ventricular mass was measured by echocardiography, and the left ventricular mass index (LVMI) was calculated. The GNB3 C825T genotype was determined by polymerase chain reaction and restriction digestion. RESULTS: 67 patients (50%) were homozygous for the C allele (CC), 56 were heterozygous (CT) (41%) and twelve (9%) were homozygous for the T allele (TT). The distribution of genotypes among the patients was in Hardy-Weinberg equilibrium and did not differ significantly when comparing patients with or without LVH. The frequency of the T allele was only slightly higher in patients with LVH (32%) compared to those without LVH (28%), NS, and the LVMI was similar in patients with the CC, CT and TT genotypes (122.3 +/- 29.8; 118.8 +/- 29.9 and 115.2 +/- 18.3 g/m2, respectively). No significant discrepancies were found among the various genotype groups in posterior wall thickness, interventricular septum thickness, or functional parameters such as ejection fraction, isovolumetric relaxation time and E/A ratio. CONCLUSIONS: These observations clearly suggest the lack of association between left ventricular structure or function and the CNB3 gene variant in the studied population.