Epidemiology of risk factors and estimating 10-year probability of osteoporotic fractures in the Russian Federation.

In assessing the risk of fractures, an important role is played by risk factors (RFs), the prevalence of which must be known among residents with different types of settlement in order to plan preventive measures in risk groups for fractures. Prevalence RFs varied depending on constituent entities and the settlement type. PURPOSE: To investigate the prevalence of osteoporotic fractures (OPF) RFs and estimate absolute risk (AR) of OPF among urban vs rural residents of the Russian Federation. METHODS: In total, 13,391 Russian women and men 40-69 years old from 12 regions participated in the study. Groups of urban (n = 12,237) and rural (n = 1154) subjects were comparable in terms of their age. Participants were interviewed using a standard modular questionnaire. AR of OPF was calculated using the Russian FRAX model. Age-dependent diagnostic and therapeutic intervention thresholds (DIT, TIT) were employed to stratify AR of OPF. RESULTS: Among the OPF RFs, the most common were as follows: previous OPF (16.3%), causes of secondary osteoporosis (20.8%), and current smoking (17.9%). The frequencies of previous OPF and alcohol abuse in rural men were higher than in urban male residents. Urban women, compared with rural females, were characterized by such more frequent RFs as smoking and glucocorticoids' intake. AR increased with age and prevailed in women, compared with men, regardless of their age, region of residence, and settlement type. According to TIT, the frequency of high AR of major OPF in the sample was 7.0%. According to DIT, high, medium, and low AR of major OPF was detected in 3.1%, 42.2%, and 54.7% of participants, respectively. Among urban women compared with rural females, high AR of major OPF was more often detected (p < 0.05), using TIT, whereas there was no such pattern for men. We discovered the territorial variability of RFs and OPF AR. CONCLUSION: Prevalence of OPF RFs varied in Russia depending on age, gender, constituent entities, and the settlement type. Our data have demonstrated the typical age-gender causation pattern of OPF AR. Over 40% of participants required densitometry and fracture risk reclassification.

Effectiveness of Trimetazidine in Patients with Stable Angina Pectoris of Various Durations: Results from ODA.

INTRODUCTION: Trimetazidine (TMZ) is an antianginal agent that acts directly at the myocardial cell level and which is now available in a once-daily (od) formulation. METHODS: ODA, a 3-month, observational, multicenter study in Russia, assessed the effectiveness and tolerability of TMZ 80 mg od in patients with stable angina and persisting symptoms, in real-life settings. The present analysis explored the effects of adding TMZ to background antianginal treatment with respect to the duration of stable angina. RESULTS: A total of 3032 patients were divided into four groups according to stable angina pectoris duration since diagnosis, ranging from less than 1 year to more than 10 years. A decrease in frequency of angina attacks was observed, including in patients with angina duration < 1 year, in whom the frequency of weekly angina attacks decreased from 3.8 ± 2.9 to 1.4 ± 1.7 at 1 month and 0.6 ± 1.0 at 3 months. Short-acting nitrate consumption and proportion of angina-free patients decreased, and self-reported physical activity and adherence to antianginal therapy improved in all patient groups, including recently diagnosed patients and starting already at month 1. CONCLUSIONS: Addition of TMZ 80 mg od to antianginal treatment was effective in reducing the frequency of angina attacks and the use of short-acting nitrates, improving Canadian Cardiovascular Society (CCS) class, self-reported physical activity, and adherence to antianginal therapy. These beneficial effects were observed in patient groups with different durations of stable angina, suggesting an opportunity for decreasing angina burden even in recently diagnosed patients. TRIAL REGISTRATION: ISRCTN registry Identifier, ISRCTN97780949.

Effectiveness of Long-acting Trimetazidine in Different Clinical Situations in Patients with Stable Angina Pectoris: Findings from ODA Trial.

INTRODUCTION: Trimetazidine (TMZ) has been shown to be efficacious for angina treatment. The TMZ 80-mg formulation allows one-daily (od) dosage, which could improve symptom control and adherence. METHODS: The 3-month, observational, multicenter, prospective ODA (antianginal effectiveness and tolerability of trimetazidine modified release 80 mg Once Daily in stable Angina patients in real-world practice) study assessed TMZ 80 mg od effectiveness in stable angina patients with persistent symptoms despite therapy. Two clinical situations were compared: patients who initiated treatment with TMZ 80 mg od (initiation group) and patients who were previously treated with TMZ 20 mg thrice daily (tid) or TMZ 35 mg MR twice daily (bid) and switched to TMZ 80 mg od (switch group). Number of angina attacks, short-acting nitrate (SAN) consumption, self-reported patient daily activity, Canadian Cardiovascular Society (CCS) class, adherence to antianginal therapy, overall efficacy and tolerability were assessed. RESULTS: A significant decrease in weekly number of angina attacks was observed for both the initiation group (n = 1841 patients) from 4.8 ± 3.5 at baseline to 0.9 ± 1.4 at 3 months (M3) (P < 0.001), and the switch group (n = 1216 patients) from 4.4 ± 1.3 at baseline to 0.9 ± 1.3 at M3 (P < 0.001). Significant reduction in SAN consumption and improvement in CCS class were observed for both groups. Adherence to antianginal therapy improved in both groups at 1 month (M1) and M3. Overall effectiveness of TMZ 80 mg od was rated by physicians as "very good" (68% initiation group, 70% switch group), "good" (31% initiation group, 29% switch group), "moderate" (1%, both groups) or "poor" (< 1%, both groups). Overall tolerability of TMZ 80 mg od was rated by physicians as "very good" (75%), "good" (25%) or "moderate" (< 1%) in both groups. CONCLUSIONS: TMZ 80 mg od, in association with other antianginal therapy, effectively reduced angina attacks and SAN consumption and improved physical activity and adherence to antianginal therapy both in patients initiating TMZ treatment and those switching from a bid or tid formulation. TRIAL REGISTRATION: ISRCTN registry Identifier, ISRCTN97780949. FUNDING: Servier. Plain language summary available for this article.

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice.

INTRODUCTION: Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients' satisfaction and adherence. METHODS: ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting. RESULTS: A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p < 0.001) decrease in angina attack frequency (from 4.7 ± 3.5 to 0.9 ± 1.3/week) and SAN use (from 4.5 ± 3.9 to 0.7 ± 1.3/week). Overall tolerability and effectiveness were rated as "very good" by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p < 0.0001) and non-adherence by 3% (vs. 36% at baseline, p < 0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p < 0.01), slight limitation (46% vs. 5% at baseline, p < 0.001) or moderate limitation (30% vs. 23%, p < 0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p < 0.001) or very marked reduction (1% vs. 19% at baseline, p < 0.01) at month 3. CONCLUSION: In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients. TRIAL REGISTRATION: ISRCTN registry Identifier, ISRCTN97780949. FUNDING: Servier. Plain language summary available for this article.

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases.

Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging. Methods: The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance-HOMA (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as "younger" (m ≤ 45 years, f ≤ 55 years) and "older" (m > 45 years, f > 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis. Results: Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, p < 0.001 for HOMA, p = 0.03 for GH, and p = 0.004 for LTL. In the model with IMT as a dependent variable, p = 0.0001 for HOMA, p = 0.044 for GH, and p = 0.004 for IGF-1. In the model with the number of plaques as a dependent variable, p = 0.0001 for HOMA, and p = 0.045 for IGF-1. In the older group, there were no independent significant associations between GH/IGF-1, LTL, HOMA, and arterial wall characteristics. Conclusions: GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants.

Atorvastatin Therapy Modulates Telomerase Activity in Patients Free of Atherosclerotic Cardiovascular Diseases.

Background: Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases (CVDs). Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now, this effect has not been investigated in prospective randomized studies. We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells. Methods: In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35-75 years, free of known CVDs and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction. Results: At study end, 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46 ± 0.05 to 0.68 ± 0.06 (p = 0.004) in the atorvastatin group and from 0.67 ± 0.06 to 0.60 ± 0.07 (p = 0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p = 0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in interleukin-6 within the normal range and a tendency toward reduction in blood urea. Conclusion: These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector. Trial registration: The trial was registered in ISRCTN registry ISRCTN55050065.

Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.

BACKGROUND: Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV). METHODS: The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis. RESULTS: Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL. CONCLUSIONS: These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk.

Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome.

INTRODUCTION: This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. METHODS: In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. RESULTS: This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. CONCLUSION: Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. FUNDING: Mitotech LLC.

Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents.

The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging.