Expression of TLR2, IL-1ß, and IL-10 Genes as a Possible Factor of Successful or Pathological Aging in Nonagenarians.

The expression of the gene of pattern recognition receptor TLR2, proinflammatory cytokine IL-1ß, and anti-inflammatory cytokine IL-10 was analyzed in the peripheral blood of nonagenarians (n=219; mean age 92.1 years, 77 men and 142 women) in comparison with healthy young donors (n=24; mean age 22.5 years, 16 women and 8 men). Nonagenarians were interviewed, medical records were analyzed, and a comprehensive geriatric assessment was performed according to the Clinical Guidelines on Frailty. The level of gene expression was determined by real-time PCR. The participation of inflammatory mechanisms in the immunosenescence was revealed. It was shown that increased expression of IL1B and TLR2 genes is associated with the development of frailty in nonagenarians and can be a factor of pathological aging. Increased expression of IL10 gene can be considered as a factor of successful aging in nonagenarians.

Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.

[Correlations between vessel stiffness and biomarkers of senescent cell in elderly patients].

Aim    To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods    This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results    The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, and cellular levels (r>0.3, р<0.05) and showed positive and negative correlations with PWV. The following blood plasma factors were selected as the markers of ageing: insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), and vascular endothelium adhesion molecule 1 (VCAM-1). A significant negative correlation between PWV and IGF-1 concentration was found. Among the tissue markers, P16INK, the key marker for tissue accumulation of senescent cells, predictably showed a positive correlation (r=0.394, p<0.05). A medium-strength correlation with parameters of the 96-h increment of mesenchymal stromal cells and fibroblasts and a weak correlation with IL-6 as a SASP (specific senescent-associated secretory phenotype) were noted. Results of the multifactorial linear regression analysis showed that the blood plasma marker, VCAM-1, and the cell marker, 96-h increment of fibroblasts, were associated with PWV regardless of the patient's age.Conclusion    Stiffness of great arteries as measured by PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.

[Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes].

Aim    Activation of the renin-angiotensin-aldosterone system, decreased nitric oxide production, chronic inflammation, and oxidative stress result in subclinical changes in the arterial wall, which favor the development of cardiovascular diseases (CVD). The effect of allelic gene variants that encode the proteins participating in pathogenetic pathways of age-associated diseases with subclinical changes in the arterial wall [increased pulse wave velocity (PWV), increased intima-media thickness, endothelial dysfunction (ED), presence of atherosclerotic plaques (ASP)] are understudied. This study analyzed the relationship between AGT, ACE, NOS3 TNF, MMP9, and CYBA gene polymorphism and the presence of subclinical changes in the arterial wall, including the dependence on risk factors for CVD, in arbitrarily healthy people of various age.Material and methods    The relationship of polymorphisms с.521С>Т of AGT gene, Ins>Del of AСE gene, с.894G>T of NOS3 gene, - 238G>A of TNF gene, - 1562С>T of MMP9 gene, and c.214Т>С of CYBA gene with indexes of changes in the arterial wall and risk factors for CVD was studied in 160 arbitrarily healthy people by building models of multiple logistic regression and also by analyzing frequencies of co-emergence of two signs with the Pearson chi-squared test (χ2) and Fisher exact test.Results    The DD-genotype of Ins>Del ACE gene polymorphism was correlated with increased PWV (p=0.006; odds ratio (OR) =3.41, 95 % confidence interval (CI): 1.48-8.67) and ED (p=0.014; OR=2.60, 95 % CI: 1.22-5.68). The GG genotype of с.894G>T NOS3 gene polymorphism was correlated with ED (p=0.0087; OR=2.65, 95 % CI: 1.26-5.72); the ТТ-genotype of с.894G>T NOS3 gene polymorphism was correlated with ASP (p=0.033; OR=0.034, 95 % CI: 0.001-0.549).Conclusion    Polymorphic variants of AСE and NOS3 genes correlated with ED, increased arterial wall stiffness, and the presence of subclinical changes in the arterial wall.

[Detection of peripheral artery disease in patients with ischemic heart disease. A quick guide for medical practitioners].

In this manual, the authors focused on the principal methods for diagnosis of peripheral artery disease in cardiological patients, from the interview and physical examination to functional tests and vascular visualization. Diagnostic and prognostic value of each method, its potentialities for reducing the risk of cardiovascular events (CVE), including myocardial infarction (MI), ischemic stroke (IS) or extremity amputation in critical ischemia, and overall mortality are discussed. The authors provided current information about a possibility of reducing the risk of CVE by intensifying the antithrombotic therapy according to results of the COMPASS study.

[New possibilities of using moxonidin for blood pressure control in female patients with osteopenia].

OBJECTIVE: To assess the effect of moxonidine on bone metabolism and bone mineral density (BMD) in postmenopausal patients with arterial hypertension (AH) and osteopenia. MATERIALS AND METHODS: A randomized, open, clinical trial included 114 postmenopausal patients with AH. All participants were evaluated bone metabolism), BMD, telomerase activity (TA). Randomization was carried out into 2 groups (moxonidine and bisoprolol therapy) using simple envelopes. After 12 months of therapy, a dynamic examination was performed. RESULTS: Both groups showed a positive effect of both moxonidine and bisoprolol on hypertension during treatment both as monotherapy and in the group of patients receiving combined antihypertensive therapy: a decrease in SBP and DBP in the 1st group was 13.6% and 12.8% respectively, and in the 2nd group - 13.7% and 15% respectively, while achieving normal values. In most patients of group 1, normalization of body weight was noted in comparison with group 2 (23.4% and 17.4%, respectively, p = 0.043), delta of body weight in the moxonidine group was -1.89%. The increase in the processes of bone formation in the form of increased markers of OC and Osteoprotegerin and a statistically signifcant increase in TA in patients receiving moxonidine were revealed, while in women who took bisoprolol there were no dynamic changes in bone metabolism rates, there was a tendency for a decrease in BMD and a signifcant decrease in AT. CONCLUSIONS: Te detected pleiotropic effect of moxonidine on bone metabolism and replicative cell aging processes will reduce the risk of development or progression of osteopenia and osteoporosis in postmenopausal women with AH.

Features of diagnostics and treatment of chronic heart failure in elderly and senile patients. Expert opinion of the Society of Experts in Heart Failure, Russian Association of Gerontologists, and Euroasian Association of Therapists.

.

[ECG Predictors of Prognostically Unfavorable Coronary Artery Lesions].

Medical treatment of most patients with ischemic heart disease is comparable to revascularization by the effect on major adverse cardiovascular events (myocardial infarction, cardiovascular and overall mortality), and in the long term, on quality of life. However, revascularization of the left main coronary artery lesion and lesions in the proximal segment of the anterior descending artery leads to a significant increase in life expectancy. ECG methods of detection of such prognostically unfavorable lesions of the coronary arteries can significantly optimize the management, hasten revascularization of the myocardium. In this review we have analyzed ECG methods of diagnosis of prognostically unfavorable lesions of the coronary arteries.

[Association of renal function, telomere length and markers of chronic inflammation for patients without chronic kidney and cardiovascular diseases].

Most of people over 60 years of age have decreased renal function and the velocity of glomerular filtration rate reduction varies greatly. Presumably, one of the probable mechanisms of accelerated decline of renal function may be a shortening of telomere length due to chronic inflammation. The main purpose of research was to appreciate the association of renal function, leukocytes telomeres length and markers of chronic inflammation in patients without chronic kidney disease and cardiovascular disease. 253 patients without chronic kidney diseases and cardiovascular diseases were included in the study. The average age of patients was 51,5±13,3 years. There were 172 women and 81 men. 55 patients had hypertension of 1-2 degree, 46 patients had normal renal function, 207 had mild failure of kidney function. Albuminuria was < 30 mg/day in all patients. Multivariate linear regression analysis revealed statistically significant correlation between albuminuria level and telomere length (p=0,023), C reactive protein (p=0,047) and fibrinogen (p=0,001). Glomerular filtration rate, urea and creatinine were not associated with telomere length and markers of inflammation but were correlated well with age, p < 0,001. CONCLUSIONS: Albuminuria is mainly associated with chronic inflammation and telomere length (from all studied indices of renal function). Albuminuria may be regarded as a marker of replicative cell senescence and a therapeutic target for the prevention of renal function reduction.

[Cellular Mechanisms of Morphological and Functional Changes of the Arterial Wall With Age and the Role of Statin Therapy in the Prevention].

We discuss the cellular and molecular mechanisms of morphological and functional changes of the arterial wall in the aging process and the possibility of using statin therapy for the prevention of early vascular aging.

[Age-related Changes of Left Ventricular Diastolic Function, NT-proBNP Level and Their Association With Leukocyte Telomere Length].

UNLABELLED: With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing of the heart is cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the diastolic function of LV and level of NT-proBNP in people of different ages free of cardiovascular diseases and to assess their relationship with LTL. Our data showed that old age is associated with diastolic dysfunction and increase in the levels of NT-proBNP. The group of older subjects had lower values of E/A (0.96 ± 0.036 vs 1.27 ± 0.03, p < 0.001), Em/Am (0.9 ± 0.035 vs 1.5 ± 0.066) and higher values of IVRT (81 ± 1.56 vs 70 ± 1.23 MS, p < 0.001), DT (198 ± 3.98 vs 175 ± 2.82 MS, p < 0.001), that reflected impairment of LV relaxation. NT-proBNP level was higher in the elderly (100.82 ± 7.1 vs 48.47 ± 6.7 ωg/ml, p < 0.01), but it did not correlate with LTL. The most sensitive to the age parameters of LV diastolic function (E/A and Em/Am ratio) were positively and independently of age associated with LTL (p < 0.001). Older individuals with shorter LTL had significantly lower values of E/A ratio. CONCLUSION: Telomere length appears to be a biomarker of myocardium ageing.

Short telomere length is associated with arterial aging in patients with type 2 diabetes mellitus.

It is known that glucose disturbances contribute to micro- and macrovascular complications and vascular aging. Telomere length is considered to be a cellular aging biomarker. It is important to determine the telomere length role in vascular structural and functional changes in patients with diabetes mellitus. We conducted a cross-sectional observational study in a high-risk population from Moscow, Russia. The study included 50 patients with diabetes and without clinical cardiovascular disease and 49 control group participants. Glucose metabolism assessment tests, measuring intima-media complex thickness and determining the presence of atherosclerotic plaques, pulse wave velocity measurement, and telomere length measurement were administered to all participants. Vascular changes were more dramatic in patients with diabetes than in the control group, and the telomeres were shorter in patients with diabetes. Significant differences were found in the vascular wall condition among diabetes patients, and there were no substantial differences in the arterial structure between patients with 'long' telomeres; however, there were statistically significant differences in the vascular wall condition between patients with 'short' telomeres. Vascular ageing signs were more prominent in patients with diabetes. However, despite diabetes, vascular changes in patients with long telomeres were very modest and were similar to the vascular walls in healthy individuals. Thus, long lymphocyte telomeres may have a protective effect on the vascular wall and may prevent vascular wall deterioration caused by glucose metabolism disorders.

[Age-related Changes of Left Ventricular Diastolic Function, NT-proBNP Level and Their Association with Leukocyte Telomere Length].

With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing of the heart is cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the diastolic function of LV and level of NT-proBNP in people of different ages free of cardiovascular diseases and to assess their relationship with LTL. Our data showed that old age is associated with diastolic dysfunction and increase in the levels of NT-proBNP. The group of older subjects had lower values of E/A (0.96+/-0.036 vs 1.27+/-0.03, p<0.001), Em/Am (0.9+/-0.035 vs 1.5+/-0.066) and higher values of IVRT (81+/-1.56 vs 70+/-1.23 s, p<0.001), DT (198+/-3.98 vs 175+/-2.82 s, p<0.001), that reflected impairment of LV relaxation. NT-proBNP level was higher in the elderly (100.82+/-7.1 vs 48.47+/-6.7 g/ml, p<0.01), but it did not correlate with LTL. The most sensitive to the age parameters of LV diastolic function (E/A and Em/Am ratio) were positively and independently of age associated with LTL (p<0.001). Older individuals with shorter LTL had significantly lower values of E/A ratio. CONCLUSION: Telomere length appears to be a biomarker of myocardium ageing.

[The renin-angiotensin-aldosterone system and vascular aging].

In this paper we discuss the role of renin-angiotensin-aldosterone system in development of morphological and functional changes in the vascular aging as well as, possibility of its correction by using different groups of drugs.

[The role of multidetector computed tomography in detection of myocardial infarction].

UNLABELLED: The aim of the study was to assess the diagnostic value of multidetector computed tomography (MDCT) in detection of myocardial infarction (MI) in acute and chromic stages. MATERIAL AND METHODS: 49 patients with suspected MI were included in the study. In 44 patients the diagnosis of acute MI had been confirmed according to standard criteria. Contrast-enhanced MDCT of the heart and vessels was performed with 4-row MDCT scanner. RESULTS: MDCT detected areas of MI in 39 of 44 patients with proven MI. In 66,7% of cases they were transmural and in 33,3% -- subendocardial. In arterial phase the density of infarcted area was significantly lower than in normal myocardium (mean, 32,6 +/- 3,7 HU versus 101,9 +/- 3,7 HU, correspondingly, p < 0,0001). Mean values of myocardial density in the area of the MI did not change during follow-up (32,6 +/- 3,7 HU vs 41,3 +/- 4,5 HU, ns). In comparison to SPECT, sensitivity and specificity of MDCT in detection of transmural MI were 96,9% and 100%. corr. In the whole group of patients, taking results of troponin test as a gold standard, the sensitivity of MDCT in detection of Q-MI and non-Q MI were 89,1% and 93,5%, correspondingly. CONCLUSION: Cardiac MDCT can reliably detect and localize areas of acute and chronic MI. Contrary to SPECT, it also gives information about stenosis and occlusions in the coronary arteries.

[Dynamic signal-averaged ECG during spontaneous stenocardia attacks in patients with ischemic heart disease]. / Dinamika sigtnal-usrednennoi EKG vo vremia spontannykh pristupov stenokardii u bol'nykh ishemicheskoi bolezn'iu serdtsa.

The dynamics of signal-averaged ECG and late potentials was studied in 19 patients with coronary heart disease during spontaneous anginal episodes. Baseline late potentials were observed in 9 (45%) patients, they remaining in all during and after anginal episodes. The occurrence of new late potentials was recorded in none of them. There were no significant differences in some parameters of signal-averaged ECG before, during, and after an anginal episode, though the duration of low-amplitude signals tended to increase at the end of the QRS complex and the mean square amplitude of late 40 msec of QRS complex decreased during transient myocardial ischemia. The differences did not achieve their statistical significance. It was concluded that transient myocardial ischemia during spontaneous anginal episodes failed to lead to the appearance of a substrate for the occurrence of late potentials.

[The effect of transient myocardial ischemia on the late potentials during transluminal coronary angioplasty in patients with ischemic heart disease]. / Vliianie prekhodiashchei ishemii miokarda na pozdnie potentsialy pri transliuminal'noi koronarnoi angioplastike u bol'nykh ishemicheskoi bolezn'iu serdtsa.

The frequency of recording late potentials and their dynamics were studied in 25 patients with coronary heart disease before, during, and after transluminal angioplasty (TAP). Baseline late potentials were observed in 6 (20.7%) cases. During TAP, late potentials were recorded significantly more frequently (48.3%) than the baseline ones (p < 0.03), in 6 (20.7%) patients, late potentials appeared only in arterial dilatation and disappeared after TAP. There was a profound decrease in root-mean-square amplitude of late 40 msec in the QRS complex and an increase in the duration of low-amplitude (less than 40 microV) signals at the end of the QRS complex as compared to the baseline values. In ST-segment elevation, the parameters of the ECG signal-average become deteriorated to a greater degree than those in ST-segment depression.

[The dynamics of the signal-averaged ECG in myocardial infarct patients]. / Dinamika signal-usrednennoi EKG u bol'nykh infarktom miokarda.

To study the dynamics of signal-averaged ECG and late potentials (LP) in the first month of myocardial infarction (MI) and the impact of coronary reperfusion on them, examinations were made of 98 patients with primary myocardial infarction, in 69 of whom coronary reperfusion was achieved. LP was found to be detectable just in the first hours of MI, their stabilization (steady-state appearance or cessation) mainly occurred at day 3 of the onset. LP detection at this time allowed them to be predicted before the patients' discharge (70% sensitivity and 95% specificity, 82% predictive value in the first 24 hours of MI, LPs are characterized by more instability than those in the subsequent period of the patients' hospitalization. Thrombolytic therapy and coronary artery patency have no impact on the frequency of LP recording and parameters of signal-averaged ECG. No significant difference was found in the frequency of recording LP in anterior and inferior MI before discharge. The frequency of LP recording does not depend on the sex and age of a patient, the maximum creatine phosphokinase levels, and the presence of postinfarction angina pectoris and heart failure.

[Impact of exercise test on signal-averaged ECG in patients with myocardial infarction]. / Vliianie nagruzochnogo testa na signal-usrednennuiu EKG u bolnykh infarktom miokarda.

To examine the impact of exercise test (bicycle ergometry) and exercise-induced transient ischemic changes in ST segment on signal-averaged ECG parameters, the authors studied a homogeneous group including 65 patients (62 males and 3 females) with a 2-3-week history of primary myocardial infarction. The findings showed that induced myocardial ischemia caused no significant changes in signal-averaged ECG and late potentials, exercise might induce late potentials without clear-cut ECG signs of myocardial ischemia. It was also indicated that exercise-labile late potentials were significantly more frequently associated with the development of ventricular arrhythmias than steady late potentials.