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 heart is a ...cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length.
The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S).
In the older people there was a higher wall thickness than in the younger (1.03 ± 0.09 vs. 0.88 ± 0.10, p<0.01), whereas LV mass index was comparable between them (85.8 ± 15.40 vs. 83.1 ± 11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (β = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV.
Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.
To study the real-world efficacy and safety of netakimab in the treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
The retrospective analysis included 23 patients (13 males; ...56.5%) aged 23 to 73 years (median 42, interquartile range 28 to 52 years) with AS (
=12) or PsA (
=11) who received netakimab therapy from February 2021 to April 2023. Disease activity was assessed every 3-6 months based on the C-reactive protein (CRP) level for all patients according to the BASDAI and ASDAS-CRP indices for AS, DAPSA and PASI for PsA. These indicators were analyzed before therapy and at the last visit to assess the effectiveness of treatment. The results are presented as median (interquartile range).
In all patients treated with netakimab (median duration of treatment 11 months), the CRP level decreased from 10.6 (3.1; 17.3) to 3.1 (1.9; 8.9) mg/L (absolute difference -7.5 mg/L, median relative reduction -60%;
=0.008), and the proportion of patients with elevated CRP decreased from 70 to 41%;
=0.039. In patients with AS (median duration of treatment 9 months), BASDAI score decreased from 5.8 (4.7; 6.5) to 3.0 (1.9; 3.8) points (absolute difference -2.8 points, median relative reduction of -45%;
=0.008) and ASDAS-CRP score decreased from 2.8 (1.9; 3.9) to 1.9 (1.7; 2.6) points (absolute difference -0.9 points, median relative reduction -21%;
=0.007). The proportion of patients with high AS activity (BASDAI≥4) decreased from 90% to 20% (
=0.031); however, there was no significant change in the CRP level (absolute difference -4.9 mg/L, median relative reduction -57%;
=0.110). In patients with PsA (median duration of treatment 18 months), the CRP level decreased from 12.0 (4.5; 17.3) to 3.3 (2.0; 7.8) mg/L (absolute difference -8.7 mg/L, median relative reduction -80%;
=0.041), the DAPSA score decreased from 23.0 (19.0; 30.5) to 6.3 (5.2; 13.5) points (absolute difference -16.7 points, median relative reduction -69%;
=0.018). Three (13%) patients reported mild to moderate adverse events.
The obtained data confirm the effectiveness and safety of netakimab in treating AS and PsA in real-world practice.
Aim: to assess the efficacy and safety of ixekizumab in the treatment of ankylosing spondyloarthritis (AS) and psoriatic arthritis (PA) in real clinical practice. Patients and Methods: this ...retrospective study included patients with AS and PA who received ixekizumab therapy from February 2021 to April 2022. Disease activity was evaluated every 3–6 months, using BASDAI and ASDAS scores for AS and DAPSA и PASI scores for PA. C-reactive protein (CRP) served as a serologic marker of disease activity. Results: the analysis included the data received for 27 patients, of whom 10 persons had AS and 17 — PA. The safety of treatment was assessed in all patients, and the data of 9 AS and 16 PA patients were included in the analysis of the treatment efficacy. In the AS group (4 males and 5 females), the median age at the therapy initiation was 34 32; 41.5 years and in the PA group (11 males and 6 females — 40 32.5; 48.5 years. Failure or intolerance of the standard therapy was reported in all patients. Prior to ixekizumab treatment, most patients did not receive targeted therapies. Of 27 patients, 4 received genetically engineered biological drugs / targeted synthesized drugs which failed to achieve remission / low disease activity. In the AS group, the elevated levels of CRP were revealed in 7 (77.8%) patients, ASDAS demonstrated the presence of disease activity in all patients. According to BASDAI, disease activity was recorded in 7 (77.8%) cases. During the treatment, there was a downtrend in the percentage of patients with high disease activity as shown by ASDAS and BASDAI scores, as well as in the percentage of patients with elevated levels of CRP, while the BASDAI values were statistically significant (p=0.031). In the PA group, elevated CRP levels were reported in 62.5% of patients, and DAPSA scores represented moderate of high activity in 75.0% of patients. As a result of the treatment, there was a decrease in the percentage of patients with higher DAPSA scores and elevated CRP levels, but the changes did not achieve statistical significance. Side effects were reported in 7.4% of patients, but there were no serious adverse events. Conclusion: acording to our data ixekizumab has shown efficacy and safety in the treatment of PA and AS in real clinical practice. KEYWORDS: ixekizumab, real clinical practice, psoriatic arthritis, ankylosing spondyloarthritis, genetically engineered biological drugs. FOR CITATION: Meshkov A.D., Ostapenko V.S., Pykhtina V.S. The efficacy and safety of ixekizumab in the treatment of spondyloarthritis under the conditions of real clinical practice. Russian Medical Inquiry. 2023;7(3):137–143 (in Russ.). DOI: 10.32364/2587-6821- 2023-7-3-137-143.
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.
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" (
≤ 45 years,
≤ 55 years) and "older" (
> 45 years,
> 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.
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,
< 0.001 for HOMA,
= 0.03 for GH, and
= 0.004 for LTL. In the model with IMT as a dependent variable,
= 0.0001 for HOMA,
= 0.044 for GH, and
= 0.004 for IGF-1. In the model with the number of plaques as a dependent variable,
= 0.0001 for HOMA, and
= 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.
GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants.
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.
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.
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 (
= 0.004) in the atorvastatin group and from 0.67 ± 0.06 to 0.60 ± 0.07 (
= 0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (
= 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.
These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector.
The trial was registered in ISRCTN registry ISRCTN55050065.
Arterial wall status is determined by several characteristics, the main of them are as follows: pulse wave velocity (PWV), carotid arteries intima-media thickness (IMT), the presence of ...atherosclerotic plaques, endothelium-dependent vasodilation (EDVD). When these parameters change, the risk for cardiovascular disease (CVD) grows. The nature of relationship between these indices in people without CVD clinical signs is understudied, especially in those of older age.Aim. To estimate correlations between different parameters of arterial wall in patients of different age without CVD.Material and methods. A total of 303 people aged 25-91 years without any manifestations of CVD or other chronic diseases and without regular medical treatment were examined. PWV estimation, carotid ultrasound with IMT measurement and atherosclerotic plaques amount calculation and EDVD estimation using reactive hyperemia test were performed. Results. Patients without CVD clinical signs rather often reveal arterial wall lesions already in the younger age group (mean age 40.9±8.7): reduced EDVD – in 26% of the cases, the presence of atherosclerotic plaques – in 22%, increased PWV – in 15%, increased IMT – in 8%. The prevalence of arterial wall alterations in the older age group (mean age 61.19±8.5) increase many-fold. All arterial wall parameters correlate with age. The stronger correlation was revealed between IMT and the amount of atherosclerotic plaques: r=0.46 (р<0.001) in the younger group and r=0.47 (р<0.001) in the older one. We didn’t find any relationship between PWV and EDVD in the younger group and between PWV and the amount of atherosclerotic plaques in the older one. Thickened carotid intima-media increases the risk of arterial stiffness by 2.3 times.Conclusion. Estimation of the state of arterial wall in people of young age without CVD allows detecting individuals who require active CVD prevention. Increased stiffness of arterial wall and the development of subclinical atherosclerosis represent different phenotypes of alterations.
Introduction 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 heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length. Methods The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S). Results In the older people there was a higher wall thickness than in the younger (1.03 plus or minus 0.09 vs. 0.88 plus or minus 0.10, p<0.01), whereas LV mass index was comparable between them (85.8 plus or minus 15.40 vs. 83.1 plus or minus 11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio ( beta = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV. Conclusions Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.
IntroductionType 2 diabetes mellitus (T2DM) contribute to vascular aging. The telomere length (TL) and telomerase activity (TA) are considered as biomarkers of cellular aging. TL and TA are ...insufficiently studied in diabetic patients.HypothesisTelomere biology is associated with vascular aging in diabetic patients.MethodsThe study group included 50 patients with T2DM (mean age 58.4±7.83 years) and 139 healthy patients (mean age 57.45±8.14 years). All subjects were measured for TL and TA by quantitative polymerase chain reaction; oxidative stress marked by malondialdehyde (MDA); inflammation marked by C-reactive protein (CRP); arterial stiffness evaluated by pulse wave velocity (PWV); carotid intima-media thickness (IMT), plaque presence (PP) and endothelial dysfunction evaluated by flow-mediated endothelium-dependent vasodilation (FMV).ResultsAll patients were divided into 4 groups by the median of TL (9.75)«short» telomeres (T2DM+ (n=15) and T2DM- (n=63) and «long» telomeres (T2DM+ (n=35) and T2DM- (n=76)). Patients with T2DM and «long» TL had the state of vessels, oxidative stress, inflammation, TA as similar as in healthy peoplePWV 11.54±3.57 (T2DM+) vs 10.98±1.83 m/s (T2DM-) ((=0.58), IMT 0.83±0.13 vs 0.76±0.16 mm (=0.13), PP 1.36±0.33 vs 1.23±0.20 (=0.79); MDA 2.81±0.78 vs 3.24±0.78 mkmol/l (=0.08); CRP 3.59±0.58 vs 3.66±0.50 mg/l (=0.93); TA 0.51±0.09 vs 0.60±0.05 (p=0.36). FMV was higher in diabetic patients11.87±3.36 vs 10.18±2.79 % (=0.049). In contrast patients with «short» TL and T2DM had more pronounced vascular aging, inflammation and lower TA than healthy peoplePWV 13.48±3.24 vs 11.59±2.03 m/s (=0.003), IMT 0.95±0.17 vs 0.78±0.14 mm (<0.001), PP 2.23±0.27 vs 1.38±0.17 (=0.006), FMV 8.51±3.20 vs 11.04±3.01% (=0.0002; CRP 7.39±1.47 vs 4.03±0.62 mg/l (=0.046); TA 0.47±0.08 vs 0.62±0.07 (p=0.06).ConclusionIn patients with short telomeres and T2DM signs of vascular aging, chronic inflammation and cellular aging were more pronounced than in healthy people. In contrast, in patients with long telomeres and T2DM vascular changes, oxidative stress, chronic inflammation and TA were as similar as in healthy people. Perhaps long telomeres protect patients with T2DM from accelerated vascular aging.
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