Number Of Atherosclerotic Plaques Research Articles

Low adherence to the Mediterranean diet is associated with increased prevalence and number of atherosclerotic plaques in the ILERVAS cohort

Background and aimsCurrent research on the association between dietary patterns and subclinical atherosclerotic disease (SAD) is still limited, and published results are inconsistent and often consist of small population sizes. We aimed to evaluate the association between the Mediterranean diet (MDiet) and SAD in a large cohort of Mediterranean individuals. MethodsThis was a cross-sectional study that included 8116 subjects from the ILERVAS cohort. The presence of atherosclerotic plaques (AP) was assessed by ultrasound examination. Adherence to the MDiet was assessed using the 14-item Mediterranean Diet Adherence Score (MEDAS). Inclusion criteria were subjects with at least one cardiovascular risk factor. Exclusion criteria were a clinical history of diabetes, chronic kidney disease, or a prior cardiovascular event. Bivariable and multivariable models were performed. ResultsCompared with subjects without SAD, participants with SAD were older and had a higher frequency of smoking habit, hypertension, dyslipidemia, HbA1c and waist circumference. The adjusted multivariable analysis showed that a higher MEDAS was associated with a lower risk of AP (incidence rate ratios [IRR] 0.97, 95% CI [0.96–0.98]; p<0.001). Furthermore, moderate or high adherence to the MDiet was associated with a lower number of AP compared with a low MDiet adherence (IRR 0.90, 95% CI [0.87–0.94]; p<0.001). In both models, female sex was associated with a lower risk of AP. ConclusionsOur findings point to a potentially protective role of MDiet for SAD in a Mediterranean population with low-to-moderate cardiovascular risk. Further research is needed to establish a causal relationship between both variables.

Associations of Arterial Stiffness and Bone Mineral Density in Postmenopausal Women

Aim. To study associations between arterial stiffness and bone mineral density in postmenopausal women.Material and methods. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation. The Bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry.Results. A significant correlation of PWV with age, duration of menopause was revealed, a more pronounced correlation was noted with blood pressure (BP), maximum IMT thickness. There was no significant correlation between PWV and BMD. AI showed a statistically significant but weak negative correlation with the HN (rs=0.12, p&lt;0.05); a more pronounced negative correlation was obtained for BMD (rs=0.16, p&lt;0.01). For indicators characterizing the degree of bone mass increased, there is a significant correlation with age (rs=-0.4, p&lt;0.01), weight (rs=0.4, p&lt;0.01), Quetelet index (rs=0.3, p&lt;0.01) and the presence of AP (rs=-0.12, p&lt;0.05). According to the results of multivariate regression analysis, the most significant predictors of arterial stiffness were indicators reflecting obesity and diastolic BP. The relationship between BMD and age-adjusted vascular stiffness was not statistically significant.Conclusion. In our study, postmenopausal women have increased arterial stiffness, suggesting a higher risk of cardiovascular disease. The relationship between bone mineral density and vascular wall stiffness was insignificant. To a greater extent, arterial stiffness depended on age, increased blood pressure, and the presence of atherosclerotic changes.

A Study of Oxidative Stress, Inflammation, and Endothelial Dysfunction in Diabetic and Nondiabetic Chronic Kidney Disease Pre-Dialysis Patients.

Oxidative stress, inflammation, and endothelial dysfunction represent a key triad for the development and progression of atherosclerosis. Due to chronic low-grade inflammation in chronic kidney disease (CKD), concentrations of various inflammatory, endothelial, and oxidative stress markers are elevated, increasing the risk of atherosclerosis. The present study was undertaken to compare oxidative stress, inflammation, and endothelial dysfunction in diabetic and nondiabetic CKD pre-dialysis patients. This was an observational study on 120 CKD pre-dialysis patients: 60 with diabetes and 60 without diabetes. Markers of oxidative stress were measured in blood - malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), paroxonase-1 (PON-1), ischemia-modified albumin (IMA); inflammation - interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP); and endothelial dysfunction - nitric oxide (NO), carotid wall intima-media thickness (CIMT). Comparisons between the two groups for continuous variables were made with the Student's unpaired t-test or Mann-Whitney test and for categorical values with χ2-test, as appropriate. MDA, IMA, IL-6, hsCRP, NO, and CIMT were significantly higher, while FRAP and PON-1 were significantly lower in the diabetic group when compared to nondiabetic group (P < 0.001). The number of atherosclerotic plaques was also significantly higher in the diabetic group compared to nondiabetic group. Our study showed increased oxidative stress, inflammation, endothelial dysfunction, and atherosclerosis in diabetic CKD pre-dialysis patients when compared to nondiabetic CKD pre-dialysis patients and in late stages when compared to early stages of CKD in both groups, indicating increased cardiovascular risk in late stages and diabetic CKD pre-dialysis patients.

Associations of bone mass and polygenic risk of osteoporosis with indicators of arterial wall condition

Background: The identification of genetic factors that are simultaneously responsible for the predisposition to the development of cardiovascular diseases (CVD) and osteoporosis (OP) is important for the prevention of both conditions.Aim: The aim of this study is to evaluate three genetic risk scales (GRS) that previously showed an association with bone mineral density (BMD) and fracture risk, as well as to study the associations of these GRS with vascular wall pathology.Materials and methods: 250 female outpatients (aged 45 to 69) were enrolled into a cross-sectional study. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. Coronary vessels calcium deposits were registered by multispiral computed tomography (MSCT) using the Agatston calcium index (CI). The BMD of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. Bone resorption marker type-1 collagen C-terminal telopeptide (CTx) was assessed solid-phase enzyme immunoassay. The genetic study included DNA extraction from whole blood samples. Targeted sequencing was performed on the Nextseq550 sequencer (Illumina, USA). Statistical analysis was carried out using the SAS software package for Windows, version 9.0 (SAS Institute Inc., USA).Results: The chance of detecting low bone mass increased more than 4 times at values of IMT ≥0.9 mm (OR=4.17; 95%CI [1.2–14.4], p&lt;0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p&gt;&lt;0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p&gt;&lt;0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p&gt;&lt;0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p&gt;&lt;0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI. Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.&gt;&lt; 0.02), 2.4 times in the presence of AP in the carotid arteries (OR=2.45; 95%CI [1.12–4.88], p&lt; 0.05), by 6.7 times with an Agatstone CI ≥ 100 units (OR=6.68; 95%CI [1.56–28.7], p&lt; 0.001), 1.4 times (OR=1.43; 95%CI [0.56–3.68], p&lt; 0.438) with a PWV ≥10 m/s, 1.2 times (OR=1.2; 95%CI [0.601–2.43], p&lt;0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.&gt;&lt; 0.60) with increased AI ≥ 27%. According to multivariate linear regression analysis (adjusted for age, duration of postmenopause, marker of bone resorption CTx), a significant association of all GRS with BMD in all parts of the skeleton was revealed. Both univariate and multivariate regression models adjusted for several covariants (age, total cholesterol, systolic blood pressure) showed a reliable association of GRS62 with the presence of plaques and GRS63 — with coronary artery CI.Conclusion: The results of the study demonstrated the association of polygenic genetic risk of GRS-based OP with BMD and vascular wall status indicators in women in the peri and postmenopausal periods.

Carotid Intima-Media Thickness in Patients with Psoriasis

Introduction: Since the early 20th century, findings have demonstrated that psoriasis is frequently associated with atherosclerosis and cardiovascular diseases. The Carotid Intima-Media Thickness (CIMT) is a surrogate marker of atherosclerotic vascular disease. Objective: The aim of this study was to investigate the CIMT in patients with psoriasis and investigate its correlation with the clinical features. Methods: The present case-control study involved 70 patients with psoriasis who visited Ho Chi Minh City Hospital of Dermato-Venereology from September 2018 to April 2019 and 35 healthy subjects. Serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were measured in both groups. Linear Doppler scanning was performed to evaluate the CIMT of the common, internal, and external carotid arteries and the presence of atherosclerotic plaques. Results: The mean CIMT value in psoriasis patients was significantly higher than that of controls [0.59 mm (0.53 - 0.71) vs. 0.54 mm (0.52 - 0.62), respectively, p = 0.036]. Multiple linear regression analysis revealed a significant correlation between the CIMT and age (p = 0.043) and CIMT and the Psoriasis Area and Severity Index (p &lt; 0.0001). Moreover, the mean number of atherosclerotic plaques in psoriasis patients was significantly higher than that in controls [0.27 ± 0.68 vs. 0.03 ± 0.17, respectively, p = 0.035]. Conclusion: Elderly patients with severe psoriasis should be evaluated carefully regarding CIMT and atherosclerotic plaques, as these signs are representative of increased cardiovascular risk.

Cardiovascular system status of long-livers in Moscow: the prevalence of cardiovascular diseases and their risk factors

Over the past century, an increase in life expectancy has been observed in Russia and in the world. According to the United Nations, by 2100, the number of centenarians worldwide will reach 25 million. Despite the annual increase in the number of super-centenarians, this age group remains poorly understood.Aim. To estimate the prevalence of cardiovascular diseases (CVD) and the main risk factors among super-centenarians in Moscow.Material and methods. According to the register of long-livers in Moscow, 82 people aged 95 to 105 were included. Participants were examined at home.The history of life and the presence of chronic diseases was collected by participant words. To assess the state of cardiovascular system, an ultrasound of the heart and main arteries was performed.Results. Conventional CVD risk factors were the exception rather than the rule among study participants (smoking — 8 patients (9,8%), alcohol abuse — 4 (4,9%), obesity — 6 (7,3%)). Dyslipidemia was relatively widespread (n=37; 45,1%), however, there were no pronounced abnormalities in the lipid profile: the maximum increase in low-density lipoproteins was 5,6 mmol/L. The most common CVDs among the participants were hypertension (n=64; 78%), coronary artery disease (n=42; 51,2%), and heart failure (n=26; 31,7%); other diseases were much less common. The most common echocardiographic changes were left atrial dilatation (n=38; 74,5%), increased left ventricular mass, thickening of left ventricular posterior wall (n=24; 48%) and interventricular septum (n=51; 100%). Diastolic and systolic heart failure were not widespread among long-livers: 16 (32%) and 2 (3,9%), respectively. Despite a rather large number of atherosclerotic plaques in the common carotid and femoral arteries, the number of hemodynamically significant plaques was low (n=3; 4,6%). An intima-media thickening up to 1,0-1,1 mm was found.Conclusion. Long-livers in Moscow are characterized by a low prevalence of traditional CVD risk factors (with the exception of hypertension) and a fairly high prevalence of atherosclerotic CVDs, which are characterized by a subclinical course.

Assessment of Subclinical Manifestations of Atherosclerosis of Coronary and Peripheral Arteries and Bone Strength Parameters in Women

Aim. To study associations between calcification of the coronary arteries (CA), the state of the peripheral vascular wall and bone strength indices.Material and methods. In a cross-sectional study were included 200 women at the age 45-69 y.o. who were observed on an outpatient basis and signed informed consent. A survey was conducted on the presence of cardiovascular risk factors and the risk of fractures. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. The presence of calcium deposits in coronary vessels was determined by multispiral computed tomography (MSCT) using the Agatston index. The bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. The marker of bone resorption C-terminal telopeptide of type-1 collagen (СТх) was determined in blood serum by the β-crosslaps method.Results. There was a positive correlation between the parameters of vascular stiffness, subclinical atherosclerosis of peripheral vessels and CA calcification: AI and calcium index (r=0.25, p&lt;0.05), IMT and calcium index (r=0.23, p&lt;0.05), presence of AP and calcium index (r=0.26, p&lt;0.05). The PWV increased as the calcium index increased, but the correlation remained at the trend level. Women with low bone mass had higher PWV (p&lt;0.05), AI (p&lt;0.01), IMT (p&lt;0.02), CTx level (p&lt;0.001) and a higher number of AP than those with normal BMD. CTx was inversely correlated with PWV and calcium index (p&lt;0.05). Based on multivariate linear regression analysis (adjusted for age, menopause duration, low body weight, smoking factor and total cholesterol) the independent nature of the relationship between the Agatstone index and BMD in all the measured parts of the skeleton, between AI and BMD of HN, and between IMT and BMD of HN was confirmed. The relationship between the marker of bone resorption CTx and BMD of the spine and PH remained highly reliable.Conclusion. The correlation of stiffness indices and subclinical atherosclerosis of peripheral arteries, which is a predictor of high risk of cardiovascular events, allows to suggest an important role of changes in the peripheral vascular wall in increasing cardiovascular risk. A decrease in BMD and an increase in the marker of bone resorption, associated with an increase in indices of vascular stiffness and subclinical atherosclerosis and, especially, CA calcification, allows us to think about the common mechanisms of development and progression of atherosclerosis and osteoporosis. Therefore, early examination of women with a high cardiovascular risk, assessed by the SCORE scale, after 45 years and before menopause to detect vascular rigidity and the presence of subclinical atherosclerosis, and performing x-ray densitometry for individuals with changes in these indices will allow stratify the risks of atherosclerosis and osteoporosis complications and recommend preventive use of drugs that reduce vascular rigidity and increase BMD.

The level of N-terminal pro-brain natriuretic peptide depending on vascular wall condition and bone mass in postmenopausal women

Aim. To assess the relationship of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with vascular wall condition and bone mineral density (BMD) in postmenopausal women.Material and methods. The cross-sectional study included 107 outpatients aged 45-82 years who signed informed consent. The inclusion criterion was a menopause during ≥1 year. The level of serum NT-proBNP was determined by electrochemiluminescence. BMD was assessed by dual energy x-ray absorptiometry. Intima-media thickness (IMT), the presence and number of atherosclerotic plaques were evaluated using carotid duplex scanning. Pulse wave velocity (PWV) and augmentation index were estimated by applanation tonometry. To assess 10-year cardiovascular risk, the SCORE high-risk charts were used. Using the Russian model of FRAX® score, 10-year fracture risk was assessed.Results. NT-proBNP level in women with postmenopause &gt;10 years was significantly higher than in those with postmenopause &lt;5 years — 98,7 vs 56,3 pg/ml (p&lt;0,001), but there was no independent relationship according to the regression analysis. According to multivariate regression analysis adjusted for age, menopause duration, systolic blood pressure, hypercholesterolemia, smoking, elevated C-reactive protein and interleukin-6 levels, there were independent relationship between the following parameters: NT-proBNP and IMT (β=2,38, p&lt;0,03), NT-proBNP and PWV (β=1,76, p&lt;0,001). NT-proBNP level in patients with osteoporosis was significantly higher than in women with normal bone mass (p&lt;0,01). A negative correlation was observed between NT-proBNP and BMD of the proximal femur (r=-0,26, p&lt;0,05), while the relationship between BMD of the lumbar vertebrae (L1-L4) and NT-proBNP did not reach significance. In multivariate regression analysis, this relationship has not been confirmed. A positive correlation was obtained between cardiovascular risk (SCORE) and NT-proBNP levels (r=0,28, p&lt;0,001). NT-proBNP levels did not differ in women with a high and low 10-year risk of both major osteoporotic fractures and femoral fractures.Conclusion. An independent relationship of NT-proBNP with vascular stiffness and preclinical atherosclerosis was demonstrated: IMT and PWV. This indicates the participation of NT-proBNP in the atherosclerosis development. The association of elevated NT-proBNP levels with osteoporosis is significant, but not independent, and is apparently related to other factors.

RELATIONSHIP OF BONE MINERAL DENSITY AND VASCULAR WALL CONDITION WITH BIOCHEMICAL MARKERS OF INFLAMMATION IN POSTMENOPAUSAL WOMEN

Objective: to investigate the correlation of bone mass, the parameters of vascular stiffness and subclinical atherosclerosis with biochemical markers of inflammation in postmenopausal women. Subjects and methods. The cross-sectional investigation included 98 patients aged 45–82 years who were followed up in the outpatient setting and signed an informed consent. The investigation did not include patients with any clinical manifestations of atherosclerosis, malignant neoplasms, with diseases causing secondary osteoporosis, as well as with the presence of symptoms of acute bacterial or viral infections and an exacerbation of chronic diseases, who took drugs affecting bone metabolism and vascular stiffness. C-reactive protein (CRP) level was determined by a high-sensitive immunoturbidimetric assay using carboxylated polystyrene particles. interleukin (IL)-6 concentration was measured by an enzyme immunoassay. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (ASP) were studied with duplex scanning. Pulse wave velocity (PWV) and augmentation index (AI) were measured by applanation tonometry using a SphygmoCor device (AtCor Medical Pty. Ltd., Sydney, Australia). Lumbar spine and hip bone mineral density (BMD) was determined using dual energy X-ray absorptiometry. Results and discussion. There was an increase in the parameters of vascular stiffness, subclinical atherosclerosis, and CRP level and a decrease in bone mass with a longer length of menopause. The vascular stiffness parameters, including IMT (r=0.26; p&lt;0.05), AI (r=0.25; p&lt;0.05), the presence of ASP (r=0.24; p&lt;0.05), and PWV (r=0.23; p&lt;0.05), directly correlated with CRP level. A negative correlation was found between LI–IV BMD and CRP (r=-0.31; p&lt;0.05). The probability of detecting increased IMT with a high CRP level was increased by 2.64 times, ASP by 3.18 times, and low BMD by 2.4 times. There was no association of bone mass, and the parameters of subclinical atherosclerosis and vascular stiffness with IL-6. Conclusion. Lower bone mass and the development of osteoporosis in postmenopausal women were associated with increased vascular stiffness and the presence of signs of subclinical atherosclerosis, and with a high level of CRP, which allows one to discuss the common mechanisms for development of osteoporosis and atherosclerosis, as well as the involvement of chronic inflammation in them.

Relationship between telomerase activity and parameters of carbohydrate metabolism and vascular wall

Aim. To study the relationship between telomerase activity and parameters of carbohydrate metabolism and vascular wall depending on the type 2 diabetes (T2D). Material and methods. The study included 50 patients with T2D and 139 healthy volunteers. All subjects were assessed for carbohydrate metabolism, chronic inflammation (C-reactive protein (CRP), fibrinogen), endothelial dysfunction, carotid intima-media thickness and number of atherosclerotic plaques by duplex scanning, carotid-femoral pulse wave velocity, lymphocyte telomere length and telomerase activity. Results. In T2D patients, telomerase activity was lower (p=0,039), telomeres were shorter (p=0,031) and CRP level was higher (p=0,031) than in patients without T2D. All patients were divided by telomerase activity. T2D patients with low telomerase activity had higher values of CRP ( р =0,016), pulse wave velocity ( р =0,010), carotid intima-media thickness ( р &lt;0,001) and number of atherosclerotic plaques ( р =0,014) than in patients without T2D. There were no significant differences in high telomerase activity group. In the group of patients with/without T2D, there were independent negative relationship between telomerase activity and glycated hemoglobin (p=0,035), fasting plasma glucose (p=0,003), arterial stiffness (p=0,044) and independent positive relationship between telomerase activity and fibrinogen (p=0,027), CRP (p=0,042). Conclusion. Vascular changes, chronic inflammation and cell aging were weightier in patients with T2D. The established relationship between telomerase activity and parameters of carbohydrate metabolism, chronic inflammation and vascular stiffness may indicate the important role of telomerase activity in the development of cardiovascular diseases in T2D patients.

P1552Different forms of evaluation of atherosclerotic load and its different predicted powers compared with framingham risk score

Abstract Introduction The screening of carotid and/or ileo-femoral subclinical atherosclerosis using vascular ultrasound could be a cost-effective tool in the reclassification of cardiovascular risk in primary cardiovascular prevention. But until today we don't have evidence indicating which atherosclerotic load indicator variable (such as plaque area, number of atherosclerotic plaques or affected territories) has the most predictive power for future cardiovascular events. Objectives a. Evaluate the prevalence of carotid and ileo-femoral subclinical atherosclerosis (SubAth). b. Evaluate the predictive power of each atherosclerotic load indicator variable for cardiovascular events (CVE). c. to compare those methods with Framingham Score for prediction of CVE. Material and methods We retrospectively evaluated patients from our registry called CARFARE (CARDIOMETABOLIC RISK FACTORS REGISTRY) conducted in the context of a cardiovascular primary prevention program (n=6108). In this analysis we included only those patients who completed a follow up ≥24 months from the first vascular evaluation. Exclusion criteria: &lt;40 or &gt;65 years old, BMI&gt;40 kg/m2, previous cardiovascular and/or cerebrovascular event, chronic stable angina. We used Framingham score for the cardiovascular risk assessment. We evaluated the following atherosclerotic load variables using high resolution vascular ultrasonography (Mannheim Consensus): carotid plaques area (AR-C), ileo-femoral plaques area (AR-IF), and total (carotid+ileo-femoral, AR-TOT), number of affected territories (N-TER). Primary composite endpoints (P-CVE): myocardial infarction, stroke, hospitalization due to angina or acute heart failure. For prediction power analysis we used ROC curves and logistic regressions (unadjusted and adjusted by age, sex, BMI, major cardiovascular risk factors and treatment). Results We included 1431 patients (55.0±9.78 y.o., 38% women, follow-up period of 789±23 days). The total P-CVE rate was 3.77% during this period (54 events). The overall prevalence of atherosclerosis in this population was 60.7%. The AUC of the ROC curves for P-CVE prediction was 0.648, for Framingham 0.706, for AR-C 0.726, for AR-IF 0.746, for AR-TOT and 0.79 for N-TER (graph). The AUC of AR-TOT and N-TER were significantly higher than the AUC of the Framingham score (p=0.017 and p=0.0004, respectively) for prediction of P-CVE. The dichotomization criteria according to ROC were: AR-C&gt;5.80 mm2, AR-IF&gt;23.0 mm2, AR-TOT&gt;43.9 mm2, and N-TER&gt;1. In the logistic regressions adjusted for prediction of P-CVE the OR were: Framingham 1.05 (95% CI: 1.02–1.07), AR-C 4.00 (95% CI: 1.89–8.47), AR-IF 4.01 (95% CI: 2.02–8.32), AR-TOT 4.35 (95% CI: 2.13- 8.91) and N-TER 6.95 (95% CI: 3.05–15.8). Comparison of ROC curves for CVE Conclusions The carotid/ileo-femoral SubAth scan was a more potent predictor of cardiovascular events than the Framingham score, particularly those variables that indicate extension of multiterritorial affection like AR-TOT or N-TER.

Increasing the Risk of Stroke by Opium Addiction

IntroductionStroke is among the leading causes of mortality and morbidity in the world. Besides the identified risk factor, Ischemic stroke evidence show drug use develops or exacerbates the atherosclerotic process. The current study aimed at comparing cerebrovascular ultrasounds’ changes in addicted and nonaddicted people who developed ischemic stroke. MethodsIn the current cross-sectional study, a total of 133 patients with ischemic stroke who were admitted to Vali-Asr hospital from June 2016 to April 2017 were enrolled. For obtaining the quantitative data, t test or Mann-Whitney test was employed to compare the addict or no-addict groups, as well as, categorical data testing was performed using chi-square test. Also, the multiple logistic regression was used for identifying the factors and the significance level was set at 5%. ResultsThe current study was performed on 133 patients, among them 41 patients (30.8%) were opium addicted, and 92 patients (69.2%) were nonaddict. The mean [IQR] number of atherosclerotic plaques were significantly higher in opium addicted group in comparison with the nonaddicted group (3.0 [1.0-4.0] versus 1.5 [0.0-3.0], P = .008). The possibility of increasing the number of plaques in addicted patients was 1.42 times higher than the nonaddicted patients (odds ratio (95% confidence interval): 1.42 (1.11-1.81), P = .005). ConclusionThe findings demonstrated a significant difference in the vessel stenosis pattern between the addict and nonaddict ischemic stroke groups. To investigate the possible effects of opium use and its associated parameters, ie, dosage, duration of use, and the way of opium use on ischemic stroke, further studies are required.

SIRT1 inhibits monocyte adhesion to the vascular endothelium by suppressing Mac-1 expression on monocytes

SIRT1 signaling pathways modulate vascular inflammation; however, the precise role of SIRT1 in monocyte adhesion to the vascular endothelium, a key event initiating vascular inflammation, is unclear. Thus, this study investigated the roles and molecular interaction of SIRT1 and TLR2 in regulating monocyte adhesion to the vascular endothelium. In vitro, both Mac-1 expression and the endothelial adhesion of THP-1 cells stimulated with Pam3CSK4, a TLR2 ligand, were markedly increased in association with a decreased expression of SIRT1. In THP-1 cells stimulated with Pam3CSK4, the promoter activity and expression of SIRT1 were decreased. The TLR2-dependent suppression of SIRT1 expression in THP-1 cells was mediated by the transcription factors NF-κB and CREB, suggesting that the TLR2-mediated NF-κB and CREB signaling downregulated SIRT1 expression in monocytes. In peripheral blood monocytes (PBMCs) isolated from SIRT1 transgenic (TG) mice and THP-1 cells treated with recombinant SIRT1, both the increased Mac-1 expression and endothelial adhesion induced by Pam3CSK4 were significantly attenuated. In addition, the en face immunohistochemical study showed a marked increase in monocyte adhesion to the aortic endothelium of WT mice treated with Pam3CSK4, which was significantly attenuated in Pam3CSK4-treated SIRT1 TG mice. Moreover, a greater number of atherosclerotic plaques formed in WT mice fed a high-fat diet than in SIRT1 TG mice, indicating a pivotal role for SIRT1 in preventing vascular inflammation. Based on these results, SIRT1 might be a potential target for researchers aiming to develop therapeutic interventions for vascular inflammation, including atherosclerosis.

Circadian locomotor output cycles kaput accelerates atherosclerotic plaque formation by upregulating plasminogen activator inhibitor-1 expression.

To explore the association between clock circadian regulator circadian locomotor output cycles kaput gene (CLOCK) and the forming of atherosclerotic plaques and its underlying mechanisms, mouse aortic endothelial cells (MAECs) and atherosclerosis (AS) mouse model were recruited for our study. The apoE gene knockout mouse was used as the model of AS and we accelerated the formation of unstable plaques through the combination of carotid artery ligation and high-fat (HF) diet administration (0.2% cholesterol, 20% fat). The mRNA and protein expressions of CLOCK in peripheral blood monouclear cells of acute coronary syndrome (ACS) patients or mouse AS model were detected by qPCR, western blot analysis and immunohistochemical staining. The number of adherent cells and atherosclerotic plaques was counted to assess the effects of CLOCK on the progression of ACS, and adherence-associated genes, such as vascular cell adhesion molecule (VCAM)-1, C-C motif chemokine ligand 2 (CCL-2), and CCL-5. The results showed that CLOCK expression was significantly increased in both ACS patients and AS mouse model. The levels of CLOCK, leukemia inhibitory factor (LIF), intercellular adhesion molecule 1 (ICAM-1), perilipin 2 (ADFP), nuclear factor kappa B (NF-κB), and plasminogen activator inhibitor-1 (PAI-1), as well as the number of atherosclerotic plaques were elevated in the AS mouse model, as compared with the control group. Chromatin immunoprecipitation assay showed that CLOCK bound directly to the promoter of PAI-1 gene and CLOCK could positively regulate the expressions of LIF, ICAM-1, ADFP, NF-κB, and PAI-1. Reduction of CLOCK expression would decrease the expressions of VCAM-1, CCL-2, and CCL-5, and the number of adherent cells and atherosclerotic plaques, but these effects were neutralized when PAI-1 was simultaneously overexpressed in either mouse model or MAECs. Our results demonstrate that CLOCK overexpression triggers the formation of atherosclerotic plaques by directly upregulating PAI-1 expression.

MACRO- AND MICROCIRCULATORY ABNORMALITIES OF VASCULAR WALL IN HYPERTENSIVE PATIENTS

Objective: To study arterial wall elasticity and stiffness in hypertensive's patients with moderate and high cardiovascular risk not receiving antihypertensive treatment. Design and method: The study included 41 hypertensive's patients (16 male and 27 female) with mean age of 61.1 ± 10.7 years, systolic, diastolic blood pressure (162.7 ± 20.8 mm Hg, 98.6 ± 11.2 mm Hg), hypertension duration 9.3 ± 7.2 years. Obesity was found in 32% of participants, 21% of patients were smokers. Carotid Doppler ultrasound study with intima-media thickness (IMT) measurement (using Aloka SSD 2000 ultrasound system) and photoplethysmography with augmentation index (AI), stiffness index (SI), delay in time between early and late systolic waves (dTPP), vascular age (VA) and stress index (SI) scores assessment (using Angioscan Professional system, Russia, 2015) were performed on all patients. Statistical analysis was done using Statistica 10.0 software. Results: There were 3 groups of patients: I (N = 14) with normal IMT (<0.9 mm) and no carotid atherosclerotic plaque present, II (N = 13) with increased IMT (>0.9 mm) and no plaques, and III (N = 14) with carotid atherosclerotic plaques (average number 2.0 ± 1.6 with the mean % narrowing of 32.4 ± 12.6). There were no differences in age, hypertension grade, obesity and smoking prevalence between the groups. With the increase in carotid atherosclerosis, a significant rise in AI was seen (−1.3 ± 19.7% in group I, 10.5 ± 12.7% in group II and 18.6 ± 13.8% in group III; p < 0.05), whereas dTPP was significantly lower in group III than in groups II and I (90.5 ± 30.7 vs 89.2 ± 17.2 ms vs 96.5 ± 29.3 ms, respectively; p < 0,05 between groups I and III). Significant difference in SI was found only between groups I and II (7.4 ± 1.07 m/s vs 8.2 ± 0.88 m/s, respectively; p < 0.05), while this parameter was 7.6 ± 1.09 m/s in group III. Patients from groups I, II, and III demonstrated a significant elevation of VA (44.7 ± 14.9 vs 58.3 ± 7.4 vs 63.5 ± 12.9 years, respectively; p < 0.05) and SI (3.1 ± 1.2 vs 3.5 ± 1.04 vs 3.9 ± 0.95, respectively; p < 0.05). A correlation between VA and carotid diameter (R = –0.7; p < 0.05), AI and the number of atherosclerotic plaques (R = 0.73; p < 0.05) was revealed in hypertensive's. Conclusions: Carotid atherosclerosis in hypertensive's is associated with microcirculatory abnormalities and increased vascular age and stress index scores.

Soluble TWEAK and atheromatosis progression in patients with chronic kidney disease

Background and aimsCirculating soluble TNF-like weak inducer of apoptosis (sTWEAK) concentrations are related to the presence of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, there are no data regarding the potential association between sTWEAK and atheromatosis progression in patients free of cardiovascular events. MethodsSoluble TWEAK serum concentration was measured in 702 CKD patients without any previous CV event from The National Observatory of Atherosclerosis in Nephrology (NEFRONA) Study. B-mode ultrasound was performed to detect the presence of carotid and/or femoral atherosclerotic plaques. The association between sTWEAK levels, atherosclerotic burden (number of plaques) and atheromatosis progression (increase in the number of plaques) after 24 months of follow-up was analyzed. ResultsA continuous decrease in sTWEAK concentrations, with an increase in the number of atherosclerotic plaques after 24 months of follow-up, was observed in the studied population. Multivariable linear regression analysis showed that age, blood pressure, HDL-c, and sTWEAK concentrations were independent predictors of atherosclerotic burden after 24 months of follow-up. In addition, sTWEAK concentrations diminished in CKD patients in whom progressive silent atherosclerosis was observed. Multivariable linear regression analysis showed that age, sex, smoking status and sTWEAK levels were independent predictors of atheromatosis progression after 24 months of follow-up. ConclusionsLower sTWEAK concentrations are associated with atherosclerotic burden and atheromatosis progression in CKD patients free of clinical CVD. These data suggest that sTWEAK could serve as a biomarker to predict CV risk before clinical manifestations.

The impact of surgical and conservative treatment of periodontal disease on structural and functional condition of major blood vessels

The study included 55 patients (24 men and 31 women aged 30-70 years) with chronic periodontal disease and atherosclerosis of brachiocephalic arteries (BCA). Patients in group 1 received only conservative treatment for periodontal disease, while in group 2 both conservative and surgical treatment were performed. The values were evaluated at baseline and 6 months after treatment. Capillaroscopy and laser Doppler flowmetry showed an improvement in periodontal regional vascular network. The level of IL-6 decreased by 3.7 pg/ml and 5.9 pg/ml, C-reactive protein - by 2.0 mg/l and 3.4 mg/l in groups 1 and 2 correspondingly. Dark-field microscopy showed the decrease in the thickness of perfused boundary region by 0.05 mm and 0.28 mm, and the increase of red blood cells filling by 1.2% and 7.8% correspondingly. According to the results of ultrasound scanning of BCA after 6 months the number of atherosclerotic plaques and lumen of the vessels in the area of the plaques has not changed. BCA tone has not changed in group 1 and increased by 1-2% in group 2. Intima-media complex thickness decreased in group 1 by 0.02-0.03 mm, in group 2 - by 0.04 mm. The obtained data prove correlation of vascular status of periodontal and major blood vessels.

CORRELATIONS OF DIFFERENT STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF ARTERIAL WALL WITH TRADITIONAL CARDIOVASCULAR RISK FACTORS IN HEALTHY PEOPLE OF DIFFERENT AGE. PART 2

Detection of principal subclinical arterial wall lesions is one of the most important aspects of effective cardiovascular disease (CVD) primary prevention. Such lesions include: arterial wall thickening, increased rigidity, endothelial dysfunction development. However, the role of traditional CVD risk factors in the development of individual arterial wall lesions in CVD-free people is understudied. This is particularly so with people of older age. Aim. To study the role of traditional CVD risk factors in development of arterial wall lesions in relatively healthy individuals of different age. Material and methods. We have examined a total of 303 people aged 25-91 years, with no signs of CVD and other chronic diseases and without any regular medical treatment. Anthropometric parameters, blood pressure, fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels were detected in all the patients. Measurement of pulse wave velocity was conducted using SphygmoCor device (AtCorMedical,Australia). Carotid ultrasound to measure intima-media thickness and number of atherosclerotic plaques was conducted using linear transducer with ultra-high resolution 17-5 MHz (PHILIPS iU22, the Netherlands) in the B-mode. Endothelium-dependent vasodilation was assessed by the reactive hyperemia test. Results. Multivariate linear regression analysis has revealed fasting hyperglycemia and increased systolic blood pressure to be to a greater degree associated with arterial wall state in both age groups. According to the results of multivariate logistic regression analysis a relationship between risk factors and arterial wall parameters is stronger in the younger group as compared with the older one. Conclusion. Systolic blood pressure and fasting hyperglycemia must be the main targets of CVD primary prevention in older age group, while in younger age group other traditional risk factors must be taken into account as well.

Abstract 19: Role of Adenosine-to-Inosine RNA Editing of Alu Elements in Human Vascular Inflammatory Diseases

Background: Adenosine to inosine (A-to-I) RNA editing is catalysed by ADARs (adenosine deaminases acting on RNA) and is an important posttranscriptional regulator of RNA metabolism. Although RNA editing is essential for life, its role in cardiovascular disease is unknown. Methods and Results: RNA-sequencing (RNA-seq) of human endothelial cells revealed that ADAR1 is the main RNA editor in HUVECs. The vast majority of editing events are detected in Alu regions due to their ability to form double-stranded structures, a prerequisite for RNA editing. A-to-I RNA editing of the primate-specific Alu elements is observed in 25% of poly(A)+ transcripts and in 44% of ribosomal RNA-depleted transcripts. Cathepsin S (CTSS), an extracellular matrix degrading enzyme, has 3 Alu elements in its 3’-untranslated region and is among the most extensively edited mRNAs. Interestingly, ADAR1 silencing downregulates CTSS mRNA expression, whereas ADAR1 overexpression results in an increase of both CTSS RNA editing rate and CTSS mRNA expression. Mechanistically, RNA immunoprecipitation (RIP), luciferase reporter and iCLIP assays showed that A-to-I RNA editing of the Alu elements in the 3’UTR of CTSS mRNA regulates the recruitment of the stabilizing RNA-binding protein HuR to CTSS 3’UTR and, thus, controls CTSS mRNA stability and expression. CTSS Alu RNA editing is increased under hypoxic or pro-inflammatory conditions in vitro , as well as in patients with coronary or carotid atherosclerotic vascular disease. Further, the extent of CTSS Alu RNA editing rate correlated with various markers of subclinical atherosclerosis including intima-media thickness and number of atherosclerotic plaques. Importantly, ADAR1 and the extent of CTSS RNA editing correlated with CTSS expression levels in patients’ samples from 6 non-overlapping cohorts of patients with inflammatory vascular diseases (total n=366), including peripheral blood mononuclear cells, carotid atherosclerotic plaques and thoracic aortic aneurysms. Conclusion: This study shows for the first time that Alu A-to-I RNA editing is a critical modulator of inflammatory gene expression in all stages of atherosclerotic vascular disease development.

Features of atherosclerosis of the cerebral arteries and pathomorphology of cerebral infarctions in patients with type 2 diabetes mellitus

Comparison of the results of 20 autopsy cases of ischemic strokes developed during atherosclerosis with 20 autopsy cases of ischemic strokes associated with atherosclerosis in combination with type 2 diabetes mellitus (T2DM) provided data indicating a high significance of T2DM in the development of severe changes in the cerebral arteries, causing cerebral infarctions of various size and localization. A significant prevalence in the number of atherosclerotic plaques in the cerebral arteries, including those causing stenosis of the lumen by 50% or more, was found in the case of T2DM compared to cases without T2DM. Cerebral infarctions in T2DM were mostly of the multiple nature that was determined by a combination of fresh or organizing extensive, large or medium, infarction with one/several organized medium, small deep, and small surface infarctions. More severe atherosclerosis of the cerebral arteries in T2DM caused a higher rate of infarctions due to occlusive atherothrombosis, arterio-arterial embolism, and tandem atherostenosis in these patients compared to cases without T2DM. In the absence of T2DM, infarctions occurred more often due to embolism of the cerebral arteries from the heart with coronary heart disease compared to cases with T2DM.