Atherosclerotic Plaques In Carotid Arteries Research Articles

Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis

BackgroundPrevious clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD.MethodsThis retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression.ResultsBaseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022–1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612–0.900, p = 0.002) levels were independent predictors of all-cause mortality.ConclusionsSclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.

Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity

Atherosclerosis, a complex cardiovascular disease, is a leading cause of mortality and morbidity worldwide. Oxidative stress and inflammation are both involved in the development of atherosclerotic plaque as they increase the biological processes associated with this pathology, such as endothelial dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque rupture leading to major ischemic events is the result of vulnerable plaque progression, which is a result of the detrimental effect of oxidative stress and inflammation on risk factors for atherosclerotic plaque rupture, such as intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both are key targets for primary and secondary interventions. It is well recognized that chronic physical activity attenuates oxidative stress in healthy subjects via the improvement of antioxidant enzyme capacities and inflammation via the enhancement of anti-inflammatory molecules. Moreover, it was recently shown that chronic physical activity could decrease oxidative stress and inflammation in atherosclerotic patients. The aim of this review is to summarize the role of oxidative stress and inflammation in atherosclerosis and the results of therapeutic interventions targeting them in both preclinical and clinical studies. The effects of chronic physical activity on these two key processes are then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid arteries.

PROGRESSION OF CAROTID ARTERY ATHEROSCLEROSIS DURING TREATMENT TO TARGET IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

Ochronne właściwości cholesterolu HDL i zwapnień w blaszce miażdżycowej w zaawansowanej miażdżycy u pacjentów z udarem niedokrwiennym mózgu

STRESZCZENIEWstęp: Zmiany miażdżycowe w tętnicach szyjnych odgrywająistotną rolę w patogenezie udaru niedokrwiennego mózgu.W znacznym procencie przypadków stwierdza się wyraźną asymetrięw rozwoju tych zmian, które zajmują tylko jedną tętnicę.Celem pracy było ustalenie wpływu sercowo‑naczyniowychczynników ryzyka na obecność istotnych hemodynamiczniezmian miażdżycowych lub niedrożności tylko w jednej tętnicyszyjnej w porównaniu do obustronnego ich zajęcia u pacjentówz udarem niedokrwiennym mózgu.Materiały i metody: Pacjenci z rozpoznaniem udaru niedokrwiennegomózgu poddani zostali retrospektywnej oceniew kierunku zwężenia ≥70% lub niedrożności, co najmniej w jednejtętnicy szyjnej wewnętrznej lub wspólnej. Do badania zostałowłączonych 104 pacjentów. Grupę I stanowili chorzy z istotnymhemodynamicznie zwężeniem (≥70%) lub niedrożnością jednejtętnicy (n = 48). Grupę II stanowiły osoby z obustronnymistotnym hemodynamicznie zwężeniem (≥70%) lub niedrożnościątętnic szyjnych (n = 56).Wyniki: Nie stwierdzono różnic w częstości występowanianiemodyfikowalnych czynników ryzyka pomiędzy grupami.W grupie I stwierdzono istotnie wyższy poziom cholesteroluHDL (45,7 vs 38,9 mg/dL, p = 0,038) i istotnie częściej obecnośćzwapnień w blaszkach miażdżycowych tętnic szyjnych(p = 0,03). Nie stwierdzono różnic w częstości występowaniainnych badanych czynników pomiędzy grupami.Wnioski: Ochronne właściwości cholesterolu HDL i wolniejszadynamika powstawania bardziej stabilnych, uwapnionych blaszekmiażdżycowych odgrywają istotną rolę w rozwoju tylkojednostronnych, zaawansowanych zmian miażdżycowych w tętnicachszyjnych. Rola HDL w patomechanizmie powstawaniaudaru mózgu wymaga dalszych badań.

Perillaldehyde prevents the formations of atherosclerotic plaques through recoupling endothelial nitric oxide synthase

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is essential for cardiovascular homeostasis owing to its anti-inflammatory, antithrombotic, antiproliferative, and antioxidant effects. Perillaldehyde (PAH), one of the major oil components in Perilla frutescens, has anti-inflammatory effects. This study was designed to explore whether PAH prevents atherosclerosis through normalizing eNOS functions. The model of atherosclerosis was induced by feeding rats and mice with high-fat diet or plus balloon injury. Oil red and hematoxylin-eosin (HE) stainings were used to assess the atherosclerotic plaque. Pretreatment of PAH for 30 minutes concentration-dependently increased tetrahydrobiopterin (BH4) levels, NO generations, and improved cell viabilities in cultured human umbilicus vessel endothelial cells (HUVEC) incubated with oxidized (OX) low-density lipoprotein (LDL), in which all protective effects of PAH were abolished by guanosinetriphosphate (GTP) cyclohydrolase 1 inhibitor 2,4-Diamino-6-hydroxypyrimidine (DAHP) or eNOS inhibitor L-NAME in those cells. In rats, high-fat diet plus balloon injury induced the formation of atherosclerotic plaque in carotid arteries. Administration of PAH or lovastatin reduced the size of atherosclerotic plaque in rats and improved the responses of aortic rings to acetylcholine isolated from rats, accompanied with increased BH4 content and NO generations. In Apoe -/- mice feeding with normal diet or high-fat diet, PAH (150 mg/kg) reduced the size of atherosclerotic plaque in aortic arteries, prevented endothelial dysfunctions, and increased both BH4 and NO generations in carotid arteries. PAH prevents the growth of atherosclerosis through increasing BH4 generation and subsequent eNOS recouping. Clinically, PAH should be considered as a new medicine to treat patients with atherosclerosis.

Atherosclerotic plaque in carotid arteries as a risk marker for cardiovascular events risk in middle aged population

Aim. To reveal the associations of carotid arteries atherosclerosis severity and cardiovascular events in mostly middle aged population. Material and methods . In the study, 1100 persons participated of the ATHEROGEN-Ivanovo trial (substudy of ESSE-RF), age 40-67 y. o. All participants underwent duplex scan of carotid arteries (Samsung Medison MySono U6) with assessment of the number of atherosclerotic plaques (AP), maximum stenosis and total stenosis with calculation of gender-specific quintiles. With the Cox regression model, risk was estimated for combinatory endpoint including all-cause death, myocardial infarction, novel onset of coronary heart disease, stroke, any area revascularization. Median follow-up 3,8 years. Results. The AP were found in 74,5% males and 58,0% females. In males atherosclerosis was more severe: maximum stenosis 27 (0-34)% in males vs 22 (0-58)% in females (р<0,001), total stenosis — 48 (0-90)% vs 22 (0-31)% (р<0,001) and plaques number — 2 (0-3) vs 1 (0-2) (р=0,000). There were 24 endpoints documented. 23 of 24 endpoints occurred in persons with at least any ultrasound marker value within quintile ≥3. Regression showed that if at least one ultrasound marker should have reached the quintile ≥3 (e. g., maximum stenosis ≥25% in men), than the risk of events from combinational endpoint would increase 8,5 times — 95% CI 1,12-64,76 (p=0,039). Also, coronary heart disease increases the risk 4,05 times — 95% CI 1,46-11,21 (p=0,007), acute stroke 3,49 times — 95% CI 1,19-10,23 (p=0,023). The number of males with AP <25% was 15%. Conclusion. The presence of AP in carotid arteries does 8,5 times increase the risk of cardiovascular events, and for 15% of males in population with AP in carotid arteries that narrow the lumen <25%, it is needed to clarify the risk.

Morphology and histology of silent and symptom-causing atherosclerotic carotid plaques – Rationale and design of the Helsinki Carotid Endarterectomy Study 2 (the HeCES2)

Introduction: Every fifth ischemic stroke is caused by thromboembolism originating from an atherosclerotic carotid artery plaque. While prevention is the most cost-effective stroke therapy, antiplatelet and cholesterol-lowering drugs have a ceiling effect in their efficacy. Therefore, discovery of novel pathophysiologic targets are needed to improve the primary and secondary prevention of stroke. This article provides a detailed study design and protocol of HeCES2, an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.Materials and Methods: Recruitment and carotid endarterectomies of the study patients with carotid atherosclerosis were performed from October 2012 to September 2015. After brain and carotid artery imaging, endarterectomised carotid plaques (CPs) and blood samples were collected from 500 patients for detailed biochemical and molecular analyses.Findings to date: We developed a morphological grading for macroscopic characteristics within CPs. The dominant macroscopic CP characteristics were: smoothness 62%, ulceration 61%, intraplaque hemorrhage 60%, atheromatous gruel 59%, luminal coral-type calcification 34%, abundant (44%) and moderate (39%) intramural calcification, and symptom-causing “hot spot” area 53%.Future plans: By combining clinically oriented and basic biomedical research, this large-scale study attempts to untangle the pathophysiological perplexities of human carotid atherosclerosis.Key MessagesThis article is a rationale and design of the HeCES2 study that is an observational prospective cohort study with the objective to investigate the pathophysiology of carotid atherosclerosis.The HeCES2 study strives to develop diagnostic algorithms including radiologic imaging to identify carotid atherosclerosis patients who warrant surgical treatment.In addition, the study aims at finding out new tools for clinical risk stratification as well as novel molecular targets for drug development.

Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study.

AimsAntithrombotic treatment plays a key role in stroke prevention, but their direct effects on the composition of carotid artery atherosclerotic plaques are unknown. To investigate the association of antithrombotic treatment with carotid artery plaque composition, with a specific focus on an intraplaque haemorrhage (IPH).Methods and resultsFrom the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis on ultrasound (mean age 72.9 years, 46.0 women) underwent magnetic resonance imaging of the carotid arteries to assess plaque composition. Information on the use of oral anticoagulants [vitamin K antagonists (VKA)] and antiplatelet agents (salicylates), including duration of use and dosage, was obtained from pharmacy records for all participants. We used logistic regression models to assess the association between the use of anticoagulants and antiplatelet agents, and the different plaque components adjusting for confounders. Current and past use of VKA [adjusted odds ratio (OR): 1.88, 95% confidence interval (CI): 0.74–4.75 and OR 1.89, 95% CI: 0.91–3.93] and antiplatelet agents (OR: 1.22, 95% CI: 0.91–1.62), and (OR: 1.23, 95% CI: 0.86–1.75) showed positive trend with a higher presence of IPH. Also, a longer duration of use was associated with a higher frequency of IPH (OR: 3.15, 95% CI: 1.23–8.05) for the use of VKA, and longer duration of the use for antiplatelet agents showed a positive trend (OR: 1.21, 95% CI: 0.88–1.67). We also found that higher levels of international normalized ratio above 2.97 for VKA (OR: 1.48, 95% CI: 1.03–2.15) and higher daily defined dosage than 1.0 for antiplatelet agents (OR: 1.50, 95% CI: 1.21–1.87) were related to a higher frequency of IPH. We found no association with lipid core or calcification.ConclusionsThe use of antithrombotic treatment relates to a higher frequency of IPH in carotid atherosclerotic plaques.

Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification.

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA-IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39-20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA-IMT values (OR 6.56; 95%CI 1.06-40.6; P = 0.036). OPG levels above the median were associated with higher CCA-IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84-72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA-IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow-up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA-IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all-cause mortality in CKD patients with advanced medial arterial calcification.

DNA‐PK Is Activated in Human Atherosclerotic Plaques And Its Partial Inhibition by Gene Heterozygosity Reduces Atherogenesis in Mouse Model of The Disease

Atherosclerosis is a chronic inflammatory condition with serious implications including coronary heart disease, cerebrovascular and thromboembolic disorders. Rupture of plaques, the subsequent formation of thrombi, and the consequent occlusion of arteries are the most important events in the onset of cardiovascular complications associated with atherosclerosis. The ultimate clinical goal to prevent plaque rupture and thrombosis is the stabilization and potential regression of vulnerable plaques. DNA‐PK is composed of a 450‐kDa catalytic subunit (DNA‐PKcs) and two DNA‐binding subunits (Ku70/Ku80). Although DNA‐PK is critical for repairing DSBs through non‐homologous end joining, only less than 1% is needed to achieve such function. We have recently reported that partial inhibition of DNA‐PK pharmacologically by NU7441 or genetically by gene heterozygosity reduces asthma‐like traits in 2 animal models of the disease in part by blocking lung VCAM‐1 expression, production of Th2 cytokines through down regulating the expression of several inflammatory genes. Since persistent inflammation is critical for plaque instability and rupture, we sought to examine the role of DNA‐PK in human atherogenesis and determine whether its activation correlates with factors of inflammation and/or markers of DNA damage/repair and to investigate whether inhibition of the enzyme promotes plaque regression in a mouse model of atherosclerosis. We report that DNA‐PKcs is activated in inflammatory as well as structural cells within human atherosclerotic plaques of carotid arteries. Reduction of DNA‐PKcs by gene heterozygosity, which reduces expression and activity of the enzyme by ~50%, promoted a significant reduction of the atherosclerotic burden in high fat diet‐fed (HFD) ApoE−/− mice. Such protective action was accompanied by a significant reduction in LDL levels and an increase in HDL. These effects were achieved without interference or activation of the DNA damage/repair pathways or the development of severe combined immunodeficiency (SCID) syndrome. Overall, our results support the notion that DNA‐PK is a key player in atherogenesis and that it may constitute a novel therapeutic target for the modulation of the disease.Support or Funding InformationNIH/COBRE 1P30GM106392‐01: COBRE Phase III Transitional Center Grant‐ Mentoring in Cardiovascular BiologyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Human Atherosclerotic Carotid Artery Plaques with Cholesterol Crystals Enhance Bacterial Growth: Risk for Plaque Destabilization*

Human Atherosclerotic Carotid Artery Plaques with Cholesterol Crystals Enhance Bacterial Growth: Risk for Plaque Destabilization*

Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque

Experimental studies showed that gut-derived lipopolysaccharide (LPS) is pro-atherogenic, however, its relationship with human atherosclerosis is still to be defined. We investigate if gut-derived LPS from Escherichia Coli localizes in human carotid plaque and its potential role as pro-inflammatory molecule in the atherosclerotic lesion. LPS from Escherichia Coli and Toll-like receptor 4 (TLR4) were studied in specimens from carotid and thyroid arteries of 10 patients undergoing endarterectomy and 15 controls matched for demographic and clinical characteristics. Blood LPS were significantly higher in patients compared to controls. Immunochemistry analysis revealed positivity for antibodies against LPS and TLR4 coincidentally with positivity for CD68 only in the atherosclerotic plaque of carotid arteries but not in thyroid arteries; the positivity for LPS and TLR4 was greater in the area with activated macrophages. LPS concentration similar to that detected in atherosclerotic plaque resulted in a dose-dependent TLR4-mediated Nox2 up-regulation by human monocytes. These data provide the first evidence that LPS from Escherichia Coli localizes in human plaque and may contribute to atherosclerotic damage via TLR4-mediated oxidative stress.

Толщина комплекса интима–медиа общих сонных артерий, уровень общего и высокомолекулярного адипонектина у женщин с абдоминальным ожирением

to investigate influence of different forms of adiponectin on carotid intima-media thickness (CIMT) in women with abdominal obesity (AO) in St.‑Petersburg. It has been recognized before that AO is associated with cardiovascular diseases, including atherosclerosis, but mechanism of this association remains unclear. AO leads to imbalance of adipokines, in particularly decrease of adiponectin, which may lead to atherosclerotic lesion of carotid arteries. We investigated 81 women with AO (IDF criteria, 2005) and 21 women with normal waist circumference. СIMT was evaluated by an ultrasound scanner. Among patients with AO 54.9 % had CIMT >0.9 mm and 38.5 % had atherosclerotic plaques in common carotid arteries. The total adiponectin level (TA) was lower in women with CIMT> 0.9 mm, than in women with normal CIMT (23.20 [2.55; 40.65] and 18.09 [1.60; 38.92] μg/ml, respectively; р0.9 mm, than in women with normal CIMT (2.21 [0.50; 6.85] and 2.88 [1.29; 15.45] μg/ml, respectively; р0.9 mm, than in women with CIMT >0.9 mm and atherosclerotic plaques in carotid arteries (3.09 [1.34; 6.85] and1.82 [0.50; 2.94] mcg/ml, respectively; р0.9 mm depended on waist circumference, diastolic blood pressure and level of C-reactive protein (CRP), while presence of atherosclerotic plaques was associated with levels of HMWA and CRP. Factors that make the greatest contribution at early stages of atherosclerosis development in carotid arteries in women with AO can be increased waist circumference, high diastolic blood pressure, and high level of CRP. At later stages of atherosclerosis development lowered HMWA level can contribute to the formation of atherosclerotic plaques.

Contrast-enhanced ultrasonography as the most perspective diagnostic method for unstable atherosclerotic plaque of carotid artery

Problem of internal carotid artery disease diagnosis appears to be crucial today. Complications of this pathology are strokes and transient ischemic attacks. There is no technology for their prediction or at least stratifying risks. Some recent researches are devoted to a new diagnostic method. This new technology is called Contrast Enhanced Ultrasonography (CEUS) and followed by outstanding results in studying the morphological peculiarities of internal carotid artery plaques and predicting the probability of complications. CEUS is a new way for atherosclerotic process analysis because it is able to detect intraplaque neovascularization and vascular wall inflammation.

Osteopontin, Cardiovascular Risk Factors and Carotid Intima-Media Thickness in Chronic Kidney Disease.

The pleiotropic cytokine osteopontin (OPN) is found to be involved in the pathogenesis of both kidney and cardiovascular disease (CVD). We evaluated the relationship between OPN, other cardiovascular risk factors and carotid intima-media thickness (CIMT) in chronic kidney disease (CKD) (predialysis) patients. This is a 2-year cross-sectional prospective study involving 75 patients with CKD from stage 1 to stage 5 attending the nephrology outpatient department and 25 healthy controls. Routine biochemical parameters were analyzed on clinical chemistry Autoanalyzer Beckman Coulter DXC 600 Synchron, USA. OPN was estimated by ELISA method. Carotid intima-media wall thickness was estimated by Doppler of carotid vessels. Serum OPN and other nontraditional cardiovascular risk factors such as CIMT, lipoprotein (a) Lp(a), fibrinogen, and homocysteine were significantly increased in patients of CKD compared to controls. OPN, Lp(a), fibrinogen, CIMT, parathyroid hormone, and homocysteine progressively increased from early stages of CKD and increased further with progression of the disease, but nitric oxide (NO) level progressively decreased with progression of CKD. OPN showed a positive correlation with CIMT, Lp(a), fibrinogen, and homocysteine and negative correlation with estimated glomerular filtration rate and NO. There was a close direct association between circulating levels of OPN and the presence of atherosclerotic plaques in carotid arteries of patients with CKD. Osteopontin and nontraditional CVD risk factors are altered in early stages of CKD and might predict adverse outcomes in these patients.

Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

Background AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood.ObjectivesTo identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS).MethodsProspective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p < 0.05.ResultsPlaques were found in 37% of the HIV group and 4% of controls (p < 0.001). Furthermore, carotid intima-media thickness was higher in the HIV group than in controls (p < 0.001). Patients with carotid plaque had higher fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides than those without plaques. The presence of HIV, adjusted for age, overweight/obesity, and smoking increased by almost fivefold the risk of atherosclerotic carotid plaque (OR: 4.9; 95%CI: 2.5-9.9; p < 0.001). Exposure to protease inhibitors did not influence carotid intima-media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx).ConclusionsHIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of atherosclerotic plaques in carotid arteries. The FCRS may be inappropriate for this population.

Imaging of neoangiogenesis of internal carotid artery's atherosclerotic plaque by contrast-enhanced sonography and histological examination

Previously, atherosclerosis was considered a disease accompanied exclusively by lipids accumulation. At present time success of fundamental and experimental science confirmed that atherosclerotic process is also associated with neovascularization and prolonged inflammatory response at all stages of atherogenesis from initial manifestations to thrombotic complications. The cause of atherosclerotic plaque instability is neovascularization, which is accompanied by intra-plaque hemorrhage and damage. Complications of carotid arteries atherosclerosis are strokes and transient ischemic attacks. The use of a wide range of diagnostic and pathohistological techniques is required for assessing this pathology. The most promising diagnostic technique is Contrast Enhanced Ultrasonography (CEUS) which allows to assess neovascularization degree in atherosclerotic plaque through the injection of a contrast agents.

Circulating α-Klotho Levels in Hemodialysis Patients and Their Relationship to Atherosclerosis

Background/Aims: Serum soluble Klotho (sKlotho) plays a role in cardiovascular disease in some populations. However, information regarding the effect of serum sKlotho on atherosclerosis in patients on maintenance hemodialysis (MHD) is limited. Therefore, we tested the level of serum sKlotho in MHD patients to investigate atherosclerosis disease and determine the relationship between sKlotho and atherosclerosis. Methods: Using cross-sectional research, anthropometric and laboratory data were collected for 330 MHD patients. The levels of serum sKlotho before dialysis were tested by enzyme-linked immunosorbent assay. Carotid intima-middle thickness (cIMT) and the number of carotid artery atherosclerotic plaques were measured by color Doppler ultrasonography. The risk factors of atherosclerosis were explored by multivariate logistic regression analysis. Results: Among 330 MHD patients, the average serum sKlotho was (379.93±143.66) pg/ml. The level of serum sKlotho was positively related to hemoglobin (P< 0.05). It was negatively correlated with systolic pressure, pulse pressure, ultrafiltration volume, serum phosphorus, corrected serum calcium×phosphorus, high-sensitivity C-reactive protein (Hs-CRP), cIMT and carotid atherosclerotic plaque quantity and atherosclerosis (P< 0.05). Multivariate logistic regression analysis showed that age (OR = 1.108, 95% CI = 1.067 ∼ 1.151, P = 0.000), dry weight (OR = 1.050, 95% CI = 1.014 ∼ 1.088, P = 0.007), Hs-CRP (OR = 1.126, 95% CI = 1.005 ∼ 1.261, P = 0.041), and serum sKlotho (OR = 0.997, 95% CI = 0.995 ∼ 1.000, P = 0.032) were risk factors for atherosclerosis in MHD patients. Conclusion: Serum sKlotho was related to systolic pressure, pulse pressure, ultrafiltration volume, hemoglobin, serum phosphorus, corrected serum calcium×phosphorus, Hs-CRP, increased cIMT, carotid atherosclerotic plaque quantity and atherosclerosis. Age, dry weight, Hs-CRP, and serum sKlotho were risk factors for atherosclerosis in MHD patients. Serum sKlotho may be a novel risk factor for atherosclerosis in MHD patients.

Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy.

Cardiovascular (CV) events are the first cause of death in patients with chronic renal disease (CKD) and in patients with type 2 diabetes mellitus (DM2). The combination of CKD and DM2 elevates the risk of both cardiovascular disease (CVD) and death in this high-risk population. Besides traditional risk factors, such as dyslipidemia, smoking, obesity, and carotid atherosclerosis, novel factors are under investigation such as genetic polymorphisms. Lipoxygenases (LOXs) and their genes are of critical importance in oxidative stress, inflammation, and atherosclerosis. The aim of the study is to clarify a potential ALOX12 role in CVD presence and progress of diabetic patients in different stages of nephropathy. We studied 145 patients with a documented history of DM2 for at least 10years and diabetic nephropathy (DN), mean age 68±9years, body mass index 31±5kg/m2, and different stages of renal disease, depending on glomerular filtration rate. The sample population consisted of two groups: 108 DM2 patients with DN in all five stages of CKD and 37 DM2 patients as controls. Anthropometric and clinical characteristics, interview for history of previous CV event, and assessment of carotid intima-media thickness (cIMT) were recorded at baseline. All patients were genotyped for ALOX12 polymorphisms with focus on rs14309. Genotypes (AA, AG, and GG) were evaluated for any possible role in CVD, and grouping was performed on A genotype, which is the dominant model. All participants were followed over a period of 7years, and the end points studied were all-cause mortality, CV mortality, and CV events. CV events were defined as myocardial infarction (MI), stroke, or peripheral artery disease. The GG genotype has been significantly associated with cIMT levels above 0.86mm and with history of MI. Regarding the presence of an atherosclerotic plaque in either carotid artery, no significant association was found when the genotypes were assessed on their own. After grouping, though, GG genotype revealed a significant association between carotid plaque formation and atheromatosis. Kaplan-Meier analysis revealed that ALOX12 gene GG genotype predicted all-cause mortality, CV mortality, and CV events. Similarly, when AA and AG genotypes were grouped, Kaplan-Meier analysis showed that patients with GG genotype presented an even more significant higher all-cause mortality, CV mortality, and CV events compared with AA and AG genotypes combined. After adjustment for several traditional risk factors, multivariate Cox proportional hazard analysis showed that patients with the GG genotype had a significant higher risk of all-cause mortality, a threefold increase in CV mortality, and a twofold increased risk for CV events compared to patients with the AA or the AG genotype. ALOX12 rs14309 GG genotype expression was found to be significantly associated with MI, higher cIMT, increased CV events, CV, and overall mortality. This phenomenon could be partially explained by the increased platelet proaggregatory activity of AA products and the control they exert in thrombotic occurrence and plaque formation.

Carotid and femoral atherosclerosis in antiphospholipid syndrome: Equivalent risk with diabetes mellitus in a case-control study.

Antiphospholipid syndrome (APS) may carry a worse prognosis for vascular complications when co-existing with subclinical atherosclerosis; however, the association between the two conditions remains ambiguous. We evaluated ultrasonographic markers of subclinical atherosclerosis in carotid and femoral arteries of 86 patients with thrombotic APS [43 primary APS (PAPS), 43 systemic lupus erythematosus-associated APS (SLE/APS)], 86 patients with diabetes mellitus (DM) and 86 healthy controls, individually matched for age and gender, and investigated their associations with traditional and disease-related factors in APS. Carotid plaques were found in 28% of PAPS, 23% of SLE/APS, and 30% of DM patients versus 9% of controls (p = 0.006). Femoral plaques were found in 33% of PAPS, 19% of SLE/APS, 20% of DM, and 9% of controls (p = 0.032). Multivariate regression-derived relative risk estimates for atherosclerotic plaques in any location were 2.72 for PAPS, 2.63 for SLE/APS, and 1.98 for DM (p = 0.004, 0.009, and 0.032 respectively), after adjusting for age, gender, hypertension, dyslipidemia, smoking, BMI, and family history of coronary disease. Among patients with APS, atherosclerotic plaques were associated with the number of traditional CVD risk factors in both PAPS (RR = 2.75, p < 0.001) and SLE/APS (RR = 1.84, p < 0.001), and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS. Patients with PAPS and SLE/APS have a nearly 2.5-fold risk of atherosclerotic plaques in carotid and femoral arteries compared to healthy controls, similar to DM patients. Atherosclerotic plaques are associated with the number of traditional risk factors in both APS and SLE/APS, and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS.