cardiovascular-agents and Carotid-Artery-Diseases

Contemporary medical therapy consists of identification and treatment of all patient-modifiable vascular risk factors. Specific atherosclerotic disease therapies are designed to reduce the risk of thrombosis, and the disease progression in order to reduce the risk of future cardiovascular events. Contemporary medical management emphasizes the need to support the patient in achieving lifestyle modifications and to adjust medication to achieve individualized target values for specific quantifiable risk factors. Antiplatelet therapy in the form of aspirin or clopidogrel is routinely used for the prevention of ischemic stroke in patients who have had a transient ischemic attack or stroke. There is evidence from a recent trial that the use of combination antiplatelet therapy with aspirin and clopidogrel started within 24 hours of minor stroke or transient ischemic attack reduces the risk of recurrent stroke compared to the use of aspirin alone, and therefore we use aspirin plus clopidogrel in recently symptomatic patients with carotid stenosis pending carotid revascularization. Anticoagulation with heparins or vitamin K antagonist is not recommended except in patients at risk for cardio-embolic events. Lowering blood pressure to target levels has been shown to slow down the progression of carotid artery stenosis and reduces the intima-media thickness of the carotid plaque, while lowering lipid levels with statins has become an essential element in the medical therapy of carotid artery stenosis. Diabetes management should be optimized. Lifestyle choices, including tobacco smoking, physical inactivity, unhealthy diet, obesity, and excessive alcohol intake, are all important modifiable vascular risk factors. The combination of dietary modification, physical exercise, and use of aspirin, a statin, and an antihypertensive agent can be expected to give a cumulative relative stroke risk reduction of 80%. The evidence suggests that intensive medical therapy is so effective that carotid revascularization may no longer be necessary in many of the patients in whom carotid surgery or stenting is currently performed. Two large ongoing trials are therefore comparing the risks and benefits of carotid revascularization versus intensive medical therapy alone.

Topics: Cardiovascular Agents; Carotid Artery Diseases; Diet, Healthy; Evidence-Based Medicine; Exercise; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Factors; Risk Reduction Behavior; Stroke; Treatment Outcome

Fibromuscular dysplasia (FMD) is a nonatheromatous, noninflammatory arteriopathy with segmental involvement of medium-sized arteries in multiple vascular beds. It most commonly involves the renal and carotid arteries. The etiology is unknown, although various hormonal and mechanical factors have been suggested. The disease can occur at any age but is usually diagnosed in middle-aged individuals, predominantly women. FMD is much more common than previously thought, perhaps affecting as many as 4% of adult women. Clinical manifestations of the internal carotid artery involvement are transitory ischemic attacks or cerebral infarction, as well as nonspecific symptoms such as headache and vertigo. In cases of cerebrovascular events, endovascular or surgical treatment is recommended; therefore, detection of FMD is of considerable importance. The gold standard for diagnosing FMD is catheter angiography (with the classic "string of beads" pattern), but this invasive procedure is only used for patients in whom it is clinically pertinent to proceed with revascularization. The optimal noninvasive modality for diagnosis and quantification for FMD is not known and little information has been recently published about new diagnostic modalities. Although angiography, computed tomography angiography, and magnetic resonance angiography are excellent in confirming the morphologic diagnosis of FMD, they are less accurate in assessing the hemodynamic significance of the lesions. Ultrasonography is useful in assessing the degree of carotid artery stenosis. Use of power Doppler ultrasound improves the ability to detect the morphologic features of carotid FMD.

Topics: Aspirin; Cardiovascular Agents; Carotid Artery Diseases; Female; Fibromuscular Dysplasia; Humans; Magnetic Resonance Angiography; Middle Aged; Predictive Value of Tests; Tomography, X-Ray Computed; Ultrasonography, Doppler; Ultrasonography, Doppler, Color

The management of carotid artery disease includes both modifications in life style as well treatment of vascular risk factors. However, strict risk factor modification, including improved antihypertensive therapy, lipid management, smoking cessation, and antiplatelet therapy, promise for reducing the vascular event rate in patients with carotid atherosclerosis. The best medical management for stroke prevention was highlighted in clinical practice guidelines issued jointly in 2006 by the American Heart Association and the American Stroke Association, and co-sponsored by the Council on Cardiovascular Radiology and Intervention and the American Academy of Neurology. Lowering blood pressure to a target below 120/80 mm Hg by life style interventions and antihypertensive treatment. Glucose control to near-normoglycemic levels (target hemoglobin A1C ≤7%) is recommended among diabetics to reduce micro-vascular complications and, with lesser certainty, macrovascular complications. The primary objective of this review is to summarize the current evidence and standards for the advanced diagnostic and management strategies used in asymptomatic and symptomatic patients with carotid atherosclerosis.

Topics: Asymptomatic Diseases; Cardiovascular Agents; Carotid Artery Diseases; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Practice Guidelines as Topic; Primary Prevention; Risk Assessment; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Stroke; Treatment Outcome

Carotid endarterectomy (CEA) has been repeatedly described as a safe and efficacious procedure to provide a stroke-risk reduction benefit in both symptomatic and asymptomatic cases. Contemporary outcomes are acceptable using the large-scale randomized trials as a metric of success. Class I and II data can be applied to improve the care process of patients undergoing CEA. Myocardial infarction remains the most significant nonstroke complication; however, there is no significant benefit to noninvasive stress testing in patients with clinically stable disease. Perioperative beta-blockade may offer up to a 10-fold reduction in the rate of perioperative myocardial infarction, but deleterious effects are attributable to high-dose regimens. Angiotensin blockade has been shown to reduce cardiovascular mortality in patients with atherosclerosis by up to 25%, although few studies have examined these agents directly in carotid surgery patients. Statins are beneficial to patients undergoing CEA with trials demonstrating up to a 3% absolute reduction in the incidence of stroke following CEA. Aspirin therapy is associated with an up to 7% absolute reduction in early stroke following CEA; however, the efficacy of combination or high-dose antiplatelet therapy remains ill-defined. A treatment strategy that involves perioperative medical optimization is likely to improve surgical outcomes and long-term cardiovascular risk for patients undergoing CEA.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Carotid Artery Diseases; Endarterectomy, Carotid; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Perioperative Care; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome

A number of therapeutic options are available to clinicians caring for patients with ischemic cerebrovascular diseases. The efficacy of some strategies that aim at mitigating the effects of cerebral infarction are presented. The optimal role of carotid surgery, platelet-antiaggregant drugs and anticoagulation in the prevention of stroke are analysed.

Topics: Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Combined Modality Therapy; Drug Therapy, Combination; Endarterectomy; Humans

Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke.. PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization.. The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization.. PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke.

Topics: Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Cerebral Hemorrhage; Cilostazol; Clinical Protocols; Double-Blind Method; Humans; Predictive Value of Tests; Probucol; Prospective Studies; Republic of Korea; Research Design; Risk Factors; Stroke; Tetrazoles; Time Factors; Treatment Outcome

The purpose of the study to assess the comparability of immediate changes in plaque/media volume (PV) on three modalities of intravascular ultrasound (IVUS) after implantation of either bioresorbable vascular scaffold (BVS) or everolimus-eluting metallic stent (EES) in Absorb II Study. The two devices have different device volume and ultrasound backscattering that may interfere with the "plaque/media" assessed by three modalities on IVUS: grayscale, backscattering of radiofrequency and brightness function. In a multicenter randomized controlled trial, 501 patients with stable or unstable angina underwent documentary IVUS pre- and post- implantation. The change in plaque/media volume (PV) was categorized into three groups according to the relative PV change in device segment: PV "increased" >+5% (PVI), PV unchanged ±5% (PVU), and PV decreased <-5% (PVD). The change in PV was re-evaluated three times: after subtraction of theoretical device volume, after analysis of echogenicity based on brightness function. In 449 patients, 483 lesions were analyzed pre- and post-implantation. "PVI" was more frequently observed in BVS (53.8%) than EES group (39.4%), p = 0.006. After subtraction of the theoretical device volume, the frequency of "PVI" decreased in both BVS (36.2%) and EES (32.1%) groups and became comparable (p = 0.581). In addition, the percentage of "PVI" was further reduced in both device groups after correction for either radiofrequency backscattering (BVS 34.4% vs. EES 22.6%) or echogenicity (BVS 25.2% vs. EES 9.7%). PV change in device segment was differently affected by BVS and EES devices implantation due to their differences in device volume and ultrasound backscattering. It implies that the lumen volume was also artifactually affected by the type of device implanted. Comparative IVUS assessment of lumen and plaque/media volume changes following implantation of BVS and EES requires specific methodological adjustment.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Carotid Artery Diseases; Coronary Vessels; Databases, Factual; Drug-Eluting Stents; Everolimus; Female; Humans; Image Interpretation, Computer-Assisted; Male; Metals; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Single-Blind Method; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Patients with rapid progression of carotid intima media thickness (CIMT) were shown to have a higher future risk for cardiovascular events.The aim of this study was to investigate the impact of multiple risk factor intervention on CIMT progression and to establish whether new cardiovascular surrogate measurements would allow prediction of CIMT changes.. In this prospective, open, 2-years study, we included 97 patients with type 2 diabetes and at least two insufficiently treated cardiovascular risk factors, i.e. HbA1c > 7.5% (58 mmol/mol); LDL-cholesterol >3.1 mmol/l or blood pressure >140/90 mmHg. Treatment was intensified according to current guidelines over 3 months with the aim to maintain intensification over 2 years.The primary outcome was the change in CIMT after 2 years. We also assessed markers of mechanical and biochemical endothelial function and endothelial progenitor cells before and after 3 months of treatment intensification. For testing differences between before and after multifactorial treatment measurements we used either the paired student's t-test or the Wilcoxon signed-rank test, depending on the distribution of the data. Additional, explorative statistical data analysis was done on CIMT progression building a linear multivariate regression model.. Blood glucose, lipids and blood pressure significantly improved during the first 3 months of intensified treatment, which was sustained over the 2-year study duration. Mean CIMT significantly decreased from baseline to 2 year (0.883 ± 0.120 mm vs. 0.860 ± 0.130 mm; p = 0.021). None of the investigated surrogate measures, however, was able to predict changes in IMT early after treatment intensification.. Intensification of risk factor intervention in type 2 diabetes results in CIMT regression over a period of 2 years. None of the biomarkers used including endothelial function parameters or endothelial progenitor cells turned out to be useful to predict CIMT changes.. Clinical Trial Registration - Unique identifier: NCT00660790.

Topics: Aged; Cardiovascular Agents; Carotid Artery Diseases; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Prospective Studies; Risk Factors

Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct antiatherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40-74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ultrasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (-0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen- rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies which enforces a view that botanicals might represent promising drugs for anti-atherosclerotic therapy.

Topics: Adult; Aged; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers; Cardiovascular Agents; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cholesterol; Disease Progression; Double-Blind Method; Garlic; Humans; Male; Middle Aged; Phytotherapy; Plant Preparations; Plants, Medicinal; Time Factors; Treatment Outcome

We investigated the effects of folic acid supplementation on plasma total homocysteine levels and carotid intima-media thickness after kidney transplant.. Sixty patients who had undergone a kidney transplant were studied in this double-blind, randomized, placebo-controlled clinical trial. Those subjects were randomized to receive either 5 mg/d of oral folic acid or an equivalent dosage of placebo. The main outcome variables were the plasma total homocysteine level and carotid intima-media thickness (determined via B-mode sonography) at baseline and 2, 4, and 6 months after kidney transplant. We used independent and paired sample t tests for data analysis.. The mean age of the patients was 40.9 -/+ 10 years, and 32 of those subjects (58.2%) were men. In the control group, the plasma total homocysteine levels were 19 micromol/L at baseline, 18.7 micromol/L after 2 months, 19.3 micromol/L after 4 months, and 20 micromol/L after 6 months; and the carotid intima-media thickness measurements were 0.81 mm at baseline, 0.82 mm after 2 months, 0.84 mm after 4 months, and 0.85 mm after 6 months. In the folic acid group, the plasma total homocysteine levels were 18.5 micromol/L at baseline, 4.7 micromol/L after 2 months, 12.9 micromol/L after 4 months, and 10.9 micromol/L after 6 months; and the carotid intima-media thickness measurements were 0.73 mm at baseline, 0.73 mm after 2 months, 0.72 mm after 4 months, and 0.71 mm after 6 months.. Folic acid supplementation reduces both the plasma total homocysteine level and carotid intima-media thickness shortly after kidney transplant.

Topics: Administration, Oral; Adult; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Common; Carotid Artery, Internal; Double-Blind Method; Female; Folic Acid; Homocysteine; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Time Factors; Treatment Outcome; Tunica Intima; Tunica Media; Ultrasonography, Doppler

We aimed to assess the safety and efficacy of lubeluzole in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in the carotid artery territory.. A randomized, double-blind, placebo-controlled multicenter trial was conducted in 232 patients. Because treatment was administered within 6 hours and a CT scan was not mandatory before the start of treatment, 39 patients with either an intracerebral hemorrhage or ischemic stroke in the vertebrobasilar circulation were excluded from the primary efficacy analysis as prespecified in the protocol. Of the 193 patients with acute ischemic stroke in the carotid artery territory (target population), 61 received placebo, 66 lubeluzole 7.5 mg over 1 hour followed by 10 mg/d for 5 days, and 66 lubeluzole 15 mg over 1 hour followed by 20 mg/d for 5 days.. The trial, initially aimed at a patient inclusion of 270, was terminated prematurely according to the advice of the Safety Committee because of an imbalance in mortality between the treatment groups. Mortality rates at the final follow-up of 28 days for placebo, lubeluzole 10 mg/d, and lubeluzole 20 mg/d were, respectively, 18%, 6%, and 35% in the target population, results that were confirmed in the intent-to-treat population. Multivariate logistic regression analysis showed that the lower mortality in the lubeluzole 10 mg/d group was significantly in favor of the 10 mg/d treatment (P = .019). The higher mortality rate in the 20 mg/d group could be explained, at least in part, by an imbalance at randomization that led to a higher number of patients in that group with severe ischemic stroke. A total of 26 of 66 patients (39%) who received lubeluzole 10 mg/d had a score on the Barthel Index of > 70 at day 28, indicating no or mild disability, compared with 21 of 61 (34%) in the placebo group and 19 of 66 (29%) in the lubeluzole 20 mg/d group (P = NS).. In patients with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced mortality. Further clinical trials in a larger number of patients are ongoing to confirm efficacy.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Injections, Intravenous; Logistic Models; Male; Middle Aged; Multivariate Analysis; Piperidines; Placebos; Safety; Thiazoles

Topics: Aneurysm; Cardiovascular Agents; Carotid Artery Diseases; Endarterectomy, Carotid; Endovascular Procedures; Humans; Popliteal Artery; Practice Guidelines as Topic; Treatment Outcome

Inhibition of the mechanistic target of rapamycin (mTOR) is a promising approach to halt atherogenesis in different animal models. This study evaluated whether the mTOR inhibitor everolimus can stabilize pre-existing plaques, prevent cardiovascular complications and improve survival in a mouse model of advanced atherosclerosis.. Everolimus enhances features of plaque stability and counters cardiovascular complications in ApoE

Topics: Animals; Antigens, Ly; Atherosclerosis; Brain; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Common; Diet, Western; Disease Models, Animal; Disease Progression; Everolimus; Female; Fibrillin-1; Heart; Hypoxia, Brain; Macrophages; Mice, Knockout, ApoE; Monocytes; Motor Activity; Myocardial Contraction; Neovascularization, Pathologic; Plaque, Atherosclerotic; Protein Kinase Inhibitors; TOR Serine-Threonine Kinases

The aim of the present work is to present the development of a computational two-way coupled (fluid and particle coupled) magnetic nanoparticle targeting model to investigate the efficacy of magnetic drug targeting (MDT) in a patient-specific diseased left carotid bifurcation artery. MDT of therapeutic agents using multifunctional carrier particles has the potential to provide effective treatment of both cancer and cardiovascular disease by enabling a variety of localized treatment and diagnostic modalities while minimizing side effects.. A computational model is developed to analyze pulsatile blood flow, particle motion, and particle capture efficiency in a diseased left carotid bifurcation artery using the magnetic properties of magnetite (Fe. The computational simulations demonstrate that the greatest particle capture efficiency results for particle diameters within the micron range, specifically 4 µm in regions where flow separation and vortices are at a minimum. It was also determined that the capture efficiency of particles decreases substantially with particle diameter, especially in the superparamagnetic regime. Particles larger than 2 μm were targeted and captured at the desired location by the external magnetic field, and the largest capture efficiency observed was approximately 98%.. The simulation results presented in the present work have shown to yield favorable capture efficiencies for micron range particles and a potential for enhancing capture efficiency of superparamagnetic particles in smaller arteries and/or using magnetized implants such as cardiovascular stents. The present work presents results for justifying further investigation of MDT as a treatment technique for cardiovascular disease.

Topics: Blood Flow Velocity; Cardiovascular Agents; Carotid Arteries; Carotid Artery Diseases; Computer Simulation; Drug Carriers; Humans; Magnetic Fields; Magnetite Nanoparticles; Models, Cardiovascular; Numerical Analysis, Computer-Assisted; Particle Size; Pulsatile Flow; Regional Blood Flow

Carotid artery web is considered an exceptional cause of recurrent ischemic strokes in the affected arterial territory. The underlying pathology proposed for this entity is an atypical fibromuscular dysplasia. We present the case of a 43-year-old woman with no cardiovascular risk factors who had experienced 2 cryptogenic ischemic strokes in the same arterial territory within an 11-month period. Although all diagnostic tests initially yielded normal results, detailed analysis of the computed tomography angiography images revealed a carotid web; catheter angiography subsequently confirmed the diagnosis. Carotid surgery was performed, since which time the patient has remained completely asymptomatic. The histological finding of intimal hyperplasia is consistent with previously reported cases of carotid artery web. Carotid artery web is an infrequent cause of stroke, and this diagnosis requires a high level of suspicion plus a detailed analysis of vascular imaging studies.

Topics: Adult; Aspirin; Atorvastatin; Biopsy; Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Internal; Computed Tomography Angiography; Female; Fibromuscular Dysplasia; Humans; Hyperplasia; Neointima; Recurrence; Risk Factors; Stroke

Topics: Cardiovascular Agents; Carotid Artery Diseases; Clinical Decision-Making; Endarterectomy, Carotid; Endovascular Procedures; Humans; Patient Selection; Risk Factors; Stents; Stroke; Treatment Outcome

Lipid mediators derived from omega-3 polyunsaturated fatty acids such as resolvin D1 (RvD1) accelerate the resolution of inflammation and have potential as vascular therapeutics. The objective of this study was to evaluate local perivascular delivery of RvD1 as a means to attenuate neointimal hyperplasia in a rat model of arterial injury.. Smooth muscle cells were harvested from rat aortas to study the effects of RvD1 on rat arterial vascular smooth muscle cell responses in vitro, with focus on inflammation, proliferation, migration, cytoskeletal changes, and cytotoxicity. The safety and efficacy of perivascular delivery of RvD1 through thin biodegradable three-layered poly(lactic-co-glycolic acid) wraps or 25% Pluronic F127 gels were studied in a rat model of carotid angioplasty. A total of 200 ng of RvD1 was loaded into each construct for perivascular delivery after injury. Morphometric and histologic analyses were performed 3 and 14 days after injury.. RvD1 attenuated rat arterial vascular smooth muscle cell inflammatory pathways, proliferation, migration, and mitogen-induced cytoskeletal changes in vitro, without evidence of cytotoxicity. RvD1-loaded wraps reduced neointimal formation after carotid angioplasty by 59% vs no-wrap controls (P = .001) and by 45% vs vehicle-wrap controls (P = .002). RvD1-loaded Pluronic gels similarly reduced neointimal formation by 49% vs no-gel controls (P = .02) and by 52% vs vehicle-gel controls (P = .02). No group was associated with infection, thrombosis, or negative vessel remodeling. Wraps were found to be easier to apply than gel constructs. Ki67 proliferation index was significantly lower in RvD1-loaded wrap-treated arteries compared with both no-wrap and vehicle-wrap controls at both 3 and 14 days after injury (65% vs no-wrap group and 70% vs vehicle-wrap group at day 3, 49% vs both control groups at day 14; P < .05). Similarly, oxidative stress (30% and 29%; P < .05) and nuclear factor κB activation (42% and 45%; P < .05) were significantly lower in the RvD1-loaded wrap group compared with both no-wrap and vehicle-wrap controls at 3 days after injury.. Local perivascular delivery of RvD1 attenuates formation of neointimal hyperplasia without associated toxicity in a rat model of carotid angioplasty. This effect is likely due to attenuation of inflammatory pathways as well as decreased arterial smooth muscle cell proliferation and migration.

Topics: Angioplasty, Balloon; Animals; Aorta; Cardiovascular Agents; Carotid Artery Diseases; Cell Movement; Cell Proliferation; Cells, Cultured; Cytoskeleton; Disease Models, Animal; Docosahexaenoic Acids; Drug Carriers; Drug Compounding; Hyperplasia; Inflammation Mediators; Ki-67 Antigen; Lactic Acid; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Oxidative Stress; Poloxamer; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Time Factors; Transcription Factor RelA

Emerging evidences indicate that heat-shock protein 90 (HSP90) is associated with atherogenesis. However, the effect of HSP90 on plaque stability is largely unknown. In this study, we explored the role of HSP90 in plaque development and its regulatory mechanisms on vasculature.. Heat-shock protein90-overexpression lentivirus (Lenti-HSP90) was used to transfect apoE. As a result, HSP90 gene overexpression led to reduction in en face plaque area and increase in unstable plaque with heavier accumulation of lipids. Concomitantly, more macrophages, less smooth muscle cells, and collagen were generated, suggesting aggravated inflammation. However, inhibition of HSP90 with 17-AAG, a HSP90-inhibitor, induced opposing effects. Moreover, HSP90 upregulated plaque MMP-8, which might be the underlying mechanism of the change in plaque vulnerability index. Further, the translocation of NF-κB was promoted by HSP90, while inhibition of NF-κB significantly reduced MMP-8 production, which is upregulated by HSP90.. These findings suggested that HSP90 governs plaque development and vulnerability, as well as inflammation, at least in part via MMP-8 and NF-κB signaling pathways.

Topics: Animals; Apolipoproteins E; Benzoquinones; Cardiovascular Agents; Carotid Arteries; Carotid Artery Diseases; Disease Models, Animal; Gene Expression Regulation; Genetic Vectors; HSP90 Heat-Shock Proteins; Inflammation; Inflammation Mediators; Lactams, Macrocyclic; Lentivirus; Male; Matrix Metalloproteinase 8; Mice; Mice, Knockout; NF-kappa B; Plaque, Atherosclerotic; RAW 264.7 Cells; Signal Transduction; Transduction, Genetic; Transfection

Topics: Aortic Diseases; Cardiovascular Agents; Carotid Artery Diseases; Humans; Leg; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Stents; Venous Thromboembolism

Current commercially available drug-eluting stents (DESs) are criticized for the problem of stent thrombosis by induced impaired re-endothelialization (RE). The solving of this challenge could be boosted by endothelial progenitor cells (EPCs). The purpose of this study was to examine the effects of hepatocyte growth factor (HGF) on this process.. The abundance and functional capacity of circulating EPC was analyzed by a fluorescence-activated cell sorter and western blot. The in vivo effect of HGF on DES patency, RE, and neointimal formation was investigated in a hypercholesterolemic rabbit model.. HGF efficiently ameliorates the vascular response to stent implantation, and has an important redeeming influence on the deleterious endothelial effects of DES.

Topics: Angioplasty, Balloon; Animals; Apoptosis; Cardiovascular Agents; Carotid Arteries; Carotid Artery Diseases; Cell Movement; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Eluting Stents; Endothelial Progenitor Cells; Hepatocyte Growth Factor; Hypercholesterolemia; Injections, Subcutaneous; Male; Neointima; Paclitaxel; Rabbits; Re-Epithelialization; Time Factors

The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol and TECA (total triterpenic fraction of Centella Asiatica) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral non-stenosing plaques.. This was an observational pilot substudy of the San Valentino epidemiological cardiovascular study. The study included 1363 subjects aged 45-60 without any conventional risk factors who had non stenosing atherosclerotic plaques (<50%) in at least one carotid or common femoral bifurcation, allocated into 6 groups: Group 1 (CONTROLS): management was based on education, exercise, diet and lifestyle changes. This same management plan was used in all groups; Group 2 Pycnogenol 50 mg/day; Group 3 Pycnogenol 100 mg/day; Group 4 Aspirin 100 mg/day or Ticlopidine 250 mg/day if intolerant to aspirin; Group 5 Aspirin 100 mg/day and Pycnogenol 100 mg/day; Group 6 Pycnogenol 100 mg/day plus TECA (total triterpenic fraction of Centella Asiatica) 100 mg/day. There was a six monthly follow-up up to 30 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed from the non-stenotic to the stenotic group. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 30 months.. The ultrasonic score increased significantly in groups 1, 2 and 4 but not in groups 3, 5 and 6 suggesting a beneficial effect of Pycnogenol 100 mg. The percentage of plaques that progressed from class IV to class V was 8.4% in group 2, 5.3% in group 3, 4% in group 5 and 1.1% in group 6 (P<0.0001) compared with 16.6% in group 4 (aspirin) and 21.3% in the control group suggesting a beneficial effect of Pycnogenol. The lowest rate of progression was in group 6 (Pycnogenol plus TECA). At 30 months, the oxidative stress in all the Pycnogenol groups was less than in the control group. The oxidative stress was lower in the Pycnogenol 100 mg group than the Pycnogenol 50 mg group (P<0.0001). In the combined group of Pycnogenol and TECA the oxidative stress was less than the Pycnogenol alone (P<0.001).. Pycnogenol and the combination of Pycnogenol+TECA appear to reduce the progression of subclinical arterial lesions in low-risk asymptomatic subjects. The reduction in plaque progression was associated with a reduction in oxidative stress. The results justify a large randomized controlled study to demonstrate the efficacy of the combined Pycnogenol and TECA prophylactic therapy in subclinical atherosclerosis.

Topics: Asymptomatic Diseases; Atherosclerosis; Cardiovascular Agents; Carotid Artery Diseases; Carotid Intima-Media Thickness; Centella; Dietary Supplements; Disease Progression; Drug Therapy, Combination; Female; Femoral Artery; Flavonoids; Humans; Italy; Male; Middle Aged; Oxidative Stress; Phytotherapy; Pilot Projects; Plant Extracts; Plants, Medicinal; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Time Factors; Treatment Outcome; Triterpenes

After an acute coronary syndrome (ACS), optimal medical therapy (OMT) has been shown to be effective in reducing subsequent cardiovascular (CV) events. However, even in populations that reach recommended secondary prevention goals, there is a subset of patients that experience subsequent CV events.. To identify biological or clinical predictors of residual risk of CV events in post-ACS patients receiving OMT.. A total of 990 post-ACS patients benefited from OMT (optimized treatment during the acute and chronic post-ACS phase, along with a therapeutic and dietary education programme). Traditional CV risk factors and atheroma disease markers (intima-media thickness measurement, carotid atheroma, peripheral arterial disease (PAD) measured by ankle brachial index, and the number of coronary arteries with a >50% stenosis) were evaluated at 3 months post ACS. Cardiovascular events were recorded at follow up.. At 20-month follow up, >80% of the patients reached the recommended secondary prevention goals. In this population, diabetes was the only CV risk factor significantly associated with CV events in multivariate analysis including traditional risk factors (HR 1.61, p = 0.017). In multivariate analyses including CV risk factors and atheroma disease markers, only PAD remained significantly associated with CV events (HR 1.83, p = 0.04). The number of vascular beds involved was associated with poorer prognosis (HR for disease in 3-vascular-beds 3.85, p = 0.001, using disease in 1-vascular-bed as a reference group).. In post-ACS patients with OMT, atheroma burden is a powerful prognostic marker of recurrent CV events, while diabetes remains the only independent marker of CV events among traditional CV risk factors.

Topics: Acute Coronary Syndrome; Aged; Ankle Brachial Index; Biomarkers; Cardiovascular Agents; Carotid Artery Diseases; Carotid Intima-Media Thickness; Coronary Angiography; Coronary Stenosis; Diabetes Mellitus; Diet, Reducing; Echocardiography; Exercise; Female; France; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Perfusion Imaging; Peripheral Arterial Disease; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Risk Reduction Behavior; Secondary Prevention; Time Factors; Treatment Outcome

Topics: Antihypertensive Agents; Asymptomatic Diseases; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Endarterectomy, Carotid; Evidence-Based Medicine; Fibrinolytic Agents; Germany; Guideline Adherence; Humans; Hypoglycemic Agents; Hypolipidemic Agents; National Health Programs; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Treatment Outcome

Topics: Antihypertensive Agents; Asymptomatic Diseases; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Endarterectomy, Carotid; Evidence-Based Medicine; Fibrinolytic Agents; Germany; Guideline Adherence; Humans; Hypoglycemic Agents; Hypolipidemic Agents; National Health Programs; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Treatment Outcome

The optimal treatment of asymptomatic carotid disease is being debated again. The conclusions of the large randomised controlled trials of the early 1980s and 1990s are increasingly being questioned due to advances in modern medical treatment. This study investigates how patients are actually managed medically related to general risk factors prior to carotid endarterectomy in a German health-care region.. A prospective data bank including 95 consecutive patients was used. The effectiveness of lipid lowering and diabetes management were investigated as well as the use of anti-thrombotic and blood pressure medication.. A total of 108 carotid endarterectomies in 95 patients were performed between January 2009 and March 2010. All 95 patients (70 male, 25 female; 39 symptomatic/56 asymptomatic) were included in the study. Nearly half (54%) of the patients were on statins; of these, 45% had low-density lipoprotein (LDL) levels >100 mg dl(-1). Of 32 patients with diabetes, one had glycohaemoglobin (HbA(1c)) <6.0. Overall, four patients were on clopidogrel. Three patients were severely hypertensive (systolic blood pressure >180 mmHg).. The best medical therapy for carotid disease is not optimal in the part of the German health-care system observed in this study. We strongly advocate similar audits in other health-care areas and systems.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Asymptomatic Diseases; Cardiovascular Agents; Carotid Artery Diseases; Cerebrovascular Disorders; Chi-Square Distribution; Clinical Audit; Endarterectomy, Carotid; Evidence-Based Medicine; Female; Fibrinolytic Agents; Germany; Guideline Adherence; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; National Health Programs; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

This paper summarizes the highlights of the 15th International Workshop of Endovascular Surgery, held in Ajaccio in June 2008. This is an annual event that attracts leading endovascular therapists from both sides of the Atlantic Ocean as well as a contingency from down-under. The layout of this meeting followed the previous events with sessions on carotid artery disease and abdominal and thoracic aortic aneurysms topped up with clinical cases, lower limb ischemia and venous disease. Generally the session takes off by summarising new evidence, followed by questions and discussion. This workshops gives the participants an excellent opportunity to get an updated perspective within these fast developing areas.

Topics: Adult; Aged, 80 and over; Aortic Aneurysm; Aortic Dissection; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Cardiovascular Diseases; Carotid Artery Diseases; Female; Humans; Male; Minimally Invasive Surgical Procedures; Peripheral Vascular Diseases; Renal Artery; Treatment Outcome; Vascular Surgical Procedures; Veins

Rho kinases have been shown to be involved in the pathogenesis of atherosclerosis. This study examined the effects of fasudil, a specific Rho kinase inhibitor, on plaque development and progression in atherosclerotic mice. Sixty apolipoprotein E-knockout (apoE-KO) mice were fed a high-fat diet. Mice started to receive fasudil at the same time as fat feeding (early treatment), or after 12 weeks of fat feeding (delayed treatment). In each administrative schedule, mice were divided into three groups: low dose fasudil group (30 mg/kg/day), high dose fasudil group (100mg/kg/day) and control group (tap water) (n=10, respectively). Plaque size was determined by using ultrasound biomicroscopy (UBM) and histological examinations. Brachiocephalic artery UBM analysis showed that in early treatment, both doses of fasudil significantly reduced lesion size compared with the controls (P<0.05). In delayed-fasudil treatment, plaque area was reduced by 54% (P<0.05) after 12 weeks of treatment at a high dose of fasudil (100mg/kg/day). The UBM findings were confirmed by histological studies at the corresponding arterial sites. The beneficial effect was also observed in the left common carotid arteries that delayed-fasudil treatment reduced the plaque size in a dose-dependent manner. The arterial intima-medial thickness (IMT) and maximal flow velocity of both arteries were lower in fasudil-treated group (100mg/kg/day) in comparison with the control mice. Furthermore, fasudil treatment (100mg/kg/day) reduced the macrophage accumulation in atherosclerotic lesions. However, fasudil had no effects on blood pressure and plasma lipid concentrations in both studies. In conclusion, our studies showed that blocking Rho kinase reduced both the early development and later progression of atherosclerotic plaques in apoE-KO mice by using a novel micro-ultrasound approach.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Apolipoproteins E; Atherosclerosis; Blood Pressure; Brachiocephalic Trunk; Cardiovascular Agents; Carotid Artery Diseases; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Immunohistochemistry; Lipids; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Acoustic; Protein Kinase Inhibitors; rho-Associated Kinases; Time Factors

The peri-operative use of antiplatelet, anticoagulant and other drugs for patients undergoing carotid endarterectomy (CEA) is unclear and consensus is lacking. This study aimed to assess the current peri-operative practice of European vascular surgeons with respect to antiplatelet and other medications for patients undergoing CEA.. Online questionnaire study.. Members of the Vascular Society of Great Britain & Ireland and European Society for Vascular Surgery were invited to complete an online survey in March 2008. Surgeons were asked about their preferences for the peri-operative administration of antiplatelet, statin and other medications for patients undergoing carotid endarterectomy.. Partial or complete responses were received from 399/650 (61.4%) surgeons with a collective annual throughput of >11500 CEA procedures. For symptomatic and asymptomatic patients, 20/392 (5%) and 47/392 (12%) of surgeons would stop aspirin before surgery and 170/392 (43%) and 217/392 (55%) of surgeons would stop Clopidogrel prior to CEA. Of surgeons who would stop Clopidogrel, 84/170 (49%) and 124/217 (57%) would do so >7 days before surgery for symptomatic and asymptomatic patients respectively. 12/393 (3%) surgeons would prescribe one 75 mg dose of Clopidogrel on the evening before surgery. Intra-operative Dextran was used selectively by 40/395 (10%). Only 78/393 (20%) would delay surgery to commence a statin. Intra-operatively, 348/394 (88%) used intravenous heparin, which was reversed routinely by 47/348 (13%) and selectively by 60/348 (17%).. There appears to be broad consensus between vascular surgeons in the pharmacological management of patients undergoing carotid endarterectomy, although some variations do exist. Further clinical studies may help clarify the optimum management strategy in this patient group.

Topics: Anticoagulants; Cardiovascular Agents; Carotid Artery Diseases; Drug Administration Schedule; Drug Utilization; Endarterectomy, Carotid; Europe; Health Care Surveys; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Internet; Perioperative Care; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Surveys and Questionnaires

Studies in animals and patients indicate that rapamycin affects vasodilatation differently in outer and inner curvatures of blood vessels. We evaluated in this study whether rapamycin affects endothelial nitric oxide synthase (eNOS) responsiveness to shear stress under normo- and hypercholesteraemic conditions to explain these findings.. Shear stress levels were varied over a large range of values in carotid arteries of transgenic mice expressing human eNOS fused to enhanced green fluorescence protein. The mice were divided into control, low-dose rapamycin (3 microg/kg/day), and high-dose rapamycin (3 mg/kg/day) groups and into normocholesteraemic and hypercholesteraemic (ApoE-/- on high cholesterol diet for 3-4 weeks) groups. The effect of rapamycin treatment on eNOS was evaluated by quantification of eNOS expression and of intracellular protein levels by en face confocal microscopy. A sigmoid curve fit was used to described these data. The efficacy of treatment was confirmed by measurement of rapamycin serum levels (2.0 +/- 0.5 ng/mL), and of p27kip1 expression in vascular tissue (increased by 2.4 +/- 0.5-fold). In control carotid arteries, eNOS expression increased by 1.8 +/- 0.3-fold in response to rapamycin. In the treated vessels, rapamycin reduced maximal eNOS expression at high shear stress levels (>5 Pa) in a dose-dependent way and shifted the sigmoid curve to the right. Hypercholesteraemia had a tendency to increase the leftward shift and the reduction in maximal eNOS expression (P = 0.07).. Rapamycin is associated with high eNOS in low shear regions, i.e. in atherogenic regions, protecting these regions against atherosclerosis, and is associated with a reduction of eNOS at high shear stress affecting vasomotion in these regions.

Topics: Animals; Apolipoproteins E; Cardiovascular Agents; Carotid Arteries; Carotid Artery Diseases; Cyclin-Dependent Kinase Inhibitor p27; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Green Fluorescent Proteins; Humans; Hypercholesterolemia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Nitric Oxide Synthase Type III; Pulsatile Flow; Recombinant Fusion Proteins; Sirolimus; Stress, Mechanical