Atherosclerotic Process In Patients Research Articles

Abstract 12853: [ 64 Cu]Cu-DOTATATE is Superior to [ 68 Ga]Ga-NODAGA-E[c(RGDyK)]2 (RGD) PET/CT Imaging In Detection and Quantification of Atherosclerosis: A Retrospective Analysis of a Phase 2 Trial Cohort

Introduction: Inflammation and angiogenesis are central to development of atherosclerosis. [ 64 Cu]Cu-DOTATATE and [ 68 Ga]Ga-NODAGA-E[c(RGDyK)]2 (RGD) are PET tracers that can non-invasively visualize somatostatin receptor subtype 2 (SSTR 2 ) and α v β 3 integrin expression that represent inflammation and angiogenesis respectively. Hypothesis: Whether an imaging tracer of inflammation can be compared with a tracer of angiogenesis for detection and quantification of the atherosclerotic process in patients from a Phase II cancer trial cohort. Methods: A cohort of patients from Phase II trial were divided in three groups as controls (N=7), at risk (N=6) & diseased (N=7). PET/CT scans with two different tracers were performed in all subjects. The scans were retrospectively analyzed, and tracer uptake (mean of maximum target-to-background ratios (mTBRmax)) were determined in 6 arterial segments. In addition, plaques from patients (N=7) undergoing carotid endarterectomy (CEA) were studied with autoradiography and immunohistochemistry. Results: [ 64 Cu]Cu-DOTATATE uptake in the disease group was significantly higher compared to the control group in the abdominal aorta (4.4 vs 2.1, p=0.02), thoracic aorta (3.0 vs 2.2, p=0.02), aortic arch (2.8 vs 2.2, p=0.03), left carotid artery (2.2 vs 1.3, p=0.02) and the average of all six aortic segments (2.7 vs 2.0, p=0.01) whereas all aortic segments in the disease group showed a higher but a non-significant difference compared to the control group with RGD uptake. A moderate correlation was found between the mean aortic uptake of [ 64 Cu]Cu-DOTATATE & RGD (r=0.41, p=0.01) in patients from the disease group. SSTR 2 and α v β 3 expression was confirmed on ex vivo plaques along with tracer binding. Conclusions: An in vivo imaging marker of inflammation was superior to a marker of angiogenesis in discriminating levels of atherosclerosis. The two markers were weakly correlated in patients with known cardiovascular disease.

Carotid Intimomedial Thickness (CIMT) in Patients with Rheumatoid Arthritis; the Need for More Aggressive Cardiovascular Screening in RA.

To use carotid intimal medial thickness as a marker of early atherosclerosis in patients with rheumatoid arthritis. Cross-sectional descriptive study. Place and Duration of the Study: Rheumatology Unit of Federal Government Polyclinic Hospital, Islamabad, from 1st June 2019 till 30th January 2022. The study included 190 patients divided equally into cases of rheumatoid arthritis and healthy control groups. Carotid intimal medial thickness was measured using the carotid doppler ultrasound. The mean values of both the study groups were evaluated using the independent sample t-tests. Different statistical tests for correlation were also used where appropriate. This study included a total of 190 patients, 95 each in case and control groups. There were 15 (15.8%) males and 80 (84.2%) females with mean age of 43.5±12.8 years among cases, while 27 (28.4%) males and 68 (71.6%) females with mean age of 43.1±10.1 years in the control group. A significantly higher number of cases had a carotid intima-media thickness of more than 0.6 mm as compared to controls (43.2% vs. 25.3%, p=0.009). Cases with seropositive status were 1.98 times more likely to have higher carotid intima-medial thickness compared with controls. Carotid intima-media thickness measurement is important as a surrogate marker of atherosclerotic process in patients with rheumatoid arthritis. Rheumatoid arthritis (RA), Carotid intimal medial thickness (CIMT), Atherosclerosis, Cardiovascular disease (CVD).

Differential expression of TLR4 in patients of coronary artery disease with and without traditional cardiovascular risk factors

Abstract Funding Acknowledgements Type of funding sources: None. Background Atherosclerosis is inherently an inflammatory process, with a complex interplay of inflammatory markers. It is established that these inflammatory markers play an important role in patients of Coronary Artery Disease(CAD) with traditional cardiovascular risk factors. However, the role of inflammation in the atherosclerotic process in patients of CAD without traditional risk factors is still not clearly known. Purpose Our purpose was to determine whether in patients of CAD without traditional risk factors, TLR4(Toll like receptor 4) expression as a marker of inflammation is similar to that in patients of CAD with traditional risk factors. Materials and Methods This observational cross sectional study was done between July’20 to Dec’21. Equal number of patients of CAD with and without traditional cardiovascular risk factors undergoing Coronary Artery Bypass Grafting (CABG) were enrolled. The risk factors considered were Hypertension, Diabetes, Dyslipidemia, Obesity and Addiction to Tobacco and/or Alcohol. A minimum of two punch biopsy samples of aortic tissue was taken from each subject undergoing CABG. Immunohistochemistry for TLR4, was done in Ventana BenchMark GX System. The primary TLR4 antibody was procured from reputed source. Results The presence or absence of TLR4 expression was associated significantly with the Syntax scores (37.40±4.74 vs 29.5±8.71; p value=0.036), total Cholesterol (187±35.06mg/dL vs 130±35.69 mg/dL ;p value 0.010) and LDL cholesterol (118.86±28.12mg/dL vs 64.21±25.61 mg/dL; p value 0.003). TLR4 expression, however, was not significantly associated with the number of coronary vessels involved (p=0.298). TLR4 expression was also not significantly associated with any other individual risk factors. However, when the traditional risk factors were considered in combination, TLR4 expression was associated significantly with the number of risk factors present(p=0.029) the strongest being in those having 4 traditional risk factors. The level of TLR4 expression gradually declined with the decrease in the number of risk factors, having mostly weak or negative expression in patients without any traditional risk factors. Conclusion Patients with CAD without any traditional risk factors, had a less severe coronary artery disease as manifested by lower Syntax scores, and had lower degree of TLR4 expression. Patients with CAD with traditional risk factors had more severe coronary artery disease as evidenced by higher Syntax scores, and had higher degree of TLR4 expression proportional to the number of traditional risk factors present. Thus, differential TLR4 expression in CAD patients with and without traditional risk factors indicated a difference in inflammatory state between the two groups and warrants further investigation.

ХРОНИЧЕСКИЙ АЛКОГОЛИЗМ В СОЧЕТАНИИ С ИЗМЕНЕНИЕМ ВНУТРЕННИХ ОРГАНОВ И АТЕРОСКЛЕРОЗОМ

Objective. Establish frequency of change of internal organs and the atherosclerotic process in patients suffering from chronic alcoholism and determine the causes of death. Material and methods. The results of autopsies of the 94 dead with chronic alcoholism in the Centre of Mental Health for 2005–2014 years. Analysis of the material was carried out on the basis of macroscopic and microscopic examination (histological specimens stained with hematoxylin-eosin, pikrofuksin on Van Gieson, on myelin by Kluver-Barrera). During the autopsy, it drew attention to the presence of atherosclerotic lesions in the aorta, coronary and cerebral arteries. Results. According to the morphological study and pathologic diagnosis all observations are as follows: delirium tremens – 24, encephalopathy Gayet-Wernicke – 13, alcoholic encephalopathy – 10, alcoholic dementia – 3, myelinolysis pontis – 8, disease Marchiafawa-Bignami – 1, alcoholic cirrhosis of the liver – 1. All observations were accompanied by severe morphological changes at least 3–4 of the internal organs. Severe atrophic gastritis occurred in 39 cases (75%), alcoholic dilated cardiomyopathy – 31 (59.6%), sclerosing pancreatitis – 32 (61.5%), morphological changes in the liver (steatosis and alcoholic hepatitis) – 43 (82.7%), two observations – alcoholic cirrhosis of the liver, bronchopneumonia – 23 (44.2%). Signs of atherosclerosis were found in 19 cases (36.5 %). The average age of the deceased in these cases was 53.4 years. Conclusion. Complications of chronic alcoholism accompanied by morphological changes of internal organs, which greatly aggravate the disease. The most significant are the changes in the heart in the form of alcoholic dilated cardiomyopathy with the development of acute or chronic cardiovascular failure. A certain importance is pancreatitis, which can result in the development of pancreatic necrosis and changes in the liver with the development of liver failure. In some cases (especially in patients with alcoholic dementia) a major role in tanatogenesis can play bronchopneumonia. Atherosclerotic process is not significant in tanatogenesis of patients with chronic alcoholism and occurs predominantly in elderly patients.

Cystatin C as a marker of the rapid development of the atherosclerosis in patients with diabetes mellitus and chronic kidney disease

Introduction. The relationship between kidney dysfunction and cardiovascular system is multifaceted. Thus, the value of such a potential marker of glomerular filtration rate (GFR) as cystatin C cannot be underestimated as a predictor of the development of cardiovascular complications and atherogenesis factor in diabetes mellitus (DM) and chronic kidney disease (CKD). Objective was to evaluate the role of cystatin C as an atherogenesis factor in patients with DM and CKD. Materials and methods. The study involved 514 patients aged 25 to 80 years (the group of interest (n=449), the control group (n=65)). All patients underwent clinical and laboratory tests, sonography of the lower extremities vessels and brachiocephalic arteries (BCA). Results. The thickness of the intima-media complex increased with an increase of cystatin C level in the right carotid artery (CA) (from 0.80 [0.70; 0.90] mm to 0.97 [0.90; 1.02] mm) and in the left CA (from 0.90 [0.80; 0.94] mm to 0.92 [0.90; 1.10] mm). Logistic regression analysis demonstrated that an increase of cystatin C level > 0.93 mg/l raises the risk of intima-media thickening by 2.5 times (OR 2.505, p=0.042) and by 5 times when increase of cystatin C>1.38 mg/l (OR 4.718, p=0.001). At the same time, the association with homocysteine was unreliable (p=0.058). The level of cystatin C ≥0.82 mg/l with a sensitivity of 72 % and a specificity of 52 % allowed to predict the development of subclinical atherosclerosis in patients with DM and CKD (ROC AUC – 0.739). Conclusion. Cystatin C is not only a highly sensitive and accurate indicator of GFR, capable of detecting early stages of renal dysfunction, but also a highly effective predictive marker of atherosclerotic process in patients with DM and CKD.

Chocolate enriched by extra virgin olive oil improves endothelial function and oxidative stress in patients with diabetes

ObjectiveEndothelial dysfunction and oxidative stress are among the most relevant mechanisms underlying the atherosclerotic process in patients with type 2 diabetes mellitus (T2 DM). Extra virgin olive oil (EVOO) reduces postprandial glycemia with a mechanism counteracting oxidative stress–mediated incretin down-regulation in healthy subjects and in patients with impaired fasting glucose. The aim of this study was to evaluate if the intake of chocolate enriched by EVOO had positive effects on endothelial function and oxidative stress in patients with T2 DM. MethodsIn this study we enrolled and randomly assigned 25 consecutive patients with T2 DM to receive 40 g of EVOO-enriched chocolate or 40 g of control chocolate spread. Participants were assessed at baseline and 2 h after chocolate intake. Endothelial function was assessed by arterial brachial flow-mediated dilation (FMD); oxidative stress was evaluated by the measurement of serum nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (Nox2) levels, nitric oxide availability, and serum hydrogen peroxide breakdown activity (HBA). ResultsWe observed a significant increase of FMD, nitric oxide (NO) availability, and HBA in the EVOO-enriched chocolate group (P < 0.001). Conversely, soluble Nox2-derived peptide (sNox2-dp) levels significantly decreased (P < 0.001). No significant change was observed in the control chocolate group. To assess the relation of EVOO-enriched chocolate to endothelial function and oxidative stress, a general linear model (GLM) analysis was performed; a significant difference for treatments was found with respect to FMD, NO availability, HBA, and sNox-dp. ConclusionsAdministration of 40 g of EVOO-enriched chocolate is associated with increased endothelial function and reduction of oxidative stress in patients with T2 DM. Future studies are needed to analyze the effect of chronic assumption of EVOO-enriched chocolate on vascular function, oxidative stress, and cardiovascular complications in patients with T2 DM.

Порівняльна характеристика факторів атероґенезу в пацієнтів із симптомним і асимптомним перебігом атеросклеротичних каротидних стенозів

To study a comparative assessment of risk factors for atherogenesis in patients with different clinical manifestations of carotid atherosclerotic stenosis. The study included 106 patients (men — 74, women — 32) aged 39 to 79 years (mean age 62.6 ± 0.9), which devided to 3 clinical groups: Group I — 35 patients with acute atherothrombotic stroke with ipsilateral carotid stenosis, group II — 41 patients after acute cerebrovascular events and carotid endarterectomy, group III — 30 patients with asymptomatic atherosclerotic carotid stenosis and the control group, which consisted of 20 relatively healthy individuals. The degree of stenosis of the internal carotid arteries was highest (&gt; 70 %) in the group of patients who underwent carotid endarterectomy. In addition in this group was prevalence younger men, compared with the group of asymptomatic stenosis and women (p = 0.00300), there was an older age of patients and moderate stenosis of 50–69 % (p = 0.00647). In patients with stenotic atherosclerosis of the internal carotid artery, there was a significant increase in the level of Lp-PLA2 compared with the control. This confirms that Lp-PLA2 can be considered as a marker of carotid atherosclerosis and influence the development of ischemic stroke. The highest level of Lp-PLA2 was observed in the clinical group of patients who underwent carotid endarterectomy after ischemic stroke and there was a tendency to a more significant increase in total cholesterol. This suggests a more aggressive course of the atherosclerotic process in patients in this group.

The Role of Garcinia Mangostana Pericarp Extract as Antioxidant to Inhibit Atherosclerosis Process in High Risk Framingham Score Patient; Original Article

Atherosclerosis is the pivotal role of cardiovascular disease (CVD) involving oxidative stress dan inflammation. Garcinia has anti-oxidant property for years. This study was performed to explore the role of α-Mangostin of Garcia Mangostana Pericarp Extract as an antioxidant in inhibiting atherosclerotic process in patients with high-risk Framingham score. Methods: This prospective cohort design was led in 90 grown-ups with high hazard cardiovascular score which were resolved dependent on Framingham criteria, age 50–70 years of age. The patients were divided into two groups. One group was administered 2520 mg/day Garcinia mangostana Linn extracts (GMLE) in 3 divided doses for 90 days and the other group was administered a placebo. Parameters were Nitric Oxide (NO), Superoxide Dismutase (SOD) and Malondialdehyde (MDA), measured at baseline and after 90 days of treatment. An Independent T-test was performed for normally distributed data and the Mann-Whitney test was performed for abnormally distributed data with a significance level of p≤0.05. Results: Among the 77 subjects, we found that the plasma, MDA, concentration was significantly decreased compared with placebo 0,29±0.5 vs -0.04±0.25, respectively p = 0.011). SOD level significantly decreased in GMLE patients compared with placebo patients (0,17±0.79 vs -0.27±0.67, respectively, p=0.010) and we found that there was slightly increased in nitric oxide (NO), but no significantly compared with placebo 4.34±10.01 and 2.35±7.39, respectively, p = 0.37). Conclusion: Garcinia mangostana pericarp extract has an antioxidant effect that significantly inhibit atherosclerosis process in high-risk Framingham score patients

FEATURES OF THE INTERCONNECTION OF TRADITIONAL RISK FACTORS AND IL-10 WITH THE ACTIVITY OF THE INFLAMMATORY PROCESS AND ATHEROSCLEROSIS DEVELOPMENT IN PATIENTS WITH PSORIATIC ARTHRITIS

The aim: To determine the features of atherosclerotic process, cardiovascular risk in patients with PsA. Materials and methods: The study included 42 patients with PsA who did not have atherosclerotic CVD, diabetes, chronic kidney disease and other serious diseases, did not take statins, the comparingl group consisted of 20 patients with psoriasis (PS) and 20 practically healthy individuals who had no signs of rheumatic, infectious and other inflammatory diseases were screened. Results: It was revealed that in patients with PsA, the severity of the atherosclerotic process is more compared with patients with PS (the RF profiles were the same). The highest levels of C-reactive protein, fibrinogen, uric acid, intima-media complex thickness, atherosclerotic plaque frequency were found in patients in the PsA group, which may indicate a pathogenetic association of additional RF with the development of a more common atherosclerotic process. Conclusions: In the development of the atherosclerotic process in patients with PsA, the pro-traditional risk factors play an important role as the immune-inflammatory factors (CRP, IL-10) and additional risk factors (uric acid).

Galectin-3 and its relationship with the state of coronary arteries in patients with acute myocardial infarction and concomitant obesity

The aim of the study - to evaluate the condition of the coronary arteries according to quartile of galectin-3 serum level in patients with acute myocardial infarction and obesity. Materials and methods. A total of 31 patients with acute myocardial infarction and I and II degree of obesity were examined. A coronaroventriculography was performed with stenting of the infarct-dependent coronary artery within 12 hours from the pain syndrome onset. Galectin-3 was determined using a Human Galectin-3 ELISA kit (China). The degree of coronary atherosclerosis severity was assessed by coronaroventriculography (CVG) using the Gensini score. Results. The most common atherosclerotic lesion was found in the right interventricular artery – 89 % of cases followed by the right coronary artery (59.3 %), about half of patients (48.1 %) had a lesion of the circumflex artery. The greatest vulnerability of the right interventricular artery was accompanied by the highest mean stenosis values – 77.3 % followed by the right coronary artery, the mean stenosis value of which was 68.2 %. The development of acute myocardial infarction predominantly (57.1 %) was due to occlusion of the right interventricular artery. The increase in the level of galectin-3 to 23.48–41.42 ng/ml, which corresponds to 3–4 quartiles of galectin-3 level, was associated with an increase in the number of affected vessels and segments with high Gensini scores. Conclusions. The right interventricular and right coronary arteries are the most vulnerable according to the angiographic findings, both in terms of frequency and degree of lesion, and frequency of hemodynamically significant stenoses in patients with acute myocardial infarction and obesity. An increase in galectin-3 level up to 3 and 4 quartiles is accompanied by a parallel increase in parameters characterizing the progression of atherosclerotic lesion of the coronary arteries. Galectin-3 can be considered as a marker of atherosclerotic process in patients with acute myocardial infarction and obesity due to the association between galectin-3 level and the degree of coronary artery lesion severity.

Preclinical atherosclerosis in patients with inflammatory bowel diseases: a case-control study.

An independent role of chronic inflammation in the atherosclerotic process in patients with inflammatory bowel diseases (IBD) has been suggested, but data are still contentious. We assessed pre-clinical atherosclerosis in the IBD patients without traditional risk factors. In this case-control study we assessed the early atherosclerotic alterations by carotid artery intima-media thickness (CIMT) measurement in IBD patients and matched controls. The normal CIMT values were ≤0.9 mm; moderate thickness when >0.9 and ≤1.2 mm, and pre-clinical atherosclerosis when >1.2 mm. We selected a homogeneous group of IBD patients, all in ongoing biologic therapy, without any traditional risk factor for atherosclerosis as well as controls. The study enrolled 23 consecutive patients (16 with ulcerative colitis and 7 with Crohn's disease) and 20 controls matched for age and sex. The mean of CIMT values was not statistically different between patients and controls (0.68±0.21 vs. 0.82±0.2 mm; P=0.4). The prevalence of moderate CIMT thickness was significantly lower in cases than in controls (8.7% vs. 42.8%; P=0.01; OR: 0.15, 95% CI: 0.03-0.85). This case-control study found that the atherosclerotic process is not more apparent in IBD patients without traditional risk factors.

Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

The influence of lipid-lowering therapy on the atherosclerotic process in patients with the second degree of essential hypertension combined with ischemic heart disease

For the purpose of studying the effect of lipid-reducing therapy on the course of the atherosclerotic process in the coronary arteries the authors have examined 30 people, undergoing a course of treatment at the Ivano-Frankivsk Regional Clinical Cardiological Dispensary (RCCD). The patients were randomized into three subgroups based on an evaluation of a risk of cardiovascular events according to the coronary calcium index, a control group of 10 persons was also formed. The concentration of total cholesterol (TCS), triglycerides (TG), cholesterol of lipoproteins of high and low density (CS LPHD and CS LPLD) as well as the index of coronary calcium were evaluated. All the patients were prescribed rosuvastatin in a single dose of 20 mg every evening during four weeks. Upon completing a full course of therapy by all the patients the experiment was repeated. It was established hereat that against a background of a decrease of the levels of TCS, TG, CS LPLD, an increase of the level of the nonatherogenic fraction of CS LPHD an elevation of the index of coronary calcium was observed.

Evaluation of early atherosclerosis markers in patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver cells. It is strongly associated with cardiovascular risk factors for atherosclerosis. Flow-mediated dilation (FMD) and carotid intima-media thickness (CIMT) are noninvasive methods for the evaluation of endothelium. They are considered early markers of atherogenesis. The aim of this study was to evaluate early atherosclerosis markers in patients with NAFLD. We examined 161 patients. All the patients underwent hepatic ultrasonography, transthoracic echocardiography, and brachial artery and carotid artery imaging. Fasting blood samples were drawn from all patients for the determination of lipids, insulin, C-peptide, and fasting blood glucose. HOMA-IR was calculated. Among the 161 patients, 44 had normal hepatic ultrasonography, 42 had stage 1 hepatosteatosis, 53 had stage 2 hepatosteatosis and 22 had stage 3 hepatosteatosis. FMD was reduced in patients with NAFLD as compared with the healthy controls (5.9 ± 3.1 vs. 9.6 ± 2.7%, P<0.001). There was a significant negative moderate correlation between ultrasonographic hepatosteatosis grade and FMD (r=-0.556, P<0.001). The mean CIMT was significantly increased in patients with NAFLD as compared with the controls (0.40 ± 0.19 vs. 0.27 ± 0.18, P<0.001). There was a significant positive weak correlation between ultrasonographic hepatosteatosis grade and mean CIMT (r=0.376, P<0.001). This study showed that NAFLD is associated with impaired CIMT and FMD, which are early markers of atherosclerosis. These findings may play a crucial role in understanding the pathophysiology of the atherosclerotic process in patients with NAFLD.

Strategies to Achieve Target LDL Levels

ACCORD Action to Control Cardiovascular Risk in Diabetes AIM-HIGH Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/ High Triglycerides and Impact on Global Health Outcomes ARBITER 6-HALTS Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies ENHANCE Effect of Combination Ezetimibe and High-Dose Simvastatin Versus Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia FIELD Fenofibrate Intervention and Event Lowering in Diabetes HPS2-THRIVE Heart Protection Study 2: Treatment of HDL to Reduce the Incidence of Vascular Events IMPROVE-IT Improved Reduction of Outcomes: Vytorin Efficacy International Trial SANDS Stop Atherosclerosis in Native Diabetics Study

Edaravone for the treatment of acute cerebral infarction: role of endothelium-derived nitric oxide and oxidative stress

Thrombolytic therapy is the most effective therapeutic strategy for the prevention of brain injury and reduction of mortality in patients with acute cerebral infarction. A combination of established thrombolytic therapy and effective neuronal protection therapy has more beneficial effects for patients with acute cerebral infarction. Edaravone (chemical name: 3-methyl-1-phenyl-2-pyrazolin-5-one) is a strong, novel scavenger of free radicals. Several lines of evidence have shown that edaravone has preventive effects on brain injury following ischaemia and reperfusion in patients with brain attack. This review focuses on putative mechanisms underlying the beneficial effects of edaravone on the atherosclerotic process in patients with stroke and on the possibility of edaravone-induced extension of the therapeutic time window in patients with acute cerebral infarction.

Is Carotid Intima-Media Thickness a Reliable Clinical Predictor?

Is Carotid Intima-Media Thickness a Reliable Clinical Predictor?

Accelerated Atherosclerotic Calcification and Mo[Combining Diaeresis]nckeberg's Sclerosis

Autopsy studies have demonstrated the near universal presence of fatty streaks and fibroatheromas in the general population from which patients with chronic kidney disease (CKD) arise. The vast majority of patients with CKD have multiple conventional cardiovascular risk factors. Vascular atherosclerotic calcification develops in most patients as they transition from the general population to significant CKD as part of cholesterol crystallization within atherosclerotic lesions. Once present, however, atherosclerotic medial calcification can become prominent and has been previously identified as Mönckeberg's sclerosis. A unifying concept supported by the preponderance of pathologic evidence contends that Mönckeberg's sclerosis is a manifestation of accelerated atherosclerosis in patients with CKD. The term has also been used in rare cases to describe vascular calcinosis not related to CKD. This clarification is critical to advance the field in terms of pathologic diagnosis and treatment of CKD bone and mineral disorder. Factors that seem to promote the osteoblastic transformation of vascular smooth muscle cells and enhance deposition of calcium hydroxyapatite crystals include phosphorus activation of the Pit-1 receptor, bone morphogenic proteins 2 and 4, leptin, endogenous 1,25 dihydroxyvitamin D, vascular calcification activating factor, and measures of oxidative stress. These entities work to accelerate the atherosclerotic process in patients with CKD and may be future targets for diagnosis and treatment because randomized trials with hydroxymethylglutaryl-CoA reductase inhibitors have failed to attenuate the rate of progressive vascular calcification.

Enhanced Hype

The recently published Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE) trial seems to raise questions regarding the notion that lipid lowering is of benefit in the prevention and treatment of vascular disease. Before one can make this conclusion, a careful analysis of the trial, including the subjects included and the surrogate end point studied, is required. The results of this study should be taken in context with those of many other studies showing that lipid lowering by many approaches is beneficial. In conclusion, the public fury over this study, with physicians making unsupported statements to the press and on the Web, is unfortunate and should be discouraged in the future.

After ENHANCE: Is More LDL Cholesterol Lowering Even Better?

After much speculation, to the point of congressional involvement, regarding the reasons for the delay in reporting the results of a relatively small trial of carotid-artery imaging in patients with familial hypercholesterolemia (FH), a brief top-line synopsis was released this year on January 14(1). The study, called ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin versus Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia), was designed to determine if an anticipated additional reduction in LDL-cholesterol (LDLc) of 18% when ezetimibe 10 mg was added to 80 mg of simvastatin (Vytorin 10/80 mg) versus 80 mg simvastatin alone would result in either less progression or more regression of carotid atherosclerosis as measured by intima-media thickening (cIMT). The study was conducted over a 2-year period and enrolled 720 FH patients, with roughly equal numbers of men and women, mean age 45 years. Although patients had very high LDLc concentrations of nearly 320 mg/dL (8.32 mmol/L) after all lipid-lowering agents were washed out, more than 80% had been on prior statin treatment, including high-dose treatment, for many years before entry into the trial. The changes in cIMT after 2 years did not significantly differ from baseline for either treatment group or from one treatment group to the other. The popular press contacted selected “experts” who gave flamboyant, misleading, and sometimes self-serving or agenda-driven comments(2) interpreting the results either as a failure of the mechanism by which LDLc was decreased, or as evidence that LDLc reduction itself was not an effective way to ameliorate the course of atherosclerosis. The complete details of ENHANCE have now been published(3), and a more complete evaluation is possible. A number of critical flaws in the trial are apparent. The most important determinant of any clinical trial such as ENHANCE is the …