Cross-Sectional Association of Dietary Patterns and Supplement Intake with Presence and Gray-Scale Median of Carotid Plaques-A Comparison between Women and Men in the Population-Based Hamburg City Health Study.

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45-74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.

The association of dietary patterns and carotid intima-media thickness: A synthesis of current evidence.

AIMS: Dietary pattern (DP) analysis has emerged as a holistic method to understand the effects of food intake on health outcomes. Though dietary intake has been associated with cardiovascular disease, the association of DPs and carotid intima-media thickness (CIMT), a robust early marker of cardiovascular disease progression has not been comprehensively investigated. This study systematically explores the association of a posteriori and a priori DPs and CIMT. DATA SYNTHESIS: Through a systematic search of MEDLINE, CINAHL, and Web of Science, twenty studies that derived DPs using a posteriori or a priori methods with CIMT as an outcome were included. Four cross-sectional studies and 1 cohort paper reported a statistically significant association between increased consumption of 'unhealthy' foods (i.e processed meat, soda drinks and refined grain) and increased CIMT. While four cross-sectional studies reported a statistically significant association of DPs characterized by increased consumption of 'healthy' foods (i.e fruit and vegetables, fish) and decreased CIMT. DPs derived from each study varied depending on derivation method, study design and use of dietary data collection method. CONCLUSION: Findings from this review are generally supportive of a trend between DPs with higher consumption of 'healthy' foods and lower consumption of 'unhealthy' foods and decreased CIMT; however, the association was largely not statistically significant. Evidence was overwhelmingly heterogeneous due to differences seen in DPs based on location and culture, sample characteristics and adjustment for confounders. Long-term prospective observational and interventional studies with standardized sample selection and dietary data collection are needed to significantly establish the role of DPs on CIMT.

Dietary quality and carotid intima media thickness in type 1 and type 2 diabetes: Follow-up of a randomised controlled trial.

BACKGROUND AND AIMS: The relationship between dietary intake and carotid intima media thickness (IMT) and pulse wave velocity (PWV) in individuals with type 1 and type 2 diabetes has not been well studied. We investigated the association between dietary intake and common carotid artery intima media thickness (CCA IMT) and PWV in a cohort with type 1 and type 2 diabetes. METHODS AND RESULTS: A one-year randomised controlled trial was conducted to investigate the effect of improving dietary quality on CCA IMT. These subjects were followed up again approximately 12 months after the completion of the trial (i.e. approximately 24 month since baseline). The study cohort included 87 subjects that had dietary intake and CCA IMT measured at baseline and after a mean of 2.3 years' follow-up. PWV was measured in a subsample of this cohort. Age and baseline mean CCA IMT were strongly associated with mean CCA IMT at 24 months. After adjustment for age and baseline mean CCA IMT, baseline consumption of carbohydrate (r = -0.28; p = 0.01), sugars (r = -0.27; p = 0.01), fibre (r = -0.26; p = 0.02), magnesium (r = -0.25; p = 0.02) and the Alternate Health Eating Index (AHEI) score (r = -0.23; p = 0.03) were inversely associated with mean CCA IMT at 24 months. Mixed linear modelling showed an interaction between mean CCA IMT and AHEI at baseline (p = 0.024). Those who were in the highest AHEI tertile at baseline had greater CCA IMT regression at 24 months compared to those in the lowest tertile, after adjustment for baseline age, BMI, smoking pack years, time since diabetes diagnosis, and mean arterial pressure at baseline (mean -0.043 mm; 95% CI -0.084, -0.003; p = 0.029). CONCLUSIONS: In this prospective analysis greater diet quality at baseline, as measured by the AHEI, was associated with greater CCA IMT regression after approximately two years. This suggests that greater diet quality is associated with better longer term vascular health in individuals with type 1 and type 2 diabetes.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Angong Niuhuang Pill (ANP) is a well known Chinese traditional therapeutic for the treatment for diseases affecting the Central Nervous System (CNS). Components of the ANP formulation, including Bovis Calculus Sativus, Pulvis Bubali Comus Concentratus, Moschus, Margarita, Cinnabaris, Realgar, Coptidis Rhizoma, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix, and Bomeolum Syntheticum, have been used for the treatment of stroke, encephalitis and emergency meningitis across Asia, especially in China for hundreds of years. OBJECTIVE: The goal of this study was to investigate the anti-atherosclerosis and cardio-protective effects of ANP administration using a rodent model of atherosclerosis induced by a high fat and vitamin D3. METHODS: Specific Pathogen-Free (SPF) 78 male SD rats were randomly divided into a control group and 5 atherosclerotic model groups. The atherosclerotic groups were divided to receive either Simvastatin (SVTT, 0.005g/kg), Low-dose ANP (0.125g/kg), Medium-dose ANP (0.25g/kg), and High-dose ANP (0.5g/kg). Following adaptive feeding for one week, atherosclerosis was induced and the atherosclerosis model was established. Experimental drugs (either simvastatin or ANP) or normal saline were administered intragastrically once daily for 9 weeks starting from the 8th week. A carotid artery ultrasound was performed at the 17th week to determine whether atherosclerosis had been induced. After the atherosclerosis model was successfully established, platelet aggregation rates, serum biochemical indices, apoptosis-related Bcl-2, Bax proteins levels in the heart were assayed. Pathological and histological analysis was completed using artery tissue from different experimental different groups to assess the effects of ANP. RESULTS: ANP significantly decreased aortic membrane thickness, the maximum platelet aggregation rates, and the ratio of low density lipoprotein cholesterol (LDL) to high density lipoprotein cholesterol (HDL). In addition, ANP significantly reduced serum contents of total cholesterol, low density lipoprotein, malondialdehyde, troponin I, high-sensitivity C-reactive protein, and lactate dehydrogenase. ANP markedly improved abnormal pathological conditions of the aorta and heart, and helped to prevent myocardial apoptosis. CONCLUSIONS: We have demonstrated that ANP has robust ant-atherosclerosis and cardio-protective effects on a high-fat and vitamin D3 - induced rodent model of atherosclerosis due to its antiplatelet aggregation, lipid regulatory, antioxidant, anti-inflammatory and anti-apoptotic properties.

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

BACKGROUND: The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. METHODS: The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. RESULTS: Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. CONCLUSIONS: Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects.

Effects of atorvastatin on apelin, visfatin (nampt), ghrelin and early carotid atherosclerosis in patients with type 2 diabetes.

To investigate the influence of atrovastatin treatment on carotid intima-media thickness (CIMT) and serum levels of novel adipokines, like apelin, visfatin (nampt), and ghrelin, in patients with type 2 diabetes mellitus (T2DM). 87 statin-free patients (50 males) with T2DM, aged 55-70, but without carotid atherosclerotic plaques were initially enrolled. CIMT was assayed in all participants by ultrasound. Patients were then treated with atorvastatin (10-80 mg) to target LDL <100 mg/dl. Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), apelin, visfatin and ghrelin were measured at baseline and after 12 months. Atorvastatin treatment significantly improved lipid profile across with increased apelin (from 0.307 ± 0.130 pg/ml to 1.537 ± 0.427 pg/ml; P < 0.001) and suppressed visfatin (from 21.54 ± 10.14 ng/ml to 15.13 ± 7.61 ng/ml; P = 0.002) serum levels in our diabetic patients. Standard multiple regression analysis showed that the atorvastatin-induced increment in apelin was independently associated with changes in total cholesterol (ß = -0.510, P = 0.030) and LDL-cholesterol (ß = -0.590, P < 0.001) (R (2) = 0.449, P = 0.014), while the reduction of visfatin concentration was independently associated with the change in hsCRP (ß = 0.589, P < 0.001; R (2) = 0.256, P = 0.006), after adjustment for age, sex and BMI. CIMT and ghrelin did not alter significantly after 12 months of atorvastatin treatment (NS). Among participants, high-dose (80 mg) rather than low-dose (10 mg) of atorvastatin treatment yielded greater (P < 0.05) changes in apelin, visfatin and CIMT levels despite the final equivalent levels of LDL. Atorvastatin administration increased apelin and decreased visfatin serum levels significantly, without change of CIMT, in patients with T2DM. However, high-dose of atorvastatin exerted more favourable impact on adipokines and CIMT than low-dose. Our results implicate another important link between adiposity and atherosclerosis.

Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults.

BACKGROUND: Observational studies have shown that low folate and elevated homocysteine concentrations are risk factors for vascular disease in the general population. Randomized controlled trials in vascular patients have failed to show that folic acid reduces the risk of recurrent vascular disease, whereas such trials are lacking in the general population. OBJECTIVE: The objective was to determine whether folic acid supplementation reduces the progression of atherosclerosis as measured by common carotid intima-media thickness (CIMT)-a validated marker of atherosclerosis and predictor of vascular disease risk. DESIGN: A randomized, double-blind, placebo-controlled study in 819 men and postmenopausal women aged 50-70 y, free-living in the Netherlands, and with a total homocysteine concentration ≥13 µmol/L at screening was conducted. Participants received either 800 µg folic acid or placebo daily for 3 y. Rate of change in CIMT and arterial distensibility were the primary and secondary outcomes, respectively. RESULTS: Compared with placebo, serum folate increased by 577% and plasma total homocysteine concentrations decreased by 26% after 3 y of folic acid supplementation. The mean (±SE) rate of change in CIMT was 1.9 ± 0.9 µm/y in the folic acid arm and 1.3 ± 0.8 µm/y in the placebo arm (mean difference: 0.7 µm/y; 95% CI: -1.8, 3.1 µm/y; P = 0.59). No difference was observed (P = 0.23) between the rates of change in distensibility in the folic acid arm (-0.53 ± 0.06 × 10(-3) kPa(-1)) and in the placebo arm (-0.62 ± 0.06 × 10(-3) kPa(-1)). CONCLUSION: Despite a considerable increase in folate concentrations and a reduction in total homocysteine concentrations, 3-y folic acid supplementation did not slow down atherosclerotic progression or arterial stiffening. This trial was registered at clinicaltrials.gov as NCT00110604.

Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids.

OBJECTIVE: To determine if niacin can confer cardiovascular benefit by inhibiting vascular inflammation and improving endothelial function independent of changes in plasma lipid and lipoprotein levels. METHODS AND RESULTS: New Zealand white rabbits received normal chow or chow supplemented with 0.6% or 1.2% (wt/wt) niacin. This regimen had no effect on plasma cholesterol, triglyceride, or high-density lipoprotein levels. Acute vascular inflammation and endothelial dysfunction were induced in the animals with a periarterial carotid collar. At the 24-hour postcollar implantation, the endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1 was markedly decreased in the niacin-supplemented animals compared with controls. Niacin also inhibited intima-media neutrophil recruitment and myeloperoxidase accumulation, enhanced endothelial-dependent vasorelaxation and cyclic guanosine monophosphate production, increased vascular reduced glutathione content, and protected against hypochlorous acid-induced endothelial dysfunction and tumor necrosis factor alpha-induced vascular inflammation. CONCLUSION: Previous human intervention studies have demonstrated that niacin inhibits coronary artery disease. This benefit is thought to be because of its ability to reduce low-density lipoprotein and plasma triglyceride levels and increase high-density lipoprotein levels. The present study showed that niacin inhibits vascular inflammation and protects against endothelial dysfunction independent of these changes in plasma lipid levels.

Diminished omega-3 fatty acids are associated with carotid plaques from neurologically symptomatic patients: Implications for carotid interventions.

The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are prevalent in fish oil and their cardioprotective effects are thought to be mediated by anti-inflammatory mechanisms. The aim of this study is to determine whether omega-3 fatty acids are associated with carotid plaques from neurologically symptomatic patients. Plaques were obtained from 41 patients (mean age 62 [44-84]; 24-asymptomatic, 17-symptomatic). Intra-plaque lipids were assessed with mass spectrometry. Compared to asymptomatic patients, significantly diminished omega-3 fatty acids DHA (545.8+/-98 ng/g vs. 270.7+/-19.6 ng/g, p=0.0096) and EPA (385.9+/-68 ng/g vs. 216.4+/-17.6 ng/g, p=0.0189) were found in carotid plaques from neurologically symptomatic patients. However, no differences were found in the levels of the omega-6 fatty acid arachidonic acid (p=0.2003). Immunohistochemistry and ELISA analysis (CD68(+) cells, 0.461+/-0.04 vs. 0.312+/-0.03, p=0.003) demonstrated an increased inflammatory infiltrate in plaques from neurologically symptomatic, compared to asymptomatic, patients. Carotid plaques from neurologically symptomatic patients are inflammatory and have decreased intra-plaque levels of omega-3 fatty acids. Future trials will determine whether interventions that increase omega-3 fatty acid incorporation into carotid plaques prevent stroke and improve the safety of carotid interventions.

Role of folic acid in atherosclerosis after kidney transplant: a double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVES: We investigated the effects of folic acid supplementation on plasma total homocysteine levels and carotid intima-media thickness after kidney transplant. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Folic acid supplementation reduces both the plasma total homocysteine level and carotid intima-media thickness shortly after kidney transplant.

Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3-year intervention study.

BACKGROUND AND AIM: Plant foods may lower the risk of cardiovascular disease. METHODS AND RESULTS: We assessed changes in the intima media thickness (IMT) of the carotid artery and diet in elderly men. Men (n=563) aged 70+/-5 years were randomly assigned to 1 of 4 groups (dietary intervention, omega-3 supplementation, both or neither) using a 2 x 2 factorial design. B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years. We previously showed that omega-3 supplementation did not influence the IMT, thus the dietary intervention (n=233) and no dietary intervention (n=231) groups were pooled. The dietary intervention group had less progression in the carotid IMT compared with the controls (0.044+/-0.091 mm versus 0.062+/-0.105 mm; P=0.047). This group increased their daily vitamin C intake (P=0.005) and intake of fruit, berries and vegetables (P

Efeitos e mecanismos de ação dos ácidos graxos poliinsaturados n-3 na prevenção de doenças cardiovasculares / Mechanisms of action of polyunsaturated n-3 fatty acids for cardiovascular disease prevention

A ingestão de óleo de peixe tem demonstrado efeitos benéficos na prevenção das doenças cardiovasculares (DCV) e este efeito está relacionado à presença de ácidos graxos poliinsaturados n-3, em especial dos ácidos eicosapentaenóico (EPA, C20:5n-3) e docosahexaenóico (DHA, C22:6n-3), encontrados nos óleos de peixes de águas frias e profundas como salmão, arenque, atum e sardinhas. Estes compostos têm demonstrado importante ação antilipêmica, antiinflamatória, antitrombótica, antiarrítimica, anti-hipertensiva, entre outras. A ingestão de óleo de peixe em pacientes com doença cardíaca isquêmica e hiperlipoproteinemia diminuiu os níveis séricos de fibrinogênio, a viscosidade plasmática e a resistência vascular periférica total. Eles também atuam ajudando a manter a elasticidade da parede das artérias, impedindo a coagulação do sangue, reduzindo a pressão sangüínea e estabilizando a arritmia cardíaca. O seu principal efeito nas doenças coronárias é a redução da produção de tromboxana A2, agregante plaquetário que favorece a trombose. Outra ação destes compostos é a redução nos níveis de triacilgliceróis e da lipoproteína de densidade muito baixa (VLDL), porém com aumento da lipoproteína de baixa densidade (LDL). O aumento da LDL com redução da VLDL parece estar relacionado com a conversão da VLDL em LDL ou à redução na atividade do receptor de LDL. O EPA e o DHA modulam a resposta inflamatória, atuando na diminuição da transcrição de citocinas pró-inflamatórias e na expressão de moléculas de adesão na superfície vascular. Este estudo propõe-se a revisar os principais mecanismos envolvidos na prevenção de DCV pelos ácidos graxos n-3.

Fish oil ingestion has shown beneficial effects for cardiovascular disease (CVD) prevention, and this effect is related to the polyunsaturated fatty acids, specially eicosapentaenoic (EPA, C20:5n-3) and docosahexaenoic (DHA, C22:6n-3), found in fish from cold and deep water, such as salmon, tune and sardine. These compounds have important antilipidemic, antiinflammatory, antithrombotic, antiarrhytmic, and antihypertensive action. Fish oil ingestion in patients with ischemic heart disease and hyperlipoproteinemia decreased fibrinogen serum levels, plasmatic viscosity and total peripheral resistance. They also act by helping to maintain artery wall elasticity, preventing blood coagulation, reducing blood pressure and preventing fatal cardiac arrhythmias. Their major effect in coronary disease isthe decrease production of thromboxane A2, platelet aggregant that favors thrombosis; another effect is the reduction of tryacylglicerol levels and very low density lipoprotein (VLDL), although with low density lipoprotein (LDL) increase. This increment seems related to the conversion of VLDL in LDL or to the decreased activity of LDL receptor. EPA and DHA modulate inflammatory reaction through the reduction of pro-inflammatory cytokines transcription and adhesion molecules expression on the vascular surface. This review proposes to study the main mechanisms evolved in CVD prevention by n-3 polyunsaturated fatty acids.

Effect of high-dose alpha-tocopherol supplementation on biomarkers of oxidative stress and inflammation and carotid atherosclerosis in patients with coronary artery disease.

BACKGROUND: Oxidative stress and inflammation are crucial in atherogenesis. alpha-Tocopherol is both an antioxidant and an antiinflammatory agent. OBJECTIVE: We evaluated the effect of RRR-alpha-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease (CAD) on drug therapy. DESIGN: Randomized, controlled, double-blind trial compared RRR-alpha-tocopherol (1200 IU/d for 2 y) with placebo in 90 patients with CAD. Intimal medial thickness (IMT) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0, 1, 1.5, and 2 y. At 6-mo intervals, plasma alpha-tocopherol concentrations, C-reactive protein (CRP), LDL oxidation, monocyte function (superoxide anion release, cytokine release, and adhesion to endothelium), and urinary F(2)-isoprostanes were measured. RESULTS: alpha-Tocopherol concentrations were significantly higher in the alpha-tocopherol group but not in the placebo group. High-sensitivity CRP concentrations were significantly lowered with alpha-tocopherol supplementation than with placebo (32%; P < 0.001). alpha-Tocopherol supplementation significantly reduced urinary F(2)-isoprostanes (P < 0.001) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo (P < 0.001). No significant difference was observed in the mean change in total carotid IMT in the placebo and alpha-tocopherol groups. In addition, no significant difference in cardiovascular events was observed (P = 0.21). CONCLUSIONS: High-dose RRR-alpha-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 y.

Carotid artery stenting: a therapeutic alternative in subtotal internal carotid artery occlusions.

Carotid artery stenting (CAS) is emerging as a less invasive modality for treating atherosclerotic occlusive disease of the internal carotid artery (ICA). Randomized trials like the SAPPHIRE trial have demonstrated that CAS is not inferior to carotid endarterectomy (CEA) in the treatment of carotid artery stenosis, and maybe even superior in high-risk symptomatic patients. However, patients with subtotal ICA occlusions with thrombus are excluded from randomized CAS trials and CAS registries. To our knowledge, carotid angioplasty with stenting has not been attempted in these cases. We present three cases of symptomatic subtotal ICA occlusions successfully treated with CAS without any periprocedural complications. With careful patient selection and technical expertise, endovascular management could be considered as a treatment option in subtotal carotid occlusions.

GliSODin, a vegetal sod with gliadin, as preventative agent vs. atherosclerosis, as confirmed with carotid ultrasound-B imaging.

Prevention of cardiovascular disease should target high-risk subjects based on genetic/familial factors, blood chemistry, blood pressure, body mass index (BMI), and a history of/or current cigarette smoking. We selected active adults (n=76) aged 30-60 and investigated these risk factors, in order to recommend preventive measures. Another interesting variable is the preclinical status or atheroma of the arterial (carotid) wall or lumen. We also investigated the presence of oxidative stress in, and the anti-oxidant status of these subjects. We studied the anti-oxidative efficacy of superoxide dismutase (SOD) and variations of malondialdehyde (MDA). Supplementation with GliSODin, a vegetal SOD associated with gliadin, was effective in controlling the thickness of the carotid artery intima and media layers as measured by ultrasonography-B. We could demonstrate the preventive efficacy of GliSODin at a preclinical stage in subjects with risk factors of cardiovascular disease.

Effect of n-3 fatty acids on carotid atherosclerosis and haemostasis in patients with combined hyperlipoproteinemia: a double-blind pilot study in primary prevention.

BACKGROUND: Intake of n-3 polyunsaturated fatty acids (n-3 PUFA) either from natural sources or dietary supplementation is inversely associated with atherothrombosis. AIM: A double-blind pilot study was designed to address the impact of n-3 PUFA on atherosclerosis, haemostasis and vascular status in patients with combined hyperlipoproteinemia. METHODS: Carotid intima-media thickness (C-IMT), texture of intima-media complex (T-IMC), lipids and platelet function were evaluated in 64 patients with combined hyperlipoproteinemia who received placebo or n-3 PUFA (6 g/day) for 2 years. C-IMT and T-IMC were assessed by B-mode ultrasound. Lipids and platelet function were determined by validated methods. RESULTS: C-IMT increased in placebo, but not in n-3 PUFA group with respect to baseline. In contrast T-IMC decreased in n-3 PUFA, but not in placebo; in both cases, however, treatment effect did not reach statistical significance. A fall of triglycerides, concomitant to a rise of high- and low-density lipoprotein cholesterol (HDL and LDL), was observed in the active treated group. Platelet function was significantly reduced by n-3 PUFA. CONCLUSIONS: Results show a favourable effectiveness of n-3 PUFA on IMT progression and T-IMC that deserves to be confirmed in larger studies. Despite the small sample size, the beneficial effect of n-3 PUFA on platelet function, triglycerides and HDL-C is clearly highlighted.

Conformation-specific blockade of the integrin GPIIb/IIIa: a novel antiplatelet strategy that selectively targets activated platelets.

Platelet activation causes conformational changes of integrin GPIIb/IIIa (alpha(IIb)beta3), resulting in the exposure of its ligand-binding pocket. This provides the unique possibility to design agents that specifically block activated platelets only. We used phage display of single-chain antibody (scFv) libraries in combination with several rounds of depletion/selection to obtain human scFvs that bind specifically to the activated conformation of GPIIb/IIIa. Functional evaluation of these scFv clones revealed that fibrinogen binding to human platelets and platelet aggregation can be effectively inhibited by activation-specific scFvs. In contrast to clinically used GPIIb/IIIa blockers, which are all conformation unspecific, activation-specific GPIIb/IIIa blockers do not induce conformational changes in GPIIb/IIIa or outside-in signaling, as evaluated by ligand-induced binding-site (LIBS) exposure in flow cytometry or P-selectin expression in immunofluorescence microscopy, respectively. In contrast to the conformation-unspecific blocker abciximab, activation-specific scFvs permit cell adhesion and spreading on immobilized fibrinogen, which is mediated by nonactivated GPIIb/IIIa. Mutagenesis studies and computer modeling indicate that exclusive binding of activation-specific scFv is mediated by RXD motifs in the heavy-chain complementary-determining region (CDR) 3 of the antibodies, which in comparison with other antibodies forms an exceptionally extended loop. In vivo experiments in a ferric-chloride thrombosis model of the mouse carotid artery demonstrate similar antithrombotic potency of activation-specific scFv, when compared with the conformation-unspecific blockers tirofiban and eptifibatide. However, in contrast to tirofiban and eptifibatide, bleeding times are not prolonged with the activation-specific scFvs, suggesting lower bleeding risks. In conclusion, activation-specific GPIIb/IIIa blockade via human single-chain antibodies represents a promising novel strategy for antiplatelet therapy.

Very long chain N-3 fatty acids intake and carotid atherosclerosis: an epidemiological study evaluated by ultrasonography.

Epidemiological studies have shown an inverse relationship between intake of N-3 fatty acids and incidence of stroke. And, there is a high incidence of stroke in patients with carotid atherosclerosis. We investigated the relationship between intake of N-3 fatty acids and carotid atherosclerosis in the cross-sectional study. A total of 1920 Japanese, aged over 40 years, received a population-based health examination in 1999. They underwent B-mode carotid ultrasonography to evaluate the carotid intimal-medial thickness (IMT). Eating patterns were evaluated by a 105 items food frequency questionnaire. A complete data set was available for 1902 subjects (785 men and 1117 women). The mean eicosapentaenoic acid (EPA) intake in men was 0.32+/-0.23 g/day and in women was 0.31+/-0.20 g/day. The mean docosahexaenoic acid (DHA) intake in men was 0.52+/-0.34 g/day and in women was 0.49+/-0.29 g/day. With multiple linear regression analysis, after adjustments for age, sex, and total energy intake, intakes of EPA (P < 0.05), DHA (P < 0.05), and docosapentaenoic acid (P < 0.05) were significantly and inversely related to IMT. These data indicate that dietary N-3 fatty acid, especially very long chain N-3 fatty acids, may protect against carotid atherosclerosis.