The effect of homocysteine-lowering therapy with folic acid on flow-mediated vasodilation in patients with coronary artery disease: a meta-analysis of randomized controlled trials.

OBJECTIVE: High level of homocysteine induces injury of endothelial cells and predicts adverse cardiovascular events. The objective was to assess the effect of homocysteine-lowering therapy with folic acid on flow-mediated vasodilation in patients with coronary artery disease. METHODS AND RESULTS: We conducted a meta-analysis of randomized controlled trials identified from PubMed, Embase, the Cochrane Library. Eight studies were included. Homocysteine-lowering therapy with folic acid in patients with coronary artery disease significantly improve FMD as compared with placebo using random-effect model (SMD = 1.65 with 95% CI 1.12-2.17, p < 0.001). Subgroup analysis of subjects revealed that lipid-lowering therapy, study duration, and Delphi criteria had no effects on FMD. CONCLUSION: Our meta-analysis demonstrated that folic acid supplementation can significantly improve endothelial dysfunction as assessed by FMD in the brachial artery in patients with coronary heart disease.

Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults.

The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6% (+2 mm) and basal blood flow volume by 22%. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.

Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults.

BACKGROUND: We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation (FMD) in the brachial artery after resveratrol consumption in mildly hypertensive, overweight/obese adults. Resveratrol supplementation has also been shown to increase cerebral blood flow acutely, without affecting cognition. OBJECTIVES: To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance. METHOD: Twenty-eight obese but otherwise healthy adults (BMI: 33.3 ± 0.6 kg/m) were randomized to take a single 75 mg capsule of trans-resveratrol (Resvida) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial. Blood pressure, arterial compliance, FMD, and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule. An additional capsule of the same supplement was then taken. FMD assessment was repeated 1 h later. RESULTS: Chronic resveratrol supplementation for 6 weeks was well tolerated and resulted in a 23% increase in FMD compared with placebo (P=0.021, paired t-test). The extent of increase correlated negatively with baseline FMD (r=-0.47, P=0.01). A single dose of resveratrol (75 mg) following chronic resveratrol supplementation resulted in a 35% greater acute FMD response than the equivalent placebo supplementation. These FMD improvements remained significant after adjusting for baseline FMD. Blood pressure, arterial compliance, and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation. CONCLUSION: Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

AIMS: Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 µg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). CONCLUSION: In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD.

Ácidos grasos omega 3 en la dilatación mediada por flujo de la arteria braquial en individuos con disfunción endotelial / Omega 3 fatty acids in flow-mediated dilation of the brachial artery in patients with endothelial dysfunction

Las enfermedades cardiovasculares son la principal causa de muerte en Venezuela. La disfunción endotelial (DE) puede ser medida con la dilatación mediada por flujo de la arteria braquial (DMFAB). Se ha afirmado que los ácidos grasos omega 3 ayudan a regular la disfunción endotelial. Establecer la relación existente entre los ácidos grados omega 3 y la disfunción endotelial, al administrar 1 gramo al día por 2 semanas y evaluar la variación en la prueba de dilatación mediada por flujo de la arteria braquial. 25 individuos con prueba positiva para disfunción endotelial al tener DMFAB menor al 10%. Los pacientes recibieron ácidos grasos omega 3 a dosis de 1000 mg diario por dos semanas y se repitió la prueba. Se midieron los niveles séricos de fibrinógeno, proteína C reactiva (PCR) y ácido úrico entre otros, antes y después del tratamiento. El porcentaje de dilatación en la prueba de DMFAB, aumentó posterior al tratamiento con ácidos grasos omega 3. De igual forma los niveles séricos de PCR, fibrinógeno y ácido úrico disminuyeron posterior al tratamiento. Los suplementos de ácidos grasos omega 3 a razón de 1000 mg diario por 2 semanas mejoran la disfunción endotelial en pacientes con factores de riesgo cardiovascular. A su vez, los marcadores serológicos disminuyen con la administración de ácidos grasos omega 3...

Cardiovascular diseases are the leading cause of death in Venezuela. When there is an Endothelial dysfunction (ED) can be measured with flow-mediated dilatation of the brachial artery (DMFAB). Omega 3 fatty acids have been associated with the regulation of this entity. 25 subjects with positive test for endothelial dysfunction measured by DMFAB of less than 10%. The patients were given omega-3 fatty acids 1000 mg daily for two weeks. Serum tests performed were fibrinogen, CRP and uric acid among others, before and after treatment. The rate of expansion by DMFAB test increased after treatment with omega-3 fatty acids. Similarly serum levels of CRP, fibrinogen and uric acid decreased after treatment. Omega 3 fatty acids at a rate of 1000 mg daily for 2 weeks improved endothelial dysfunction in patients with CRF. Serological markers decrease with the administration of omega 3 fatty acids to the mentioned dose...

Disminución de la presión arterial en pacientes con arteriopatía periférica mediante el masaje reflejo del tejido conjuntivo / Decrease in blood pressure in patients with peripheral arterial disease by connective tissue reflex massage

Objetivos: Evaluar la eficacia del masaje reflejo del tejido conjuntivo en la presión arterial sistólica y diastólica en pacientes con enfermedad arterial periférica. Metodología: Participaron en el estudio 26 pacientes con enfermedad arterial periférica del Distrito Sanitario de Granada durante un período de intervención de 15 semanas. La muestra de estudio se dividió de forma aleatoria en grupo experimental y grupo control. Los criterios de exclusión fueron los siguientes: insuficiencia arterial periférica en estadios más avanzados, insuficiencia venosa periférica, insuficiencia cardíaca, renal o hepática. La variable independiente considerada ha sido la aplicación del masaje reflejo del tejido conjuntivo según el método de Elizabeth Dicke. Asimismo, la variable dependiente estudiada ha sido la evaluación de la presión arterial sistólica y diastólica en ambas extremidades superiores. Resultados: Se observan diferencias significativas entre la valoración basal y las valoraciones posbasales, entre los dos grupos de estudio, en la presión arterial diastólica derecha (basal, p<0,043; primera valoración, p<0,041; segunda valoración, p<0,047) y la presión arterial sistólica izquierda (basal, p<0,042; primera valoración, p<0,04; segunda valoración, p<0,049). Conclusiones: El masaje reflejo del tejido conjuntivo genera un descenso de la presión arterial en pacientes con enfermedad arterial periférica en estadio I(AU)

Aims: Evaluate the effectiveness of connective tissue reflex massage on systolic and diastolic blood pressure in patients with peripheral arterial disease. Methodology: Twenty-six patients with peripheral arterial disease from the Health District of Granada participated in the study during a 15-week intervention period. The study sample was randomly divided into an experimental group and a control group. Exclusion criteria were peripheral arterial insufficiency at more advanced stages, peripheral venous insufficiency, cardiac, renal or hepatic insufficiency. Application of the connective tissue reflex massage according to the method of Elizabeth Dicke was regarded as the independent variable. The dependent variable was evaluation of systolic and diastolic blood pressure in both upper limbs. Outcomes: Significant differences could be observed between the baseline and post-baseline evaluations between the two study groups in the right diastolic blood pressure (baseline, p<0.043; 1st evaluation, p<0.041; 2nd evaluation, p<0.047), and left systolic blood pressure (basal, p<0.042; 1st evaluation, p<0.04; 2nd evaluation, p<0.049). Conclusions: Connective tissue reflex massage causes a blood pressure decrease in patients with stage I peripheral arterial disease(AU)

Effect of Ginkgo leaf extract on vascular endothelial function in patients with early stage diabetic nephropathy.

OBJECTIVE: To explore the effect of ginkgo leaf extract (GLE) on vascular endothelial function (VEF) in patients with early stage diabetic nephropathy (DN). METHODS: Sixty-four patients were randomized equally by a randomzing digital table into two groups, the treated group and the control group. They were all treated for 8 weeks with conventional therapy for diabetes, but GLE tablets were given to the treated group additionally. Changes in VEF were estimated before and after treatment by ultrasonic examination of the brachial artery. In the meantime, changes in plasma levels of the von Willebrand factor (vWF), nitric oxide (NO) and endothelin-1 (ET-1) were observed as well. RESULTS: The brachial arterial endothelium dependent dilating function in the treated group increased from 4.91+/-2.31% before treatment to 6.78+/-3.89% after treatment (P<0.05), while the level of vWF decreased from 182.05+/-64.13% to 128.56+/-48.98%, and that of NO increased from 50.16+/-24.64 micromol/L to 70.65+/-28.71 micromol/L (P<0.01). However, these indexes were not significantly changed in the control group after treatment (P>0.05). CONCLUSION: GLE could decrease the plasma level of vWF, raise the plasma NO level and improve the endothelium dependent vascular dilating function in DN patients.

Cardiovascular involvement in patients with beta-thalassemia major without cardiac iron overload.

BACKGROUND: Cardiovascular complications are common in beta-thalassemia major (beta-TM), mainly attributed to increased cardiac iron depositions. Early cardiovascular involvement in patients without cardiac symptoms and without cardiac iron overload has not been adequately investigated. METHODS: Twenty six patients (11 males) with beta-TM, on chelation therapy, age 23+/-4 years without cardiac iron overload (measured by magnetic resonance imaging), and 30 age and gender matched healthy controls were included in the study. Carotid-femoral and carotid-radial pulse wave velocity (PWVc-f and PWVc-r) and augmentation index (AI) were measured by SphygmoCor device; carotid intima-media thickness; left ventricular (LV) dimensions and function; left atrial (LA) volume and function were assessed by echocardiography. RESULTS: Patients with beta-TM had higher PWVc-f (8.4+/-1.4 vs 7.2+/-1.1 m/s, p=0.002) and augmentation index (21.7+/-10.9 vs 14.7+/-9.7%, p=0.04) indicating decreased aortic elastic properties; greater LV mass index (72.0+/-13.3 vs 63.8+/-11.5 g/m(2), p=0.04) and greater LA volumes. Multivariate logistic regression analysis revealed that higher PWVc-f was independently associated with higher LV mass [OR 1.74 95%CI (1.09-2.88), p=0.026]; and greater LA dimensions [OR 1.68 95%CI (1.04-2.72), p=0.035]. CONCLUSIONS: In the absence of cardiac iron overload, asymptomatic patients with beta-TM demonstrated aortic stiffening associated with increased LV mass and LA enlargement. These alterations may represent signs of early cardiovascular involvement.

Global vasomotor dysfunction and accelerated vascular aging in beta-thalassemia major.

BACKGROUND: Patients with beta-thalassemia major (beta-TM) demonstrate an increased incidence of vascular complications, which are thought to result from a procoagulant/proinflammatory environment. We investigated the arterial vasorelaxing capacity and sought for early carotid atherosclerosis and underlying pathophysiological correlates in these transfusion-dependent patients. METHODS AND RESULTS: The vasodilatory properties of the brachial artery and the carotid intima-media thickness (IMT) were examined with ultrasonography in 35 non-diabetic young adults with beta-TM (patient group) and 35 control subjects (control group). Among thalassemic patients, both endothelium-dependent (FMD) and -independent dilatation (FID) as well as their ratio was impaired, whereas IMT was increased (p<0.01). Patients on optimal, as compared with those on non-optimal chelation treatment had a non-significantly lower IMT. Vasodilatory capacity in the patient group was inversely correlated with IMT and independently associated either with the quality of chelation therapy (FMD) or serum ferritin levels (FID). Plasma concentrations of D-dimers, circulating markers of endothelial activation, inflammation and apoptosis were higher, while plasma cholesterol and fibrinogen levels were lower-than-normal in the patient group. Independent predictors of IMT among thalassemic patients were tumor necrosis factor-alpha levels and age. CONCLUSIONS: Young adults with beta-TM exhibit both a global impairment of arterial vasorelaxation and early carotid atherosclerosis. A procoagulant/proinflammatory state in these transfusion-dependent patients may overwhelm atheroprotective mechanisms, including an optimal chelation regimen, and promote vascular injury and atherogenesis.

Folate supplementation fails to affect vascular function and carotid artery intima media thickness in cyclosporin A-treated renal transplant recipients.

BACKGROUND: Cyclosporin A (CsA)-treated renal transplant recipients (RTR) exhibit relative hyperhomocystinemia and vascular dysfunction. Folate supplementation lowers homocysteine and has been shown to improve vascular function in healthy subjects and patients with coronary artery disease. The aim of this study was to assess the effects of 3 months of folate supplementation (5 mg/day) on vascular function and structure in RTR. METHODS: A double-blind, placebo-controlled crossover study was conducted in 10 CsA-treated RTR. Vascular structure was measured as carotid artery intima media thickness (IMT) and function was assessed as changes in brachial artery diameter during reactive hyperemia (RH) and in response to glyceryl trinitrate (GTN). Function data were analyzed as absolute and percent change from baseline and area under the diameter/time curve. Blood samples were collected before and after supplementation and analyzed for total plasma homocysteine, folate, vitamin B12 and asymmetric dimethyl arginine (ADMA) in addition to regular measures of hemoglobin, hematocrit, mean corpuscular volume (MCV) and serum creatinine. RESULTS: Folate supplementation significantly increased plasma folate by 687% (p < 0.005) and decreased homocysteine by 37% (p < 0.05) with no changes (p > 0.05) in vitamin B12 or ADMA. There were no significant (p > 0.05) changes in vascular structure or function during the placebo or the folate supplementation phases; IMT; placebo pre mean +/- SD, 0.52 +/- 0.12, post 0.50 +/- 0.11; folate pre 0.55 +/- 0.17, post 0.49 +/- 0.20 mm, 5% change in brachial artery diameter (RH, placebo pre 10 +/- 8, post 6 +/- 5; folate pre 9 +/- 7, post 7 +/- 5; GTN, placebo pre 18 +/- 10, post 17 +/- 9, folate pre 16 +/- 9, post-supplementation 18 +/- 8). CONCLUSION: Three months of folate supplementation decreases plasma homocysteine but has no effect on endothelial function or carotid artery IMT in RTR.

Avaliação da função endotelial pela reatividade braquial em pacientes com cardiopatia isquêmica documentada, antes e após a utilização de suplementos vitamínicos / Evaluation of endothelial function by braquial reactivity in patients with documented ischemic heart disease, before and after using vitamin supplements

Introdução: Várias drogas e substâncias vêm sendo testadas visando melhorar a função endotelial, porém a utilização de suplementos vitamínicos em pacientes portadores de doença ateromatosa ainda é controversa, Método: Para avaliar a resposta da função endotelial antes e após a utilização de suplementos vitamínicos (vitaminas C,E e C mais E)foi utilizada a técnica de reatividade braquial em 21 pacientes com doença ateromatosa coronariana documentada pela cinecoronariografia. Foram comparados os percentuais de dilatação da artéria braquial antes e após a a utilização dos suplementos vitamínicos. Resultados: Após a utilização da E, o percentual de dilatação da artéria elevou-se de 8,24 por cento para 9,48 por cento (variação de 1,23 por cento), após a utilização da vitamina C, o percentual de dilatação elevou-se de 8,24 por cento para 10,29 por cento(variação de 2,05 por cento) e após a utilização de vitamina E associada a vitamina C, o percentual de dilatação elevou-se de 8,24 por cento para 10,81 por cento (variação de 2,57 por cento). Conclusão A vitamina C administrada na forma isolada ou em associação com a vitamina E, promoveu a melhora da função endotelial avaliada pela técnica da reatividade braquial pelo ultra-som