Presence Of Endothelial Dysfunction Research Articles

Peripheral vascular dysfunction in migraine: a review

Numerous studies have indicated an increased risk of vascular disease among migraineurs. Alterations in endothelial and arterial function, which predispose to atherosclerosis and cardiovascular diseases, have been suggested as an important link between migraine and vascular disease. However, the available evidence is inconsistent. We aimed to review and summarize the published evidence about the peripheral vascular dysfunction of migraineurs.We systematically searched in BIOSIS, the Cochrane database, Embase, Google scholar, ISI Web of Science, and Medline to identify articles, published up to April 2013, evaluating the endothelial and arterial function of migraineurs.Several lines of evidence for vascular dysfunction were reported in migraineurs. Findings regarding endothelial function are particularly controversial since studies variously indicated the presence of endothelial dysfunction in migraineurs, the absence of any difference in endothelial function between migraineurs and non-migraineurs, and even an enhanced endothelial function in migraineurs. Reports on arterial function are more consistent and suggest that functional properties of large arteries are altered in migraineurs.Peripheral vascular function, particularly arterial function, is a promising non-invasive indicator of the vascular health of subjects with migraine. However, further targeted research is needed to understand whether altered arterial function explains the increased risk of vascular disease among patients with migraine.

TCT-604 Impact of endothelial dysfunction evaluated by peripheral arterial tonometry in the extension of ST elevation myocardial infarction treated with primary angioplasty

The role of endothelial function in patients with acute ST elevation myocardial infarction (STEMI) is not clear. The presence of endothelial dysfunction may eventually contribute the pathophysiological processes occurring after STEMI and, consequently, influence the extension of myocardial necrosis

Endothelial Dysfunction is a Marker of Systemic Response to the Cardiac Resynchronization Therapy in Heart Failure

BackgroundCardiac resynchronization therapy (CRT) induces a significant improvement in patients with heart failure (HF), who are often characterized by the presence of endothelial dysfunction (ED) with impaired flow-mediated vasodilation (FMD). We aimed to study the ED in patients with HF candidates to CRT with defibrillator (CRT-D). Methods and ResultsWe studied 57 consecutive patients affected by HF and undergoing CRT-D. At the baseline we recorded a high prevalence of ED (64.9%) with impaired FMD (4.1 ± 3.8%). After 12 months of CRT, we reported a marked increase of the mean FMD (8.8 ± 4.8% vs 4.1 ± 3.8%; P < .05) along with significant improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) functional class, and 6-minute walk test (6MWT); 42 patients (73.7%) were classified as responders according to standard criteria. FMD was related to LVEF (r = 0.169; P < .05), LVESV (r = −0.169; P < .05), NYHA functional class (r = −0.27; P < .051), and 6MWT (r = 0.360; P < .01). ConclusionsED is not an independent predictor of CRT response, but it is able to intercept the systemic effects of CRT and is an affordable marker of response to CRT, especially in patients unable to perform the 6MWT.

AB0030 The LP13.3 genomic region -RS599839- is associated with endothelial dysfunction in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a complex polygenic autoimmune inflammatory disease with high risk of cardiovascular (CV) complications as consequence of accelerated atherosclerosis [1]. Recent studies have emphasized the relevance of...

Smooth muscle cell mineralocorticoid receptors: role in vascular function and contribution to cardiovascular disease

The mineralocorticoid receptor (MR), a member of the steroid receptor family, regulates blood pressure by mediating the effects of the hormone aldosterone on renal sodium handling. In recent years, it has become clear that MR is expressed in vascular smooth muscle cells (SMCs), and interest has grown in understanding the direct role of SMC MR in regulating vascular function. This interest stems from multiple clinical studies where MR inhibitor treatment reduced the incidence of cardiovascular events and mortality. This review summarizes the most recent advances in our understanding of SMC MR in regulating normal vascular function and in promoting vascular disease. Many new studies suggest a role for SMC MR activation in stimulating vascular contraction and contributing to vessel inflammation, fibrosis, and remodeling. These detrimental vascular effects of MR activation appear to be independent of changes in blood pressure and are synergistic with the presence of endothelial dysfunction or damage. Thus, in humans with underlying cardiovascular disease or cardiovascular risk factors, SMC MR activation may promote hypertension, atherosclerosis, and vascular aging. Further exploration of the molecular mechanisms for the effects of SMC MR activation has the potential to identify novel therapeutic targets to prevent or treat common cardiovascular disorders.

Association of Lipid Peroxidation with Endothelial Dysfunction in Patients with Overt Hypothyroidism

Hypothyroidism is associated with increased oxidative stress. The mechanism underlying the endothelial dysfunction in thyroid disease is not yet clear. This study aims to investigate lipid peroxidation and its association with endothelial dysfunction in overt hypothyroidism (OHT).Plasma malondialdehyde (MDA) as a marker of oxidative stress and plasma nitrates and asymmetric dimethyl arginine levels (ADMA) as markers of endothelial dysfunction were estimated in 25 OHT patients in comparison to 25 euthyroid controls. Plasma MDA, ADMA levels were significantly increased, whereas plasma nitrates were significantly decreased in the patient group compared to control group (p<0.01). Moreover, a significant positive association between plasma MDA and ADMA was found in the patient group (ρ=0.472, p=0.036). Our results reveal the presence of endothelial dysfunction in OHT patients as evidenced by decreased plasma nitrates and increased ADMA levels. Increased levels of MDA represent an increased generation of reactive oxygen species in these patients. A finding of significant direct relation of plasma MDA with ADMA indicates that oxidative stress has a strong impact on endothelial dysfunction in overt hypothyroidism. Further studies focusing on the role of oxidative stress in endothelial dysfunction and the effects of antioxidant supplementation on endothelial function in OHT patients are required.

Long-term evaluation of endothelial function in Kawasaki disease patients

Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. So far, the presence of endothelial dysfunction in patients with no coronary lesions has not been demonstrated. Peripheral arterial tonometry (Endo-PAT) measures the microvascular function in response to local ischaemia and has been validated in adult population, but its use in children is scarce. Aim To evaluate endothelial dysfunction in children as a long-term complication after Kawasaki disease using Endo-PAT. We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed for >5 years, with no coronary lesions, or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically accessed. Endo-PAT was performed to determine reactive hyperaemia index and augmentation index. A total of 35 individuals (21 males, age 21 ± 6 years) were evaluated (group 1: 19; controls: 16). Kawasaki disease patients presented significant lower reactive hyperaemia index (1.68 ± 0.49 versus 2.31 ± 0.53; p = 0.001). Augmentation index was similar in both groups (-10 ± 7 versus -11 ± 5; p > 0.005). Most patients with Kawasaki disease disclosed endothelial dysfunction (68%) compared with only 12% in controls. Endo-PAT is feasible and reproducible in the child population. Endothelial dysfunction is a frequent long-term complication in patients after Kawasaki disease with normal appearing coronary arteries. However, these results need validation in a larger population.

PP167-SUN FLOW-MEDIATED VASODILATATION IN THE PATIENTS WITH ANOREXIA NERVOSA

Rationale: Flow-mediated vasodilatation has not been yet evaluated in the patients with anorexia nervosa despite the presence of endothelial dysfunction. Methods: Flow-mediated vasodilatation in the brachial artery was examined in 30 patients with anorexia nervosa admitted to metabolic care unit for realimentation and compared with 30 control subjects. Results: The average age of the patients with mental anorexia was 25.0±5.2 comparing to 25.5±4.5 years of healthy control subjects (NS). BMI was in 14.0±1.7 kg/m2 in patients with anorexia nervosa comparing to 20.4±1.0 kg/m2 in healthy control subjects (p < 0.001). The mean diameter of the right brachial artery was 0.33±0.06 cm in anorexia nervosa patients and 0.35±0.05 cm in control subjects (N.S.). The increase of brachial artery size after reactive hyperemia was 0.029±0.006 cm (9%) in anorexia nervosa patients and 0.039±0.006 cm (11%) in control subjects (p = 0.002). After realimentation brachial artery reactive hyperemia has significantly increased comparing to the first examination in patients with anorexia (0.036±0.05 cm, 10.5%, p < 0.001). Conclusion: Flow-mediated vasodilatation is decreased in the patients with anorexia nervosa in comparison with healthy control subjects and improves after realimentation.

Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis

Diets rich in plant-derived polyphenols such as olive oil (OO) and/or catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the incidence of cardiovascular diseases, potentially by improving endothelial function, an important surrogate for atherosclerosis. The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing, yet unknown. Eighty-two patients with early atherosclerosis (presence of endothelial dysfunction) were enrolled in this double-blind, randomized trial with 52 completing the study. The aim of the study was to compare the effect of a daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on endothelial function as well as on inflammation and oxidative stress after a period of 4 months. Endothelial function was assessed noninvasively via peripheral arterial tonometry (Endo-PAT®). After 4 months, when OO and EGCG-supplemented OO groups were combined, OO significantly improved endothelial function (RHI, 1.59 ± 0.25-1.75 ± 0.45; p < 0.05). However, there were no significant differences in results between the two olive oil groups. Interestingly, with OO supplementation there was a significant reduction in inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells (WBCs) (6.0 × 10⁹/L-5.8 × 10⁹/L, p < 0.05); monocytes (0.48 × 10⁹/L to 0.44 × 10⁹/L, p = 0.05); lymphocytes (1.85 × 10⁹/L to 1.6 × 10⁹/L, p = 0.01); and platelets (242-229 × 10⁹/L, p = 0.047). Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function. The current study supports one potential mechanism for the role of olive oil, independent of EGCG, modestly supplemented to a healthy cardiovascular diet.

Insulin resistance: Is it time for primary prevention?

Insulin resistance is a clinical condition characterized by a decrease in sensitivity and responsiveness to the metabolic actions of insulin, so that a given concentration of insulin produces a less-than-expected biological effect. As a result, higher levels of insulin are needed to maintain normal glucose tolerance. Hyperinsulinemia, indeed, is one of the principal characteristics of insulin resistance states. This feature is common in several pathologic conditions, such as type 2 diabetes, obesity, and dyslipidemia, and it is also a prominent component of hypertension, coronary heart disease, and atherosclerosis. The presence of endothelial dysfunction, related to insulin resistance, plays a key role in the development and progression of atherosclerosis in all of these disorders. Insulin resistance represents the earliest detectable abnormality in type 2 diabetes, and is one of the major underlying mechanisms of hypertension and cardiovascular diseases. Its early detection could be of great importance, in order to set a therapeutic attack and to counteract the higher risk of diabetes and cardiovascular diseases.

The lp13.3 genomic region -rs599839- is associated with endothelial dysfunction in patients with rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular (CV) disease. Since genome-wide association studies demonstrated association between rs599839 polymorphism and coronary artery disease, in the present study we assessed the potential association of this polymorphism with endothelial dysfunction, an early step in atherogenesis.MethodsA total of 128 RA patients without history of CV events were genotyped for rs599839 A/G polymorphism. The presence of endothelial dysfunction was assessed by brachial ultrasonography (brachial flow-mediated endothelium-dependent (FMD)).ResultsPatients carrying the allele G exhibited more severe endothelial dysfunction (FMD%: 4.61 ± 3.94%) than those carrying the wild allele A (FMD%: 6.01 ± 5.15%) (P = 0.08). Adjustment for gender, age at the time of study, follow-up time and classic CV risk factors disclosed a significant association between the rs599839 polymorphism and FMD (G vs. A: P = 0.0062).ConclusionsOur results confirm an association of the rs599839 polymorphism with endothelial dysfunction in RA.

E-Selectin is Elevated in Cord Blood of South Asian Neonates Compared with Caucasian Neonates

To test the hypothesis that the increased risk of type 2 diabetes mellitus and coronary artery disease in South Asian subjects could be caused by the presence of endothelial dysfunction in early life. We studied markers of endothelial dysfunction in umbilical cord blood of South Asian neonates and compared these with that of Caucasian control subjects. From South Asian (n = 57) and Caucasian (n = 21) neonates, cord blood was collected and levels of glucose, insulin, lipids, and markers of endothelial dysfunction (E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1) and inflammation (C-reactive protein) were measured. Plasma E-selectin levels were significantly higher in South Asian neonates (46.7 versus 33.5 ng/mL, P < .001), and levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 did not differ. Furthermore, South Asian neonates had hyperinsulinemia (P = .043), dyslipidemia (with significantly higher triglyceride and lower high-density lipoprotein cholesterol levels), and higher C-reactive protein levels (75.7 versus 43.8 ng/mL, P=.009). South Asian newborns are characterized by elevated E-selectin levels in line with the hypothesis that endothelial dysfunction is present early in life. In addition, hyperinsulinemia, dyslipidemia, and inflammation are present. Because many pathogenic variables for coronary artery disease and type 2 diabetes are already present at birth in South Asian patients, the question arises whether rigorous childhood lifestyle intervention could be beneficial.

Abstract 8926: Rosiglitazone Acutely Improves Flow Mediated Dilation and Favorably Alters Endothelial Microparticle and Progenitor Cell Numbers in Euglycemic, Senescent Monkeys

Background: Rosiglitazone, 6 hours after dosing, rapidly increases endothelial-dependent flow mediated dilation (FMD) in subjects with healthy endothelium. Whether this acute improvement in FMD occurs in the presence of endothelial dysfunction is unknown. We test the hypothesis that rosiglitazone acutely improves FMD in senescent monkeys with endothelial dysfunction and that the improvement coincides with favorable changes in circulating biomarkers of endothelial health, endothelial progenitor cells (EPC) and endothelial microparticles (EMP). Euglycemic monkeys were used to avoid rosiglitazone’s glucose-lowering effects. Methods and Results: In a crossover design, 6 fasted M. fascicularis monkeys (5M/1F; 17 ± 1 yr) were dosed ≥2 weeks apart with vehicle or rosiglitazone at a dose (1 mg/kg, PO) that did not affect baseline hemodynamics, fasting plasma glucose (65 ± 6 mg/dL), insulin (10 ± 3 µlU/mL), total cholesterol (79 ± 7 mg/dL) or triglycerides (59 ± 6 mg/dL). EPC and EMP were sampled 6 h after dosing and measured by flow cytometry. Monkeys were then sedated (midazolam + torbugesic) and baseline femoral artery diameter (4mm segment) measured by ultrasonography. FMD was calculated as the peak %change from baseline following a 5-minute cessation of blood flow below the knee. FMD was lower in these monkeys (17.6 ± 1.3%) vs. young adults (≥25%). Rosiglitazone (vs. vehicle) increased (p&lt;0.01) FMD to 21.3 ± 1.6% (vs.16.9 ± 1.4%) without affecting baseline diameter (1.52 ± 0.04 vs.1.51 ± 0.04 mm). Rosiglitazone (vs. vehicle) increased (p&lt;0.01) EPC [CD45- CD31+ CD34+ VEGFR2+] to 7116 ± 1296 (vs. 4786 ± 1102) cells/ml and decreased (p&lt;0.04) EMP [CD45- CD42a- CD54(ICAM-1)+] to 26669 ± 11112 (vs. 62245 ± 9772) EMP/ml; EMP [CD45- CD42a- CD105(endoglin)+] and EMP [CD45- CD42a- CD144(VE-cadherin)+] also trended lower. (Mean ± SEM; paired t-test). Conclusion: Rosiglitazone acutely improves the endothelial dysfunction in senescent monkeys. This increased FMD is independent of its metabolic effects on glucose and lipids and coincides with stimulation of EPC and with suppression of EMP linked to endothelial cell adhesion and potentially apoptosis. Whether these EPC and EMP changes directly contribute to the enhanced endothelial function warrants further study.

Lack of association between flow-mediated endothelium-dependent vasodilatation and biomarkers of endothelial dysfunction in patients with severe rheumatoid arthritis

Accelerated atherogenesis is one of the main reasons for the increased mortality observed in patients with rheumatoid arthritis (RA) [1]. Progressive impairment of macrovascular and microvascular endothelium-dependent vasodilatation is associated with increased risk of cardiovascular complications. Endothelial function can be noninvasively assessed by postocclusive reactive hyperemia, either as increase in the brachial artery blood flow, as flowmediated vasodilatation of the afferent artery (macrovascular), or as increase in skin microcirculatory flow detected by laser Doppler. Both macrovascular and microvascular studies have confirmed the presence of endothelial dysfunction in patients with long-standing RA [2, 3]. Elevated circulating levels of soluble adhesion molecules are also associated with cardiovascular risk factors and predict atherosclerosis and CV events [4, 5]. Measurement of these biomarkers of endothelial activation and dysfunction has confirmed the presence of endothelial dysfunction in patients with RA [6]. Since administration of anti-TNF-a resulted in a rapid improvement in endothelial function in patients with this chronic inflammatory disease [7], and reduction in some biomarkers of endothelial dysfunction was also observed in these patients following anti-TNF-a drugs [8], an issue of potential interest may be to establish whether a correlation between the levels of soluble biomarkers of endothelial dysfunction and the presence of impairment of endothelium-dependent vasodilatation exists in patients with RA. In this regard, Meyer et al. [9] assessed whether microvascular changes in capillary blood cell velocity had correlation with levels of soluble adhesion molecules in 30 patients with RA. However, no correlation between capillary blood cell velocity and serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) was found. To further investigate into this issue, we aimed to determine whether levels of serum biomarkers of endothelial dysfunction might correlate with values of macrovascular flowmediated endothelium-dependent vasodilatation in 14 patients with severe RA refractory to conventional diseasemodifying anti-rheumatic drugs. Ethical approval and informed consent were obtained. All patients had severe disease (DAS28 in all cases greater than 3.2), refractory to conventional disease-modifying anti-rheumatic drugs including methotrexate, and were receiving periodical treatment with infliximab therapy. Evaluation of brachial M. A. Gonzalez-Gay (&) Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IFIMAV, Avenida de Valdecilla s/n, 39008 Santander, Spain e-mail: miguelaggay@hotmail.com

Assessment of endothelial function and arterial rigidity in patients with type 1 diabetes at different stages of diabetic nephropathy

Aim. Assessment of vascular stiffness and endothelial function in patients with type 1 diabetes at different stages of diabetic nephropathy and without it. Materials and methods. We examined 93 patients with DM1 aged 18 to 40 years, and disease duration of more than 5 years. The criterion for forming groups is the stage of diabetic nephropathy. Control group consisted of 23 healthy people. The study included an evaluation of the contour of pulse wave analysis, and conducting tests with reactive hyperemia on the unit Angioskan (LTD Angioskan, Russia). Prior to the study of each patients written informed consent. Results. In conducting the analysis of the pulse wave contour index of aortic stiffness was significantly higher in all groups of patients with diabetic nephropathy (DN) compared with healthy subjects. However, when comparing patients with T1D without DN and the control group, significant differences of stiffness index (SI) was not been determined. It should be noted that the increase in value of SI is almost independent of the presence of hypertension in the patient groups. In the analysis of reflection index (RI) values of statistically significant relationships were found. In analyzing the test data with reactive hyperemia we showed a reduction in growth of the signal amplitude in a significant number of patients, which is a sign of endothelial dysfunction, and occurs even in patients without clinical and laboratory signs of kidney damage. However, along with a decrease of this index, a large number of patients have paradoxically high its value, which may indicate a high level of basal nitric oxide. Conclusion. Increase in the stiffness of the aorta, the progression of DN may be an early marker of macrovascular lesions even in patients without hypertension. Reduced growth of the amplitude of the signal after occlusion in patients with no signs of kidney disease, indicates the presence of endothelial dysfunction even in the preclinical stage of diabetic nephropathy. Paradoxically high increase of the amplitude of the signal can indicate the presence of abnormally high basal level of nitric oxide, which is a marker of inflammation, high-risk factor of progression of angiopathies and fibrosis.

Effects of nicorandil on the reduction of BNP levels in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) still frequently experience cardiovascular events despite recent progress in treatment. We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events. Patients with advanced stage CKD (stage III-V with or without peritoneal dialysis) were included in this trial if they were considered at high risk for cardiovascular events [past history of cardiovascular diseases, past history of coronary angiography, presence of endothelial dysfunction measured by reactive hyperemia peripheral arterial tonometry, and presence of high brain natriuretic peptide (BNP) values]. Patients were randomly assigned to be treated with or without oral nicorandil, 15 mg/day. BNP values and endothelial function (augmentation index, pulse wave velocity, and reactive hyperemia peripheral arterial tonometry) before and 1 month after the initiation of the trial were assessed. Nineteen patients (15 men, 4 women) with a mean age of 61 ± 10 (SD) years were included. The median baseline BNP value was 75.3 (interquartile range, 32.1-138.8) pg/ml, and the BNP level was significantly reduced in the nicorandil group (P < 0.05). Regression analysis demonstrated that only the use of nicorandil is related to a decrease of BNP levels [standardized β coefficient, -75.1 (95% CI, -19.7 to -130.6), P = 0.01]. There were no significant changes in the rest of the parameters in the nicorandil group in comparison to the control group. The change in BNP levels was correlated with changes in the augmentation index (P < 0.01) and central pulse pressure (P = 0.03). Nicorandil treatment may reduce the level of BNP by reducing the central blood pressure in CKD patients.

Vascular endothelial growth factor A and cardiovascular disease in rheumatoid arthritis patients

To determine the contribution of the vascular endothelial growth factor A (VEGFA) rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms to the risk of cardiovascular (CV) disease in a series of patients with rheumatoid arthritis (RA). Six hundred sixty-one patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of the Hospital Xeral-Calde, Lugo, and the Hospital San Carlos, Madrid, Spain, were studied. Patients were genotyped for the VEGFA rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms using predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA). Also, human leukocyte antigen (HLA) DRB1 genotyping was performed using molecular-based methods. Clinical histories of the patients were reviewed for the presence of CV events that were considered to be present if the patient had ischemic heart disease, heart failure, cerebrovascular accident, or peripheral arteriopathy. Also, a subgroup of patients without the history of CV events was assessed for the presence of subclinical atherosclerosis manifested by the presence of endothelial dysfunction by brachial artery reactivity (n = 126) and increased carotid artery intima-media thickness (n = 105) using high resolution Doppler ultrasonography. No significant association between the VEGFA rs2010963 and the rs1570360 polymorphisms (neither isolated nor joined as allelic combinations) with clinically evident CV disease was found in this series of patients with RA. It was also the case when we examined the contribution of these polymorphisms to the development of subclinical atherosclerosis. VEGFA polymorphisms do not seem to exert a significant influence on the risk of CV disease in patients with RA.

Erectile Dysfunction and Coronary Artery Disease in Patients with Diabetes

The review deals with recent findings regarding the association between erectile dysfunction (ED) and coronary artery disease (CAD) in patients with diabetes. Indeed recent longitudinal studies have shown that ED is able to predict future cardiovascular events not only in nondiabetic but also in diabetic patients. In addition, in diabetic patients ED seems to be strongly associated with the presence of silent CAD. The mechanism by which ED is linked to CAD seems to be the presence of endothelial dysfunction. This pathophysiological mechanism has been extensively analysed. The possible clinical usefulness of ED to identify diabetic patients with silent CAD or at particularly high cardiovascular risk has been discussed in the review. At last, the review reports current guidelines and recent data available in the literature on the treatment of ED in patients with and without CAD and on the prevention of CAD in patients with ED.

Improvement in endothelial dysfunction in patients with systemic lupus erythematosus with N-acetylcysteine and atorvastatin

Objective:To study the effects of N-acetylcysteine (NAC) and atorvastatin on endothelial dysfunction in patients with systemic lupus erythematosus (SLE).Materials and Methods:Thirty-two SLE patients and age, sex-matched 10 healthy control subjects were studied. The patients were between 17 and 65 years of age and positive for diagnostic tests, such as antinuclear antibodies (ANA). Photoplethysmogram (PPG) detects the changes in the amount of light absorbed by hemoglobin, which reflects changes in the blood volume. Pulse wave analysis was performed at rest, 30 s, 90 s after shear stress, and 10 min after 300 μm of salbutamol inhalation.Results:Stiffness index (SI) of patients before the treatment was 8.46±2.78 cm/s and of controls was 6.07±1.4 cm/s (P = 0.002) and that of reflection index (RI) was 73±13 for patients and 65±7 for controls (P = 0.001). The percentage change in RI after salbutamol inhalation for controls and patients were -16±6 and -7±4 (P = 0.001), respectively, indicating the presence of endothelial dysfunction. The percentage decrease in RI after salbutamol inhalation was from -2.36±0.76 to ?7.92±1.46 in patients treated with N-acetylcysteine (NAC, P = 0.007). The percentage decrease in RI after salbutamol inhalation was from ?6.36΁1.21 to -9.92±1.21 in patients treated with atorvastatin (P = 0.05). This indicated the improvement in endothelial function. There was decrease in C-reactive protein (CRP) from 1.03±0.72 mg/dL to 0.52±0.22 mg/dL and that of malondialdehyde (MDA) from 11.20±4.07 nmol/mL to 8.81±2.79 nmol/mL with N-acetylcysteine treatment (P < 0.05). The CRP was decreased from 1.11±0.92 mg/dL to 0.440.16 mg/dL (P = 0.05) and that of MDA was decreased from 9.37±3.29 nmol/mL to 8.51±3.27 nmol/mL after treatment with atorvastatin. It showed improvement in oxidative stress with these treatments.Conclusion:The presence of arterial stiffness indicated endothelial dysfunction. There was reduction in RI and SI with treatment of N-acetylcysteine and atorvastatin suggesting improvement in endothelial dysfunction. There was decrease in CRP (a marker of inflammation) and MDA after treatment with N-acetylcysteine suggesting improvement in endothelial dysfunction. There was reduction in CRP after treatment with atorvastatin, suggesting improvement in endothelial function. Improvement in endothelial dysfunction is associated with decreased incidence of cardiovascular and cerebrovascular accidents.

Endothelial function in migraine: a cross-sectional study

BackgroundMigraine has been associated with cardiovascular disorders. Endothelial dysfunction may be a mechanism underlying this association. The present study tested the hypothesis that endothelium-dependent vasodilation, basal endothelial nitric oxide release and endothelial fibrinolytic capacity are impaired in migraine patients.MethodsGraded doses of sodium nitroprusside (SNP, 0.2 to 0.8 μg.min-1.dL-1 forearm), substance P (0.2 to 0.8 pmol.min-1.dL-1 forearm) and NG-monomethyl-L-arginine (L-NMMA, 0.1 to 0.4 μmol.min-1.dL-1 forearm) were infused into the brachial artery of 16 migraine patients with or without aura during a headache-free interval and 16 age- and sex-matched subjects without a history of migraine. Forearm blood flow (FBF) was measured by strain-gauge venous occlusion plethysmography. Local forearm release of tissue plasminogen activator (t-PA) in response to substance P infusion was assessed using the arteriovenous plasma concentration gradient. Responses to infused drugs were compared between patients and matched controls by analysis of variance.ResultsIn both migraine patients and control subjects, SNP and substance P caused a dose-dependent increase, and L-NMMA a dose-dependent decrease in FBF (P < 0.001 for all responses). In both groups, substance P caused an increase in t-PA release (P < 0.001). FBF responses and t-PA release were comparable between migraine patients and control subjects.ConclusionsThe absence of differences in endothelium-dependent vasodilation, basal endothelial nitric oxide production and stimulated t-PA release between migraine patients and healthy control subjects argues against the presence of endothelial dysfunction in forearm resistance vessels of migraine patients.