The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers

Abstract Background : Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role.
Aims : The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects.
Methods : Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19–35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD).
Results : Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p <0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia ( p <0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different ( p =0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%).
Conclusions : These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.     

The evaluation of endothelial functions in patients with celiac disease

Aim: Celiac disease is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. This study aimed to identify individuals who are at risk of heart failure and increased risk for cardiovascular events by evaluating endothelial function in patients with celiac disease. Materials and Methods: The study included 36 patients with celiac disease and 35 healthy volunteers. After all routine laboratory examination, left ventricular functions were evaluated with standard two‐dimensional, M‐mode conventional Doppler methods. Then, flow‐mediated dilatation and nitroglycerin‐dependent dilatation tests on brachial artery were performed to all patients and controls. Results: A total of 36 celiac patients and 35 healthy volunteers were included in the study. The brachial artery diameter at baseline was similar between both groups. Measured brachial artery diameter after hyperemia was 30.19 ± 4.47 mm in celiac patients and 32.35 ± 3.77 mm in the control group. Differences between two groups were statistically significant (P = 0.031). Flow‐mediated vasodilatation was lower in celiac patients compared with in controls (10.61 ± 2.64% vs 13.09 ± 2.9%; P = 0.0003). Measured endothelium‐independent vasodilatation in the brachial artery before and after nitroglycerin was similar between both groups (P = 0.09 and P = 0.07, respectively). Conclusion: This research which aimed to evaluate endothelial dysfunction in patients with celiac disease is the first in the literature. As a result of this study, we found endothelial dysfunction at the macrovascular level in celiac patients. (Echocardiography 2012;29:471‐477)     

Association of asymptomatic hyperuricemia and endothelial dysfunction in psoriatic arthritis

IntroductionCardiovascular disease is an increasingly recognized contributor to excess morbidity and mortality in psoriatic arthritis (PsA). Traditional cardiovascular risk factors do not adequately account for the extent of cardiovascular disease in PsA.Aim of the workTo examine the prevalence of subclinical atherosclerosis in patients with PsA to emphasize the potential role of serum uric acid on endothelial dysfunction, as an early predictor for atherosclerosis in PsA patients.Patients and methodsThis study included 60 PsA patients as well as 60 age and sex matched healthy controls. Assay of serum uric acid, interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) was done for all patients and controls. Patients were subjected to psoriasis area severity index (PASI) and assessment of disease activity. Patients and controls underwent brachial flow-mediated dilatation (FMD) assessment by color duplex sonography to determine endothelial dysfunction as well as extracranial carotid arteries assessment by high-resolution B-mode ultrasound to measure the common carotid intima-media thickness (CIMT) and the detection of atheromatous plaques.ResultsPsA patients have a high significant difference in CIMT, FMD of the brachial artery and mean levels of serum uric acid compared to healthy controls (p < 0.001). PsA patients with hyperuricemia have a high significant difference in CIMT and FMD of the brachial artery than those with normal serum uric acid. Serum uric acid levels showed a high significant positive correlation with each of CIMT, disease duration, markers of inflammation (ESR, CRP, IL-6, sICAM-1), disease activity score in 28 joints (DAS 28) and PASI (r = 0.71, 0.893, 0.956, 0.858, 0.853, 0.877, 0.907, 0.847, respectively, as p < 0.001). A high significant negative correlation was found between serum uric acid levels and FMD of the brachial artery as r = ?0.634, p < 0.001.ConclusionPatients with PsA have a high prevalence of subclinical atherosclerosis dependent on serum uric acid, suggesting that chronic systemic inflammation and endothelial dysfunction appear to be the link between asymptomatic hyperuricemia and atherosclerosis. Therefore, proper control of serum uric acid may play a preventive role in the development of atherosclerosis in PsA patients.     

Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis

OBJECTIVE: To evaluate the cardiovascular risk profile of spondylarthropathy patients, particularly ankylosing spondylitis and psoriatic arthritis. METHODS: A Pubmed literature search was performed to collect English-language articles for this clinically orientated review. Studies were selected if they included (cardiovascular) mortality and morbidity and/or data about cardiovascular risk factors in spondylarthropathies. RESULTS: Ankylosing spondylitis as well as psoriatic arthritis appear to be associated with an increased cardiovascular mortality and morbidity. Several factors, ie, smoking, altered lipid profile, hypertension, increased fibrinogen level, enhanced number of platelets, and hypercoagulability might explain the enhanced cardiovascular risk. Moreover, a decline in physical activity, the presence of HLA-B27, and inflammation may play a role. Finally, undertreatment of cardiovascular morbidity also may contribute to the higher cardiovascular risk. CONCLUSIONS: The available data indicate an increased cardiovascular risk in spondylarthropathy patients, particularly those with ankylosing spondylitis and psoriatic arthritis. RELEVANCE: Rheumatologists should be aware of the enhanced cardiovascular risk in patients with ankylosing spondylitis and psoriatic arthritis. If modifiable cardiovascular risk factors are identified, treatment could ultimately result in a lower cardiovascular morbidity and mortality.     

Vascular endothelial dysfunction in patients with newly diagnosed type 2 diabetes and effects of 2-year and 5-year multifactorial intervention

Objectives: Investigate short‐ and long‐term effect of multifactorial intervention on endothelial dysfunction in patients with newly diagnosed type 2 diabetes. Background: Whether multifactorial intervention reduces cardiovascular risk in type 2 diabetes is largely controversial, partially because of lack of reliable method for endothelial dysfunction detection. Using high‐resolution ultrasonographical flow‐mediated vasodilatation (FMD), we completed a 5‐year randomized prospective intervention trial in patients with newly diagnosed type 2 diabetes. We have studied the effect of multifactorial intervention therapy on their endothelial dysfunction. Methods: One hundred eight patients with newly diagnosed type 2 diabetes, and 83 healthy subjects received measurement of brachial artery FMD and endothelium‐independent dilatation (EID). Diabetic patients were assigned into four groups, treated with: (A) hypoglycemic and antihypertensive agents, (B) hypoglycemic, antihypertensive and lipid‐lowering agents, (C) hypoglycemic, antihypertensive and lipid‐lowering agents, and vitamin E, and (D) hypoglycemic, antihypertensive and lipid‐lowering agents, and compound salvia tablets. Both FMD and EID were remeasured after 24‐ and 60‐month treatment. Results: FMD in diabetic patients was significantly lower than those in healthy subjects. After 24‐month treatment, there was no FMD change. However, FMD improved significantly after 60‐month treatment. The differences between 24‐ and 60‐month are also significant. EID did not change significantly after both 24‐ and 60‐month treatments. Conclusions: (1) FMD‐detectable endothelial dysfunction exists in newly diagnosed type 2 diabetic patients. (2) Reverse of endothelial function occurs only after long‐term (60‐month) multifactorial intervention. (3) FMD could potentially help early identification, stratification, and treatment of endothelial dysfunction in type 2 diabetic patients. (Echocardiography 2011;28:1133‐1140)     

Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis

Aim: Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 μg, Vonder^® (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA). Methods: Twenty‐four patients with established active RA with high disease activity (Disease Activity Score of 28 joints [DAS28 score] > 5.1) despite treatment with stable doses of conventional disease‐modifying antirheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Questionnaire‐Disability Index [HAQ‐DI] scores, erythrocyte sedimentation rate [ESR] and C‐reactive protein [CRP]), markers of endothelial dysfunction, serum nitrite concentration and endothelium‐dependent and ‐independent vasodilation of the brachial artery were measured before and after 12 weeks therapy with twice a day oral AGEs inhibitor. Results: After treatment, flow‐mediated vasodilation improved from 9.64 ± 0.65% to 15.82 ± 1.02% (P < 0.01), whereas there was no significant change in endothelium‐independent vasodilation with nitroglycerin and baseline diameter; serum nitrite concentration significantly reduced from 5.6 ± 0.13 to 5.1 ± 0.14 μmol/L (P = 0.004), ESR from 63.00 ± 3.5 to 28.08 ± 1.5 mm in the first h (P < 0.01) and CRP levels from 16.7 ± 4.1 to 10.74 ± 2.9 mg/dL (P < 0.01). DAS28 and HAQ‐DI scores were significantly reduced, from 5.9 ± 0.17 to 3.9 ± 0.17 (P < 0.01) and 4.6 ± 0.17 to 1.7 ± 0.22 (P < 0.01), respectively. Conclusions: Advanced glycation end products inhibitor improves endothelial dysfunction and inflammatory disease activity in RA. In RA, endothelial dysfunction is part of the disease process and is mediated by AGEs‐induced inflammation.     

Correlation of endothelial dysfunction measured by flow-mediated vasodilatation to severity of coronary artery disease

ObjectivesBrachial artery ultrasound imaging during reactive hyperemia is widely used tool for quantifying endothelium dependent vasomotion. Angiodefender device is used for non invasive determination of percentage flow mediated vasodilation (FMD). An attempt is made to study whether endothelial dysfunction determined by FMD of brachial artery predicts the presence or absence of coronary artery disease and its correlation with the severity of coronary artery disease.MethodsOne hundred six patients admitted between May 2014 and April 2015 who were posted for coronary angiography diagnosed to have chronic stable angina on clinical basis and/or by exercise stress test, for evaluation of coronary artery disease were submitted to standard clinical evaluation, calculation of percentage FMD by Angiodefender device. Statistical significance of difference of categorical variables was tested using Fisher’s exact test. Sensitivity, specificity, positive predictive value and negative predictive value of FMD were studied.ResultsThere was no correlation between number of risk factors and percentage of FMD. Significantly higher proportion of cases with less FMD had higher prevalence of coronary artery disease and vice-versa. Significantly higher proportion of cases with positive stress test had less percentage of FMD and vice-versa. Significantly higher proportion of cases with less percentage of FMD and positive stress test had higher prevalence of obstructive coronary artery disease and vice-versa. Specificity was 100% when percentage of FMD was ≤10.ConclusionsFMD an inexpensive and non-invasive test provides information regarding extent and severity of coronary artery disease.     

Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis

OBJECTIVES: To evaluate the extent of subclinical atherosclerosis by measuring the intima-media wall thickness (IMT) of the common carotid artery in patients with psoriatic arthritis (PsA) and to identify vascular risk factors associated with PsA. METHODS: Forty-seven patients with PsA were compared with 100 allegedly healthy subjects. Carotid duplex scanning was used to measure common carotid artery IMT. Traditional risk factors, such as gender, age, body mass index (BMI), hypertension, smoking, and lipids were checked. Assessment of PsA activity included clinical patterns of involvement, degree of severity, duration of morning stiffness, number of tender and swollen joints, degree of pain and fatigue, the Bath Ankylosing Spondylitis Disease Activity Index, the Psoriasis Area and Severity Index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen. RESULTS: The average IMT (mean +/- standard deviation) for PsA patients was significantly higher compared with controls (0.76 +/- 0.11 versus 0.64 +/- 0.27, respectively, P < 0.00001) for the whole group and after adjustment for age, gender, BMI, hypertension, and hyperlipidemia. The PsA subjects had significantly higher levels of hypertension, hyperlipidemia, ESR, CRP, and fibrinogen, and their average IMT significantly correlated with age, BMI, duration of skin and joint disease, spine involvement, ESR, and fibrinogen. IMT did not correlate with the presence of oligo- or polyarthritis but was increased in patients with clinical spinal involvement. IMT was not associated with the degree of severity or the use of different therapies for PsA, including methotrexate or tumor necrosis factor-alpha-blocking agents. CONCLUSIONS: PsA patients exhibited greater IMT than healthy controls. Increased IMT independently correlated with parameters of disease activity and conventional risk factors of atherosclerosis.     

Endothelial dysfunction in haemophilia patients

Summary. Haemophilia patients may develop cardiovascular diseases, suggesting that their clotting defect does not protect them completely from atherosclerosis and its complications. We aimed to evaluate cardiovascular risk factors and, for the first time, the presence of endothelial dysfunction in middle‐aged haemophilia patients. We studied 40 patients with haemophilia A and B (24 with moderate–severe disease and 16 with mild disease), and 40 healthy controls. Flow‐mediated dilation (FMD), carotid ultrasound (US) intima media thickness (IMT), arterial blood pressure, body mass index (BMI), cholesterol, triglycerides, glucose, insulin, lipoprotein(a) and homocysteine levels were measured, and PAI‐1 and t‐PA levels before and after venous occlusion (VO), and antibodies to HIV, HBV and HCV were assayed. At least one cardiovascular risk factor was detected in 87.5% of patients, and 2 or more in 47.5% of cases. At US exam, none of the patients had significant carotid stenosis or significant differences in IMT compared to controls. In contrast, all the patients had a significant FMD impairment, associated with a reduced t‐PA release after VO in 70% of cases. PAI‐1 levels significantly correlated with BMI, triglycerides and insulin values. Fifteen haemophilia patients with chronic viral hepatitis and/or HIV infection showed a significantly lower FMD than patients without active infection. We found an endothelial dysfunction with impaired FMD and t‐PA release in our haemophilia patients, usually associated with cardiovascular risk factors. Other pathogenic mechanisms, such as chronic viral infections, are likely to be involved in this endothelial damage, however.     

Relationship between endothelial function in the coronary and brachial arteries

BACKGROUND: Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries. HYPOTHESIS: We investigated the relationship between coronary and peripheral endothelial function. METHODS: In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 microg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values. RESULTS: Flow-mediated dilation (FMD) of the brachial artery was 5.0 +/- 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 microg/min, r = 0.31, p < 0.05) but also with the change in CBF (ACh at 3 microg/min, r = 0.39, p < 0.05; ACh at 30 microg/min, r = 0.46, p < 0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF. CONCLUSIONS: These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.     

Lack of echocardiographic and Doppler abnormalities in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors

OBJECTIVE: To assess the prevalence of echocardiographic and Doppler abnormalities in psoriatic arthritis (PsA) patients without clinically evident cardiovascular manifestations or classic atherosclerosis risk factors. METHODS: Fifty PsA patients were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients seen during the period of recruitment that had classic cardiovascular risk factors or had suffered cardiovascular or cerebrovascular events were excluded. Fifty healthy matched controls were also studied. Echocardiographic and Doppler studies were performed in all cases and controls. RESULTS: In PsA patients the frequency of aortic and tricuspid (10%) and mitral regurgitation (16%) was not different from that seen in matched controls (10, 4, and 12%). Also, the pulmonary artery systolic pressure was normal in the group of PsA patients (23.4+/-3.9 mm Hg). The prevalence of diastolic dysfunction, in all cases due to impaired relaxation, was similar in PsA patients (28%) and controls (24%) (P=0.65). In addition, no significant echocardiographic and Doppler differences were observed when PsA patients with polyarticular pattern were compared with the remaining PsA patients. CONCLUSIONS: The present study shows that actively treated PsA patients without cardiovascular risk factors or clinically evident cardiovascular disease do not exhibit silent subclinical echocardiographic abnormalities.     

非阻塞性冠状动脉粥样硬化患者内皮功能不全的影响因素

目的探讨非阻塞性冠状动脉粥样硬化患者内皮功能不全的影响因素。方法选取2013年6月至2015年6月首都医科大学宣武医院心脏内科收治的因胸痛疑诊冠心病、经冠状动脉造影检查证实为非阻塞性冠状动脉粥样硬化症(冠状动脉狭窄<50%)的患者110例。行肱动脉血流介导内皮依赖性血管舒张功能(FMD)检测,用流式细胞仪检测外周血CD133+/KDR+、CD34+/KDR+以及CD34+/CD133+/KDR+内皮祖细胞(EPCs)。根据FMD分为对照组(FMD>10%)和内皮功能不全组(FMD≤10%)。采用SPSS 19.0软件进行统计分析。应用logistic回归模型分析影响内皮功能不全的因素。结果2组患者CD133+/CDR+、CD34+/KDR+或CD34+/CD133+/KDR+循环EPCs数量比较,差异无统计学意义(P>0.05)。多因素logistic回归分析显示,年龄是影响内皮功能不全的独立危险因素(95%CI 1.004~1.104,P=0.033)。结论非阻塞性冠状动脉粥样硬化患者内皮功能不全的独立影响因素是年龄,而非循环EPCs数量。