Circulating Reactive Oxygen Species in Adults with Congenital Heart Disease.

Oxidative stress is an important pathophysiological mechanism in the development of numerous cardiovascular disorders, but few studies have examined the levels of oxidative stress in adults with congenital heart disease (CHD). The objective of this study was to investigate oxidative stress levels in adults with CHD and the association with inflammation, exercise capacity and endothelial function. To this end, 36 adults with different types of CHD and 36 age- and gender-matched healthy controls were enrolled. Blood cell counts, hs-CRP, NT-proBNP, fasting glucose, cholesterol levels, iron saturation and folic acid concentrations were determined in venous blood samples. Levels of superoxide anion radical in whole blood were determined using electron paramagnetic resonance spectroscopy in combination with the spin probe CMH. Physical activity was assessed with the IPAQ-SF questionnaire. Vascular function assessment (EndoPAT) and cardiopulmonary exercise testing were performed in the patient group. Superoxide anion radical levels were not statistically significantly different between adults with CHD and the matched controls. Moreover, oxidative stress did not correlate with inflammation, or with endothelial function or cardiorespiratory fitness in CHD; however, a significant negative correlation with iron saturation was observed. Overall, whole blood superoxide anion radical levels in adults with CHD were not elevated, but iron levels seem to play a more important role in oxidative stress mechanisms in CHD than in healthy controls. More research will be needed to improve our understanding of the underlying pathophysiology of CHD.

The impact of obstructive sleep apnea on endothelial function during weight loss in an obese pediatric population.

BACKGROUND: Childhood obesity is an increasing problem with substantial comorbidities such as obstructive sleep apnea (OSA) and increased cardiovascular morbidity. Endothelial dysfunction is an underlying mechanism related to both obesity and OSA. RESEARCH QUESTION: To investigate the effect of weight loss on endothelial function and OSA in obese children and to determine whether a change in endothelial function can be linked to an improvement in OSA. METHODS: Obese children between 8 and 18 years of age were recruited while entering a 12-month inpatient weight loss program. Patients were followed at 3 study visits: baseline, after 10 months of weight loss, and 6 months after ending the program (18 months). Anthropometry and endothelial function (EndoPAT) were determined at all study visits. At baseline, sleep screening with a portable device (ApneaLink) was performed. This was repeated after 10 months if OSA was diagnosed at baseline. RESULTS: At baseline, 130 children were included, of which 87 had OSA (67%). Seventy-two patients attended the follow-up visit at 10 months, and 28 patients attended the follow-up visit at 18 months. The BMI z-score decreased after 10 months (from 2.7 (1.4-3.4) to 1.7 (0.5-2.7); p < 0.001) and remained stable at 18 months. Endothelial function improved significantly after weight loss, evidenced by a shorter time to peak response (TPR) and higher reactive hyperemia index (p = 0.02 and p < 0.001), and remained improved after 18 months (p < 0.001 and p = 0.007). After 10 months of weight loss, 10 patients had residual OSA. These patients had a higher TPR at 10 months (225 (75-285)s) than those without OSA (135 (45-225)s) and patients with a normalized sleep study (105 (45-285)s; p = 0.02). Linear mixed models showed that more severe OSA was associated with a worse TPR at baseline and less improvement after weight loss. CONCLUSION: Weight loss improves endothelial function in an obese pediatric population. However, even after weight loss, endothelial function improved less in the presence of OSA.

Effect of Mitral Regurgitation on Thrombotic Risk in Patients With Nonrheumatic Atrial Fibrillation: A New CHA2DS2-VASc Score Risk Modifier?

The current study assessed the effect of mitral regurgitation (MR) on thrombotic risk in nonrheumatic atrial fibrillation (AF). AF carries a thrombotic risk related to left atrial blood stasis. The prevalence of atrial thrombosis, defined as the presence of left atrial appendage thrombus and/or left atrial spontaneous echo contrast grade >2, was determined in 686 consecutive nonrheumatic AF patients without (adequate) anticoagulation scheduled for transesophageal echocardiography before electrical cardioversion and was related to the severity of MR adjusted for the CHA2DS2-VASc score. A total of 103 (15%) patients had severe MR, 210 (31%) had moderate MR, and 373 (54%) had no-mild MR; the median CHA2DS2-VASc score was 3.0 (interquartile range 2.0 to 4.0). Atrial thrombosis was observed in 118 patients (17%). The prevalence of atrial thrombosis decreased with increasing MR severity: 19.9% versus 15.2% versus 11.6% for no-mild, moderate, and severe MR, respectively (p value for trend = 0.03). Patients with moderate and severe MR had a lower risk of atrial thrombosis than patients with no-mild MR, with adjusted odds ratios of 0.51 (95% confidence interval 0.31 to 0.84) and 0.24 (95% confidence interval 0.11 to 0.49), respectively. The protective effect of MR was present across all levels of the CHA2DS2-VASc risk score and the presence of moderate-severe MR in patients with an intermediate CHA2DS2-VASc score (2 to 3) lowered the atrial thrombotic risk to the level of patients with a low CHA2DS2-VASc score (0 to 1). In conclusion, our data show that the presence of MR attenuated the atrial thrombotic risk by more than 50% in patients with nonrheumatic AF.

The European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI)-clinical phenotypes and their predictors based on a cohort of 1000 patients.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

A non-contact approach for PWV detection: application in a clinical setting.

A need for screening methods for arteriosclerosis led to the development of several approaches to measure pulse wave velocity (PWV) being indicative of arterial stiffness. Carotid-femoral PWV (cfPWV) can be measured between common carotid artery (CCA) and femoral artery (FA) displaying the physiologically important stiffness of the conduit arteries. However, this measurement approach has several disadvantages, and a local PWV-measurement of CCA-stiffness has been proposed as an alternative in the past. In the presented pilot study, laser Doppler vibrometry (LDV) is used to measure PWV locally in the CCA (PWVLDV) in 48 patients aged between 48 and 70, with known atherosclerotic arterial disease: stabilized coronary artery disease (CAD), cerebro-vascular disease (CVD) or peripheral artery disease (PAD). Additionally, cfPWV, CCA distensibility coefficient (DC), CCA intima-media thickness (IMT), blood pressure (BP) and age were evaluated. LDV is a valid method for local PWV-measurement. The method is potentially easy to use, and causes no discomfort to the patient. PWVLDV correlates with age (R = 0.432; p = 0.002) as reported in related studies using other techniques, and measured values lay between 2.5 and 5.8 m s(-1), which is well in line with literature measures of local PWV in the CCA. In conclusion, PWVLDV potentially is a marker for arterial health, but more research in a larger and more homogeneous patient population is mandatory. In future studies, blood velocity measurements should be incorporated, as well as a reference method such as pulse wave imaging (PWI) or magnetic resonance imaging (MRI).

Digital image correlation for full-field time-resolved assessment of arterial stiffness.

Pulse wave velocity (PWV) of the arterial system is a very important parameter to evaluate cardiovascular health. Currently, however, there is no golden standard for PWV measurement. Digital image correlation (DIC) was used for full-field time-resolved assessment of displacement, velocity, acceleration, and strains of the skin in the neck directly above the common carotid artery. By assessing these parameters, propagation of the pulse wave could be tracked, leading to a new method for PWV detection based on DIC. The method was tested on five healthy subjects. As a means of validation, PWV was measured with ultrasound (US) as well. Measured PWV values were between 3.68 and 5.19 m/s as measured with DIC and between 5.14 and 6.58 m/s as measured with US, with a maximum absolute difference of 2.78 m/s between the two methods. DIC measurements of the neck region can serve as a test base for determining a robust strategy for PWV detection, they can serve as reference for three-dimensional fluid-structure interaction models, or they may even evolve into a screening method of their own. Moreover, full-field, time-resolved DIC can be adapted for other applications in biomechanics.

The evolution of hypertension treatment in Belgium, a pharmacoepidemiological study.

OBJECTIVES: The aim of this paper is to study the number of patients treated for hypertension and the evolution in usage of different classes of antihypertensive medication. METHODS: Data from 1997 to 2009 was extracted from Pharmanet, a nation-wide database of prescriptions of reimbursed medication in Belgium. RESULTS: In 2009, 25% of women and 20% of men were prescribed at least one antihypertensive drug. Prescription rates rose with age but already 25% of the population aged between 41 and 60 years were treated. More than 50% of the Belgians above 60 years took antihypertensive medication. From 1997 to 2009, a rise in absolute prescription rate was observed for all antihypertensive drug classes. Diuretics and beta blockers remain by far the most frequently delivered drugs with stable prescription rates of 30% over this period. The largest rise is observed for angiotensin II receptor blockers (ARBs), which were only sporadically prescribed in 1997 and now account for 10.5% of the delivered antihypertensive drugs. A small rise is also noted for angiotensin-converting enzyme inhibitors (ACE-inhibitors) (12.3% in 1997 vs 15.6% in 2009). Their success comes at the expense of calcium antagonists, of which the delivered amount declined from 19.8% in 1997 tot 14.1% in 2009. A progressive rise in the prescription of fixed combination products is observed (from 15% in 1997 to 21% in 2009), and can probably be attributed to their growing availability but also to the recent guidelines, promoting their usage. CONCLUSION: Above age 60, the majority of the Belgians are treated with antihypertensive medication. There is a growing tendency for the use of renin angiotensin aldosterone system (RAAS) blockers and fixed combination products.

Carotid artery intima-media thickness is associated with coronary artery disease.

OBJECTIVE: The intima-media thickness (IMT) of the carotid artery is dependent on the risk factor load during life and correlates well with the degree of atherosclerosis, also in other vascular beds. METHODS: We reviewed our database of IMT measurements, from January 2002 to February 2007. We compared the mean IMT values of patients without a history of coronary artery disease (group 1) with those with a history of coronary artery disease (group 2). For both groups we divided the results of measurements according to age. We compared the IMT between both groups and looked for a correlation with increasing age. The IMT was measured with high-resolution echography at the posterior wall of the common carotid artery, using an automated edge-tracking method. RESULTS: The database contained 598 IMT measurements in group 1 and 672 in group 2. In both groups we observed a significant increase in IMT with increasing age. Within a certain age group, a significant difference in IMT between group 1 and 2 occurred at an age of 40 years or above (age 40-65: IMT 645.54 versus 671.71 microm, respectively, P = 0.04, and age > 65 years: IMT 715.2 versus 772.91 microm, respectively, P = 0.01). CONCLUSIONS: IMT increases with age and is higher in patients with a history of vascular disease. This difference is significant in patients of 40 years or older. This finding supports the recommendations of the prevention conference of the American Heart Association, that carefully performed IMT measurement can add incremental information to traditional risk factor assessment in asymptomatic individuals above the age of 45 years.

Impact of oxidative stress on the endothelial dysfunction of children and adolescents with type 1 diabetes mellitus: protection by superoxide dismutase?

Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). We investigated whether these abnormalities are interrelated in children and adolescents with type 1 diabetes mellitus (T1DM) and if early OS markers predictive of vascular dysfunction can be identified. Thirty-five T1DM patients were matched for sex, age, height, and weight with nondiabetic subjects as healthy controls (CO). Flow-mediated dilatation (FMD), carotid intima media thickness (IMT), and OS status in fasting blood were measured. Diabetic children had impaired FMD (6.68+/-1.98 versus 7.92+/-1.60% in CO, p=0.004), which was more pronounced in boys. The degree of FMD impairment was not related to the lower plasma levels of antioxidants or to the higher glucose, glycation, lipids, and peroxidation products. Erythrocyte superoxide dismutase activity, copper/zinc superoxide dismutase (Cu/Zn SOD), was higher in diabetic subjects (1008+/-224 versus 845+/-195 U/g Hb in CO, p=0.003) and was positively associated with FMD. After correcting for diabetes and gender, the subgroup of children with high Cu/Zn SOD (>955 U/g Hb) had a significantly better FMD (p=0.035). These results suggest that higher circulating Cu/Zn SOD could protect T1DM children and adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease.

Can measurement of the intima-media thickness of the carotid artery improve the diagnostic value of exercise stress tests?

OBJECTIVE: The diagnostic value of the exercise electrocardiogram (ECG) for the detection of coronary artery disease is hampered by a high proportion of equivocal results, especially in asymptomatic patients. The intima-media thickness of the carotid artery correlates well with the degree of atherosclerosis, also in other vascular beds, such as the coronary arteries. The aim of this study is to evaluate whether measurements of intima-media thickness can improve the diagnostic value of stress ECG in the detection of coronary artery disease. METHODS: Patients without a history of vascular disease and with equivocal exercise stress ECG results were included. The intima-media thickness was measured with high resolution echography at the posterior wall of the common carotid artery, using an automated edge-tracking method. The diagnosis of coronary artery disease was based on the presence of reversible perfusion defects on exercise MIBI-scintigrams. RESULTS: A total of 90 patients (46 men, 44 women) with a mean age of 53.7 years were included. The MIBI-scintigraphy was positive in 17. There was no difference in mean intima-media thickness between MIBI positive and MIBI negative patients (635.76 +/- 84.56 microm and 643.89 +/- 107.06 microm, respectively, p = 0.8). Using multiple regression analysis, neither intima-media thickness measurements, nor classic risk factors could predict the result of MIBI-scintigraphy. Intima-media thickness was mainly influenced by age and hypertension. CONCLUSIONS: In this study, neither intima-media thickness measurements, nor classic risk factors could improve the diagnostic value of stress ECG in the detection of coronary artery disease. In case of equivocal stress results, additional cardiovascular imaging techniques remain recommended.