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Objective: Ultrasound protocols to measure carotid intima-media thickness (CIMT) differ in the number of carotid walls, segments and angles measured. No published evidence is available to help decide which approach is best, i.e. the most reproducible and providing the largest CIMT progression rate measured with highest precision. We compared different ultrasound protocols in a post-hoc analysis in the 'Osteoporosis Prevention and Arterial effects of tiboLone' (OPAL) study, a 3-year randomized controlled trial among healthy postmenopausal women.Research Design and Methods: Based on combinations of 60 CIMT measurements per participant (two sides, two walls, three segments, five angles), 66 theoretical protocols were constructed. Each protocol was assessed and ranked on: (1) reproducibility (intra-class correlation (ICC), mean difference of duplicate scans) and (2) CIMT progression rate and its precision (standard error) in the placebo group.Results: Duplicate scans at baseline and end of study were available for 675 women (89% of 759 subjects). ICC ranged from 0.69 to 0.88. Mean difference in CIMT of duplicate scans and its standard deviation, ranged from 0.0010 to 0.0137 mm and from 0.0561 to 0.1770, respectively. CIMT rate of progression ranged from -0.0001 to 0.0113 mm/year. The protocols with highest reproducibility and highest CIMT progression-precision were mean common CIMT protocols measuring both near and far wall at > or = 2 angles. The mean maximum protocol measuring three segments at > or = 2 angles performed best, yet with lower estimates as for common CIMT protocols.Conclusions: In healthy middle-aged subjects mean common CIMT protocols that include measurements at both near and far walls at multiple (> or = 2) angles provide highest reproducibility combined with largest estimates of CIMT progression measured with high precision and are to be recommended in this population. [ABSTRACT FROM AUTHOR]

The article presents study of comparison of two methods, Automated Radio Frequency and Manual B-mode ultrasound common carotid intima used in clinical practice and their relation to risk factor and future events, and presents conclusion of this study by using data from SMART-study of participants.

The article presents study to determine the early vascular abnormalities associated with the presence or absence of the metabolic syndrome (MS) in normotensive patients at risk of developing diabetes mellitus.

The article discusses study conducted to evaluate association of daily dietary intake of antioxidants vitamins C and E with augmentation index and endothelial function in hypertensive patients and normotensive subjects revealing that vitamin C and E supplement is necessary on vascular function.

This pilot study evaluated the predictive value of flow-mediated dilation (FMD) for damage accrual in a cohort of SLE patients. Thirty-eight female SLE patients without cardiovascular involvement were enrolled. Clinical history, traditional cardiovascular risk factors, laboratory parameters, disease activity and damage and brachial artery FMD were collected at study entry and after a mean follow-up of 4.5 years. At enrollment, 18 patients (47%) presented active disease; mean FMD was 7.9 ± 3.1%, with no statistically significant differences between women with active and inactive disease. During the follow-up, 3 patients died and 14 accrued organ damage. Baseline FMD did not predict death and damage accrual. FMD showed significant decline over time, which was greater in patients with poor outcome (-3.9% vs -1.9%, p = 0.03). In conclusion, in a cohort of SLE patients, baseline FMD was not predictive of damage accrual. However, the latter was associated with progressive loss of FMD., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Background: Animal studies suggest that dietary cis-9,trans-11 (c9,t11) conjugated linoleic acid (CLA) may inhibit or regress the development of atherosclerosis. The effect of CLA on atherosclerosis has not been assessed in humans., Objective: We investigated the effect of c9,t11 CLA supplementation on aortic pulse wave velocity (a marker of atherosclerosis) and on cardiovascular risk factors in overweight and obese but otherwise apparently healthy subjects., Design: In a double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned 401 subjects, aged 40-70 y and with a body mass index (in kg/m(2)) > or = 25, to receive either 4 g CLA/d (2.5 g c9,t11 CLA/d and 0.6 g trans-10,cis-12 CLA/d) or placebo supplements for 6 mo. Aortic pulse wave velocity, blood pressure, anthropometric characteristics, and concentrations of fasting lipid, glucose, insulin, and C-reactive protein were measured before and after supplementation., Results: During the intervention, mean (+/-SE) pulse wave velocity did not change in the c9,t11 CLA group (Delta0.00 +/- 0.07) compared with the placebo group (Delta0.09 +/- 0.06). There was no effect of c9,t11 CLA supplementation on blood pressure, body composition, insulin resistance, or concentrations of lipid, glucose, and C-reactive protein., Conclusion: This study does not support an antiatherosclerotic effect or an effect on cardiovascular risk factors of c9,t11 CLA. This trial was registered at www.clinicaltrials.gov as NCT00706745.

Support for the notion that a carotid intima-media thickness (CIMT) measurement is useful in individual cardiovascular risk prediction in addition to a risk function may come from studies showing that for an individual a high or low CIMT measurement leads to a correct shift from one to another risk category and this shift is followed by different treatment consequences. We set out to systematically review the published evidence by performing a PubMed search (2 March 2009). Out of 50 publications on CIMT and future events, 31 reported on the relation in the correct domain, [i.e. those free from symptomatic vascular disease or diabetes mellitus in which assessment of risk using a risk function (e.g. Framingham or SCORE) to base initiation of drug treatment upon is recommended]. Most studies reported relative risks (or equivalents) for the entire population only, and no information on relative risks within certain risk categories that may be of use to reclassify individuals based on combination of absolute and relative risks. No data on potential shifts of participants was presented. Eight studies specifically focused on the added value of CIMT in risk prediction. In seven studies the area under the curve (AUC) of a receiver operating characteristic was used to assess improvements in risk prediction. These analyses showed that addition of a CIMT measurement to established risk factors led to small and sometimes significant improvements in the AUC. However, change in AUC should not be the only parameter to rely on to judge the appropriateness of CIMT in risk stratification. In one study (n = 242), evidence was presented in participants with an intermediate Framingham risk score, a CIMT measurement above the 60th (men) and 80th (women) percentile of age-specific normal CIMT values, shifted participants above the threshold for initiation of drug therapy. Yet, the study was based on 24 events, and no information was presented on the proportion of participants correctly shifted. At present it seems that the published evidence to quantitatively support the use of a CIMT measurement to help in risk stratification on top of a risk function is limited.

Background: Carotid intima-media thickness (CIMT) serves as an indicator of atherosclerosis and cardiovascular risk. Manual measurements of B-mode ultrasound images are the most applied method. Automated measurements with radiofrequency (RF) ultrasound have been suggested as an alternative. The aim of this study was to compare these methods in terms of risk-factor relations and associations with future events., Methods: Data from participants of the Second Manifestations of Arterial Disease (SMART) study were used. Far wall common CIMT was measured online with manual B-mode and automated RF ultrasound. Measurements were performed by a group of 6 sonographers. Risk-factor information was obtained. All participants were followed for the occurrence of vascular events (mean follow-up, 2.1 years). CIMT was related to risk factors with linear regression models and to future events with Cox proportional-hazards models., Results: Data were available for 2,146 participants. Agreement between the methods was modest (intraclass correlation coefficient = 0.34). Risk-factor relations with age and systolic blood pressure were stronger for B-mode than for RF ultrasound. Association with future events was better for B-mode than for RF ultrasound (vascular death, 1.27 vs 1.00; ischemic stroke, 1.45 vs 1.03). In participants with CIMT < 0.9 mm (without plaque), the intraclass correlation between the measures was 0.50. In addition, in that subgroup, RF ultrasound showed a stronger association with future events than B-mode ultrasound (all events, 1.59 vs 1.09; vascular death, 1.72 vs 0.93; coronary ischemic events, 1.65 vs 1.05)., Conclusions: The preference for either B-mode or RF measurements may be driven by the type of study population, the expected presence of local atherosclerotic abnormalities, and the main aim of the study (assessing risk factors or events). However, in this study, as in many others, the B-mode approach was shown to be robust in risk-factor relations and the prediction of events.

Background: Whether pulse pressure amplification (PPA) relates to established markers of cardiovascular risk is unknown. The purpose of this study was to investigate the relationship between PPA and cardiovascular risk factors and cardiovascular risk in a population-based sample of 40- to 80-year old men., Methods: A cross-sectional, single-center study was performed in 400 men aged 40-80 years. PPA was calculated as a ratio (brachial pulse pressure/central pulse pressure). Detailed information on vascular risk factors was obtained. Aortic pulse wave velocity (PWV) and common carotid intima-media thickness (CIMT), as markers of vascular risk, were measured. We calculated the absolute 10-year risk of coronary heart disease using the Framingham risk score. Regression analysis was used to evaluate the relations under study., Results: In models adjusted for age, mean arterial pressure (MAP), heart rate, and height, significant inverse relations with PPA were found for waist-to-hip ratio, triglycerides, smoking, pack-years, and hypertension. Furthermore, an increased PPA was significantly inversely related to aortic PWV, common CIMT, and history of symptomatic vascular disease. Finally, the Framingham risk score decreased with increasing PPA., Conclusion: Our study shows that a higher PPA reflects a lower vascular risk in men between 40 and 80 years of age, as shown by a better cardiovascular risk profile, a reduced PWV, common CIMT, and a lower Framingham risk of coronary heart disease.

The methods commonly used for noninvasive ultrasound assessment of endothelium-dependent flow-mediated dilation (FMD) require an electrocardiogram (ECG) signal to synchronize the measurements with the cardiac cycle. In this article, we present a method for assessing FMD that does not require ECG gating. The approach is based on temporal filtering of the diameter-time curve, which is obtained by means of a B-mode image processing system. The method was tested on 22 healthy volunteers without cardiovascular risk factors. The measurements obtained with the proposed approach were compared with those obtained with ECG gating and with both systolic and end-diastolic measurements. Results showed good agreement between the methods and a higher precision of the new method due to the fact that it is based on a larger number of measurements. Further advantages were also found both in terms of reliability of the measure and simplification of the instrumentation. (E-mail: gemi@ifc.cnr.it).

We evaluated the possible association between early vascular abnormalities and the metabolic syndrome (MS) in 77 normotensive subjects (mean age: 50 years) at risk of developing diabetes for family history of diabetes, obesity, or impaired fasting glucose. Fifty healthy subjects were recruited as controls. MS was defined according to the ATP III criteria. Brachial artery endothelium-dependent and -independent vasodilation were assessed as flow-mediated dilation (FMD) and response to glyceryl trinitrate (GTN, 25 microg sublingual), respectively, by automatic computerized edge detection system. Carotid-femoral pulse wave velocity (PWV) and radial augmentation index (AIx) were assessed by applanation tonometry. PWV was significantly (P<0.01) higher in subjects with MS (n=29, 9.0+/-1.9 m/s) as compared with those without MS (n=48, 7.7+/-1.2 m/s) and controls (7.2+/-1.5 m/s). FMD was significantly (P<0.05) reduced in both subjects with (5.8+/-2.7%) and without MS (6.1+/-3.7%) as compared with controls (6.9+/-2.5%). No significant differences were found for response to GTN and AIx. PWV and FMD were significantly (P<0.05) affected by increasing number of MS components. Among the components of the MS, only blood pressure significantly affected PWV, whereas blood pressure and fasting glucose influenced FMD. Logistic regression analysis showed that MS was associated with increased risk of altered PVW (odd ratio: 7.95, confidence limits: 1.06 to 69.11), whereas only blood pressure component was significantly related with increased risk of impaired FMD (odd ratio: 3.60, confidence limits: 1.01 to 12.78). In conclusion, in normotensive subjects at risk of developing diabetes mellitus, the presence of MS is associated with a selective alteration of central PWV.

Background: Essential hypertension is characterized by endothelial dysfunction, arterial stiffness, and increased oxidative stress. We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function, arterial stiffness, and oxidative stress in untreated essential hypertensive patients., Methods: A randomized, double-blind, placebo-controlled, crossover study design was used to assign 30 male essential hypertensive patients to either vitamin C (1 g) and vitamin E (400 IU) or placebo for 8 weeks. Endothelium-dependent response was assessed as flow-mediated dilation (FMD) of the brachial artery. Arterial stiffness was assessed as central pulse wave velocity (PWV) and augmentation index (AIx). Plasma markers of oxidative stress and antioxidant status were measured., Results: After vitamin supplementation, FMD was significantly improved. Central PWV was significantly reduced, while AIx tended to decrease. Plasma vitamin levels and antioxidant capacity increased significantly. Levels of oxidative stress decreased. Changes in central PWV were related to changes in levels of oxidative stress., Conclusions: Combined treatment with vitamins C and E has beneficial effects on endothelium-dependent vasodilation and arterial stiffness in untreated, essential hypertensive patients. This effect is associated with changes in plasma markers of oxidative stress.

There is a large body of evidence indicating that inflammation plays a crucial role in all steps characterizing the atherosclerotic process. C-Reactive Protein is a circulating marker of inflammation which recently emerged as a powerful independent determinant of cardiovascular events. Hypertension is closely linked to inflammation. Experimental data and results from cross-sectional studies in humans indicate a relationship between CRP levels and blood pressure. In particular, CRP seems to be related with markers of arterial stiffness, thus suggesting a specific interaction between CRP and systolic blood pressure. However, such observational studies cannot provide any direct evidence for a cause-effect relation. Prospective studies are likely candidates to better define the putative causal relationship on this association. Available results from longitudinal studies are scanty, and do not allow to draw definitive conclusions. Moreover, prospective, placebo-controlled intervention trials documenting that reduction of CRP levels by pharmacological treatment might lead to a reduced risk to develop hypertension are not yet available. Without such crucial information, at the present time the causal connection between inflammation and blood pressure, although regarded as an intriguing possibility, remains undiscovered.

Aim: We evaluated endothelial-dependent vasodilation after administration of recombinant human TSH (rhTSH) in patients monitored for differentiated thyroid carcinoma. The role of inflammation and oxidative stress was also assessed., Protocol: Twenty-four patients (21 women, mean age 40.5 +/- 9.2 yr) received rhTSH (0.9 mg daily) on 2 consecutive days. At baseline and the day after the second rhTSH injection, endothelium-dependent vasodilation as flow-mediated dilation (FMD, induced by 5 min of forearm ischemia) and endothelium-independent vasodilation (glyceril trinitrate 25 microg, sublingual) were evaluated by high-resolution ultrasound in the brachial artery. At each experimental time, blood was drawn for the evaluation of thyroglobulin, TSH, free T(3), free T(4), as well as IL-6, C reactive protein, TNFalpha, lipoperoxides, and ferric reducing antioxidant power levels as markers of inflammation and oxidative stress., Results: At baseline, patients' serum TSH values were below the normal range [0.12 mIU/liter (range 0.01-0.30)] in the face of normal free T(4) and free T(3) levels; FMD (8.9 +/- 3.4 vs. 9.2 +/- 3.1%, respectively) and response to glyceril trinitrate (11.0 +/- 4.3 vs. 10.8 +/- 4.7%, respectively) were similar in patients and controls. All the patients had serum thyroglobulin value less than 1 ng/ml, suggesting the absence of cancer recurrences. Besides the expected elevation of serum TSH, rhTSH induced a significant impairment of FMD (7.4 +/- 3.0 vs. 8.9 +/- 3.4%; P < 0.01) along with a significant elevation of blood IL-6 (P = 0.01), TNFalpha (P < 0.001), and lipoperoxide levels (P = 0.01), as well as a reduction of ferric reducing antioxidant power (P = 0.01)., Conclusions: rhTSH administration acutely impaired endothelium-dependent vasodilation, possibly through the induction of low-grade inflammation and reduced nitric oxide availability by oxidative stress.

Myocardial involvement is a common finding in certain myopathies, while it has not been extensively investigated in facioscapulohumeral muscular dystrophy (FSHD1A). Aim of this study was to assess in FSHD1A patients the electrical and functional properties of the myocardium. Twenty-four patients with FSHD1A (mean age 41.2+/-14.5 years) and 24 matched healthy subjects were studied. Standard- and signal-averaged electrocardiography were recorded to determine QT dispersion and the presence of ventricular late potentials (VLPs). Standard echocardiography with systo-diastolic variations of integrated backscatter signal (CV-IBS) were performed to assess functional properties of the myocardium. Compared with control subjects, patients with FSHD1A had significantly lower CV-IBS and higher QT dispersion. Nine patients had positive VLPs. QT and QTc dispersion were inversely related to CV-IBS at both septum and posterior wall levels. Moreover, septal CV-IBS was inversely related to the Kpnl-BinI4q fragment size. These results suggest a subclinical cardiac involvement in FSHD1A patients, which can represent a substrate for ventricular arrhythmias and heart failure.

Background: Sedentary aging is associated with oxidative stress and endothelial dysfunction. The aim of this study was to evaluate the relationship between long-term physical activity, plasma antioxidant status, and conduit artery endothelial function in young and older healthy men., Methods: In young (n = 16) and older athletes (n = 16) and in matched healthy sedentary subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, were measured in the brachial artery from high-resolution ultrasonography. Plasma malondialdehyde (MDA) and antioxidant capacity as total oxyradical scavenging capacity (TOSC) were also evaluated., Results: We found that FMD was lower (< or =0.01) in sedentary older subjects (2.3% +/- 1.0%) as compared with older athletes (5.3% +/- 3.2%) and both sedentary (5.4% +/- 2.0%) and athletically trained (6.1% +/- 3.2%) young subjects. Sedentary older subjects showed higher (P < or = .05) MDA levels and lower (P < .0001) plasma antioxidant capacity as compared with the other subgroups, whereas in older athletes MDA levels and antioxidant capacity were similar to those observed in the young subgroups. In the whole group, FMD, but not GTN, was negatively related to age (r = -0.31, P < .05) and directly related (P < or = .01) to VO2max (r = 0.49) and TOSC against peroxyl (r = 0.69) and hydroxyl radicals (r = 0.53). In the multivariate analysis, TOSC against peroxyl radicals resulted as the most significant predictor of FMD (R2 = 0.60; P = .003)., Conclusions: These results suggest that regular physical activity is associated with preserved antioxidant defenses and endothelial function in older individuals.

Aging is associated with endothelial dysfunction in both conduit arteries and peripheral microcirculation. Furthermore, aging is associated with an increased susceptibility to free radical mediated tissue damage. The aim of this study was to assess the relationship between age, regular aerobic-endurance training, plasma antioxidant activity and microcirculatory skin blood flow in healthy individuals. Thirty-six male athletes (range: 22-74 years; VO2max 54.3 +/- 5.2 ml/kg/min) and 36 age-sex-matched sedentary controls (range: 20-75 years; VO2max 34.2 +/- 3.4 ml/kg/min) were studied. Each group was divided into a younger (<30 years) and an older (>60 years) subgroup. Hand and foot baseline and stimulated skin blood flow (SBF) was measured by laser-Doppler flowmetry. Plasma free radicals antioxidant capacity against both peroxyl and hydroxyl radicals was also evaluated as Total Oxyradical Scavenging Capacity (TOSC) units. Baseline SBFs were not significantly different between athletes and sedentary groups, while plasma TOSC values against peroxyl radicals (18.4 +/- 3.1 vs. 13.8.0 +/- 3.4 units/ml, P < 0.001) and hydroxyl radicals (8.7 +/- 2.5 vs 4.9 +/- 2.3 units/ml, P <0.001) was higher in athletes. Hand SBF after heating and ischemia and foot SBF after heating were higher in athletes (P <0.0001) than in the sedentary group. In the sedentary groups, the lowest tertile of age had higher plasma TOSC values than the highest tertile of age (ROO- 18.2 +/- 2.2 vs 8.8 +/- 1.4 units/ml; HO- 9.2 +/- 1.3 vs 3.7 +/- 0.5 units/ml, P < 0.001). Among athletes, the lowest and the highest tertile of age did not show significantly different plasma TOSC (young: ROO- 20.3 +/- 1.5 and HO-: 9.7 +/- 1.4 units/ml; older: ROO-: 17.1 +/- 1.3 and HO-: 9.0 +/- 0.8 units/ml, n.s.). Resting SBF was similar in all the subgroups; stimulated SBFs were lower in both subgroups of untrained respect to trained individuals (P <0.001). In the sedentary subjects, SBF was inversely related to age (r = -0.63; P <0.0001) and directly related to TOSC against peroxyl (r = 0.59, P <0.001) and hydroxyl radicals (r = 0.47, P <0.01). In athletes SBF was related only to VO2max (r = 0.36; P <0.05) and TOSC vs ROO. (r = 0.41, P <0.01). In conclusion, these results suggest that regular physical activity is associated with a better microvascular endothelial function in older athletes probably due to increased antioxidant defenses.

Amlodipine has been reported to improve endothelial function in patients with arterial hypertension and to significantly limit the progression of carotid atherosclerosis. The aim of this study was to assess the total antioxidant activity of amlodipine. We measured the in vitro antioxidant activity of amlodipine as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Reduced glutathione, uric acid and trolox were used as the reference antioxidants. Amlodipine showed an efficiency as scavenger of peroxyl radicals (TOSC: 5945 +/- 544 units/mg) significantly higher (>50%, P <0.001) than that of GSH (2733 +/- 636 units/mg), and 70% lower (P < 0.0001) than the value obtained with uric acid (18144 +/- 696 units/mg) and trolox (17522 +/- 734 units/mg). Of interest, the scavenging capacity of amlodipine towards hydroxyl radicals (1455 +/- 154 units/mg) was 320% higher (P < 0.00001) than that of GSH (358 +/- 112 units/mg), 20% higher than that of uric acid (1198 +/- 121 units/mg), and 100% higher than that of trolox (759 +/- 143 units/mg). Amlodipine has intrinsic antioxidant activity with both anti-hydroxyl and anti-peroxyl radicals activity.

High-frequency ultrasonographic imaging of flow-mediated dilatation (FMD) in a brachial artery, as non-invasive technique, was used for the clinical evaluation of endothelial function (EF) in 115 subjects (ages 44.19+/-12.23 (26 to 83) free of coronary heart disease or its equivalents. Our aim was to study the normative ranges for FMD in subjects of different age groups with low cardiovascular risk factors. The mean FMD was 8.23+/-4.51% (0 to 20.9). Multivariate analysis revealed that there were only two independent predictors of FMD: resting vessel diameter (r = -0.45, p<0.0001) and age (r = -0.55, p<0.0001). The multiple regression equation for this data was FMD = 25.5-0.17 x age-2.6 x resting vessel diameter. Our study demonstrates that FMD in low cardiovascular risk patients inversely correlates with age as well as brachial artery diameter. Normative ranges of FMD could be predicted for different age groups. In addition to conventional methods for the assessment of cardiovascular risk by using a population-based approach (score indexes such as SCORE, FRAMINGH, PROCAM), high-frequency ultrasonographic imaging of flow-mediated dilatation (FMD) in the brachial artery is now becoming an accepted method for the assessment of an individual patient's cardiovascular risk. Although preliminary guidelines have been published, this technique has interpretive limitations. In a study that was published earlier, the authors estimated diameter-related normal ranges of FMD. Several articles reported cut points between control and diseased groups. Data about the impact of age on FMD are also available in the literature. However, this is the first attempt to classify normal values into groups according to age and diameter.