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Patients with glaucoma can show blood flow anomalies at the eye vessel level. A causal relationship is reasonably expected, but so far, it has not been demonstrated. Traditional Chinese medicine indicates that acupuncture can promote specific blood perfusion in specific body districts. Ninety-eight patients with open-angle glaucoma were treated with an ultralow light–level laser, according to a specific acupuncture protocol, and their blood flow was measured before and after a six-week treatment cycle. Doppler measurements showed significant modifications in both pulsatility and resistivity indexes. The most relevant outcome of this study is that the applied treatment demonstrated its effectiveness not only in vasodilation but also in perfusion control that seems to restore appropriate functionality. The protocol therefore should be investigated in future controlled studies and perhaps in other blood perfusion–related pathologies. [ABSTRACT FROM AUTHOR]

Aims: The most recent European guidelines have proposed new definitions of pulmonary hypertension (PH) in left heart disease, to better approach the characteristics required to reflect the presence of pulmonary vascular disease. The purpose of this study was to assess whether different haemodynamic definitions of post-capillary PH imply a different reversibility of PH in response to acute vasodilator administration in heart failure patients with reduced ejection fraction and PH (HFrEF-PH).Methods and Results: Right heart catheterization and reversibility testing was performed in 156 HFrEF-PH patients. Patients were classified as combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH) vs. isolated post-capillary pulmonary hypertension (Ipc-PH) and on the basis of diastolic pulmonary gradient (DPG) ≥ 7 vs. < 7 mmHg or of transpulmonary gradient (TPG) >12 vs. ≤12 mmHg. After vasodilator administration, Cpc-PH patients showed a greater per cent improvement in pulmonary vascular resistance (PVR), DPG and TPG as compared with Ipc-PH patients (all Pint < 0.001); only pulmonary compliance (PCa) improved less in Cpc-PH than in Ipc-PH patients (Pint = 0.007). However, despite vasodilatation, Cpc-PH patients remained in an unfavourable portion of the inverse hyperbolic relationship between PVR and PCa. The number of patients in whom PVR was reduced below 2.5 wood units was similar in Cpc-PH, DPG ≥7 mmHg and TPG >12 mmHg groups (28.3, 26.7 and 18.9%, respectively).Conclusion: Although substantial improvements in PVR, DPG and TPG were observed in Cpc-PH patients after acute vasodilator administration, this response was associated with persistent abnormalities in the PVR vs. PCa relationship. The link between baseline right heart haemodynamics and pulmonary vascular disease remains elusive. [ABSTRACT FROM AUTHOR]

Background: Little is known about brachial artery flow-mediated vasodilatation (FMD) in active and medium-term withdrawing heavy alcoholics (HA). Methods: FMD and some parameters of cardiovascular (CV) risk were measured in 29 HA (average alcohol intake 135, range 86 to 215 g per day) at baseline and after a 9 ± 7 months withdrawal and in 35 teetotalers. Results: HA showed baseline impaired maximal % FMD (8.5 ± 5.4 SD vs. 14.9 ± 7.4, <0.001 vs. teetotalers), higher systolic (SBP) and diastolic (DBP) blood pressure (+24 mm Hg, <0.001; +15 mm Hg, <0.01), uric acid (5.3 ± 1.1 vs. 4.4 ± 0.8 mg/dl, <0.05), high-sensitivity C-reactive protein (hs-CRP; 2.7 ± 2.0 vs. 1.0 ± 0.9 mg/l, <0.02), endothelin-1 (ET-1, 0.88 ± 0.36 vs. 0.37 ± 0.10 pg/ml,<0.001), asymmetric dimethylarginine (ADMA, 0.50 ± 0.21 vs. 0.41 ± 0.12 μmol/l, p < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (2.3 ± 1.1 vs. 1.2 ± 0.4, <0.001), and urinary 8-isoprostane (U8-iso-PGF2α) (237.2 ± 172.4 vs. 168.5 ± 96.6 pg/mg creatinine, <0.05). After withdrawal, SBP fell by 15 mm Hg, DBP by 11 mm Hg ( p < 0.001), and hs-CRP by 0.94 mg/l ( p < 0.02), all remaining still higher than teetotalers (<0.05, 0.01, 0.05 respectively). ET-1, HOMA-IR, and U8-iso-PGF2α were unchanged ( p = NS vs. baseline, <0.05 to 0.001 vs. teetotalers). Maximal % FMD rose (to 10.6 ± 6.2, p < 0.04), but it still remained impaired (<0.04 vs. teetotalers). ADMA increased further to 0.64 ± 0.15 μmol/l (<0.05 vs. baseline, <0.02 vs. teetotalers). Conclusions: HA show marked endothelial dysfunction (ED) and high BP, impaired insulin sensitivity, inflammation, increased oxidative stress, and elevated ET-1 and ADMA, which are unaffected or only partially reversed by a medium-term alcohol withdrawal. ED and related abnormalities persist in detoxified alcoholics, thus contributing to a greater CV morbidity and mortality. [ABSTRACT FROM AUTHOR]

Abstract: Bergamot juice produces hypolipemic activity in rats though the mechanism remains unclear. Here we investigated on the effect of bergamot extract (BPF) in diet-induced hyperlipemia in Wistar rats and in 237 patients suffering from hyperlipemia either associated or not with hyperglycaemia. BPF, given orally for 30days to both rats and patients, reduces total and LDL cholesterol levels (an effect accompanied by elevation of cHDL), triglyceride levels and by a significant decrease in blood glucose. Moreover, BPF inhibited HMG-CoA reductase activity and enhanced reactive vasodilation thus representing an efficient phytotherapeutic approach in combating hyperlipemic and hyperglycaemic disorders. [Copyright &y& Elsevier]

Objective: To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30-46 years, with BMI 30-43 kg/m(2).Research Design and Methods: Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 microg x ml(-1) x min(-1)) and sodium nitroprusside (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity.Results: We observed a significant reduction in BMI (from 33.1 +/- 4.2 to 27.5 +/- 4.5 kg/m(2), -16.9%, P < 0.0001) and in waist circumference (from 108.2 +/- 12.1 to 96.8 +/- 12.9 cm, -10.5%, P < 0.0001). Weight loss was also associated with a significant increase in ACh-stimulated forearm blood flow (FBF), from 7.4 +/- 2.8 to 12.9 +/- 3.4 ml. 100 ml(-1) of tissue x min(-1) kg/m(2) (P < 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation.Conclusions: Our data demonstrate that energy-restricted diet associated with physical activity induce a significant and clinically relevant improvement in ACh-stimulated vasodilation in obese healthy subjects. [ABSTRACT FROM AUTHOR]

Background: The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known., Methods: l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses., Results: Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 μmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 μmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032]., Conclusions: ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Aims: The relationship between resistance artery remodelling and endothelial function remains unknown. In this study, we assessed (i) the capacity of endothelial function and nitric oxide (NO) availability to provide more information on the severity of resistance artery remodelling than common cardiovascular risk factors in subjects at low or high cardiovascular risk; and (ii) differences between patterns of resistance artery remodelling associated with deficit of NO availability and with exposure to cardiovascular risk factors., Methods and Results: All analyses were conducted on the microvascular data set of the Italian Society for Arterial Hypertension (SIIA) that includes 356 patients with measures of small resistance arteries remodelling acquired with pressure or wire myography. Information on endothelial function and NO availability were also available in 116 patients. The European Heart Score (HS) was used to define the total cardiovascular risk of each patient. Endothelial function was inversely related with the severity of the resistance artery remodelling, and this association remained significant after adjustment for the HS. By contrast, the HS lost its significant association with the media-to-lumen (M/L) ratio and the media cross-sectional area after adjustment for endothelial function. The strength of these associations was similar in subjects at high and low cardiovascular risk. The addition of endothelial function and NO availability to the HS significantly improved the identification of subjects at more and less severe resistance artery remodelling. A severe deficit of NO availability was associated with hypertrophic remodelling, while a higher HS was more clearly associated with eutrophic remodelling., Conclusion: Resistance artery endothelial function and NO availability might represent important factors involved in resistance artery remodelling, independently from cardiovascular risk factor exposure., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiovascular disease (CVD) is associated with impairments in microvascular responsiveness. Therefore, reliably assessing microvascular function is clinically relevant. Thus, this study aimed to examine the reliability of the near-infrared spectroscopy (NIRS)-derived oxygen saturation (StO 2 ) reperfusion slope, a measure of microvascular responsiveness, to four different vascular occlusion tests (VOT) of different durations in young and older participants., Methods: Eight healthy young (29 ± 5 yr) and seven older (67 ± 4 yr) men participated in four NIRS combined with VOT (NIRS-VOT; 30 s, 1, 3, and 5 min) in the leg microvasculature on two visits separated by 1-2 weeks. Vascular responsiveness was determined by the StO 2 reperfusion slope. The coefficient of variation (CV), repeatability, reliability (ICC), and the limits of agreement (LOA) were calculated for the NIRS-derived reperfusion slopes for each occlusion duration and visit., Results: CV for the StO 2 reperfusion slope following 30 s, 1, 3 and 5 min of occlusion were 33 ± 29%, 19 ± 21%, 14 ± 12%, and 12 ± 10%, respectively. Repeatability values following 30 s, 1, 3 and 5 min occlusions were 20%, 1%, 4% and 21%, respectively. The ICC for the StO 2 reperfusion slopes for each occlusion duration were 0.29, 0.42, 0.84, and 0.88 following 30 s, 1, 3 and 5 min of occlusion, respectively. LOA values between visit 1 and 2 for occlusions were not different from zero. There were no age-related differences for all variables of the study., Conclusion: NIRS-derived StO 2 reperfusion slope, has good reliability across a range of occlusion durations with the strongest reliability during longer occlusion durations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aims: PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk., Methods: The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy. Our primary objective was to evaluate changes in carotid intima- media thickness (IMT). Secondary endpoints included changes in flow mediated vasodilation (FMD), inflammatory markers, triglycerides and cholesterol. Patients were evaluated at time 0, and after 3, 6 and 12 months., Results: We enrolled 119 patients, stratified into three different groups: patients receiving atazanavir/ritonavir boosted (ATV/r) based regimens, efavirenz (EFV) based regimens and darunavir/ritonavir boosted (DRV/r) based regimens. At baseline, advanced naïve patients showed a relevant deterioration of CV conditions in terms of traditional CV risk factors, endothelial dysfunction and serum biomarkers. During the 12-month follow up period, mean blood lipids significantly increased: total cholesterol from 159 to 190 mg/dL, HDL-C from 31 to 41 mg/dL, and LDL-C from 99 to 117 mg/dL. D-dimers steadily decreased (median level 624 at baseline and 214 at T3), whereas ICAM and VCAM consistently raised. DRV/r and ATV/r determined a more marked decrease of D-dimers as compared to EFV. Regarding the epi-aortic changes (IMT >1 mm or presence of atherosclerotic plaques), patients in the DRV/r group were at risk of developing pathological IMT during the study (OR 6.0, 95% CI 0.9-36.9), as compared to EFV ones., Conclusions: CV risk was elevated in advanced naïve patients and tended to remain high in the first year of therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aims: Lifestyle modification has been the mainstay of controlling childhood obesity and has proved to be effective in reducing cardiovascular risk factors. However, it is currently unknown whether the subclinical atherosclerotic changes associated with nonalcoholic fatty liver disease (NAFLD) in such population are reversible., Methods and Results: We analyzed changes of brachial flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), clinical, laboratory, and imaging data in 120 obese children with NAFLD, at the end of a 1-year intervention program with diet and physical exercise. The lifestyle intervention led to a significant mean decrease of body mass index (BMI)-standard deviation score (SDS), waist circumference (WC) and fat mass, along with diastolic blood pressure, triglycerides, liver enzymes, insulin, insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and high-sensitivity C-reactive protein. At the end of the study, FMD improved (P < 0.0001), while cIMT did not change significantly (P = 0.20). A significant decrease in hepatic fat content as measured by magnetic resonance imaging was also observed. Changes in FMD were inversely associated with changes in BMI-SDS, WC, total cholesterol, non-HDL cholesterol, liver enzymes, HOMA-IR, physical activity, and hepatic fat content. After including in the model all the significant variables as well as age, gender, pubertal status, and baseline FMD values, changes in FMD were significantly and independently associated with changes in WC and total cholesterol., Conclusion: Also in obese children with NAFLD arterial function may be restored by improving metabolic risk factors and reducing visceral adiposity following a 1-year lifestyle intervention., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Impaired flow-mediated dilation (FMD) is associated with cardiovascular risk factors and provides prognostic information. Despite the noninvasive nature of this technique, a major limitation to its widespread use is low reproducibility. The aim of this study was to evaluate impact of methodological standardization among different investigation sites on brachial artery FMD reproducibility., Methods: Seven Italian centers recruited 135 healthy volunteers, aged 20-60 years. FMD was assessed by high-resolution ultrasound equipped with a stereotactic probe-holding device. Certified sonographers recorded brachial artery scans at baseline (day 1a), 1 h after (day 1b), and 1 month later (day 30). Endothelium-independent vasodilation (EIVD) to sublingual glyceril-trinitrate was recorded at day 1 and day 30. FMD and EIVD were blindly evaluated at the coordinating center by an automated edge detection system. The intra-session (day 1a versus 1b) and inter-session (day 1a versus 30) coefficients of variation were calculated., Results: FMD was not significantly (P = 0.91) different at day 1a, day 1b and day 30 (6.52 ± 2.9, 6.42 ± 3.1, 6.57 ± 2.8%, respectively). The FMD intra-session coefficient of variation was 9.9 ± 8.4% (from 7.6 to 11.9% across centers). The FMD inter-session coefficient of variation was 12.9 ± 11.6% (from 11.6 to 16.1% across centers). Inter-session coefficient of variation for EIDV was 19.7 ± 16.8%., Conclusions: This study shows a homogeneous coefficient of variation for FMD among different centers. The inter-session coefficient of variation was similar to the intra-session coefficient of variation, representing the intrinsic FMD variability. We demonstrate for the first time that rigorous and standardized procedure may provide reproducible FMD assessment to study endothelial function in multicenter clinical trials.

A reduced coronary flow reserve (CFR) has been demonstrated in diabetes, but the underlying mechanisms are unknown. We assessed thermodilution-derived CFR after 5-min intravenous adenosine infusion through a pressure-temperature sensor-tipped wire in 30 coronary arteries without significant lumen reduction in 30 patients: 13 with and 17 without a history of diabetes. We determined CFR as the ratio of basal and hyperemic mean transit times (T(mn)); fractional flow reserve (FFR) as the ratio of distal and proximal pressures at maximal hyperemia to exclude local macrovascular disease; and an index of microvascular resistance (IMR) as the distal coronary pressure at maximal hyperemia divided by the inverse of the hyperemic T(mn). We also assessed insulin resistance by the homeostasis model assessment (HOMA) index. FFR was normal in all investigated arteries. CFR was significantly lower in diabetic vs. nondiabetic patients [median (interquartile range): 2.2 (1.4-3.2) vs. 4.1 (2.7-4.4); P = 0.02]. Basal T(mn) was lower in diabetic vs. nondiabetic subjects [median (interquartile range): 0.53 (0.25-0.71) vs. 0.64 (0.50-1.17); P = 0.04], while hyperemic T(mn) and IMR were similar. We found significant correlations at linear regression analysis between logCFR and the HOMA index (r(2) = 0.35; P = 0.0005) and between basal T(mn) and the HOMA index (r(2) = 0.44; P < 0.0001). In conclusion, compared with nondiabetic subjects, CFR is lower in patients with diabetes and epicardial coronary arteries free of severe stenosis, because of increased basal coronary flow, while hyperemic coronary flow is similar. Basal coronary flow relates to insulin resistance, suggesting a key role of cellular metabolism in the regulation of coronary blood flow.

Background and Objectives: Hemoglobin (Hb) is an important nitric oxide (NO) buffer and a modulator of NO bioavailability. In addition, endothelial dysfunction is common in hypertensive patients, suggesting a pivotal role of hemoglobin concentration ([Hb]) in vascular function. To investigate the potential role of [Hb] in endothelium-dependent vasodilation, the relationship between Hb and endothelial function was tested in a group of patients with essential hypertension., Design, Setting, Participants, & Measurements: In this retrospective study, 174 nonsmoking, uncomplicated, never-treated hypertensives were enrolled. Endothelium-dependent and -independent vasodilation was assessed by measurement of forearm blood flow response during intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside (SNP) using strain-gauge plethysmography. Correlation with established risk factors of endothelial dysfunction was performed., Results: The vasodilatory response to ACh was inversely (P < 0.001) related to [Hb], and this relationship was dose dependent (P < 0.001), being minimal at the lowest dose and maximal at the highest dose. No association was found between Hb and the vasodilatory response to SNP. In a multiple linear regression model adjusted for Framingham risk factors (age, sex, BP, cholesterol, body mass index, glucose) and emerging risk factors (homeostasis model assessment index, C-reactive protein, estimated GFR), [Hb] maintained a strong and independent link with the vasodilatory response to ACh (P < 0.001)., Conclusions: In a large group of nonsmoking untreated hypertensives, [Hb] is inversely related to forearm endothelium-dependent vasodilation. [Hb] should be taken into account, especially in conditions associated with low [Hb], when performing vascular function studies.

Background: Whether Doppler echocardiography allows reliable assessment of left ventricular (LV) diastolic parameters in multicenter studies is disputed., Methods: To assess interstudy reproducibility of Doppler echocardiographic parameters of LV filling and relaxation in multicenter setting, two laboratories assessed Doppler parameters of LV filling and relaxation twice within 24 hours in 56 participants. The study sample included hospitalized patients, clinically healthy outpatients, and healthy volunteers. All studies were performed according to a standardized protocol, and read by a single reader., Results: In the whole study sample the reproducibility of the assessment of the ratio between the peak velocities of the early (E) and late (A) LV filling waves (E/A), of the E wave deceleration time and atrial filling fraction, measured at the mitral valve leaflet tips, was good (intraclass correlation coefficients, rho: 0.89-0.76); the reproducibility performance of the same parameters measured at the mitral anulus was less good. The reproducibility of the assessment of the isovolumic relaxation time was good (rho: 0.81), and that of the E-wave propagation rate (E-Vp), by color M-mode, was excellent (rho: 0.96). The reproducibility of the ratio E wave peak velocity/E-Vp was also fairly good (rho: 0.87). The classification of E-Vp < 45 cm/s and E-Vp > or = 55 cm/s showed the highest between-study reliability performance (agreement index kappa = 0.92 and 0.83, respectively, both P < .001), followed by E/A at mitral leaflet tips >1.5 or <0.8 (kappa = 0.78 and 0.74, respectively, both P < .01), whereas the worst reliability performance was shown by isovolumic relaxation time < 60 milliseconds (kappa = 0.05, P = not significant)., Conclusions: Standardized procedures for imaging and readings allowed good reliability of serial Doppler echocardiographic evaluations of LV filling and relaxation parameters in multicenter setting.

In August 2003 an exceptional heatwave was recorded in Europe. The authors would like to describe 6 patients for which the intensivist was called as a consultant. All patients had a skin temperature >40 degrees C, central nervous system impairment, severe hyponatremia [124.7 mEq/l+/-5.6 (range 117-130)] and severe metabolic acidosis [BE -6.28 mEq/l+/-3.55 (range -9.5-0), HCO3- 17.75 mEq/l+/-3.25 (range 13.4-21.9)]. All patients had decreased platelet count and coagulation abnormalities. Two patients were hypertensive, 4 hypotensive. The heat stress due to the hot environment is characterized by systemic inflammatory response (as in severe sepsis) and hemodynamic impairment (as in hypovolemic shock). The association between hypovolemia and altered microcirculation leads to cell energy failure with metabolic lactic acidosis. The energy failure may induce structural irreversible damage of mitochondria. It is possible to differentiate, during energy failure, the irreversible or reversible condition by volume loading and vasoactive drugs challenge tests. In fact, if the hemodynamic correction is associated with normalization of SvO2 with disappearance of metabolic acidosis, this suggests hemodynamic impairment with intact mitochondrial function. In contrast, if the hemodynamic improvement with normalization of SvO2 is associated and acidosis persists, this suggests irreversible structural mitochondrial damage. The threshold between reversibility and irreversibility is likely time dependent, as suggested by biochemical consideration and by 2 large randomized studies on hemodynamic treatment. The comparative analysis of these 2 studies suggests that the time of intervention may lead to significant differences in mortality. In these patients time is essential.