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Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The risk of CVD disease in these patients appears to be far greater than in the general population and even after the stratification for age, gender, race and the presence or absence of diabetes, cardiovascular mortality in dialysis patients is about 10 to 20 times higher than in the general population. As a diagnostic categorie, CVD includes two principal conditions, i.e., cardiac complications stricto sensu, and vascular complications. These two complications are interrelated and arterial alterations can be the primary reason for the development of cardiac complications. Macrovascular disease develops rapidly in ESRD patients and is responsible for the high incidence of congestive heart failure, left ventricular hypertrophy (LVH), ischemic heart disease, sudden death, cerebrovascular accidents and peripheral artery diseases. Although the most frequent cause of these complications is occlusive lesions due to atheromatous plaques, many complications arise in ESRD patients in the absence of clinically significant atherosclerotic disease. Atherosclerosis, disease characterized by the presence of plaques, represents only one form of structural response to metabolic and hemodynamic alterations which interfere with the “natural” process of aging. The spectrum of arterial alterations in ESRD is broader, including large artery remodeling and changes in viscoelastic properties of arterial walls. The consequences of these alterations are different from those attibuted to plaques. While atheromatous lesions alter principally the conduit function of arteries and perfusion of tissue and organs downstream the lesions, non-atheromatous remodelling result principally in changes in dampening function of arteries, characterized by stiffening of arterial walls and with deleterious effects on the left ventricle and coronary perfusion. Arterial stiffening in ESRD patients is multifactorial at origin with extensive arterial calcifications as an important covariate.

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/highfat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P < 0.05) mean arterial pressure than SHR-C (148 3 vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium- dependent (acetylcholine) relaxation of mesenteric arteries was improved (P < 0.05) in SHR-HF vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P < 0.05). Phosphorylation of eNOSSer1177 increased (P < 0.05) in arteries from SHR-HF vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P < 0.05) in SHR-HF vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P < 0.05) phosphorylation of AktSer473 and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature. [ABSTRACT FROM AUTHOR]

In this article we trace the history of nitrites and nitrates from their discovery to their widespread use in clinical medicine. The cardiovascular actions and uses of these molecules [namely endogenous nitric oxide (NO) and exogenous nitroglycerin (NTG)] are described along with their similar mechanisms of action. The major vasodilating effect of both NO and NTG is on muscular arteries with less effect on arterioles and veins. By decreasing arterial stiffness, these agents reduce pulse wave velocity (PWV) and attenuate wave reflection amplitude and duration. These alterations in arterial properties and wave reflection characteristics reduce pulsatile left ventricular (LV) afterload (systolic and pulse blood pressure) and LV wasted energy, which decrease myocardial oxygen requirements. These agents can also increase arteriolar and venous caliber, which decreases distal resistance and increases venous capacity, respectively. These mechanistic effects help to explain the benefit of nitrites and nitrates in control of angina pectoris, congestive heart failure, and systolic hypertension. [ABSTRACT FROM AUTHOR]

Background The impact of whole-body vibration ( WBV) upon the cardiovascular system is receiving increasing attention. Despite numerous studies addressing the acute cardiovascular effects of WBV training, very little is known regarding long-term adaptations in healthy humans. Methods A 6-week training study, with a 70 days follow-up was designed to compare resistive exercise with or without super-imposed whole-body vibrations. Arterial diameter, intima media thickness and flow-mediated dilation ( FMD) were assessed by ultrasonography in the superficial femoral artery ( SFA), the brachial ( BA) and the carotid arteries ( CA). Results SFA resting diameter was increased from 6·22 mm ( SD = 0·69 mm) at baseline to 6·52 mm ( SD = 0·74 mm) at the end of the training period ( P = 0·03) with no difference between groups ( P = 0·48). Arterial wall thickness was significantly reduced by 4·3% ( SD = 11%) in the CA only ( P = 0·04). FMD was not affected by any of the interventions and in any of the investigated arteries. Conclusion To the best of our knowledge, this has been the first study to show that the superposition of vibration upon conventional resistance exercise does not have a specific effect upon long-term vascular adaptation in asymptomatic humans. Our findings seem to be at variance with the findings observed in a bed-rest setting. One possible explanation could be that the independently saturable effects of flow-mediated versus acceleration-related endothelial shear stresses on arterial structure and function differ between ambulatory and bed-rest conditions. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s)., Methods: Data was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models., Results: Of the 1,217 included women (age range 22-62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: -0.48%/10 years (95% CI:-0.65 to -0.30%/10 years), NGMD: -1.13%/10 years (-1.49 to -0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls ( p -values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD., Conclusion: In young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Janssen, Hooijschuur, Lopes van Balen, Morina-Shijaku, Spaan, Mulder, Hoeks, Reesink, van Kuijk, van't Hof, van Bussel, Spaanderman and Ghossein-Doha.)

Research shows that certain antihypertensives taken during midlife confer Alzheimer's disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-β (Aβ) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ℇ4 (APOE ℇ4) status and randomized to receive 5 mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aβ1-42 and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE ℇ4 carriers. While results did not show a treatment effect on CSF Aβ1-42 (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF Aβ1-42. While larger trials are needed to confirm our CSF Aβ results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine. [ABSTRACT FROM AUTHOR]

The decline in arterial function with aging is considered to be part of a physiological process reflecting elevated blood pressure. However, the extent and rate of this decline can be manipulated. Various types of exercise programs are recommended for improving and/or maintaining the arterial function in middle-aged to older individuals. To establish an optimal exercise prescription or guideline, it is necessary to determine the exercise mode, intensity, and frequency that provide the best outcomes. The puipose of this review is to introduce the potential of exercise for improving arterial function, and to review the exercise programs that can be used to reduce the risk of cardiovascular diseases. Regular endurance training has beneficial effects in arterial function in middle-age and older people. In contrast to endurance training, high-intensity resistance training decreases arterial compliance, which indicates reduced arterial function. In the case of low-intensity resistance training, eccentric resistance training, or combined endurance and resistance training, arterial function is unchanged or improved after a few of months training. To establish an optimal exercise prescription, it is also necessary to determine the training frequency. A recent study indicated that two days per week of training resulted in a decrease in the pulse wave velocity. These findings indicate that, in order to improve and/or maintain arterial function during the aging process, endurance exercise, relative low-intensity resistance training, or a combination of both types of training at least two days per week for several weeks, should be recommended for middle-aged and older individuals. [ABSTRACT FROM AUTHOR]

Background: Patients with uncomplicated diabetes have reduced left ventricular long-axis function, related to poor glycemic control and increased conduit arterial stiffness, with increased radial function. It is unknown if improved control of risk factors can reverse these subclinical changes. Patients and methods: We studied 27 patients with type 2 diabetes (18 men) 57 ± 1 months (mean ± SD) after an initial visit when they were compared with healthy age- and sex-matched controls. On both visits patients had detailed echocardiographic studies including tissue Doppler, noninvasive tests of conduit arterial function, and metabolic and lipid profiling. Results: Mean age at this second review was 63.4 ± 8.1 years; 48% of patients received insulin. Mean HbA1c had decreased by 13% to 8 ± 1.6% and cholesterol by 17% to 4.3 ± 1.3 mmol/L (both, P < 0.01), but long-axis systolic and early diastolic myocardial velocities had also declined, by 13% and 20%, respectively (both, P < 0.001). Body mass index had increased by 4%, arterial pulse pressure by 17% (both P < 0.01), and carotid arterial stiffness by 49% (P < 0.01). Fractional shortening (by 21%, P < 0.001), radial systolic velocity (by 13%, P < 0.05), and ejection fraction (by 9% to 68 ± 7%, P < 0.01) had all declined. Reductions in longitudinal function were best predicted by its baseline measurements, duration of diabetes, fasting triglycerides, and arterial stiffness (epsilon index). Conclusions: Despite improved diabetic control, subclinical left ventricular dysfunction progressed over 5 years. Radial compensation was reversed. Prevention of subclinical myocardial dysfunction in diabetes might require more intensive control of net cardiovascular risk. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the hypothesis that obesity, blood pressure (BP), and dietary habits (adherence to the Mediterranean diet) are related to indices of arterial stiffness (AS) in childhood. Two hundred and seventy-seven children aged 12 years were measured with the R6.5 Pulsecor® monitor, which performs measurements using an upper arm BP cuff held at above systolic pressure for a short time. The augmentation index (AI) in the brachial artery, the peripheral pulse pressure to central pulse pressure (PPP/CPP) ratio, and the reflected wave transit time to height ratio were used as indices of AS. The degree of adherence to the Mediterranean diet was assessed by the KIDMED index which includes 16 questions on specific dietary habits. Forty-three percent of the children were overweight and obese. Overweight and obese children had significantly lower PPP/CPP and KIDMED score in comparison to children with normal body mass index (BMI). In multivariate regression models, indices of AS were related to mean peripheral BP, heart rate, and height, while BMI had an independent correlation to PPP/CPP. The KIDMED index also had a negative correlation with AI independently of obesity. Conclusion: Obesity and adherence to the Mediterranean diet patterns are factors related independently to indices of AS even in 12-year-old children. [ABSTRACT FROM AUTHOR]

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133VEGFR2 and CD34VEGFR2 cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133VEGFR2 and CD34VEGFR2 cells, transfusion-dependent patients had significantly reduced CFUs compared with controls ( p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load ( p = 0.011). The CFUs correlated with brachial FMD ( p = 0.029) and arterial stiffness ( p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD ( p = 0.043) and arterial stiffness ( p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133VEGFR2 and CD34VEGFR2 cells. [ABSTRACT FROM AUTHOR]

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve ⩾15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients. [ABSTRACT FROM AUTHOR]

Myocardial oxygen consumption is increased by arterial stiffening. It is not known precisely how. This study aimed to evaluate the role of the incident and reflected pressure wave in raising myocardial oxygen demand. Central (aortic) pressure waveforms were generated from radial waveforms using a generalized transfer function in 1628 cardiology outpatients (1038 males and 590 females). Aortic waveforms were used to derive measures of incident and reflected waves, as well as to measure mean central systolic pressure (an indicator of systolic ventricular load), left ventricular ejection duration, and tension time index (a surrogate of myocardial oxygen demand) using validated techniques. Incident and reflected waves were measured using the conventional and an alternative method (aortic flow triangulation). Relationships were tested before and after correction for age, height, weight, heart rate, and mean arterial pressure using simple and multivariate linear regression models. Analyses were conducted separately by gender. In both genders (according to conventional or alternative methods of wave measurement), both the incident and reflected wave were strong predictors of tension time index (P<0.001). Both pressure waves raised the mean central systolic pressure (P<0.001). The reflected wave (P<0.001), unlike the incident wave (P>0.05), was also associated with a longer cardiac ejection duration. Tension time index (P<0.0001), mean central systolic pressure (P<0.001), and ejection duration (P<0.0001) were greater in women. Changes in arterial properties alter the nature of pressure wave propagation and predispose to cardiac ischemia (especially in women). [ABSTRACT FROM AUTHOR]

Aims: The present study was performed to investigate the contribution of NADPH oxidases (Nox) to superoxide formation in human renal proximal resistance arteries and to test whether superoxide formation contributes to acute vasoconstrictor responses and endothelium-dependent vasodilation in these vessels. [ABSTRACT FROM PUBLISHER]

Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 ± 2 yr; old, 71 ± 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and α-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = ∼3.0 and ∼6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = ∼7.0%) to match the young. KE training also improved exerciseinduced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young. [ABSTRACT FROM AUTHOR]

Aim: The relationship was investigated between endothelial progenitor cells (EPCs) level and arterial functions in the convalescence of Kawasaki disease (KD). Methods: Sixty-three children were divided into coronary artery lesion (CAL) group (group 1, n = 21), non-CAL group (group 2, n = 20) and control group (group 3, n = 22). EPCs were examined by flow cytometry and arterial functions (flow-mediated dilation [FMD], carotid artery stiffness index [SI]) were measured by ultrasound. Results: From group1 to group 3, FMD was 4.5%± 1.5%, 9.5%± 2.8% and 12.1%± 2.3% (p < 0.01 between any two groups); carotid artery SI was 4.10 ± 0.44, 3.81 ± 0.50 and 3.59 ± 0.46 (group 1 vs. group 2, p < 0.05; group 1 vs. group 3, p < 0.01; group 2 vs. group 3, p = 0.142) and the number of EPCs was 2.0 ± 0.6/μL, 4.2 ± 0.8/μL, 4.5 ± 0.7/μL (p < 0.01 for group1 vs. group 2 and group 1 vs. group 3; group 2 vs. group 3, p = 0.292). Multiple linear regressions analysis and correlation analysis identified that FMD and carotid artery SI were significant determinants of EPCs level and were all independently correlated with EPCs level. Conclusions: Our results indicate decreased EPCs are associated with arterial dysfunction in patients with CAL in the convalescence of KD. Our findings suggest EPCs may have a role in alteration of arterial functions. [ABSTRACT FROM AUTHOR]

Abstract: Background: The study was conducted to determine whether the use of a combined oral contraceptive (COC) or depot medroxyprogesterone acetate (DMPA) interferes with endothelial function. Study Design: The study was conducted on 100 women between the ages of 18 and 30 years. Fifty women had not used hormonal contraception (control group) for at least 12 months, 25 were current users of a COC (ethinylestradiol 30 mcg+levonorgestrel 150 mcg) and 25 were current users of DMPA (150 mg) for at least a 6-month period. All women were evaluated for brachial flow-mediated dilation (FMD), intima-media thickness, carotid distensibility and stiffness index, arterial pressure, body mass index, waist circumference, heart rate and lipid profile. Results: A significant difference in FMD was observed between the COC and control groups (6.4±2.2% vs. 8.7±3.4%, p<.01) and between the DMPA and control groups (6.2±2.1% vs. 8.7±3.4%, p<.01). The DMPA group had lower values of total cholesterol (TC) and low-density lipoprotein (LDL-C) than COC users and the control group (TC: DMPA=139.9±21.5 mg/dL vs. controls=167.1±29.2 mg/dL vs. COC=168.2±37.5, p=.001; LDL-C: DMPA=85.3±20.1 mg/dL vs. controls=102±24.5 mg/dL vs. COC=106.7±33.3 mg/dL, p=.01). The control group had higher levels of high-density lipoprotein (HDL-C) than the DMPA and COC groups (controls=52.4±14.1 mg/dL vs. DMPA=42.2±7.2 mg/dL vs. COC=45.4±9.1 mg/dL, p=.001). No significant differences were observed regarding the other variables. Conclusions: FMD was lower among COC and DMPA users, suggesting that these hormonal contraceptives may promote endothelial dysfunction. [Copyright &y& Elsevier]

We evaluated the effects of different training frequencies on arterial stiffness. 77 elderly women (mean 68.8 years and 7.0 SD) were divided into two training (1DW and 2DW) and a CONTROL group (n = 23). 1DW (n = 29) participated in 90-min group training once a week for 12 weeks, while 2DW (n = 25) attended twice a week. Each training program included recreational activities, six to eight resistance exercises for circuit training, and leg exercises for chair-based exercise. Brachial systolic and diastolic blood pressures and the brachial-to-ankle pulse-wave velocity (baPWV) were obtained in the supine position. Muscle strength and ventilatory threshold were also measured. After the training program, a reduction (P < 0.01) in baPWV was observed in 2DW (-7.8 +/- 7.0%) but not in 1DW (-1.5 +/- 7.5%) and CONTROL (-0.4 +/- 7.5%) without any changes in other measurements. The results suggest that, in order to improve arterial stiffness, an exercise frequency of at least twice a week is to be recommended for elderly. [ABSTRACT FROM AUTHOR]

Summary: Cardiovascular risk assessment more and more makes use of the diagnostic information hidden in the arterial waves propagating in the cardiovascular system. An important factor determining the morphology of the arterial waves is wave reflection which becomes more significant with increasing age and can be related to an augmented risk for cardiovascular disease. This paper describes three currently existing techniques to analyze wave reflections with their pros and cons to give the reader more insight into this still debated field. The first method is the augmentation index which only requires information on the pressure wave but although commonly used, hasn''t yet revealed any strong prognostic value in the general population, possibly due to the composite character of the index. More advanced and unequivocal methods exist, requiring information on both pressure and flow waves and thus having added value from a patho-physiological point of view: impedance analysis and wave intensity analysis. The former consists of decomposing the waves in the frequency domain, and has the disadvantage that the analysis is only valid in a linear system and requires the complex Fourier analysis. A more intuitive approach executed in the time domain is wave intensity analysis which doesn''t have the previously mentioned restrictions but is highly susceptible to noise. We will further discuss how according to our experience both the time and frequency domain methods can stand along each other and can be used in a complementary way. [Copyright &y& Elsevier]

Aim: To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits to arteries in uremic rats. Methods: 5/6-nephrectomized rats were treated (NX+Pari) or not treated (NX) with paricalcitol (200 ng/kg, thrice weekly) for 12 weeks. Aortic histology and isolated segments of the main and 2nd-order mesenteric arterial branches were studied. Results: Creatinine clearance was reduced by 54–61%, plasma phosphate increased 2.1- to 2.5-fold, and blood pressure by 40 mm Hg in both NX groups. PTH increased 13-fold in NX and 5-fold in NX+Pari rats. Calcification in aortic cross-sections increased from 2.1 to 7.1% after paricalcitol. In the large mesenteric artery, vasoconstriction to noradrenaline was reduced in NX+Pari rats. In the large and small arteries, vasorelaxation to acetylcholine was impaired in NX rats and unaffected by paricalcitol. In the small artery, paricalcitol increased nitric oxide synthase inhibition-resistant relaxation to acetylcholine, and maximal relaxation to levcromakalim. The small arteries of NX rats featured increased wall cross-sectional area, while paricalcitol further increased wall thickness and the wall:lumen ratio. Conclusion: Paricalcitol treatment showed both benefits and harmful effects in uremic rats: in the large artery vasoconstriction was reduced but calcification increased, while in the small artery vasorelaxation via potassium channels was moderately improved but hypertrophic remodeling was aggravated. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Deferasirox (ICL670) has been shown to have rapid accessibility to intracellular labile iron. We tested the hypothesis that oral deferasirox improves arterial dysfunction in patients with beta-thalassaemia major. Nineteen thalassaemia patients, aged 23 ± 7 years, with normal left ventricular (LV) function were treated with deferasirox at 25–35 mg/kg/d for 12 months. LV function, brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, and serum ferritin levels were determined at baseline prior to initiation, after 6 months and after 12 months of therapy. The baseline cardiovascular indices were compared with those of 17 age-matched controls. Longitudinal changes in patients during the treatment period were also determined. Compared with controls, patients had similar echocardiographic indices of LV function (all P > 0·05), while their baseline brachial FMD was reduced ( P < 0·001) and carotid stiffness increased ( P = 0·019). An increase in FMD ( P < 0·001) and a decrease in carotid stiffness ( P = 0·007) were found at 6 and 12 months follow-up. The stiffness index correlated inversely with FMD (r = −0·42, P = 0·001). Although there was an increase in ferritin level at 12 months (3303 ± 1185 ng/ml vs. 2714 ± 780 ng/ml at baseline, P = 0·006), no significant correlation existed between ferritin level and FMD or carotid stiffness. In conclusion, deferasirox therapy in thalassaemia patients is associated with improved arterial function. [ABSTRACT FROM AUTHOR]

Resting whole leg blood flow and vascular conductance decrease linearly with advancing age in healthy adult men. The potential role of age-related increases in oxidative stress in these changes is unknown. Resting leg blood flow during saline and ascorbic acid infusion was studied in 10 young (25 ± 1 yr) and 11 older (63 ± 2 yr) healthy normotensive men. Plasma oxidized LDL, a marker of oxidative stress, was greater in the older men (P < 0.05). Absolute resting femoral artery blood flow at baseline (iv saline control infusion) was 25% lower in the older men (238 ± 25 vs. 316 ± 38 mI/min; P < 0.05), and it was inversely related to plasma oxidized LDL (r = -0.56, P < 0.01) in all subjects. Infusion of supraphysiological concentrations of ascorbic acid increased femoral artery blood flow by 37% in the older men (to 327 ± 52 mI/min; P < 0.05), but not in the young men (352 ± 41 ml/min; P = 0.28), thus abolishing group differences (P = 0.72). Mean arterial blood pressure was greater in the older men at baseline (86 ± 4 vs. 78 ± 2 mmHg; P < 0.05), but it was unaffected by ascorbic acid infusion (P ≥ 0.70). As a result, the lower baseline femoral artery blood flow in the older men was mediated solely by a 32% lower femoral artery vascular conductance (P < 0.05). Baseline femoral vascular conductance also was inversely related to plasma oxidized LDL (r = -0.65, P < 0.01). Ascorbic acid increased femoral vascular conductance by 36% in the older men (P < 0.05) but not in the young men (P = 0.31). In conclusion, ascorbic acid infused at concentrations known to scavenge reactive oxygen species restores resting femoral artery blood flow in healthy older adult men by increasing vascular conductance. These results support the hypothesis that oxidative stress plays a major role in the reduced resting whole leg blood flow and increased leg vasoconstriction observed with aging in men. [ABSTRACT FROM AUTHOR]

Summary Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The risk of CVD disease in these patients appears to be far greater than in the general population and even after the stratification for age, gender, race and the presence or absence of diabetes, cardiovascular mortality in dialysis patients is about 10 to 20 times higher than in the general population. As a diagnostic categorie, CVD includes two principal conditions, i.e., cardiac complications stricto sensu , and vascular complications. These two complications are interrelated and arterial alterations can be the primary reason for the development of cardiac complications. Macrovascular disease develops rapidly in ESRD patients and is responsible for the high incidence of congestive heart failure, left ventricular hypertrophy (LVH), ischemic heart disease, sudden death, cerebrovascular accidents and peripheral artery diseases. Although the most frequent cause of these complications is occlusive lesions due to atheromatous plaques, many complications arise in ESRD patients in the absence of clinically significant atherosclerotic disease. Atherosclerosis, disease characterized by the presence of plaques, represents only one form of structural response to metabolic and hemodynamic alterations which interfere with the “natural” process of aging. The spectrum of arterial alterations in ESRD is broader, including large artery remodeling and changes in viscoelastic properties of arterial walls. The consequences of these alterations are different from those attibuted to plaques. While atheromatous lesions alter principally the conduit function of arteries and perfusion of tissue and organs downstream the lesions, non-atheromatous remodelling result principally in changes in dampening function of arteries, characterized by stiffening of arterial walls and with deleterious effects on the left ventricle and coronary perfusion. Arterial stiffening in ESRD patients is multifactorial at origin with extensive arterial calcifications as an important covariate. [ABSTRACT FROM AUTHOR]

Abstract: Metabolic syndrome includes most widely distributed clinical conditions such as obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation-sensitive genes at the sites of perturbed shear-stress. The aim of this study was to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and seed oil on the biological actions of nitric oxide (NO) and the arterial function in obese Zucker rats, a model of metabolic syndrome. Our results indicated that supplementation with PFE or PJ significantly decreased the expression of vascular inflammation markers, thrombospondin (TSP), and cytokine TGFβ1 (P <0.05), whereas seed oil supplementation had a significant effect only on TSP-1 expression (P <0.05). Plasma nitrate and nitrite (NO x ) levels were significantly increased by PFE and PJ (P <0.05). Furthermore, the effect of PFE in increasing endothelial NO synthase (eNOS) expression was comparable to that of PJ. These data highlight possible clinical applications of PFE in metabolic syndrome. [Copyright &y& Elsevier]

1. This commentary reviews and discusses the association between increased arterial stiffness and indices of glucose and insulin metabolism and diabetes mellitus (DM). 2. Diabetes mellitus is associated with increased cardiovascular events, is an established major independent risk factor for cardiovascular disease and is included in current risk assessment algorithms. Based on Framingham risk assessment, the incremental risk due to DM, at a given level of baseline risk in non-diabetics, is approximately equivalent to 10 years and, at any given level of other major risk factors, DM increases risk three- to fourfold. 3. Increased aortic stiffness has been shown to be an independent risk factor for both cardiovascular and overall mortality in high-risk groups and recently in the general population. Both DM1 and DM2 are associated with accelerated stiffening of the elastic arteries, over and above that associated with normal ageing, and DM can be considered as imparting added biological age and, thus, added cardiovascular risk. 4. Aortic stiffness provides a plausible mechanism relating diabetes to increase cardiovascular disease. 5. A proportion of the increased risk of cardiovascular events in DM is a sequel of stiff arteries. Direct measures of arterial stiffness, such as aortic pulse wave velocity, are likely to be better candidates than pulse wave analysis for refining interventions to improve outcomes in diabetes. [ABSTRACT FROM AUTHOR]

Objective: To assess the interchangeability of carotid tonometry and synthesized aorta pressure waveforms for estimating central systolic blood pressure (SBP) and augmentation index (AIx). Methods: Tonometry waveforms were acquired with a custom built hardware and software platform in 276 subjects (179 men/97 women; aged 45.5 ± 5.7 years; mean ± standard deviation) at the radial (Pwf,ra), brachial (Pwf,ba), and carotid artery (Pwf,ca). The Pwf,ba was calibrated using systolic (SBPba) and diastolic (DBPba) sphygmomanometer pressure. The DBPba and calculated mean (MAPba) brachial pressure were subsequently used for calibration of Pwf,ra and Pwf,ca. A central pressure waveform (Pwf,sao) was synthesized from Pwf,ra using a generalized pressure transfer function (TFF). The AIx and SBP were measured on Pwf,ra, Pwf,ca, and Pwf,sao. Results: The SBPra, SBPca, and SBPsao were 138.5 ± 16.8, 130.0 ± 16.2, and 131.1 ± 16.6 mm Hg, respectively. The SBPra correlated well with the SBPca (r = 0.93) and the SBPsao (r = 0.94), as did the SBPca and the SBPsao (r = 0.97) with a mean bias of 1.35 ± 3.90 mm Hg. The AIx derived from Pwf,ra, Pwf,ca, and Pwf,sao were −20.8% ± 14.5%, 12.4% ± 13.9%, and 20.0% ± 11.7%, respectively. The correlation between radial and carotid, and radial and central AIx was 0.72 and 0.94, respectively. The correlation between AIx derived from Pwf,ca and Pwf,sao was 0.75 with a bias of 11.0% ± 14% (all correlations P < .001). Conclusions: The use of a generalized TFF in combination with well-calibrated radial pressure curves yields estimates of SBP in good agreement with carotid tonometry. Although AIx derived from a measured radial pressure curve correlates surprisingly closely with AIx measured on a synthesized aortic pressure curve, the correlation with a directly measured AIx on carotid signals is relatively poor. [Copyright &y& Elsevier]

Hormone replacement therapy (HRT) has profound metabolic effects which impact on the cardiovascular system. These effects include changes in lipids and lipoproteins, glucose and insulin metabolism, haemostatic factors, inflammatory markers and body composition, as well as changes in vascular function and remodelling. Observational studies have demonstrated coronary heart disease benefit with HRT use, in contrast to the outcomes from randomised clinical trials. Lack of benefit in the latter studies appears to arise from early harm caused by HRT which outweighs any later benefit. Such early harm could result from transient increases in thrombogenesis and adverse vascular remodelling, which in turn could arise from starting doses of such therapies that are inappropriately high for the women's age. This problem is avoided in observational studies because the women are much younger and those same starting doses are appropriate for their age. Later benefit could result from oestrogen action on metabolic risk factors and direct arterial effects resulting in reduced atherogenesis. It is therefore possible that more appropriate HRT regimens could be devised to provide coronary benefit without risk of stroke, even in older age groups. Such strategies need to be tested in large clinical trials. The metabolic effects of HRTs are key to providing cardiovascular benefit. [ABSTRACT FROM AUTHOR]

Adult aging in humans is associated with marked and sustained increases in sympathetic nervous system (SNS) activity to several peripheral tissues, including the heart, the gut-liver circulation, and skeletal muscle. This chronic activation of the peripheral SNS likely is, at least in part, a primary response of the central nervous system to stimulate thermogenesis to prevent further fat storage in the face of increasing adiposity with aging. However, as has been proposed in obesity hypertension, this tonic activation of the peripheral SNS has a number of adverse secondary cardiovascular consequences. These include chronic reductions in leg blood flow and vascular conductance, increased tonic support of arterial blood pressure, reduced limb and systemic α-adrenergic vasoconstrictor responsiveness, impaired baroreflex buffering, large conduit artery hypertrophy, and decreased vascular and cardiac responsiveness to β-adrenergic stimulation. These effects of chronic age-associated SNS activation on the structure and function of the cardiovascular system, in turn, may have important implications for the maintenance of physiological function and homeostasis, as well as the risk of developing clinical cardiovascular and metabolic diseases in middle-aged and older adults. [ABSTRACT FROM AUTHOR]

: BackgroundAn increasing number of arterial function assessments are available, including small and large arterial elasticity (SAE/C2, LAE/C1), endothelial function as measured by flow mediated dilation (FMD), carotid intima–medial thickness (IMT), ankle brachial index (ABI), pulse pressure (PP), and pulse wave velocity (PWV). We have consecutively performed these measures in subjects with low and high vascular disease risks to assess the interrelationships.: Methods and resultsTwenty healthy subjects (HS) and 20 older subjects with type 2 diabetes mellitus (DM) were studied with all techniques at a single sitting by a single operator. In HS, C2 correlated with FMD (R = 0.577, P = .008), PWV (R = 0.522, P = .046), and ABI (R = 0.463, P = .04). There was no significant correlation of C1 and FMD or blood pressure (BP) measurements. In DM, C2 correlated with FMD (R = 0.443, P = .05), systolic BP (R = −0.553, P = .01), PP (R = −0.601, P = .005), and systemic vascular resistance (R = −0.577, P = .008). There was no significant correlation between anthropometric measures and arterial function measures in either group. The IMT was not correlated with any measure of arterial function in either group.: ConclusionsC2 assessed by pulse wave analysis correlated with endothelial function measured by FMD in young apparently healthy subjects and older subjects with type 2 diabetes. Systolic BP and PP correlated with C2 and FMD in older diabetic subjects but not healthy subjects. The interrelationships between arterial function measures are different in high and low risk populations. This variability needs to be considered when applying these techniques to individuals in different populations. [Copyright &y& Elsevier]

Background: A reduction of heart rate (HR) by surgical means or pharmacological agents affects the progression and/or regression of atherosclerotic lesions. Nevertheless, the effect of bradycardia per se on large artery structure and function has never been investigated in rat models of hypertension. Methods: Four groups of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were treated for 28 days either by placebo or by the selective HR-reducing agent ivabradine (8.4 mg/kg/day), a novel compound devoid of inotropic or vasodilating effects and without direct action on the autonomic nervous system. At the end of the follow-up period, intra-arterial blood pressure, carotid pulsatile arterial hemodynamics (echo tracking techniques) and the medial cross-sectional area (MCSA) of the aorta and the carotid artery were determined. Results: In conscious animals, chronic administration of ivabradine significantly reduced HR by 26–30% with no change in tail systolic blood pressure. In anesthetized animals, the decrease in HR and the subsequent increase in the diastolic period were responsible for a decrease in diastolic blood pressure. At the site of the large arteries, ivabradine produced a decrease in the MCSA of the thoracic but not of the abdominal aorta, as well as an increase in pulsatile change of the carotid diameter without change in the isobaric distensibility and MCSA. The changes in pulsatile diameter were significantly larger in WKY rats than in SHRs. Conclusion: In normotensive and mainly in SHRs, selective chronic HR reduction by ivabradine is associated with alterations in large arteries involving an aortic antihypertrophic effect.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Nephrotic syndrome (NS) is associated with an increased risk of cardiovascular disease (CVD). We have shown previously that endothelial function, measured by post‐ischaemic flow‐mediated dilatation (FMD) of the brachial artery, is impaired in NS. In this study our aim was to assess the potential roles of insulin resistance, plasma non‐esterified fatty acids (NEFAs) and inflammation in endothelial dysfunction in NS patients. [ABSTRACT FROM PUBLISHER]

Aims/hypothesis. Type I (insulin-dependent) diabetes mellitus is accompanied by reduced arterial distensibility and increased arterial wall thickness even in normotensive subjects with no micro-macrovascular complications. It is not known whether, and how fast, these subclinical markers of vascular damage develop over time. Methods. We measured arterial wall distensibility in radial, common carotid artery and abdominal aorta in 60 normotensive patients (aged 35.0 ± 1.2 years, means ± SE) with Type I diabetes with no microvascular or macrovascular complications and in 20 healthy control subjects matched for age. Arterial distensibility was determined by continuous measurements of arterial diameter through echotracking techniques and by using either the Langewouters (radial artery) or the Reneman formula (carotid artery and aorta). The same echotracking techniques allowed us to ascertain the radial and carotid artery wall thickness. Data were collected before and after 23 ± 1 months. Results. In the first study, carotid artery distensibility was similar but radial artey and aortic distensibility was less (p < 0.01) in patients with diabetes than in control subjects (–39 % and 25 % respectively). This was accompanied by an increase (p < 0.01) in both radial (42 %) and carotid artery wall thickness (46 %). After 23 ± 1 months diabetic subjects showed a further reduction in arterial distensibility (radial–12 %, p < 0.05; carotid–8 %, NS; aorta–20 % p < 0.05) and an increase in arterial wall thickness (radial + 15 %; carotid 14 %, p < 0,05). No change in distensibility and wall thickness values occurred in control subjects. Conclusion/interpretation. The early reduction in arterial distensibility and increase in arterial wall thickness characterizing uncomplicated normotensive Type I diabetes patients shows a measurable worsening over the short term. [Diabetologia (2001) 44: 203–208] [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare, auto-immune disease with variably progressive fibrosis of the skin and internal organs, as well as vascular dysfunction. Recently, we demonstrated a decrement in exercising skeletal muscle blood flow and endothelium-dependent vasodilation in SSc, but the mechanisms responsible for these impairments have not been investigated. Thus, we sought to determine if acute administration of tetrahydrobiopterin (BH 4 ), an essential cofactor for endothelial nitric oxide synthase (eNOS), would improve hyperemia and brachial artery vasodilation during progressive handgrip exercise in SSc. Thirteen patients with SSc (63 ± 11 years) participated in this placebo-controlled, randomized, double-blind, crossover study. Tetrahydrobiopterin (10 mg/kg) administration resulted in a ~4-fold increase in circulating BH 4 concentrations ( P < 0.05). Cardiovascular variables at rest were unaffected by BH 4 ( P > 0.05). During handgrip exercise, BH 4 administration increased brachial artery blood flow (placebo: 200 ± 87; BH 4 : 261 ± 115 ml/min; P < 0.05) and vascular conductance (placebo: 2.0 ± 0.8; BH 4 : 2.5 ± 1.0 ml/min/mmHg; P < 0.05), indicating augmented resistance artery vasodilation. Tetrahydrobiopterin administration also increased brachial artery vasodilation in response to exercise (placebo: 12 ± 6; BH 4 : 17 ± 7%; P < 0.05), resulting in a significant upward shift in the slope relationship between Δ brachial artery vasodilation and Δ shear rate (placebo: 0.030 ± 0.007; BH 4 : 0.047 ± 0.007; P < 0.05) that indicates augmented sensitivity of the brachial artery to vasodilate to the sustained elevations in shear rate during handgrip exercise. These results demonstrate the efficacy of acute BH 4 administration to improve both resistance and conduit vessel endothelial function in SSc, suggesting that eNOS recoupling may be an effective strategy for improving vasodilatory capacity in this patient group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Machin, Clifton, Wray, Frech and Donato.)