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TMAO is elevated in individuals with cardiometabolic diseases, but it is unknown whether the metabolite is a biomarker of concern in healthy individuals. We conducted a cross-sectional study in metabolically healthy adults aged 18-66 years with BMI 18-44 kg/m2 and assessed the relationship between TMAO and diet, the fecal microbiome, and cardiometabolic risk factors. TMAO was measured in fasted plasma samples by liquid chromatography mass spectrometry. The fecal microbiome was assessed by 16S ribosomal RNA sequencing and recent food intake was captured by multiple ASA24 dietary recalls. Endothelial function was assessed via EndoPAT. Descriptive statistics were computed by fasting plasma TMAO tertiles and evaluated by ANOVA and Tukey's post-hoc test. Multiple linear regression was used to assess the relationship between plasma TMAO and dietary food intake and metabolic health parameters. TMAO concentrations were not associated with average intake of animal protein foods, fruits, vegetables, dairy, or grains. TMAO was related to the fecal microbiome and the genera Butyribrio, Roseburia, Coprobaciullus, and Catenibacterium were enriched in individuals in the lowest versus the highest TMAO tertile. TMAO was positively associated with α-diversity and compositional differences were identified between groups. TMAO was not associated with classic cardiovascular risk factors in the healthy cohort. Similarly, endothelial function was not related to fasting TMAO, whereas the inflammatory marker TNF-α was significantly associated. Fasting plasma TMAO may not be a metabolite of concern in generally healthy adults unmedicated for chronic disease. Prospective studies in healthy individuals are necessary.

Abstract Background This study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D). Methods Patients aged ≥ 12 years completed a clinical–epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays. Results Data were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6–15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI. Conclusions In our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D.

Kidney transplantation (KTx) is the preferred form of renal replacement therapy in chronic kidney disease (CKD) patients, owing to increased quality of life and reduced mortality when compared to chronic dialysis. Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk. [ABSTRACT FROM AUTHOR]

High-intensity interval exercise (HIIE) is more effective than moderate-intensity interval exercise (MICE) for improving macrovascular function (e.g., flow-mediated dilation), but less is known regarding the effect of HIIE on microvascular function. We used peripheral artery tonometry to measure the reactive hyperemia index (RHI) and examine the acute effects of HIIE and MICE on microvascular function.Ten healthy participants (50% men, age: 26 ± 5 years, mass: 75.6 ± 15.1 kg, height: 170 ± 10 cm, body mass index: 26.0 ± 3.1 kg∙m–2) performed single bouts of HIIE and MICE cycling on separate occasions. The MICE protocol was 20 min at 60% of maximum power output. The HIIE protocol was a 12-min warm up at 50% of maximum power output immediately followed by an 8-min Tabata protocol where participants alternated between cycling at ⩾ 100% max power (20 sec) and rest (10 sec). The RHI was measured before, immediately after, and 1 h after exercise and compared by two-way repeated measures analysis of variance (condition [MICE, HIIE] and time [pre-, post-, and 1-h postexercise]).Compared to baseline, RHI increased 1 h after MICE only (p = 0.02). Heart rate was higher during MICE at 5 and 10 min (p = 0.02) and higher during HIIE at min 20 (p < 0.01).Within a sample of healthy adults, the RHI was improved 1 h after a single session of MICE but not HIIE. Future research is needed to determine the significance of the differential effects of exercise regimens on the macro- and microvasculature. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate whether soluble vascular cytoadhesive molecule-1 (sVCAM-1), intracellular cytoadhesive molecule-1 (sICAM-1), and endothelial function as assessed by EndoPat outweighed traditional risk factors for the presence of diabetic retinopathy (DR) in patients with type 1 diabetes (T1D). Methods: Patients aged ≥ 12 years completed a clinical–epidemiological questionnaire. Fasting venous blood samples were obtained (lipid profile, glycemic control, and C-reactive protein levels). Vascular reactivity was assessed via peripheral arterial tonometry performed by supplying the reactive hyperemia index (RHI) through the EndoPAT device. sVCAM-1 and sICAM-1 levels were measured using multiplex assays. Results: Data were obtained from 187 patients (51.3% female), aged 32 ± 13 years with a disease duration of 14 (6–15) years and mean hemoglobin A1c (HbA1c) of 9.1% ± 2.1%. After adjustments were made, age, HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function were found to be associated with DR. No association was noted with sVCAM-1 and sICAM-1 levels and RHI. Conclusions: In our sample, sVCAM-1, sICAM and EndoPAT did not outweigh the traditional DR risk factors, such as age, high HbA1c, arterial blood pressure, and use of drugs that could interfere with endothelial function and are significantly associated with DR. Further prospective studies should evaluate if markers of endothelial dysfunction could predict diabetes-related micro and macrovascular complications in T1D. [ABSTRACT FROM AUTHOR]

Abstract Background The effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD. Methods In a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR)

Kidney transplantation (KTx) is the preferred form of renal replacement therapy in chronic kidney disease (CKD) patients, owing to increased quality of life and reduced mortality when compared to chronic dialysis. Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk.

Background: The long-term association between physical activity and endothelial function has not previously been investigated in patients with type 2 diabetes. Therefore, we aimed to evaluate the relationship between physical activity and endothelial function, assessed by peripheral arterial tonometry, in patients with type 2 diabetes and non-diabetic controls after 5 years of follow-up. Methods: We included 51 patients with newly diagnosed type 2 diabetes and 53 sex- and age matched controls. Participants underwent baseline clinical characterization including objective measurement of physical activity level using accelerometery. After 5 years of follow-up, participants were re-examined, and endothelial function was assessed as natural logarithm of reactive hyperemia index (lnRHI). Results: Physical activity at baseline was associated with lnRHI after 5 years of follow-up in both patients with type 2 diabetes and controls. An increase of 1 standard deviation (SD) in daytime physical activity corresponded to a 6.7 % increase in RHI (95 % confidence interval: 1.1;12.5 %, p = 0.02). We found no difference in lnRHI between patients with diabetes and controls (0.67 ± 0.29 vs. 0.73 ± 0.31, p = 0.28). Conclusions: Daytime physical activity is associated with endothelial function after 5 years of follow-up in patients with type 2 diabetes and controls. [ABSTRACT FROM AUTHOR]

Aims: Better understanding of the timeline and risk factors for the appearance of complications in pediatric Type‐1‐diabetes is key for developing prevention strategies. We studied endothelial markers and their determinants in adolescents with Type‐1‐diabetes at different time points from diagnosis. Methods: A cross‐sectional study of 58 adolescents, mean age 15.0 ± 2.4 years; 20 with recent‐onset Type‐1‐diabetes, 20 with over 7 years of Type‐1‐diabetes and 18 controls. Clinical and biochemical data were collected. Fingertip arterial reactive hyperemia (EndoPAT) and carotid intima‐media‐thickness (cIMT) were measured to assess endothelial function and structure. Results: Compared to controls, individuals with prolonged Type‐1‐diabetes had higher mean cIMT (0.49 ± 0.07 mm vs. 0.43 ± 0.05 mm p = 0.021) and maximal cIMT (0.61 ± 0.08 mm 0.52 ± 0.08 mm, p = 0.025). Endothelin‐1 levels were significantly lower in subjects with prolonged Type‐1‐diabetes (1.2 ± 1.0 pg/ml) compared to controls (3.0 ± 1.7, p = 0.008 pg/ml); they negatively correlated with the mean cIMT (c = − 0.291, p = 0.031) and mean 6 months hemoglobin A1c (c = − 0.301, p = 0.022) and positively correlated with mean c‐peptide levels (c = 0.356, p = 0.006) and the weekly exercise time (c = 0.485, p < 0.001). Endothelin‐1 levels did not correlate with EndoPAT results. Conclusions: Our results suggest that the early years after the diagnosis of Type‐1‐diabetes are an important window for prevention of arterial damage in the pediatric population. The trajectories of relationships of Endothelin‐1 with metabolic and vascular measures were opposite from the anticipated, yet consistent. Endothelin‐1 related indirectly to adverse measures and directly to favorable measures. Decreased Endothelin‐1 levels might reflect early stages in endothelial impairment in Type‐1‐diabetes, yet its' exact role in the development of complications is yet to be unraveled. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study is to determine whether there is correlation between endothelial function and skeletal muscle function measured by hand grip strength in elderly women. Methods This cross‐sectional study used data of NAMGARAM‐2 cohort. The NAMGARAM‐2 cohort consisted of a group of people living in three rural communities. They were enrolled for studies on activity limitation due to age‐related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. They were residents aged 40 years or older. They agreed to participate in this cohort from March 2016 to May 2017. Peripheral endothelial function was assessed by reactive hyperaemia‐peripheral arterial tonometry using EndoPAT2000 system. Hand grip strength was measured using a digital hand dynamometer. Results Endothelial function index assessed by EndoPAT was worse in the low grip strength group than that in the normal group of elderly women (1.54 ± 0.51 in the low grip strength group vs. 1.77 ± 0.67 in the normal group, P = 0.003). There was a positive correlation between hand grip strength and endothelial function (r = 0.176, P = 0.007). On stepwise multivariate analysis, endothelial dysfunction (reactive hyperaemia‐peripheral arterial tonometry index

Background: The effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD. Methods: In a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia. Results: LnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62–0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40–0.81; P = 0.34). Conclusions: CMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed. [ABSTRACT FROM AUTHOR]

Aging is associated with reductions in endothelial function, observations primarily reported using brachial artery ultrasound. There is growing interest in the use of peripheral artery tonometry (PAT) of microvessels in the fingertip to assess endothelial function because it is less technically demanding and has a high sensitivity and specificity for assessing coronary endothelial function. Moreover, similar to brachial artery flow-mediated dilation (FMD), PAT predicts cardiovascular disease outcomes. However, the relationship between PAT and FMD have yet to be examined in the context of aging. To address this question, reactive hyperemic index (RHI) using EndoPAT and FMD using brachial artery ultrasound were assessed after 5 min of forearm ischemia in 20 younger (18-40 yr old; 29 ± 4 yr) and 20 older (60-75 yr old; 65 ± 4 yr) healthy adult men. Higher values of both FMD and RHI indicate better endothelial function. Endothelial function assessed via brachial artery FMD was lower in older (4.8 ± 2.1%), compared with younger (7.5 ± 1.6%) men (P < 0.001). In contrast, the RHI assessed via PAT was greater in older (2.2 ± 0.6), compared with younger (1.8 ± 0.5) men (P = 0.014). FMD and RHI were not correlated (r = -0.15; P = 0.35). We conclude that PAT may not be an appropriate measure to evaluate age-associated changes in endothelial function. [ABSTRACT FROM AUTHOR]

Context: Gonadotropin-releasing hormone agonist (GnRH-a) serves as an alternative to human chorionic gonadotropin (hCG) to trigger final oocyte maturation, while it significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS), probably by attenuating vascular/endothelial activation.Objectives: The objectives of this work are to compare the effect of different modes of final follicular maturation (hCG vs GnRH-a) following ovarian stimulation (OS) for in vitro fertilization (IVF) on endothelial function.Design and Setting: A prospective cohort study was conducted at a tertiary medical center.Participants: Patients age 37 years or younger, undergoing OS for IVF, were allocated into 2 groups according to the type of final follicle maturation: the hCG group (n = 7) or the GnRH-a group (n = 8).Intervention: Endothelial function was assessed by measurement of the peripheral arterial tonometry in reaction to temporary ischemia at 3 study points: day 3 of menstrual cycle (day 0), day of hCG/GnRH-a administration (day trigger) and day of oocyte pick-up (day OPU). The ratio of arterial tonometry readings before and after ischemia is called the reactive hyperemia index (RHI). Decreased RHI (< 1.67) indicates endothelial dysfunction.Main Outcome Measures: The main outcomes measures of this study included endothelial function at 3 study points during OS with different modes of triggering final follicular maturation.Results: The mean RHI values at day 0 were within the normal range for all patients and comparable between both groups (hCG: 1.7 ± 0.3 vs GnRH-a: 1.79 ± 0.4, P = .6). All patients presented a decrease in RHI values on day trigger, which did not differ between the 2 groups (1.62 ± 0.3 vs 1.4 ± 0.2, respectively, P = .2). However, the hCG group demonstrated a further decrease in RHI on day OPU, whereas patients who received GnRH-a had restored normal endothelial function reflected by increased RHI values (1.4 ± 0.2 vs 1.75 ± 0.2, respectively, P = .03).Conclusions: Triggering final follicular maturation with GnRH-a restored normal endothelial function, whereas hCG trigger resulted in a decrease in endothelial function. [ABSTRACT FROM AUTHOR]

In women who conceived with or without assisted reproduction, we evaluated endothelial function by EndoPAT [reactive hyperemia index (RHI)], circulating numbers of endothelial cells (CEC) and endothelial progenitor cells (EPC), and their function before during and after pregnancy. In vitro fertilization (IVF) pregnancies were stratified by method of conception and corpus luteum (CL) number— controlled ovarian stimulation (>1 CL) or programmed (0 CL) cycles and spontaneous singleton pregnancies (1 CL). We observed 1) comparable gestational decline of RHI in the three participant groups secondary to gestational rise of baseline preocclusion pulse-wave amplitude (PWA) incorporated into the RHI calculation by EndoPAT software; 2) progressive rise in “normalized” RHI throughout pregnancy (calculated by substituting prepregnancy baseline preocclusion PWA into the RHI equation), greater in spontaneous conception vs. IVF cohorts; 3) similar gestational increase of maximum PWA and time to maximum PWA after the ischemia stimulus among the three participant groups; 4) modest gestational increase of ischemia rsponse (reactive hyperemia) in the spontaneous conception group and no change or significant decline, respectively, in women who conceived using programmed or controlled ovarian stimulation cycles; 5) enhanced basal nitric oxide production by early (primitive) outgrowth EPC during pregnancy in women who conceived spontaneously, but not through IVF; and 6) gestational increase in CEC in all three participant cohorts, more pronounced in women who conceived by IVF using programmed cycles. On balance, the evidence supported enhanced endothelial function during pregnancy in spontaneous conceptions but less so in IVF pregnancies using either controlled ovarian stimulation or programmed cycles. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the effects of a 12-wk in-home self-monitored physical activity (PA) program targeting a combination of lifestyle PA program on changes in endothelial reactivity, arterial stiffness, sedentary behaviors, and upright and stepping activities in individuals with asymptomatic peripheral arterial disease (APAD). Methods: Participants (n = 38) with APAD (ages 52–87 yr) were randomized to attention control (AC) or a PA sedentary reduction (PASR) group using an interactive online 3-month program focusing on increasing lifestyle PA and decreasing sedentary behaviors. The ActivPal™ PA monitor was used to measure postural and stepping parameters. Endothelial reactivity (peripheral arterial tone–reactive hyperemia index [PAT-RHI]) and augmentation index (AIx) were measured using the EndoPAT™ system at baseline and 3 months. Results: The PASR group significantly decreased daily sit/lie hours (−0.80 ± 0.87 vs 0.18 ± 0.77 P = 0.001), increased sit-to-stand transitions per day (7.1 ± 10.5 vs −1.4 ± 5.71, P < 0.001), and increased daily step counts (2814 ± 1753 vs 742 ± 1321, P < 0.001). The PASR group also increased steps per day accumulated within specific cadence bands 61–80 steps per minute (1252 ± 447 vs 177 ± 359, P < 0.001), 81–100 steps per minute band (919 ± 511 vs −98 ± 697, P < 0.001), and within the 101–120 steps per minute band (415 ± 625 vs −327 ± 467, P < 0.001) versus the AC group. PAT-RHI significantly increased in the PASR group (0.179 ± 0.180 vs 0.0.044 ± 0.101, P = 0.019), whereas no significant changes were observed in PAT-AIx. Conclusions: Modest improvements in microvascular reactivity, PA, sedentary behavior, but not arterial stiffness were demonstrated after a 12-wk intervention targeting sedentary behavior reduction and increased lifestyle PA in individuals with APAD. [ABSTRACT FROM AUTHOR]

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RHPAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04). Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine whether there is correlation between endothelial function and skeletal muscle function measured by hand grip strength in elderly women. Methods: This cross‐sectional study used data of NAMGARAM‐2 cohort. The NAMGARAM‐2 cohort consisted of a group of people living in three rural communities. They were enrolled for studies on activity limitation due to age‐related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. They were residents aged 40 years or older. They agreed to participate in this cohort from March 2016 to May 2017. Peripheral endothelial function was assessed by reactive hyperaemia‐peripheral arterial tonometry using EndoPAT2000 system. Hand grip strength was measured using a digital hand dynamometer. Results: Endothelial function index assessed by EndoPAT was worse in the low grip strength group than that in the normal group of elderly women (1.54 ± 0.51 in the low grip strength group vs. 1.77 ± 0.67 in the normal group, P = 0.003). There was a positive correlation between hand grip strength and endothelial function (r = 0.176, P = 0.007). On stepwise multivariate analysis, endothelial dysfunction (reactive hyperaemia‐peripheral arterial tonometry index < 1.67) significantly increased the risk of low hand grip strength (odds ratio = 2.019; 95% confidence interval = 1.107–3.682; P = 0.022). Conclusions: Endothelial function and skeletal muscle strength had a significant correlation in elderly women, providing additional support for the relevant role of vascular system in sarcopenia. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular parameters characterizing blood pressure (BP), heart rate (HR), endothelial function and arterial stiffness predict cerebro-cardiovascular events (CCVE) in the general population. Considering the paucity of data in stroke patients, we assessed these parameters as potential predictors of recurrent CCVE at acute stroke stroke., Patients and Methods: This is a secondary outcome analysis of a prospective observational longitudinal Sleep Deficiency & Stroke Outcome Study (ClinicalTrials.gov Identifier: NCT02559739). The study consecutively recruited acute ischemic stroke patients. Cardiovascular parameters (blood pressure variability [BPV], heart rate variability [HRV], endothelial function, and arterial stiffness) were assessed within the first week post-stroke. Future CCVE were recorded over a 3-year follow-up. Multivariate Cox regression analysis was used to investigate the prognostic value of 48 cardiovascular parameters regarding CCVE risk., Results: Out of 447 recruited patients, 359 were included in this analysis. 20% of patients developed a future CCVE. A high variability of systolic BP ( n  = 333) and nocturnal HR (non-linear parameters; n  = 187) at acute stroke predicted CCVE risk after adjustment for demographic parameters, cardiovascular risk factors and mean BP or HR, respectively. Endothelial dysfunction ( n  = 105) at acute stroke predicted CCVE risk after adjustment for age and sex, but not after adjustment for cardiovascular risk factors. Diurnal HR and arterial stiffness at acute stroke were not associated with CCVE risk., Conclusion: High blood pressure variability, high nocturnal HRV and endothelial function contribute to the risk for future CCVE after stroke., 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., (© 2023 Filchenko, Mürner, Dekkers, Baillieul, Duss, Brill, Horvarth, Heldner, Rexhaj, Bernasconi, Bassetti and Schmidt.)

Beneficial effects of flavonoid-rich black and green tea on macrocirculation have been well established. Theaflavins are unique to black tea as they are formed from catechins during the enzymatic oxidation of tea leaves. The study was performed to gain more insight into the effects of theaflavins on microcirculation and to compare effects with another important flavonoid class, the green tea derived catechins, which have been reported to improve vascular function. Twenty-four healthy subjects were included in a double-blind, placebo-controlled, randomised, cross-over study. On six different days, subjects received capsules with a single dose of catechins (500 mg), four varying doses of theaflavins (100 to 500 mg) or placebo. Microcirculation was assessed after each treatment by Pulse Amplitude Tonometry (EndoPAT) at baseline and 2, 4 and 6 h after test product intake. The EndoPAT reactive hyperemia response was improved by 500 mg catechins (reactive hyperemia index (RHI): 0.2; p = 0.04) and by 500 mg theaflavins (RHI: 0.19; p = 0.06) compared to placebo. Also, 300 mg theaflavins increased the RHI (0.28; p = 0.02), but no effects were observed at lower doses. The study suggests moderate effects of single doses of catechins and theaflavins on peripheral microcirculation.

Abstract Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean change in systolic pressure of 10 mmHg (P-value < 0.01; diastolic arterial pressure and mean arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value < 0.01). Reactive hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P-value < 0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was reduced by 49,96 ± 31 ms, P-value < 0.05 and early diastolic tissue Doppler velocity (e′) by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we did not observe events of grade 3 or 4. We observe correlation between events and endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05–5.804, P- value: 0.038 for RHI<1.67; OR 1,4, CI 95%0.99–2.56, P- value: 0.04 for age). Our results suggest that therapy with carfilzomib when used as first line therapy is responsible for increase in systemic blood pressure, alteration of endothelium-mediated vascular dilatation and early myocardial diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To compare vascular endothelial function between dipping (D) and nondipping (ND) patterns in patients with and without mild obstructive sleep apnea (OSA) using EndoPAT, a test of reactive hyperemia used to assess peripheral vascular endothelial function.Methods: The sample consisted of individuals of both genders between 18 and 65 years of age with a body mass index (BMI) of ≤35 kg/m2 and apnea/hypopnea index (AHI) of ≤15. The nondipping pattern was considered present when the dip of nocturnal blood pressure (NBP) was <10%. All of the sample underwent clinical and physical evaluation, full polysomnography, 24-hour ambulatory blood pressure monitoring, and EndoPAT evaluation. A generalized linear model was used for statistical analysis.Results: The sample comprised 120 individuals, 35 in the control group and 85 in the mild OSA group. Four groups were formed: Control-ND, Control-D, Mild OSA-ND, and Mild OSA-D according to nocturnal ABPM patterns. The frequency of nondipping was (34.1%) in the Mild OSA group and (17.1%) in the Control group (p = 0.07). The Mild OSA-ND group had a higher augmentation index (AIx) than the Mild OSA-D group. Regression analysis showed that male gender, higher age, and nondipping status were associated with these results, whereas oxygen desaturation index (ODI) and AHI did not. With respect to the reactive hyperemia index (RHI), the Mild OSA-D group had lower values compared to the Control-ND group, but an association with OSA was not confirmed in the regression model.Conclusion: Nondipping status was associated with a worse augmentation index in both groups independently of AHI or oxygen desaturation index. Male gender, higher age, and nondipping status were associated with augmentation index. ClinicalTrials.gov Identifier: NCT01461486. [ABSTRACT FROM AUTHOR]

BackgroundDecreased endothelial function (EF) may be a prognostic marker for stroke. Measuring pharmacological effects on EF may be of interest in the development of personalized medicine for stroke prevention. In this study, we assessed the reliability of repeated EF measurements using a pulse amplitude tonometry technology in acute stroke patients. Similarly, reliability was tested in healthy subjects devoid of vascular disease to estimate reactivity and reliability in a younger non-stroke population.Materials and methodsEF was assessed using the EndoPAT2000 in 20 healthy volunteers (men 50%, mean age 35.85 ± 3.47 years) and 21 stroke patients (men 52%, mean age 66.38 ± 2.85 years, and mean NIHSS 4.09 ± 0.53) under standardized conditions. EF was measured as the reactive hyperemia index (RHI), logarithm of RHI (lnRHI), and Framingham RHI (fRHI). Measurements were separated by 1.5 and 24 h to assess same-day and day-to-day reliability, respectively.ResultsFair to moderate correlations of measurements [intraclass correlation coefficient (ICC)same-day 0.29 and ICCday-to-day 0.52] were detected in healthy subjects. In stroke patients, we found moderate to substantial correlation of both same-day and day-to-day repeated measurements (ICCsame-day 0.40 and ICCday-to-day 0.62). fRHI compared with RHI and lnRHI showed best reliability.ConclusionRepeated measurements of fRHI in stroke patients show moderate reliability on same-day and substantial on day-to-day measurements. Likewise, in healthy subjects there was substantial reliability on day-to-day measurement, but only moderate on same-day measurements. In general, day-to-day correlation of repeated EF measurements was far better than that of same-day measurements, which ranged from poor to moderate depending on the specific outcome measure of EF. A possible carryover effect should be considered if same-day repeated testing of drug effects is applied in future studies.

Objectives: To assess endothelial function and arterial stiffness in women with a previous pregnancy complicated by pre-eclampsia (PE) with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, and to compare these findings to those in women with previous PE but no HELLP and to those in controls with previous uncomplicated pregnancy, in order to investigate the influence of HELLP syndrome on subsequent cardiovascular impairment.Methods: In this prospective single-center case-control study, we performed peripheral arterial tonometry (PAT) (using the EndoPAT method) and pulse-wave velocity (PWV) assessment in 109 women who had had a singleton pregnancy complicated by PE with (n = 49) or without (n = 60) HELLP syndrome, as well as in 60 controls with previous uncomplicated pregnancy, between 6 months and 4 years after delivery. The following EndoPAT and PWV indices were compared between groups: reactive hyperemia index (RHI), as an indication of endothelial function, and peripheral and aortic heart-rate-corrected augmentation indices (AIx) standardized for a heart rate of 75 bpm (AIx@75) and carotid-femoral pulse-wave velocity (cfPWV), as indications of arterial stiffness.Results: PAT and arterial stiffness indices were significantly different between PE cases, with or without previous HELLP, and controls, except for carotid-femoral PWV. There were no significant differences among PE groups: women who had experienced HELLP and those with a history of PE without HELLP showed similar rates of RHI ≤ 1.67 (28.6% vs 18.3%, P = 0.254) and RHI ≤ 2.00 (61.2% vs 41.7%, P = 0.055), peripheral AIx@75 ≥ 17% (38.8% vs 30.0%, P = 0.417), aortic AIx@75 ≥ 35% (29.2% vs 20.0%, P = 0.461) and cfPWV × 0.8 > 9.6 m/s, which occurred in only three women, all in the group without previous HELLP (0% vs 5.0%, P = 0.251). On multivariate regression analysis, HELLP syndrome, intrauterine growth restriction (IUGR) and early-onset PE independently predicted endothelial dysfunction at 6 months to 4 years postpartum, after correcting for uterine artery pulsatility index, birth-weight percentile, and maternal blood pressure, age and body mass index. Women with both previous HELLP and early-onset IUGR had a significantly higher prevalence of endothelial dysfunction (P = 0.001).Conclusion: Similar vascular abnormalities were found in women previously affected by HELLP syndrome and those with previous PE without HELLP. However, a history of HELLP syndrome, IUGR and early-onset PE seems to identify a subgroup of women with a higher risk for future development of endothelial dysfunction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) (n=25), heart failure with reduced ejection fraction (HFrEF) (n=22), diabetic nephropathy (n=21), and arterial hypertension (n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. [ABSTRACT FROM AUTHOR]

Background: Decreased endothelial function (EF) may be a prognostic marker for stroke. Measuring pharmacological effects on EF may be of interest in the development of personalized medicine for stroke prevention. In this study, we assessed the reliability of repeated EF measurements using a pulse amplitude tonometry technology in acute stroke patients. Similarly, reliability was tested in healthy subjects devoid of vascular disease to estimate reactivity and reliability in a younger non-stroke population. Materials and methods: EF was assessed using the EndoPAT2000 in 20 healthy volunteers (men 50%, mean age 35.85 ± 3.47 years) and 21 stroke patients (men 52%, mean age 66.38 ± 2.85 years, and mean NIHSS 4.09 ± 0.53) under standardized conditions. EF was measured as the reactive hyperemia index (RHI), logarithm of RHI (lnRHI), and Framingham RHI (fRHI). Measurements were separated by 1.5 and 24 h to assess same-day and day-to-day reliability, respectively. results: Fair to moderate correlations of measurements [intraclass correlation coefficient (ICC)same-day 0.29 and ICCday-to-day 0.52] were detected in healthy subjects. In stroke patients, we found moderate to substantial correlation of both same-day and day-to-day repeated measurements (ICCsame-day 0.40 and ICCday-to-day 0.62). fRHI compared with RHI and lnRHI showed best reliability. conclusion: Repeated measurements of fRHI in stroke patients show moderate reliability on same-day and substantial on day-to-day measurements. Likewise, in healthy subjects there was substantial reliability on day-to-day measurement, but only moderate on same-day measurements. In general, day-to-day correlation of repeated EF measurements was far better than that of same-day measurements, which ranged from poor to moderate depending on the specific outcome measure of EF. A possible carryover effect should be considered if same-day repeated testing of drug effects is applied in future studies. [ABSTRACT FROM AUTHOR]

Objectives: Pre-eclampsia (PE) is associated with an increased cardiovascular risk later in life. The persistence of endothelial dysfunction after delivery may represent the link between PE and cardiovascular disease. We aimed to evaluate endothelial function and arterial stiffness after delivery of pregnancy complicated by early-onset (EO) or late-onset (LO) PE and their correlation with gestational age and mean uterine artery pulsatility index at PE diagnosis and birth-weight percentile.Methods: The study included 30 women with previous EO-PE, 30 with previous LO-PE and 30 controls with no previous PE. Participants were examined at between 6 months and 4 years after delivery. All included women were free from cardiovascular risk factors and drugs. Data on demographic and clinical characteristics during pregnancy were collected retrospectively from obstetrical charts. Endothelial function and arterial stiffness were assessed by peripheral arterial tonometry and pulse-wave analysis.Results: All vascular parameters were significantly different, indicating circulatory impairment, in women with previous EO-PE. Women with previous LO-PE had higher vascular rigidity than did controls and all had normal values of reactive hyperemia index, although they were significantly lower when compared with those of controls. On multivariate analysis, gestational age and mean uterine artery pulsatility index at the time of PE diagnosis, and birth-weight percentile were all statistically related to the vascular indices studied, after correcting for confounding parameters.Conclusions: Women with previous pregnancy complicated by PE, in particular those with early-onset disease, showed persistent microcirculatory dysfunction, as suggested by a significant reduction in reactive hyperemia index value, and increased arterial stiffness. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background We sought to determine whether heart rate variability (HRV), blood pressure (BP) variability, and baroreceptor-heart rate reflex sensitivity can be reliably assessed using finger volume pulse waveforms obtained from the commercially available EndoPAT device. Methods Non-invasive BP (Finometer Pro as a non-invasive standard) and finger volume (EndoPAT) waveforms were recorded in 65 adults (37 ± 14 years; 60% female) and systolic BP and heart rate (HR) time series were derived after calibrating the EndoPAT signal based on systolic and diastolic BP values obtained by a sphygomomanometer. Transfer function analyses were performed to test for coherence between systolic BP and HR time series derived from the Finometer and EndoPAT devices. Time-domain HRV parameters, frequency domain HR and systolic BP variability parameters, and baroreflex sensitivity (sequence technique) were computed from Finometer- and EndoPAT-derived time series and intraclass correlation coefficients (ICC) were calculated. Results Squared coherence between systolic BP time series derived from the Finometer and EndoPAT devices was low, suggesting poor correlation. In contrast, squared coherence between HR time series derived from the two devices was excellent [High Frequency (HF) = 0.80, Low Frequency (LF) = 0.81], with gain values close to 1.0. ICC values for time- and frequency-domain HRV parameters were excellent (>0.9 except for relative HF HRV, which was 0.77), while ICC values for frequency-domain BP variability parameters and baroreceptor-HR reflex sensitivity were low. Conclusions Finger volume pulse waveforms can be used to reliably assess both time-domain and frequency-domain HR variability. However, frequency domain BP variability parameters cannot be reliably assessed from finger volume pulse waveforms using the simple calibration technique used in this study. [ABSTRACT FROM AUTHOR]

Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores. Methods One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation ( FMD) expressed as percent dilatation ( FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (Ln RHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models. Results Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and Ln RHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). Ln RHI was associated negatively with risk scores in the latter model only (p < 0.05). Conclusions Uric acid was neither associated with FMD% nor Ln RHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores. [ABSTRACT FROM AUTHOR]

The combination of risk stratification by assessment of conventional risk factors for cardiovascular disease (CVD) with not only a morphological assessment of vascular damage (such as carotid ultrasound examination) but also vascular function tests may be a useful strategy for the management of CVD and its related risk factors. Endothelial dysfunction is present in a great variety of pathological conditions: it is considered the first alteration of vascular function in atherosclerosis and one of the phenomena involved in the progression of heart failure. Assessing endothelial function with noninvasive methods could have a central role for evaluation of treatment, prognostic stratification, and pharmacological studies in CVD. In this review, we focus on noninvasive techniques that have recently become available to assess endothelial function and express the possible clinical role in different clinical settings. [ABSTRACT FROM AUTHOR]

Aims: In the latest years an emerging interest has risen towards the role of endothelial dysfunction (ED) in the pathogenesis of heart failure (HF) since the very first steps of the disease. Since the prevalent etiology of HF is ischemic cardiomyopathy (ICM), it is still not clear whether the connection with ED is linked to HF itself or to atherosclerosis. The aim is to determine the presence of ED in subjects with idiopathic dilated cardiomyopathy (IDCM) compared to ICM., Methods: In this observational study 107 patients were enrolled, 65 of them suffering from IDCM and 42 from ICM. ED was assessed as peripheral arterial tonometry by means of EndoPAT device. The Reactive Hyperaemia Index (RHI) was calculated, ED being established with RHI values ≤1.67 and normal endothelial function >2.00 (grey area between 1.67 and 2.00)., Results: ED, expressed both as RHI ≤1.67 and RHI ≤2.00, showed a similar prevalence in the two groups. However, they differed as regards sex, dyslipidemia and statin use., Conclusion: Endothelial function, evaluated through peripheral artery tonometry, seems equally compromised in patients with IDCM and ICM., Competing Interests: None., (AJCD Copyright © 2022.)

Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week. [ABSTRACT FROM AUTHOR]

Background: SCD is characterized by hemolysis and oxidative stress, resulting in endothelial dysfunction (EDF). Peripheral arterial tonometry (PAT), a noninvasive technology for measuring EDF, utilizes reactive hyperemia following mini-ischemic stress (reactive hyperemia index or RHI). Methods: The authors studied PAT in 36 SCD children to determine the influence of hemoglobin genotype and treatment on EDF. Results and Conclusions: Blunted RHI was seen in the majority of children with SCD, especially with increased symptomatology (1.53 and 1.71; p value .032). RHI was not normal in children on chronic transfusion or hydroxyurea. RHI correlated with reticulocyte fraction (Spearman r = −.47, p = .037). PAT merits further exploration as a measure of EDF in SCD. [ABSTRACT FROM AUTHOR]

The life expectancy of patients with Tetralogy of Fallot (ToF) has increased in recent years. As a result, other risk factors with later onset in life are in the focus of patient care. Endothelial function is an early indicator of cardiovascular risk and was investigated along further structural vessel properties. A total of 17 patients (41.7 ± 7.1 years, 8 women) with Tetralogy of Fallot were 1:2 matched for sex with 34 (38.9 ± 8.1 years, 16 women) healthy volunteers. Participants received an assessment of their endothelial function and a structural assessment of the aorta. Patients with ToF showed a reduced endothelial function determined by reactive hyperaemia index after adjusting for age, weight and height (ToF: 1.55 ± 0.31 vs. controls: 1.84 ± 0.47; p = 0.023). No differences in carotid intima-media thickness (cIMT) between the ToF and healthy controls (ToF: 0.542 ± 0.063 mm vs. controls: 0.521 ± 0.164 mm; p = 0.319) were found. Patients with ToF had reduced vascular function compared to healthy subjects. As the structural component is not affected, endothelial dysfunction seems not to have yet manifested itself as a morphological change. Nevertheless, long-term management of these patients should include vascular parameters. [ABSTRACT FROM AUTHOR]