Reactive Hyperemia Index Values Research Articles

A nutraceutical with Citrus bergamia and Cynara cardunculus improves endothelial function in adults with non-alcoholic fatty liver disease

ObjectivePolyphenol intake may prevent hepatic steatosis and cardiovascular disease by potentially improving endothelial function. The purposes of this study are to investigate the association between fatty liver disease and endothelial dysfunction and to test the effects of a nutraceutical containing extracts made from Citrus bergamia and Cynara cardunculus on peripheral vascular endothelial function in adults with liver steatosis. MethodsWe analyzed data from 32 individuals with hepatic steatosis and endothelial dysfunction (reactive hyperemia index ≤ 1.67). Sixteen subjects took 1 capsule/d (300 mg/d) containing Cynara cardunculus extract and bergamot polyphenol fraction, while the other 16 subjects matched for age, sex, and body mass index took 1 capsule/d of placebo (maltodextrin) for 12 wk. All anthropometric parameters were assessed at baseline and after 12 wk as were lipids, glucose, and reactive hyperemia index using an EndoPAT 2000. ResultsThe mean age was 52 ± 9 y. The mean reactive hyperemia index was 1.15 ± 0.4. After 12 wk, we found a greater increase in reactive hyperemia index in the participants taking the nutraceutical rather than placebo (0.58 ± 0.5 versus 0.13 ± 0.5; P = 0.02, respectively). The stepwise multivariable analysis confirmed a positive association between reactive hyperemia index change and the nutraceutical treatment (B = 0.38; P = 0.025) and negative association with reactive hyperemia index values at baseline (B = –0.81; P < 0.001). No association was found between the reduction in the amount of intrahepatic fat and the improvement of endothelial function (B = 0.002; P = 0.56). ConclusionsA nutraceutical containing bergamot and artichoke extracts improves peripheral vascular endothelial function in adults with hepatic steatosis and early phase of atherosclerosis.

Relationship Between Endothelial Dysfunction and the Outcomes After Atrial Fibrillation Ablation.

Background Endothelial dysfunction (ED) is associated with cardiovascular events in patients with atrial fibrillation (AF). However, the utility of ED as a prognostic marker after AF ablation supplementary to the CHA2DS2-VASc score is unclear. This study aimed to investigate the relationship between ED and 5-year cardiovascular events in patients undergoing AF ablation. Methods and Results We conducted a prospective cohort study of patients who underwent a first-time AF ablation and for whom the endothelial function was assessed by the peripheral vascular reactive hyperemia index (RHI) before ablation. We defined ED as an RHI of <2.1. Cardiovascular events included strokes, heart failure requiring hospitalization, arteriosclerotic disease requiring treatment, venous thromboses, and ventricular arrhythmias or sudden cardiac death. We compared the 5-year incidence of cardiovascular events after AF ablation between those with and without ED. Among the 1040 patients who were enrolled, 829 (79.7%) had ED, and the RHI value was found to be associated with the CHA2DS2-VASc score (P=0.004). The 5-year incidence of cardiovascular events was higher among patients with ED than those without ED (98 [11.8%] versus 13 [6.2%]; log-rank P=0.014). We found ED to be an independent predictor of cardiovascular events after AF ablation (hazard ratio [HR], 1.91 [95% CI, 1.04-3.50]; P=0.036) along with a CHA2DS2-VASc score of ≥2 (≥3 for women) (HR, 3.68 [95% CI, 1.89-7.15]; P<0.001). Conclusions The prevalence of ED among patients with AF was high. Assessing the endothelial function could enable the risk stratification of cardiovascular events after AF ablation.

Abstract P407: Sex Differences in Microvascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Introduction: Microvascular dysfunction during acute mental stress may be an important determinant of major adverse cardiovascular outcomes (MACE) especially among middle-aged women survivors of an acute myocardial infarction (MI). Hypothesis: There are sex differences in the association between microvascular dysfunction and MACE. Methods: The Myocardial Infarction and Mental Stress Study 2 enrolled individuals who had been hospitalized for an MI in the past 8 months at the age of 60 years or younger, with an oversampling of women. Reactive hyperemia index (RHI) was used to measure digital microvascular function before and 30 minutes after a public-speaking mental stress task. This assessment was contrasted with macrovascular endothelial function at the brachial artery through flow-mediated dilation (FMD). Participants were followed for 5-years, and MACE was defined as a composite of cardiovascular death, first/recurring events for nonfatal MI, and hospitalizations for heart failure. Cox proportional hazards models were used to examine vascular response to stress (difference between post-stress and resting values) and MACE adjusting for demographics, clinical risk factors, medications, psychological factors, and mental stress ischemia. Lower RHI and FMD values are indicative of greater microvascular and endothelial dysfunction, respectively. Results: Of 263 participants, the mean age was 51 years and 48% were women. There were 64 patients with 141 adverse cardiovascular events (first and repeated). In the overall sample, there was no significant association between microvascular response to stress and MACE, but there was a significant interaction with sex (p = 0.03). Each standard deviation decrease in RHI response to stress was associated with 50% greater risk of MACE (HR: 1.50, 95% CI: 1.05, 2.13) among women only, while no association was observed in men (HR 0.93, 95% CI: 0.69, 1.26). Transient endothelial dysfunction in response to stress (for each standard deviation decrease in FMD) was associated with 35% greater risk of MACE (HR: 1.35; 95% CI: 1.07, 1.71), and was similar in women and men. Conclusions: Peripheral microvascular dysfunction with mental stress is associated with MACE among women but not among men. In contrast, brachial artery endothelial dysfunction is similarly related to MACE among both men and women. These results suggest that microvascular dysfunction is a female-specific mechanism linking psychological stress to adverse outcomes.

Prognostic value of reactive hyperemia index using peripheral artery tonometry in patients with heart failure

Given the high prevalence and poor prognosis of heart failure (HF), finding prognostic factors for patients with HF is crucial. This study investigated the prognostic value of reactive hyperemia index (RHI), a measure of endothelial function, in HF. A total of 90 HF patients (mean age, 63.7 ± 13.2 years; female, 25.6%) with a history of hospitalization for HF treatment were prospectively enrolled. RHI was measured using digital arterial tonometry in a stable condition. Clinical events, including all-cause death and HF admission, were assessed. During the median follow-up of 3.66 years (interquartile range, 0.91–4.94 years), 26 clinical events (28.9%) occurred. Although there were no significant differences in risk factors and laboratory findings according to the occurrence of clinical events, the RHI value was significantly lower in patients with clinical events than in those without (1.21 ± 0.34 vs. 1.68 ± 0.48; P < 0.001). Kaplan–Meier survival analysis showed that a lower RHI value (< 1.48) was associated with a significantly higher incidence rate of clinical events (log-rank P < 0.001). In multivariable cox regression analysis, a low RHI value (< 1.48) was associated with an increased risk of clinical events (hazard ratio, 14.09; 95% confidence interval, 3.61–54.99; P < 0.001) even after controlling for potential confounders. Our study showed that reduced RHI was associated with an increased risk of adverse clinical outcomes in HF. This suggests that endothelial dysfunction may be an important prognostic marker in patients with HF.

Endothelial function testing before conditioning therapy is useful for predicting transplant-related complications after allogeneic hematopoietic cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is a useful tool for the treatment of hematologic malignancies. However, transplantation-related complications are the main cause of non-relapse mortality. Previous reports suggest that endothelial damage is related to early complications after HSCT. Non-invasive reactive hyperemia peripheral arterial tonometry (RH-PAT) was performed to evaluate endothelial function as a predictive marker for these complications. The reactive hyperemia index (RHI) obtained from RH-PAT was evaluated before the conditioning regimen. The relationship between the RHI and the appearance of engraftment syndrome, thrombotic microangiopathy, and acute graft-versus-host disease (aGVHD) was assessed. Receiver operating characteristic curve analysis showed that an RHI value of 1.58 was the optimal cut-off for predicting transplantation-related complications. In total, 49 patients (22 acute myelogenous leukemia, 7 acute lymphocytic leukemia, 6 myelodysplastic syndrome, 6 adult T-cell leukemia, 6 non-Hodgkin lymphoma, and 2 others) were enrolled; 34 had a normal RHI (≥ 1.59), and 15 had an abnormally low RHI (≤ 1.58). Thrombotic microangiopathy (20.2% vs 0.0%, P = 0.025) and aGVHD (80.0% vs 41.2%, P = 0.015) were significantly more frequent in patients with a low RHI. Endothelial dysfunction assessed by RH-PAT before HSCT was able to predict transplantation-related complications.

Abstract 9921: E-cigarette Use and Markers of Endothelial Function in Diverse Young Adults From New York City: The VapeScan Study

Introduction: Compared to traditional tobacco use, the cardiovascular effects of e-cigarette use, or vaping, an increasing behavior especially among young adults, are poorly understood. The ongoing VapeScan Longitudinal Study aims to determine the effects of vaping on participants’ endothelial health and other subclinical markers. Hypothesis: We hypothesized that e-cigarette use (alone or in combination with smoking), compared to never using e-cigarettes or smoking products, is associated with an adverse profile in markers of endothelial health in a diverse cohort of healthy young adults. Methods: We recruited 132 participants, aged 18-49 and residing in the greater New York area, between May 2021 and May 2022. Participants who were pregnant, had a history of cardiovascular or respiratory disease, smoked but did not vape, or formerly vaped, were excluded. Endothelial health was assessed via endothelium-dependent vasodilation using an EndoPAT2000 machine. Reactive Hyperemia Index (RHI) and Framingham RHI (fRHI) values were computed from the results. Participants missing EndoPAT data (n=3) were excluded from analysis, leaving 129 participants (17 vaping/never smoking, 19 vaping/former smoking, 24 vaping/smoking (dual use), and 69 never vaping/never smoking). Results: Participants’ median age was 26 years and 61% were female. Participants classified as vaping/never smoking and dual users were younger than the other groups (Table). Median levels of RHI and fRHI were lowest for dual users, although the differences across the four groups were not statistically significant (one-way ANOVA p-value = 0.27 for RHI and 0.10 for fRHI). Participants’ vaping/smoking status was not associated with RHI or fRHI in linear regression models adjusted for age and sex. Conclusions: Preliminary findings from the VapeScan Study support that subclinical measures of endothelial function are a promising tool to help identify early effects of tobacco product use in young adults.

Bronchial Asthma as a Cardiovascular Risk Factor: A Prospective Observational Study.

Introduction: Asthma as a chronic inflammatory disorder has been suggested as a risk factor for endothelial dysfunction (ED), but studies on the association between asthma and cardiovascular disease (CVD) risk are limited. Background: We assessed associations of ED with the severity of asthma, eosinophilic inflammation, lung function, and asthma control. Methods: 52 young asthmatics (median age of 25.22 years) and 45 healthy individuals were included. Demographic, clinical, and laboratory findings were recorded. We evaluated microvascular responsiveness by recording the reactive hyperemia index (RHI) indicating post-occlusive peripheral endothelium-dependent changes in vascular tone using the Itamar Medical EndoPAT2000. VCAM-1, ADMA, high-sensitive CRP (hsCRP), and E-selectin were measured. Results: Asthmatics had considerably lower RHI values (p < 0.001) with a dynamic decreasing trend by asthma severity and higher hsCRP levels (p < 0.001). A substantial increase in hsCRP and E-selectin with asthma severity (p < 0.05) was also observed. We confirmed a higher body mass index (BMI) in asthmatics (p < 0.001), especially in women and in severe asthma. Conclusions: We demonstrated the progression of CVD in asthmatics and the association of the ongoing deterioration of ED with the inflammatory severity, suggesting that the increased risk of CVD in young asthmatics is dependent on disease severity. The underlying mechanisms of risk factors for CVD and disease control require further study.

Synergistic effects of liver fibrosis and sarcopenia on endothelial dysfunction and arterial stiffness in patients with type 2 diabetes.

AimsTo investigate synergistic effects of liver fibrosis evaluated by FibroScan and sarcopenia on endothelial function and arterial stiffness in patients with type 2 diabetes.MethodsThis cross-sectional study evaluated liver fibrosis (LF) and sarcopenia in 115 patients with type 2 diabetes. LF was assessed as the liver stiffness measurement (LSM) in transient elastography (FibroScan) and was defined as an LSM greater than or equal to 8.0 kPa. Sarcopenia was defined as a ratio of appendicula skeletal muscle mass to body mass index of<0.789 in men and<0.512 in women. Endothelial function was measured by reactive hyperemia index (RHI) with tonometry, and arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Endothelial dysfunction was defined an RHI value below 1.67, while arterial stiffness was defined a CAVI value above 9.0. Patients were divided into four groups: no LF and no sarcopenia; LF but no sarcopenia; no LF but sarcopenia; and LF and sarcopenia. The composite of endothelial dysfunction of arterial stiffness was defined as an outcome.ResultsIn patients with LF, RHI was significantly lower and CAVI was significantly higher than in patients without LF. Furthermore, RHI was significantly lower in patients with sarcopenia than in those without it. Patients with both LF and sarcopenia had the lowest RHI and the highest CAVI and urinary albumin levels. Sarcopenia and HDL cholesterol were independent factor the composite of endothelial dysfunction and arterial stiffness.ConclusionLF and sarcopenia are independently associated with endothelial dysfunction and arterial stiffness in patients with type 2 diabetes. Coexistence of LF and sarcopenia may synergistically lead to vascular damage and thus contribute to the high risk of cardiovascular disease in people with type 2 diabetes.

Characterization and assessment of endothelial dysfunction in adolescents with obesity and vitamin D deficiency

Background. Obesity and vitamin D deficiency in children are widespread in economically developed countries. Among children with obesity and components of the metabolic syndrome, vitamin D deficiency is more common than in children with a normal body mass index (BMI). The growth of metabolic disorders, atherosclerosis, early onset of type 2 diabetes mellitus lead to fatal vascular accidents in young people, and therefore the search for new ways of early diagnosis of these processes is relevant.&#x0D; Aim. To study of the relationship of endothelial dysfunction with vitamin D deficiency, obesity and associated metabolic disorders among adolescents in Saint Petersburg.&#x0D; Materials and methods. 5 adolescents aged 1416 years (150.76 years) with primary obesity were examined. Anthropometric parameters were studied: waist circumference, weight, height, calculation of BMI, stage of puberty according to Tanner. Laboratory examination included the following parameters: serum glucose, cholesterol, triglycerides, high density lipoproteins, low density lipoproteins, insulin, 25(OH)D. Atherogenicity index (AI), insulin resistance index (HOMA-IR), vitamin D sufficiency were calculated. Endothelial function was assessed by the value of the reactive hyperemia index (RHI), automatically calculated by the EndoPAT 2000 device (Itamar Medical, Israel).&#x0D; Results. All examined patients had abdominal obesity (median BMI 33.5 kg/m2 [30.9; 34.2]) and reduced vitamin D supply (median 25(OH)D 17.2 ng/ml). Hypercholesterolemia and dyslipidemia due to an increase in low density lipoproteins were diagnosed in 1 (20%) case. Dyslipidemia due to a decrease in high density lipoproteins was detected in 3 (60%) patients. An increase in IA was found in 4 (80%) people. Insulin resistance was present in 60% of the examined, the median value of HOMA-IR was 5.6. The median RHI was 1.74 [1.72; 2.13]. Optimum RHI values were observed in 2 (40%) patients; in most (60%) adolescents, the RHI values corresponded to subnormal values and were close to the lower limit of this zone. A significant inverse correlation of RHI with AI was obtained (R=-0.63, p0.05).&#x0D; Conclusion. Taking into account the risk factors previously identified in the examined patients (dyslipidemia, insulin resistance, reduced vitamin D supply), endothelial dysfunction in these patients was regarded as a cardiovascular risk factor. A manageable risk factor is a reduced supply of vitamin D, which can be corrected by an additional donation of cholecalciferol.

Effects of endoplasmic reticulum stress, liver function, insulin resistance and vascular endothelial function in patients with nonalcoholic fatty liver disease.

It is aimed to compare whether there are differences in endoplasmic reticulum stress, liver function, insulin resistance, and vascular endothelial function in patients with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus (T2DM). Forty patients with NAFLD, 38 patients with NAFLD combined with T2DM, and 30 patients with normal liver tissue were selected. They were set as Group A, Group B and Group C respectively. The expression level of glucose-regulated protein 94 (GRP94) and biochemical indicators such as alanine aminotransferase (ALT), free fatty acids (FFA), triglycerides (TG), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), fasting blood glucose (FBG), and fasting insulin (FINS) were measured. Also, the calculation of the homeostatic model assessment for insulin resistance (HOMA-IR) index was performed. The reactive hyperemia index (RHI) was detected to evaluate the vascular endothelial function of patients. The comparison between groups and multi-factor analysis of the influencing factors of RHI was conducted. Compared with Group C, the expressions in Group A and Group B were distinctly enhanced (P <0.05). Also, the expression of GRP94 protein in Group B was distinctly higher than that in Group A (P <0.05). The average optical density values of Groups A, B, and C were 0.327 ± 0.007, 0.350 ± 0.009, and 0.299 ± 0.006, respectively. A comparison between the three groups was performed. The differences had statistical significance (P <0.05). The differences in the TG, ALT, AST, GGT, FINS and HOMA-IR between Group A and Group B had statistical significance (P <0.05). The RHI values of Groups A, B, and C were 1.59 ± 0.23, 1.79 ± 0.32, and 2.05 ± 0.47, respectively. A comparison between the three groups was performed. The differences had statistical significance (P <0.05). FFA, ALT and FBG in patients with NAFLD are risk factors for endothelial dysfunction (P <0.05). The liver damage caused by NAFLD may be related to the expression of GRP94. FFA, ALT and FBG are risk factors for endothelial dysfunction in NAFLD patients.

Validity of flow-mediated dilation and reactive hyperemia index in assessing the risk of coronary artery disease based on the new definition by the Japan Society for Vascular Failure

Background: Flow-mediated dilation (FMD) measurement and reactive hyperemia-peripheral arterial tonometry (RH-PAT) are established methods for assessing vascular endothelial function. Recently, the Japan Society for Vascular Failure proposed a new definition for the values of FMD (≥7.0%, normal; 7.0%> and ≥4.0%, borderline; 4.0%≥, abnormal) and reactive hyperemia index (RHI) measured using RH-PAT (≥2.10, normal; 2.10≥ and >1.67, borderline; 1.67≥, abnormal). This study aimed to assess the clinical significance of FMD and RHI in coronary artery disease (CAD) based on the new definition. Methods: We performed simultaneous FMD and RH-PAT measurements in 131 patients undergoing coronary angiography for suspected CAD. The patients were divided into subgroups according to the normal, borderline, and abnormal values of FMD and RHI in the new definition. Results: No significant correlation was found between the FMD and RHI values in the overall patients. In the normal FMD/normal RHI, normal FMD/abnormal RHI, abnormal FMD/normal RHI, and abnormal FMD/abnormal RHI groups, the prevalence of multivessel CAD was 0%, 25%, 36%, and 56% (P=0.038), respectively. Furthermore, multivessel CAD was observed in 17% of patients in the borderline FMD/borderline RHI group, and the prevalence showed a significant difference among the normal FMD/normal RHI, borderline FMD/borderline RHI, and abnormal FMD/abnormal RHI groups (P=0.006). Multivariate logistic regression analysis showed that abnormal FMD/abnormal RHI was an independent predictor of multivessel CAD (odds ratio: 3.172, 95% confidence interval: 1.012-7.336, P=0.042). Conclusions: The evaluation of simultaneously measured FMD and RHI values based on the new definition would be advantageous for predicting the severity of CAD.

Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p&lt;0.005). HsCRP (p&lt;0.005), E-selectin (p&lt;0.001) and VCAM-1 (p&lt;0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes.

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

Impact of Serum Uric Acid Level on Systemic Endothelial Dysfunction in Patients with a Broad Spectrum of Ischemic Heart Disease.

Previous studies indicated that serum uric acid (SUA) level is a marker of endothelial function in subsets of ischemic heart disease (IHD). In the present study, we aimed to evaluate the relation between the SUA level and endothelial function in patients with a broad spectrum of IHD, including obstructive coronary artery disease (CAD) and ischemia with no obstructive CAD (INOCA). Three prospective studies and one retrospective study were pooled, in which the SUA level was measured, and systemic endothelial function was assessed using the reactive hyperemia index (RHI). The primary endpoint of the present study was a correlation of the SUA level with RHI. A total of 181 patients with a broad spectrum of IHD were included, among whom, 46 (25%) had acute coronary syndrome presentation and 15 (8%) had INOCA. Overall, the SUA level was negatively correlated with the RHI (r = −0.22, p = 0.003). Multivariable analysis identified the SUA level and INOCA as significant factors associated with RHI values. In conclusion, in patients with a broad spectrum of IHD, including obstructive epicardial CAD (chronic and acute coronary syndromes) and INOCA, the SUA level was significantly and negatively correlated with systemic endothelial function assessed with the RHI. INOCA, rather than obstructive CAD, was more associated with endothelial dysfunction.

Endothelial function in patients with critical and non-critical limb ischemia undergoing endovascular treatment.

Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease. CLI patients, compared to non-CLI, achieve worse treatment outcomes and generate higher costs. The aim of the study was to compare endothelial function and clinical outcomes in CLI and non-CLI patients after percutaneous transluminal angioplasty (PTA). In this prospective, follow-up study, 30 CLI patients and 40 non-CLI patients underwent PTA. Endothelial function was assessed based on flow mediated dilatation (FMD), reactive-hyperemia index (RHI), while the ankle-brachial index, toe-brachial index and the Rutherford scale were used for peripheral artery disease progression evaluation. The results were assessed before PTA, as well as 1, 3, 6 and 12 months after the procedure. There were no differences at the baseline regarding to endothelial function between both groups. Neither FMD nor RHI changed after PTA in any of the groups, although there was a difference in median RHI value between CLI and non-CLI patients regarding the 1st and 6th month of the follow-up (RHI6-RHI1 = 0.08 in CLI and -0.15 in non-CLI; P = 0.01). The larger baseline intima-media thickness (IMT) in the CLI group allowed to predict a greater number of re-intervention (P = 0.01) and major adverse event rates (P = 0.03). CLI patients presented larger decrease in the Rutherford scale compared to non-CLI (P <0.001). Baseline IMT was predictive for re-interventions and major adverse event rates. Although neither of groups exhibited significant changes in endothelial function, we proved differences between them regarding to changes in RHI.

Is endothelial function impaired among women with placenta-mediated fetal growth restriction? Evidence from a prospective cohort study using peripheral artery tonometry

IntroductionWomen with pregnancies complicated by IUGR are at increased risk for future cardiovascular disease. Nevertheless, it is unknown whether endothelial function of women with pregnancies complicated by IUGR is already impaired during pregnancy. Hence, we evaluated maternal endothelial function in pregnancies complicated by IUGR due to placental dysfunction. MethodsProspective cohort study assessing systemic endothelial function of women with singleton pregnancies and estimated fetal weight (EFW) below 10th percentile and abnormal umbilical artery flow (n = 15). Control group included women with singleton pregnancies and normal EFW (n = 22). Endothelial function was assessed using EndoPAT™ device which evaluates the change in peripheral vascular tone in reaction to temporal ischemia, a process called reactive hyperemia. The ratio of the readings before and after ischemia is used to assess endothelial function and called reactive hyperemia index (RHI). Low RHI values indicate endothelial dysfunction. ResultsThe median gestational age at endoPAT examination was comparable between the IUGR and control groups (32; IQR 31,33; p = 0.18). The median RHI was significantly lower in the IUGR group compared to the control group (1.3 vs 1.5, p = 0.02). Median gestational age at delivery and mean neonatal birth weight were lower in the IUGR group compared to the control group (36.7 (35.6,37.2) vs 37.7 (35.3, 39.3), p = 0.04 and 1647 ± 414 g vs 2785 ± 587 g, p < 0.001). Discussion-Pregnant women with IUGR due to placental dysfunction are characterized by impaired systemic endothelial function.

Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis.

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.

Evaluation of Vascular Endothelial Function in Young and Middle-Aged Women with Respect to a History of Pregnancy, Pregnancy-Related Complications, Classical Cardiovascular Risk Factors, and Epigenetics.

The aim of the study was to examine the effect of previous pregnancies and classical cardiovascular risk factors on vascular endothelial function in a group of 264 young and middle-aged women 3 to 11 years postpartum. We examined microvascular functions by peripheral arterial tonometry and EndoPAT 2000 device with respect to a history of gestational hypertension, preeclampsia, fetal growth restriction, the severity of the disease with regard to the degree of clinical signs and delivery date. Besides, we compared Reactive Hyperemia Index (RHI) values and the prevalence of vascular endothelial dysfunction among the groups of women with normal and abnormal values of BMI, waist circumference, systolic and diastolic blood pressures, heart rate, total serum cholesterol levels, serum high-density lipoprotein cholesterol levels, serum low-density lipoprotein cholesterol levels, serum triglycerides levels, serum lipoprotein A levels, serum C-reactive protein levels, serum uric acid levels, and plasma homocysteine levels. Furthermore, we determined the effect of total number of pregnancies and total parity per woman, infertility and blood pressure treatment, presence of trombophilic gene mutations, current smoking of cigarettes, and current hormonal contraceptive use on the vascular endothelial function. We also examined the association between the vascular endothelial function and postpartum whole peripheral blood expression of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p). A proportion of overweight women (17.94% and 20.59%) and women with central obesity (18.64% and 21.19%) had significantly lower RHI values at 10.0% false positive rate (FPR) both before and after adjustment of the data for the age of patients. At 10.0% FPR, a proportion of women with vascular endothelial dysfunction (RHI ≤ 1.67) was identified to have up-regulated expression profile of miR-1-3p (11.76%), miR-23a-3p (17.65%), and miR-499a-5p (18.82%) in whole peripheral blood. RHI values also negatively correlated with expression of miR-1-3p, miR-23a-3p, and miR-499a-5p in whole peripheral blood. Otherwise, no significant impact of other studied factors on vascular endothelial function was found. We suppose that screening of these particular microRNAs associated with vascular endothelial dysfunction may help to stratify a highly risky group of young and middle-aged women that would benefit from early implementation of primary prevention strategies. Nevertheless, it is obvious, that vascular endothelial dysfunction is just one out of multiple cardiovascular risk factors which has only a partial impact on abnormal expression of cardiovascular and cerebrovascular disease associated microRNAs in whole peripheral blood of young and middle-aged women.

Reactive Hyperemia Index Associated With Atherosclerotic Cardiovascular Disease Under Treatment for Lifestyle Diseases.

BackgroundEndothelial dysfunction is an early phase of atherosclerosis and causes atherosclerotic cardiovascular disease (ASCVD), but the cutoff reactive hyperemia index (RHI) for identifying ASCVD patients under treatment for lifestyle diseases is unknown.MethodsPatients who visited Cardiology Section, Izumi General Medical Center, Kagoshima, Japan and were measured RHI using Endo-PAT 2000 during May 2014 and March 2016 were enrolled. We divided them into ASCVD and non-ASCVD groups and investigated the association with RHI between the groups.ResultsASCVD group included 195 patients and non-ASCVD group included 288 patients. Age, body mass index and the rate of male, hypertension, diabetes, dyslipidemia and chronic kidney disease in the ASCVD group were significantly higher than those in non-ASCVD group. RHI in the ASCVD group (1.65 (1.40 - 1.92)) was significantly lower than that in the non-ASCVD group (1.73 (1.45 - 2.24)) (P < 0.05). In multi-regression analysis, RHI (odds ratio: 0.67, 95% confidence interval: 0.45 - 0.99, P = 0.04) was independently associated with ASCVD after adjusted by age, sex, body mass index, smoking, hypertension, diabetes, dyslipidemia and chronic kidney disease. The cutoff RHI value between the groups was 1.80.ConclusionRHI was significantly associated with ASCVD under treatment for lifestyle diseases and the cutoff value was 1.80.

Ubiquinol Improves Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Single-Center, Randomized Double-Blind Placebo-Controlled Crossover Pilot Study

Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400mg/day or placebo for 3months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400mg/day for 3months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39-1.80], post-RHI 1.74 [IQR 1.63-2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53-1.85], post-RHI 1.51 [IQR 1.39-2.11], p = 0.198). Ubiquinol 400mg/day for 3months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.