The effect of short-term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study.

AIM: Patients with chronic kidney disease (CKD) are more susceptible to endothelial dysfunction and cardiovascular disease (CV). Remote ischemic preconditioning (rIPC) has been proven efficient in improving endothelial function and lowering the risk of CV. However, the safety and effect of rIPC on endothelial function in patients with CKD have not been effectively assessed. METHODS: 45 patients with CKD (average estimated glomerular filtration rate: 48.4 mL/min/1.73 m2) were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 200 mmHg, interspaced by 5-min reperfusion) or control (4 × 5 min 60 mmHg, interspaced by 5-min reperfusion). Vascular endothelial function was assessed by natural log-transformed reactive hyperemia index (LnRHI) before and after a 7-day intervention. Arterial elasticity was assessed by augmentation index (AI). RESULTS: The results showed that LnRHI could be improved by rIPC treatment (Pre = 0.57 ± 0.04 vs. Post = 0.67 ± 0.04, p = .001) with no changes relative to control (Pre = 0.68 ± 0.06 vs. Post = 0.64 ± 0.05, p = .470). Compared with the control group, the improvement of LnRHI was greater after rIPC treatment (rIPC vs. Control: 0.10 ± 0.03 vs. -0.04 ± 0.06, between-group mean difference, -0.15 [95% CI, -0.27 to -0.02], p = .027), while there was no significant difference in the change of AI@75 bpm (p = .312) between the two groups. CONCLUSION: RIPC is safe and well tolerated in patients with CKD. This pilot study suggests that rIPC seems to have the potential therapeutic effect to improve endothelial function. Of note, further larger trials are still warranted to confirm the efficacy of rIPC in improving endothelial function in CKD patients.

Association Between Endothelial Dysfunction and Left Ventricular Diastolic Stiffness　- Subanalysis of the Flow-Mediated Dilation Japan (FMD-J) Study.

BACKGROUND: Endothelial dysfunction and increased left ventricular (LV) stiffness are associated with the incidence of heart failure with preserved ejection fraction (HFpEF). This study evaluated the association between endothelial dysfunction and LV diastolic stiffness.Methods and Results: Endothelial dysfunction evaluated by flow-medicated vasodilation (FMD) and the reactive hyperemia index (RHI), which reflects endothelial dysfunction in the microvasculature, was measured in 112 subjects with hypertension in the Flow-Mediated Dilation Japan (FMD-J) study. Using transthoracic echocardiography, LV diastolic stiffness was evaluated by measuring diastolic wall strain (DWS) in the LV posterior wall. In this cross-sectional study, associations among FMD, RHI, and DWS were investigated using multiple regression analyses. The mean (±SD) age of the subjects 65±9 years, and 63% were men. DWS was significantly associated with RHI, but not FMD, on multivariate linear regression analysis (ß=0.39; P<0.0001). This association was preserved in subjects without LV hypertrophy (ß=0.46; P<0.0001). A DWS ≤median, suggesting increased LV diastolic stiffness, was significantly associated with RHI on multivariate logistic regression analysis (odds ratio 20.58; 95% confidence interval 4.83-87.63; P<0.0001). The receiver operating characteristic curve presented a cut-off value of 2.21 for RHI, with a sensitivity of 77% and a specificity of 71%, for DWS ≤median. CONCLUSIONS: RHI, rather than FMD, was associated with DWS. Endothelial dysfunction in the microvasculature may be associated with increased LV diastolic stiffness.

Increased soluble endoglin levels in newly-diagnosed type 2 diabetic patients are associated with endothelial dysfunction.

Endothelial dysfunction (ED) contributes to the pathologic process underlying macrovascular complications, a common complication of type 2 diabetes mellitus (T2DM). Soluble endoglin (sEng) shed from the extracellular domain of the entire endoglin molecule blocks endothelial protection mediated by transforming growth factor-beta 1 (TGF-ß1). The reactive hyperemia index (RHI), which is determined by reactive hyperemia peripheral arterial tonometry (RH-PAT), is a new index with which to evaluate ED. This study determined the changes in serum sEng levels in newly-diagnosed (untreated) T2DM patients and the correlation with the RHI. The T2DM group included 34 newly-diagnosed T2DM patients, while the control group included 53 healthy adults. The clinical data from the two groups were evaluated retrospectively. The intima-media thickness (IMT) of the common carotid artery (CCA) and the ankle-brachial index (ABI) of both legs were used to assess structural vascular changes. The serum sEng level was determined using an ELISA kit. Endothelial function was assessed using RH-PAT and the RHI was computed. The serum sEng level in the T2DM group was significantly greater than the control group, although the RHI was significantly lower in the T2DM group (p < 0.05). The serum sEng level was negatively correlated with the RHI in T2DM patents (r = 0.354, p = 0.041). The serum sEng level, CCA-IMT, and ABI were not significantly correlated with T2DM (p > 0.05). In summary, among newly-diagnosed T2DM patients, the serum sEng levels were inversely correlated with the RHI, and an elevated sEng level may be associated with ED.

The association between baseline circulating progenitor cells and vascular function: The role of aging and risk factors.

BACKGROUND: To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. METHODS: In 797 adult participants, CPCs were enumerated by flow cytometry as CD45med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). RESULTS: In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors (p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions (p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts (p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. CONCLUSION: A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.

Noninvasive Investigation of the Presence and Extent of Coronary Artery Disease by the Evaluation of Fingertip-Reactive Hyperemia.

OBJECTIVE: Fingertip-reactive hyperemia-peripheral artery tonometry (RH-PAT) is an emerging novel noninvasive method for evaluating endothelial function. We aimed to evaluate endothelial function with fingertip-reactive hyperemia by RH-PAT in symptomatic patients undergoing elective coronary angiography and to assess the relationship between the degree of endothelial dysfunction (ED) and the presence and the severity of coronary artery disease (CAD). SUBJECTS AND METHODS: We assessed 92 patients. Before coronary angiography, endothelial function was measured by RH-PAT and reactive hyperemia index (RHI) was obtained. For each patient, the Gensini score was calculated according to the coronary angiographic findings to evaluate the severity of CAD. RESULTS: In CAD (+) group, RHI (1.35 ± 0.57 vs. 1.74 ± 0.46, p = 0.001) mean values were lower than CAD (-) group. In multivariate logistic regression analysis, age, high-density lipoprotein, and RHI were found to be independent parameters predicting the presence of CAD. In multivariate linear regression analysis, RHI was found to be an independent predictor associated with the severity of CAD. In receiver operating characteristic curve analysis, RHI achieved an area under the curve of 0.763 (95% confidence interval 0.663-0.846, p = 0.001) for the ability to predict the presence of CAD. A cut-off value of 1.49 for an RHI predicted the presence of CAD with a sensitivity of 75% and a specificity of 72.9%. CONCLUSION: RH-PAT is an objective and highly reproducible test with superior diagnostic accuracy for the evaluation of ED. We found significant correlations between ED and the presence and the severity of CAD.

Low physical activity is associated with impaired endothelial function in patients with type 2 diabetes and controls after 5 years of follow-up.

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.

Does overnight duty affect vascular endothelial function?

BACKGROUND: The reactive hyperemia index (RHI), which is obtained from the measurement of peripheral arterial tonometry (PAT), is highly associated with the percentage change in the end-diastolic arterial diameter (%flow-mediated dilatation) at reactive hyperemia. Low RHI is reported to be a mortality risk in patients with a high risk of cardiovascular (CV) disease. CV events are thought to be induced by physical and mental stress, including long-term fatigue and lack of sleep. However, the relationship between fatigue, lack of sleep, and endothelial function has not yet been established. METHODS: Healthy hospital workers (n = 13, 6 men and 7 women) with an average age of 31.6 years were assigned to this study after they provided written informed consent. During the study period, we conducted 72 measurements of reactive hyperemia-peripheral arterial tonometry (RH-PAT) in the morning before or after their duty. At each measurement of the RH-PAT, we recorded the participants' hours of sleep and evaluated their degree of fatigue using a visual analog scale (VAS). RESULTS: Although the VAS was significantly less (36 ± 16% and 64 ± 12%, p < 0.001) and the hours of sleep were longer (6.0 ± 1.1 h and 2.3 ± 1.0 h, p < 0.001) before duty compared to those after duty, the RHI was comparable between them (2.12 ± 0.53 vs. 1.97 ± 0.50, p = 0.21). The VAS score was significantly higher in participants with low RHI (< 1.67) than in those with normal RHI (≥ 2.07) (59 ± 13% and 46 ± 21%, respectively, p < 0.05). However, binary logistic regression showed no significant association between low RHI and the VAS when adjusted for systemic blood pressure (SBP) and heart rate variability (HRV). In a simple regression analysis, the RHI was significantly correlated with the VAS score but not with sleep duration. A multiple linear regression analysis also showed no significant association between the RHI and VAS scores after adjustment for SBP and HRV. CONCLUSIONS: Vascular endothelial function was not associated with overnight duty, hours of sleep, or degree of fatigue in healthy young adults. Since the RHI may be decreased in severe fatigue conditions through autonomic nerve activity, one should consider the physical and mental conditions of the examinee when evaluating the RH-PAT results.

Association between lipid profile and endothelial dysfunction as assessed by the reactive hyperemia index.

INTRODUCTION: We investigated the associations between endothelial dysfunction (ED) as evaluated by the reactive hyperemia index (RHI) obtained using Endo-PAT2000® and atherosclerotic risk factors in patients who underwent coronary artery angiography (CAG). METHODS: The subjects consisted of 191 patients who were clinically suspected to have CAD and underwent CAG, and in whom we could perform Endo-PAT2000®. We divided the patients into ED (RHI<1.67, n = 71) and non-ED (RHI≥1.67, n = 120) groups. RESULTS: The ED group was significantly older and showed a higher ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) (L/H) than the non-ED group. A multivariate logistic regression analysis was performed to examine the associations between the presence of ED and age, gender, and BMI in addition to L/H. Age [odds ratio (OR) = 1.03, p = .02] and L/H (OR = 1.64, p = .01) were identified as significant independent markers of the presence of ED. Next, we divided 122 patients with statin treatment into ED (n = 40) and non-ED (n = 82) groups. The ED group tended to have higher L/H and lower HDL-C than the non-ED group. HDL-C (OR = 0.95, p = .01) and age (OR = 1.05, p = .04) were identified as independent markers of the presence of ED. CONCLUSIONS: L/H was an independent marker of the presence of ED in patients without dyslipidemia. In addition, among patients with statin treatment, HDL-C was an independent marker of the presence of ED.

Endothelial Dysfunction during Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is characterized by high cardiovascular risk, which is further amplified during acute COPD exacerbations (AECOPD). Endothelial dysfunction has been previously suggested as one of the potential pathogenetic mechanisms. In order to study the effects of AECOPD on endothelial function assessed by available functional methods, we performed a literature search involving Pubmed and Scopus databases. Eligible studies were those that included adult patients with COPD and evaluated endothelial damage via semi-invasive or noninvasive functional methods, during AECOPD and after recovery or in stable condition. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved studies. Endothelial function was significantly impaired during AECOPD compared to recovery/stable condition (SMD: -0.87, 95%CI [-1.19, -0.55]). Patients during AECOPD presented a significantly worse response in endothelium-dependent (flow-mediated dilatation WMD: -2.59, 95%CI [-3.75, -1.42]) and independent vasodilation (nitroglycerine-mediated dilatation WMD: -3.13, 95%CI [-5.18, -1.09]) compared to recovery. Sensitivity analyses confirmed the above results. In conclusion, endothelium-dependent and independent vasodilation is worse during AECOPD compared to the stable condition. Endothelial dysfunction could play a role in the high cardiovascular risk during AECOPD.

Eplerenone Improves Vascular Endothelial Function in Patients with Primary Aldosteronism: A Pilot Study.

Primary aldosteronism (PA) is associated with a high risk of cardiovascular complications. Large-scale clinical studies have demonstrated that mineralocorticoid receptor antagonists (MRA) exhibit organ-protective effects and improve the prognosis of patients with heart failure and myocardial infarction, and daily clinical practice suggests that MRA seem to improve vascular endothelial dysfunction. In this pilot study, we treated 10 PA patients with eplerenone for 3 months. We used Endo-PAT to evaluate the effects of MRA on vascular endothelial function and analyzed the data for correlative factors. The primary outcome measure, the reactive hyperemia index (RHI), was 1.71 before therapy and increased significantly to 2.21. Univariate analysis showed a significant correlation between the rate of change in RHI and that in plasma renin activity (PRA). Since plasma aldosterone concentration increases during MRA therapy, PRA may be the best marker for selecting the most appropriate dose of MRA. PRA can potentially be used for adjusting the dose of MRA, in addition to adjusting blood pressure and serum potassium level.

Maternal endothelial function, circulating endothelial cells, and endothelial progenitor cells in pregnancies conceived with or without in vitro fertilization.

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 response (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.

Predictive value of combining the SYNTAX score with reactive hyperemia index in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: To investigate the predictive value of SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS) combined with reactive hyperemia index (RHI) in predicting 2-year major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Both SS and RHI are good predictors of MACE; however, it is unknown whether combining SS and RHI could improve predictability of MACE in patients with ACS undergoing PCI. METHODS: We undertook a prospective study in 401 ACS patients that underwent PCI. The RHI-SYNTAX score (RSS) was calculated by categorizing and summing up the RHI and SS of individual patients. Patients with RHI < 1.67 are given 1 point, RHI ≥ 1.67 given 0 points, and those with SS ≤ 22 scored as 0 and SS > 22 as 1 point. Patients were classified into three groups: low RSS (group 0), moderate RSS (group 1), and high RSS (group 2). RESULTS: Among patients in the low, moderate, and high groups, the 2-year rates of MACE were 5.50, 10.66, and 23.33%, respectively (p < .0001). Total revascularization rates were 1.83, 2.54, and 8.89%, respectively (p = .015). Ischemic stroke rates were 0.00, 3.67, and 5.56%, respectively (p = .031). By multivariate analysis, the RSS was an independent predictor of 2-year MACE (hazard ratio: 2.09, 95% CI: 1.36-3.21, p = .001). Receiver-operator characteristic analysis indicated that the area under the curve significantly improved from 0.63 to 0.69, when RHI was added to SS (p < .0001). CONCLUSIONS: RSS is correlated with 2-year MACE in patients presenting with ACS undergoing PCI.

Exposure to airborne fine particulate matter is associated with impaired endothelial function and biomarkers of oxidative stress and inflammation.

Epidemiological evidence suggests that exposure to air pollution is a leading risk factor for cardiovascular disease (CVD). However, there is little direct evidence linking exposure to vascular dysfunction. We conducted a cross-sectional study of 100 participants, recruited from the University of Louisville Clinics. Endothelial function was assessed by calculating the reactive hyperemia index (RHI). Oxidative stress was indexed by measuring urinary levels of isoprostanes (n = 91). Inflammatory biomarkers were measured in the plasma (n = 80). Daily average PM2.5 levels were obtained from regional monitoring stations. Adjusted associations between PM2.5 levels and measured outcomes were tested using generalized linear models. The average age of participants was 48 years (44% male, 62% white); 52% had a diagnosis of hypertension, and 44% had type-2 diabetes. A 12.4% decrease in RHI was associated with 10 µg/m3 increase in PM2.5 (95% CI: 21.0, -2.7). The F-2 isoprostane metabolite showed a positive association of 28.4% (95% CI: 2.7, 60.3) per 10 µg/m3 increase in PM2.5. Positive associations were observed with angiopoietin 1 (17.4%; 95% CI: 2.8, 33.8), vascular endothelial growth factor (10.4%; 95% CI: 0.6, 21.0), placental growth factor (31.7%; 95% CI: 12.2, 54.5), intracellular adhesion molecule-1 (24.6%; 95% CI: 1.6, 52.8), and matrix metalloproteinase-9 (30.3%; 95% CI: 8.0, 57.5) per 10 µg/m3 increase in PM2.5. Additionally, a 10 µg/m3 increase in PM2.5 was associated with 15.9% decrease in vascular cell adhesion molecule-1 (95% CI: 28.3, -1.3). These findings suggest that exposure to PM2.5 is associated with impaired vascular function, which may result from oxidative stress and inflammation, thereby leading to a pro-atherogenic state.

Acute effects of oral triglyceride load on dynamic changes in peripheral endothelial function in heart failure patients with reduced ejection fraction and healthy controls.

BACHGROUND: Postprandial hyperlipaemia impairs endothelial function, possibly via oxidative-stress-mediated mechanisms. The aim of this study was to evaluate the acute effects of an oral triglyceride load (OTGL) on peripheral endothelial function in heart failure patients with reduced ejection fraction (HFrEF) compared to healthy controls. DESIGN: Prospective cross-sectional. METHODS: We enrolled 47 patients with HFrEF and 20 healthy controls. Peripheral endothelial function was assessed with EndoPAT2000 technology using a reactive hyperaemia index (RHI) and pulse wave amplitude (PWA) at baseline (after 8-h overnight fasting) as well as 1, 2, 3 and 4-h post-OTGL consumption (250-ml cream drink). Pulse wave amplitude index (PWAI) was calculated as a ratio of PWA at each time point to the baseline PWA. RESULTS: RHI at baseline was lower in HFrEF patients compared to controls (1.7 ± 0.3 and 2.3 ± 0.6, respectively; P = 0.001). The OTGL accounted for a physiologic increase in PWA in healthy controls (p = 0.01), but this change was not observed in HFrEF patients. After 4 h, vasodilator response was significantly increased in healthy controls but not patients with HFrEF (2.3 ± 1.3 vs. 1.3 ± 0.8 respectively, P < 0.05). CONCLUSIONS: The main finding of this study was the impaired postprandial dynamic changes in peripheral endothelial function in patients with HFrEF compared to healthy controls. A high-fat load that caused acute hypertriglyceridaemia significantly increased resting blood flow and peak flow at reactive hyperaemia in healthy subjects. By contrast, patients with HFrEF exhibited impaired dynamic changes in peripheral endothelial function after oral triglyceride load.

High-dose atorvastatin improves vascular endothelial function in patients with leukoaraiosis.

OBJECTIVE: Leukoaraiosis (LA), as an age-related white matter degeneration, is mainly caused by chronic ischemia. Our study aims to explore the efficacy of different doses of atorvastatin (ATV) in the vascular endothelial function in patients with LA. METHODS: Our study enrolled 402 LA patients who were then randomly included as control or treated with ATV (10 mg), ATV (20 mg), or ATV (30 mg). The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected by enzyme colorimetric assay. The high-sensitivity C-reactive protein (hs-CRP) level, reactive hyperemia index (RHI), endothelin-1 (ET-1) content, and nitric oxide (NO) level were tested by latex agglutination test, peripheral arterial tonometry technology, radioimmunoassay, and nitrate reductase assay, respectively. RESULTS: After 8 weeks of ATV treatment, the levels of TC, LDL-C, and HS-CRP decreased significantly, and the trends were demonstrated in a more significant way with the increases of dose of ATV. The treatment with ATV at different doses elevated NO level and RHI and declined ET-1 content. Gastrointestinal reaction, muscular pain, and increased aminopherase were observed after treatment with the ATV at different doses with more obvious symptoms detected accompanied by the increase of the dose. The RHI was in negative correlation with the ET-1 and HS-CRP while in positive correlation with NO. CONCLUSION: Our study demonstrates that ATV can significantly improve the vascular endothelial function in LA patients with a dose-dependent effect.

Effect of drug-coated balloons versus bare-metal stents on endothelial function in patients with severe lower limb peripheral artery disease.

BACKGROUND: Research shows impaired endothelial function in patients with vascular diseases and improved endothelial function following revascularization and medical treatment. There is, however, a dearth of data on the effects of different endovascular therapeutic strategies on endothelial function. We sought to compare the effects of two endovascular strategies of drug-coated balloons versus stenting on endothelial function. METHODS: The reactive hyperemia index, the ankle-brachial index, and the toe-brachial index were measured in patients undergoing endovascular revascularization preprocedurally and on the 90th postprocedural day. After adjusting for baseline line characteristics, reactive hyperemia index were compared between the two groups at baseline and at 90 days. RESULTS: Between January 2018 and March 2019, 86 patients were prospectively included in a non-randomized manner. Drug-coated ballooning alone was carried out on 46 patients, and bailout stenting after plain balloon angioplasty was performed on the remaining 40 patients The post-revascularization reactive hyperemia index exhibited a significant rise in both groups (1.58 ± 0.21 vs. 1.43 ± 0.20; P = 0.0001). There was no difference in the postprocedural reactive hyperemia index between the two treatment groups. Additionally, the follow-up reactive hyperemia index showed no significant change compared with the postprocedural reactive hyperemia index (1.58 ± 0.23 vs. 1.57 ± 0.22). The results of subgroup analysis between a group of clinically high-risk patients and a group of patients with complex lesions were similar to the aforementioned results. CONCLUSIONS: The reactive hyperemia index was significantly improved by endovascular therapy in our study population. However, no difference was observed between drug-coated ballooning and bare-metal stenting, which highlights the effects of vessel patency on endothelial function.

Preoperative endothelial function and long-term cardiovascular events in patients undergoing cardiovascular surgery.

We recently reported that preoperative endothelial dysfunction [i.e., reactive hyperemia index (RHI) ≤ 1.64] predicted short-term postoperative adverse events in patients undergoing cardiovascular surgery. However, the relationship between preoperative RHI and long-term cardiovascular risk in these patients is unclear. A total of 195 patients with at least 1-year follow-up who underwent cardiovascular surgery were included. Preoperative endothelial function was assessed by RHI. The primary outcome was a composite of cardiac death, stroke, myocardial infarction, rehospitalization due to heart failure, and any coronary revascularization. Nineteen patients (9.7%) met the primary outcome, including cardiac death (n = 7), stroke (n = 5), heart failure (n = 9), and coronary revascularization (n = 2) during a median follow-up of 20 months. There was no significant difference in the baseline characteristics between patients with RHI ≤ 1.64 (n = 86) and those with RHI > 1.64 (n = 109). The primary outcome occurred in 13 patients with RHI ≤ 1.64 (15.1%) and in 6 patients with RHI > 1.64 (5.5%). Kaplan-Meier analysis demonstrated a significantly higher incidence of the primary outcome in patients with RHI ≤ 1.64 compared to their counterpart (hazard ratio 2.94; 95% confidence interval 1.12-7.75; p = 0.02). Multivariate analysis showed diabetes and RHI ≤ 1.64 as independent predictors for the primary outcome. In conclusion, preoperative endothelial dysfunction assessed by RHI was associated with long-term cardiovascular events in patients undergoing cardiovascular surgery.

Digital microvascular reactivity does not decline with impaired renal function in chronic kidney disease.

BACKGROUND: The reactive hyperemia index (RHI), measured by peripheral arterial tonometry (PAT), is a novel measurement of endothelial function and has been proven to be valuable in cardiovascular risk stratification in several populations. The current study aims to explore its relation to renal function and its association with traditional cardiovascular risk factors in patients with chronic kidney disease (CKD). METHODS: Subjects with non-dialysis dependent CKD were recruited and 252 of them had a successful PAT test. In addition to general demographic and medical information, carotid-femoral pulse wave velocity (cfPWV), carotid-radial pulse wave velocity (crPWV) and augmentation index (AIx) were recorded. RESULTS: The mean age of the study population was 57.7 (±14.7) years and 155 (61.5%) were males. The average RHI was 1.92 (±14.7) with no difference noted between males and females. There was no statistically significant correlation between RHI and eGFR (r = - 0.107, p = 0.089) or urine protein-to-creatinine ratio (r = 0.036, p = 0.570). With adjustment for age and sex, RHI was associated with systolic blood pressure (BP) (ß = 0.006, p = 0.001), diastolic BP (ß = 0.008, p = 0.010), heart rate (ß = - 0.007, p = 0.015) crPWV (ß = 0.037, p = 0.022) and AIx (ß = 0.006, p = 0.001), but not with cfPWV or any other conventional risk factors analyzed. Systolic BP remained the only predictor for RHI in the stepwise regression analysis. CONCLUSIONS: RHI did not decline with reduced renal function in CKD patients and had a modest association with traditional cardiovascular risk factors. Further studies are warranted to determine if RHI could predict cardiovascular outcome in CKD patients.

Endothelial function estimated by digital reactive hyperemia in patients with atherosclerotic risk factors or coronary artery disease.

Due to the complex profile of atherosclerotic risk factors, an integrated analysis of a specific individual is difficult. Endothelial function reflects a composite of various risk factors, and may be used as an optimal tool to estimate the overall atherosclerotic risk. In this study, we investigated the value of digital Reactive Hyperemia Index (RHI) in an actual population with multiple atherosclerotic risk factors or coronary artery disease (CAD). A total of 417 patients from the Seoul National University Boramae Medical Center RHI registry were enrolled in this study. Patients were enrolled from January, 2013 to July, 2016. RHI was measured using the EndoPAT2000 system (Itamiar Medical Inc. Israel). The mean value of RHI was 1.67 ± 0.48 in total study population. Among various atherosclerotic risk factors, RHI was significantly lower in older (> 60 years) patients, diabetics, smokers' patients on statin therapy, and those with coronary or cerebrovascular disease. Most of these findings were consistent after adjustment with multiple regression analysis. RHI was significantly associated with CAD, with a hazard ratio of 1.80 (95% confidence interval 1.15-2.80, p = 0.010). In the subgroup with CAD, current smoking was the only finding showing a lower RHI. Brachial-ankle pulse wave velocity, which is a surrogate marker of arterial atherosclerotic change, was not correlated with RHI in patients with clinically significant atherosclerotic disease. RHI was significantly reduced by major atherosclerotic risk factors and in clinical atherosclerotic disease. RHI may reflect a composite effect of risk factors pertaining to the endothelial function.