Reactive Hyperemia Index Research Articles

Salivary Microbiota Associated with Peripheral Microvascular Endothelial Dysfunction

Oral health is associated with atherosclerotic cardiovascular disease (ACVD). We previously identified the salivary microbiota characteristics of patients with ACVD. However, whether salivary microbiota is characteristic under impaired vascular endothelial function before ACVD onset remains unclear. Therefore, we aimed to evaluate the characteristics of salivary microbiota associated with peripheral microvascular endothelial dysfunction. We collected saliva samples from 172 community-dwelling elderly individuals without a history of ACVD and performed 16S rRNA metagenomic analysis. We assessed the peripheral microvascular endothelial function using reactive hyperemia index (RHI) and compared the salivary microbiota in the groups with normal (RHI ≥ 2.10), borderline, and abnormal (RHI ＜1.67) peripheral endothelial function. Furthermore, we applied machine learning techniques to evaluate whether salivary microbiota could discriminate between individuals with normal and abnormal endothelial function. The number of operational taxonomic units (OTUs) was higher in the abnormal group than in the normal group (p=0.037), and differences were found in the overall salivary microbiota structure (unweighted UniFrac distances, p=0.038). The linear discriminant analysis (LDA) effect size (LEfSe) algorithm revealed several significantly differentially abundant bacterial genera between the two groups. An Extra Trees classifier model was built to discriminate between groups with normal and abnormal vascular endothelial function based on the microbial composition at the genus level (AUC=0.810). The salivary microbiota in individuals with endothelial dysfunction was distinct from that in individuals with normal endothelial function, indicating that the salivary microbiota may be related to endothelial function.

Decreased role of neuropeptides in the microvascular function in migraine patients with polycystic ovary syndrome

Background and aimsTo understand pathophysiological mechanisms underlying migraine as a cardiovascular risk factor, we studied neuropeptide action and endothelial function as measures of peripheral microvascular function in middle-aged women with or without migraine. MethodsWe included women with the endocrine disorder polycystic ovary syndrome (PCOS), a population with supposed elevated cardiovascular risk, with and without comorbid migraine. In 26 women without and 23 women with migraine in the interictal phase (mean age 50.8 ± 2.9 years) local thermal hyperemia (LTH) of the skin of the volar forearm was measured cross-sectionally under control conditions, after inhibition of neuropeptide release by 5% lidocaine/prilocaine (EMLA) cream application, and after inhibition of nitric oxide formation by iontophoresis of NG-monomethyl-l-arginine (L-NMMA). Hereafter, changes in the natural logarithm of the reactive hyperemia index (lnRHI) and augmentation index (AI) during reperfusion after occlusion-derived ischemia were measured. ResultsWhile mean values under control conditions and L-NMMA conditions were similar, migraine patients had a significantly higher mean area of the curve (AUC) of the total LTH response after EMLA application than those without (86.7 ± 26.5% versus 67.9 ± 24.2%; p = 0.014). This was also reflected by a higher median AUC of the plateau phase under similar conditions in women with migraine compared to those without (83.2% (IQR[73.2–109.5]) versus 73.2% (IQR[54.3–92.0]); p = 0.039). Mean changes in lnRHI and AI scores were similar in both groups. ConclusionsIn PCOS patients with migraine, neuropeptide action was lower compared with those without migraine. While larger studies are warranted, these findings provide a potential mechanism supporting previous findings that migraine may be independent from traditional risk factors, including atherosclerosis.

1311-P: Insulin Resistance in Non-obese Young Adults with Type 1 Diabetes

Insulin resistance has been noted in youth and adults with type 1 diabetes (T1D) and is associated with higher levels of cardiovascular and kidney complications. Obesity is increasing in populations with T1D, and the degree of insulin resistance in younger adults with T1D who are free from complications and non-obese isn’t clear. We performed hyperinsulinemic euglycemic clamps in non-obese adults aged 20-45 with and without T1D. Inclusion criteria included diabetes duration > 5 years and HbA1c <9% among people with T1D, or no diabetes based on fasting glucose and HbA1c among controls; Body mass index (BMI) < 30 kg/m2, no use of statins or other medication affecting insulin sensitivity, non-smokers and normal thyroid function. Participants were given a fixed macronutrients study diet for 2 days and were asked to refrain from vigorous exercise for 72 hours. Clamps were performed by a single investigator after an overnight stay. A sliding scale insulin infusion was used overnight for participants with T1D. Arterial stiffness (brachial artery distensibility, pulse wave velocity and reactive hyperemia index) was assessed. There were 47 participants, 24 with T1D and 23 without diabetes. 53% were women (25/47), and the average age did not differ between controls and people with T1D (31 ± 6 years vs. 28 ± 6 years, p=0.12). Whole body insulin sensitivity estimated by glucose infusion rate (GIR) per kg fat free mass was reduced by more than half in adults with T1D (LS mean ± SE =5.4 ± 1.0 mg/kg FFM/min) compared to adults without diabetes (12.7 ± 1.0 mg/kg FFM/min, p<0.0001). In contrast, there were no differences in BMI, body fat, urinary albumin, or measures of arterial stiffness by diabetes status. Young, non-obese adults with T1D are profoundly insulin resistant compared to nondiabetic adults, even when no differences in vascular stiffness or kidney complications are apparent. These results suggest that insulin resistance may occur earlier than vascular or kidney complications in people with T1D and is independent of obesity. Disclosure C.J. Chartier-Logan: None. I.E. Schauer: None. M. Cree-Green: Consultant; Pollie Inc. Research Support; Amino Corp LLC. L. Pyle: None. B.C. Bergman: Research Support; Eli Lilly and Company. J.K. Snell-Bergeon: None. Funding JDRF (2-SRA-2019-849-S-B)

1093-P: Incretins and Cardiac Autonomic Function in Youth with Obesity across the Glycemia Spectrum

Incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been related to vascular function with variable effects depending on obesity status in adults. The relationship of incretins to vascular function in youth is unclear. We hypothesized that endothelial and cardiac autonomic dysfunction (CAD) are related to lower GLP-1 and GIP in response to glucose ingestion in youth with dysglycemia compared with those with overweight (OW) or normal weight (NW) and normal glucose tolerance (NGT). Adolescents [50 male/52 female; 15.6±1.8 yrs; 24 NW-NGT, 22 OW-NGT, 27 prediabetes and 29 with type 2 diabetes (T2D)] underwent assessment of body composition (DXA scan), 2-hour oral glucose tolerance test (OGTT) with calculation of whole body insulin sensitivity index (WBISI), area under the curve (AUC) of glucose (BG), GLP-1 and GIP. Reactive hyperemia index (RHI), and heart rate variability (HRV), were measured by peripheral arterial tonometry. For HRV, a higher LF/HF (low frequency to high frequency ratio) is indicative of CAD with loss of parasympathetic tone and decreased HRV. The ratios of AUC-GLP-1 and AUC-GIP to AUC-BG were lower in the groups with dysglycemia compared NGT groups (p=0.016 and 0.001, respectively). GLP-1 and GIP were not related to RHI. Fasting and AUC-GLP-1, but not GIP, negatively related to LF/HF (r=-0.37, p=0.002 and r=-0.43, p<0.001 respectively). In a linear regression model with LnLF/HF as the dependent variable, AUC-BG (β=0.31, p=0.04) and AUC-GLP-1 (β=-0.44, p=0.002) contributed to the variance in LnLF/HF independent of %body fat, hs-CRP, WBISI, age, sex, race-ethnicity and Tanner stage (R2= 0.27, p=0.04). Youth with obesity and dysglycemia have impaired incretin response. Glycemia is negatively, whereas GLP-1 is positively associated with HRV after accounting for adiposity, WBIS and inflammation. GLP-1 may be an important determinant of CA function in youth with obesity across the glycemia spectrum. Disclosure H.El ayash: None. F.Bacha: Other Relationship; Takeda Pharmaceutical Co., Ltd., AstraZeneca. Funding U.S. Department of Agriculture-Agricultural Research Service

Systolic function of the single ventricle and exercise capacity, endothelial function, muscle mass and strength in paediatric Fontan patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NHLBI. Background By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Poor exercise capacity, diminished muscle mass and strength, and endothelial dysfunction all impact disease progression. Purpose Here, we present the baseline systolic function data of the single ventricle (SV) in paediatric Fontan patients prior to entering an exercise intervention (RE-ENERGIZE FONTAN) and assess its relationship to exercise capacity, endothelial function, muscle mass, and strength. Methods This randomised controlled trial in Fontan patients utilizes live-video conferencing to deliver a supervised exercise intervention. The patients are randomised to intervention or usual care at baseline. Inclusion criteria include: (1) Age 8–19 years; (2) Exercise clearance by primary cardiologist; (3) English-speaking patient. Exclusion criteria include: (1) NYHA Class IV, (2) Acute illness within the past three months; (3) Active protein losing enteropathy (albumin <2.5 mg/dL); 4) Pacemaker; and/or 5) Cognitive delay impeding participation in the intervention. At baseline, patients underwent a 2D and 3D echocardiogram to measure SV systolic function, a cardiopulmonary exercise test to obtain peak oxygen consumption (peak VO2), endothelial pulse amplitude testing (EndoPAT) to assess endothelial function, Dual Energy X-ray Absorptiometry (DEXA) to assess muscle mass and isokinetic dynamometry to assess handgrip and leg strength. Tom-Tec derived 3D ejection fraction (EF) was calculated. Reactive hyperaemia index (RHI) and the natural log of RHI (lnRHI) were obtained using EndoPAT as measures of endothelial function. Leg lean mass was expressed as sex and age-specific z-score adjusted for leg length. Results We have enrolled 73 Fontan patients. The median age at baseline visit was 13.2 years [IQR, 10.8–15.6]. The median time from Fontan operation was 9.2 years [IQR, 7.1–12.0]. 43 (60%) had a single right ventricle. 3D EF was 49.9±7.2%. Peak VO2 was 1366±520 ml/min and indexed peak VO2 was 27.7±6.5 ml/min/kg. RHI and lnRHI were 1.41±0.51 and 0.31±0.31, respectively. Leg lean mass z-score was −0.84±1.41. Handgrip strength was 18.6±8.01 kg, while leg strength extension and flexion were 58.0±32.9 and 27.2±15.11 ft bls, respectively. 3D EF correlated positively with RHI and lnRHI (Figure 1, p-values: 0.04 and 0.02, respectively). Conclusions In this cohort of paediatric Fontan patients, SV systolic function was diminished and there was a direct correlation between SV systolic function and endothelial function. However, there was no correlation between SV systolic function and exercise capacity, leg lean mass, or muscle strength. Our exercise intervention is designed to demonstrate the impact of aerobic and strength training on cardiac function, exercise capacity, endothelial function, and muscle mass and strength with the ultimate goal of instituting an "exercise prescription" in Fontan patients to decrease long-term morbidity and mortality.

Examining the association of habitual e-cigarette use with inflammation and endothelial dysfunction in young adults: The VAPORS-Endothelial function study.

Acute exposure to e-cigarette aerosol has been shown to have potentially deleterious effects on the cardiovascular system. However, the cardiovascular effects of habitual e-cigarette use have not been fully elucidated. Therefore, we aimed to assess the association of habitual e-cigarette use with endothelial dysfunction and inflammation - subclinical markers known to be associated with increased cardiovascular risk. In this cross-sectional study, we analyzed data from 46 participants (23 exclusive e-cigarette users; 23 non-users) enrolled in the VAPORS-Endothelial function study. E-cigarette users had used e-cigarettes for ≥6 consecutive months. Non-users had used e-cigarettes <5 times and had a negative urine cotinine test (<30 ng/mL). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) were used to assess endothelial dysfunction, and we assayed high-sensitivity C-reactive protein, interleukin-6, fibrinogen, p-selectin, and myeloperoxidase as serum measures of inflammation. We used multivariable linear regression to assess the association of e-cigarette use with the markers of endothelial dysfunction and inflammation. Of the 46 participants with mean age of 24.3 ± 4.0 years, the majority were males (78%), non-Hispanic (89%), and White (59%). Among non-users, 6 had cotinine levels <10 ng/mL while 17 had levels 10-30 ng/mL. Conversely, among e-cigarette users, the majority (14 of 23) had cotinine ≥500 ng/mL. At baseline, the systolic blood pressure was higher among e-cigarette users than non-users (p=0.011). The mean FMD was slightly lower among e-cigarette users (6.32%) compared to non-users (6.53%). However, in the adjusted analysis, current e-cigarette users did not differ significantly from non-users in their mean FMD (Coefficient=2.05; 95% CI: -2.52-6.63) or RHI (Coefficient= -0.20; 95% CI: -0.88-0.49). Similarly, the levels of inflammatory markers were generally low and did not differ between e-cigarette users and non-users. Our findings suggest that e-cigarette use may not be significantly associated with endothelial dysfunction and systemic inflammation in relatively young and healthy individuals. Longer term studies with larger sample sizes are needed to validate these findings.

Endothelial dysfunction in patients with non-ST-segment elevation myocardial infarction

Purpose: Evaluation of peripheral endothelial function using EndoPAT 2000 device in patients with non-ST-elevation myocardial infarction (NSTEMI) and correlation with clinical characteristics of the patients. Material and methods: The study included 39 patients with NSTEMI, hospitalized in 2 PCI centers, in the period 03.2022-03.2023. At 72 hours after admission, peripheral endothelial function was assessed using the EndoPAT 2000 device. Patients were divided into 2 groups according to the presence of peripheral endothelial dysfunction (RHI &lt;1.67). Statistical analysis of the data was performed using the t-test and the χ2 test. Results: The average value of the reactive hyperemia index (RHI) was 1.73 ± 0.47. Endothelial dysfunction was diagnosed in 51,3% of NSTEMI patients. Group I included 19 patients with normal endothelial function (RHI&gt;1.67), and group II – 20 patients with endothelial dysfunction (RHI&lt;1.67). In the group of patients with endothelial dysfunction, two- or three-vessel disease prevailed (χ2=2.7, p=0.43) and a higher rate of coronary angioplasty was recorded (χ2=4.36, p=0.037). Conclusion: Peripheral endothelial dysfunction estimated by the EndoPat 2000 method is identified in 51,3% of patients with NSTEMI. The endothelial dysfunction correlated with severity of coronary lesions. Further studies are needed to assess the diagnostic and prognostic value of the method.

Longitudinal changes in echocardiographic variables and endothelial function to predict cardiovascular toxicities in patients with multiple myeloma receiving carfilzomib.

e20012 Background: Carfilzomib (CFZ) is a second-generation proteasome inhibitor with activity in multiple myeloma (MM) that is associated with cardiotoxicity and dyspnea. The pathophysiology and risk factors for developing these toxicities are not well described. We are conducting a prospective observational study (NCT04827563) of longitudinal changes in cardiovascular and endothelial function among MM patients receiving CFZ. We hypothesize that baseline and longitudinal variations in cardiovascular and endothelial function correlate with development of cardiotoxicity and dyspnea in MM patients receiving CFZ. Methods: Patients with MM receiving first-time CFZ therapy are prospectively enrolled and undergo the following study procedures prior to CFZ initiation and then every 2 weeks for the first 6 weeks of CFZ therapy (C1D1, C1D15, C2D1, C2D15): 24-hour ambulatory blood pressure monitoring, echocardiography, pulse wave velocity, and EndoPAT endothelial function assessment. Patient-reported outcomes are also collected. Cardiovascular adverse events (CVAEs) and dyspnea are assessed at all timepoints, as well as at 3 and 6 months after enrollment, by CTCAE v5.0 and are adjudicated by a cardio-oncologist. Patients with endothelial dysfunction will be defined as reactive hyperemia index (RHI) &lt;1.67 via EndoPAT. Baseline variables were analyzed with unpaired t-tests and longitudinal variables were analyzed by one-way repeated measures ANOVA. Results: Ten patients have completed 6 months of follow-up. Demographic data is summarized in the table. Four patients (40%) developed dyspnea, 2 with grade 1 and 2 with grade 3 at maximum, with most patients developing dyspnea by C1D15. Two patients had ongoing grade 1 dyspnea at follow-up. Four patients (40%) developed grade 3 or higher CVAEs, most of which were grade 3 hypertension and/or grade 3 HFpEF. Baseline left ventricular mass was significantly higher in patients who developed dyspnea compared to those who did not (p=0.040). EndoPAT values were significantly different between C1D1 and C1D15 in those with CVAEs (2.28 vs 1.74, p=0.0223). NTproBNP values were also significantly different between C1D1 and C1D15 in those with dyspnea (74.5 vs 129.3, p=0.006). Conclusions: MM patients that developed dyspnea during treatment with CFZ had a higher baseline LV mass and were more likely to develop increases in NTproBNP despite preserved ejection fraction, consistent with HFpEF. This group also had a greater change in EndoPAT values suggesting that short-term alterations in endothelial function may have a role in the development of dyspnea in those who may have the anatomic substrate for HFpEF. Clinical trial information: NCT04827563 . [Table: see text]

0455 Association of high-risk obstructive sleep apnea with endothelial dysfunction in a large population-based sample in MiHeart Study

Abstract Introduction Obstructive Sleep Apnea (OSA) is associated with endothelial dysfunction and cardiovascular disease (CVD). There are limited data evaluating the association with endothelial dysfunction measured by reactive hyperemia index (RHI) in an asymptomatic population free of CVD. We hypothesized that there would be a significant association between high risk of OSA and endothelial dysfunction in the Miami Heart (MiHeart) study, a population-based cohort of relatively young individuals free of known cardiovascular disease (CVD). Methods Cross-sectional data from 2097 participants (mean age: 53 years, 50% female) enrolled in the MiHeart study and underwent flow-mediated dilation using the EndoPat 2000 system was analyzed for this study. OSA was determined by Berlin questionnaire (high vs. low risk); logistic regression was utilized to examine the association between high OSA risk (reference low-risk OSA) and RHI (cut off &amp;lt; 1.67 vs. ≥1.67) in unadjusted models, and after accounting for age, sex, race/ethnicity (model 2), and BMI, diabetes, hypertension, high cholesterol, and smoking (model 3). Results 704 (34%) participants were categorized as high OSA risk, according to the Berlin questionnaire. These participants were more likely to be male, Hispanic and had a higher CVD risk factor burden when compared to low OSA risk. In addition, those with high OSA risk had higher prevalence of endothelial dysfunction (17.5% vs. 13.9%) than the low OSA risk (p &amp;lt; 0.05) group. High risk of OSA was associated with a higher risk of endothelial dysfunction in the unadjusted model (OR=1.32, 95% CI 1.03, 1.68). When adjusted for age, sex, and race/ethnicity, this association was slightly attenuated (OR 1.26, 95% CI 0.97, 1.62). Upon adjusting for CVD risk factors (model 3), the association between high-risk OSA and endothelial dysfunction was further attenuated and was not statistically significant (OR=1.18, 95% CI 0.87, 1.59). There was a strong, independent association between presence of diabetes and endothelial dysfunction (OR= 2.01, 95% CI 1.35, 2.94). Conclusion Younger individuals with high risk for OSA have elevated odds of endothelial dysfunction, and this relationship is likely mediated by demographics and cardiometabolic risk factors such as diabetes. Support (if any) The Miami Heart Study is funded by Baptist Health South Florida.

0757 Associations between Objective Sleep Health and Cardiovascular Health in Adolescents with Type 1 Diabetes

Abstract Introduction Adolescents with type 1 diabetes (T1D) are at risk for early-onset cardiovascular disease due to increased arterial stiffness, decreased endothelial function, and early-stage hypertension compared to healthy peers. Poor sleep health has been associated with greater glycemic variability, increased insulin resistance, and poorer cardiovascular health; however, the relationship between sleep and vascular health has not been studied in adolescents with T1D. The aim of this study was to evaluate associations between objectively measured sleep and cardiovascular health in this population. We hypothesized that better sleep health would correlate with better cardiovascular health. Methods Twenty-four adolescents with T1D completed the study during the academic year. Sleep was monitored for one week at home with actigraphy. Watchpat-assessed apnea hypopnea index (AHI) and vascular measures were obtained during an overnight study visit. EndoPAT estimated reactive hyperemia index (RHI) and augmentation index (AI). Dynapulse measured systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), heart rate (HR), pulse wave velocity (PWV), and brachial distensibility and resistance (BrachD, BrachR). Correlations between sleep and vascular measures were examined. Results Participants were an average age of 15.5±1.1 years (54.2% female, 83.3% White non-Hispanic, BMI 58.8 ±25.8%ile, HbA1c 7.5±1.2%). Average school night (weekday) sleep duration was 6.7±0.8 hours and average sleep efficiency (SE) was 82.8±6.9%. The majority (87.5%) of participants slept less than the clinical recommendation of 8-10 hours per night. Worse actigraphy-estimated SE was associated with higher DBP (r=-0.52, p=0.02; mean= 59.2±6.7mmHg) and MAP (r=-0.46, p=0.04; mean= 79.5±7.5mmHg). Higher AHI was associated with higher BrachR (r=0.81, p&amp;lt; 0.001). No significant associations were identified between sleep variables and RHI, AI, HR, PWV, or BrachD (all p&amp;gt;0.05). Conclusion Poorer SE and higher AHI were associated with poorer indicators of vascular health in adolescents with T1D, consistent with prior literature linking poorer sleep health with risk factors for hypertension in adults with T1D. Further research is needed to determine if improving sleep can improve cardiovascular comorbidities in adolescents with T1D. Support (if any) JDRF 2-SRA-2019-848-S-B; JDRF 2-SRA-2022-1144-M-B; Ludeman Center for Women’s Health Research COVID-19 Relief Supplemental Grant; Colorado Clinical &amp; Translational Research Center Maternal &amp; Child Health Pilot Award; CTSA UL1 TR002535

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.

Endothelial function predicts 5-year adverse outcome in patients hospitalized in an emergency department chest pain unit.

Although endothelial function is a marker for cardiovascular risk, endothelial dysfunction assessment is not routinely used in daily clinical practice. A growing challenge has emerged in identifying patients prone to cardiovascular events. We aim to investigate whether abnormal endothelial function may be associated with adverse 5-year outcomes in patients presenting to a chest pain unit (CPU). Following endothelial function testing using EndoPAT 2000 in 300 consecutive patients without a history of coronary artery disease, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability. Mean 10-year Framingham risk score (FRS) was 6.6 ± 5.9%; mean 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 7.1 ± 7.2%; median reactive hyperemia index (RHI) as a measure of an endothelial function 2.0 and mean was 2.0 ± 0.4. During a 5-year follow-up, the 30 patients who developed major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions, had higher 10-year FRS (9.6 ± 7.8 vs. 6.3 ± 5.6%; P = 0.032), higher 10-year ASCVD risk (10.4 ± 9.2 vs. 6.7 ± 6.9%; P = 0.042), lower baseline RHI (1.6 ± 0.5 vs. 2.1 ± 0.4; P < 0.001) and a greater degree of coronary atherosclerotic lesions (53 vs. 3%, P < 0.001) on CCTA compared with patients without MACE. Multivariate analysis demonstrated that RHI below the median was an independent predictor of 5-year MACE (odds ratio 5.567, 95% confidence interval 1.955-15.853; P = 0.001). Our findings suggest that noninvasive endothelial function testing may contribute to clinical efficacy in triaging patients in the CPU and in predicting 5-year MACE. NCT01618123.

Endothelial Function in Youth With Bipolar Disorder: Preliminary Evidence for Mood Polarity Differences.

Background: Bipolar disorder (BD) confers risk for accelerated atherosclerosis and early cardiovascular disease (CVD). In adults, mood symptom burden is associated with CVD. Here we examine endothelial dysfunction, considered an early predictor of CVD, in relation to mood states and symptoms among youth with BD.Methods: Participants were 209 youth, aged 13-20 years, including 114 with BD and 95 healthy controls (HC) recruited between 2012 and 2020. Diagnoses and mood symptoms were ascertained using validated, semi-structured interviews based on DSM-IV-TR criteria. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry (PAT). RHI was compared across 4 groups: BD-euthymic (n = 34), BD-depressed (n = 36), BD-hypomanic/mixed (n = 44), and HC (n = 95) controlling for age, sex, and obesity. Analyses also examined for RHI-mood associations in the overall BD group.Results: RHI was significantly different between groups (F3,202 = 4.47, P = .005, ηp2 = 0.06). Specifically, RHI was lower in the BD-depressed group compared to HC (P = .04, d = 0.4). Additionally, the BD-hypomanic/mixed group had higher RHI compared to the BD-euthymic (P = .02, d = 0.55), BD-depressed (P < .001, d = 0.79), and HC (P = .04, d = 0.55) groups. Lastly, within the BD group, higher RHI was associated with higher mania scores (P = .006, β = 0.26), but not depression scores. All analyses remained significant in sensitivity analyses further controlling for cardiovascular risk factors and for current lithium, second-generation antipsychotic, and any medication use.Conclusions: We found that symptomatic youth with BD have anomalous RHI, which varies according to mood polarity. Future studies in larger samples, with prospective repeated measures, should investigate whether endothelial dysfunction partially subserves the psychiatric symptoms and cardiovascular risk observed in BD.

Sleep quality and PTSD symptoms predict vascular dysfunction in young, trauma-exposed women

Introduction: Cardiovascular disease (CVD) remains the leading cause of death among women in the United States. Although premenopausal women are thought to be protected from CVD, trauma exposure increases their CVD risk. Poor sleep – a CVD risk factor – is common after trauma exposure. Further, accumulating evidence suggests that vascular dysfunction is independently associated with CVD. However, the link between sleep and vascular function in otherwise healthy, trauma-exposed young women is not known. Therefore, the purpose of the present study was to investigate the individual and combined effects of sleep quality and post-traumatic stress disorder (PTSD) symptom severity on endothelial function and arterial stiffness. Methods: We recruited 42 otherwise healthy women (18 –­ 40 years) from diverse backgrounds who had been exposed to trauma. We successfully collected data on sleep, vascular function, depression and PTSD symptom severity in 35 women, across two visits. Sleep efficiency (SE) was objectively measured as the relative time (%) spent asleep while in bed, using wrist actigraphy. Participants wore the ActiWatch for seven days between visits. During visit one, PTSD symptom severity was assessed using the PTSD checklist for DSM 5 (PCL5) and depressive symptom severity with the Beck Depression Inventory (BDI). At visit two, we assessed endothelial function via reactive hyperemia index (RHI) using peripheral arterial tone and arterial stiffness via pulse wave velocity (PWV) using applanation tonometry. Results: Participants’ mean age and body mass index (BMI) were 27±7 years and 27±6 kg/m 2 respectively. Mean systolic and diastolic blood pressures were 103±9 and 67±8 mmHg respectively, and heart rate was 74±12 bpm. SE was positively correlated with RHI (r=0.35, p=0.019), and negatively correlated with PWV (r=-0.46, p=0.004). PCL5 score was negatively correlated with RHI (r=-0.52, p&lt;0.001), and not PWV (r=0.12, p=0.253). Additionally, a positive association was observed between age and PWV (r=0.50, p=0.001). BDI score was only correlated with PCL5 (r=0.60, p&lt;0.001). Next, to explore the predictive value of SE and PCL5 on RHI and PWV, we conducted separate multiple linear regression models with SE, PCL5 scores and age as predictors. The model predicting RHI was significant (R 2 =0.48, p&lt;0.001), with PCL5 emerging as the strongest predictor (β=-0.56, p&lt;0.001). Similarly, the model predicting PWV was significant (R 2 =0.45, p&lt;0.001), with both SE and age as the strongest predictors (β=-0.44, p=0.004 and β=0.49, p=0.001, respectively). Conclusion: Our results suggest that poor sleep may contribute to increased arterial stiffness after trauma exposure, while endothelial dysfunction could be driven by PTSD symptom severity. These findings could serve to distinguish trauma-exposed women at risk of CVD and identify specific interventions (i.e., targeting sleep efficiency or PTSD symptoms) to prevent or delay vascular dysfunction. UL1TR002494, NIH K01HL161027 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparison of the EndoPAT device with a unique vascular assessment of reactive hyperemia

The EndoPAT device (Itamar Medical) is used to determine endothelial function by using peripheral arterial tonometry during reactive hyperemia. It has been shown to be related to the gold standard non-invasive technique of flow-mediated dilation ultrasound assessment. These methodologies have technical requirements and/or ongoing operational costs that could be prohibitive to under-resourced clinics or researchers. We hypothesized that using a re-usable and cost-effective procedure of determining the reactive hyperemic response using piezo-electric pulse transducers (ADInstruments) would give similar results to the EndoPAT. Reactive hyperemia was induced by occluding blood flow to the forearm for 5 minutes using a blood pressure cuff inflated to +50mmHg above systolic blood pressure. The vascular response to the release of the occlusion was assessed using EndoPAT on the index fingers and using piezo-electric transducers on the middle fingers, concurrently. Twenty-five healthy participants (15 female; 31±12years) participated in the study. Participants refrained from caffeine, alcohol, fatty foods, smoking and strenuous exercise for at least 12 hours prior to testing. The EndoPAT reactive hyperemia index (RHI) was determined using proprietary software. The area under the curve (AUC) of the finger pulse waves from the piezoelectric pulse transducers was also determined. The ratio of the AUC of the peak hyperemic response (10s average) compared to the baseline period (3.5min) in the occluded arm was compared to the equivalent ratio in the control arm to determine the pulse-wave reactive hyperemia index (PWRHI). Univariate linear regression and correlation analysis was conducted between RHI and PWRHI. When comparing the two methods, Spearman’s r was 0.67 (p=0.0002) with a coefficient of determination of 0.58. We have found that the two methods correlate well to each other and the PWRHI technique has the potential to make microvascular assessments more accessible to clinicians and researchers. Our PWRHI method still needs to be validated in larger populations with vascular dysfunction and over a wider age-range. Funding provided by the Natural Sciences and Engineering Research Council of Canada. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Reduction in global tissue deformation of the left ventricle as a cause of heart failure and worse quality of life in patients with takotsubo syndrome in the long period of the disease: prospective cohort study

Objective. This study evaluates the severity of chronic heart failure (CHF), ejection fraction (EF), and global contractility of the left ventricle (LV) using Speckletracking (STE) in patients with takotsubo syndrome (TS) in the early and late disease stages of the disease and compares these data with an assessment of the quality of life (QoL) of patients.&#x0D; Material and methods. The study included 60 patients with TS, with a mean age of 65.513.4 years. The severity of CHF symptoms was assessed using the SHOKS scale (assessment of the clinical condition in CHF). The Minnesota Questionnaire and the HeartQol questionnaire were used to study QoL. Echocardiography data (ECHOCG) were recorded during the acute period and at discharge from the hospital. In the late disease period, ECHOCG was performed using the STE method. After 1 year, endothelial function was studied using the EndoPAT 2000 device to determine the reactive hyperemia index.&#x0D; Results. According to the SHOKS scale, the severity of CHF symptoms corresponded to 12 functional class (FC) in all patients with TS in the long-term disease; however, before the development of TS, only 15 people had signs of CHF at the level of 12 FC. According to ECHOCG, LVEF in patients with TS was 44.59.7% at admission, 60.27.6% at discharge, 61.69.2% after a year, and 60.09.0% after 2 years. The average values of global longitudinal and global circular deformation of the left ventricle in patients with TS were 14.03.1 and 15.04.1%, respectively, after 1 year from disease onset and 12.31.9 and 13.11.9%, respectively, after 2 years. When comparing the data of the Minnesota Questionnaire and HeartQol questionnaires, QoL in the long-term of ST was significantly lower than the initial one before disease development. Mean reactive hyperemia index values after 1 year were 1.740.19.&#x0D; Conclusion. Despite the complete restoration of LVEF in patients with TS, clinical manifestations of CHF persist. Using the STE technique during the long term, 90% of patients had abnormalities in the global tissue deformity of the left ventricle. These changes may explain the CHF clinical manifestations and QoL decrease in patients with TS during long-term disease.

Serum MOTS-C Levels are Decreased in Obese Children and Associated with Vascular Endothelial Function.

The increasing prevalence of obesity in children and its associated risk with cardiovascular diseases demand more discovery of the novel biomarkers for developing new treatment options for this complex disease. This study aimed to investigate the association of serum MOTS-C (a peptide encoded in the mitochondrial genome) levels and vascular endothelial function in obese children. A total of 225 obese children (aged 8.1 ± 2.6 years) and 218 healthy children (aged 7.9 ± 2.2 years) were enrolled. Related anthropometric assessment and biochemical evaluation were done in all subjects. Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry, was used for evaluation of peripheral endothelial function. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of serum MOTS-C. Levels of serum MOTS-C and RHI were lower in the obese children compared with the healthy children (P < 0.01). The RHI level was independently associated with body mass index, high-density lipoprotein cholesterol, and MOTS-C in linear regression analysis. Further analysis showed a significant mediating effect of MOTS-C on the correlation between body mass index and RHI in children, with the ratio of mediating effect value of 9.12%. These data identify that MOTS-C is a previously unknown regulator in the development process of obesity-induced vascular changes.

Endothelial Dysfunction in Patients With Takotsubo Syndrome and its Role in Acute and Long Terms Of the Disease

Aim To evaluate the endothelial function using an Endo-PAT2000 instrument before and after mental stress tests in patients with Tacotsubo syndrome (TS) during acute and long-term periods and to compare the obtained results with laboratory markers of endothelial dysfunction (ED).Material and methods This study included 45 patients with TS (mean age, 63.5±13.7 years) and 40 healthy volunteers (control group, CG). All patients of the main group during the acute period (first 7-14 days) and long-term period (at 1 and 2 years), as well as CG subjects, underwent evaluation of the endothelial function with an Endo-PAT 2000 instrument, and the reactive hyperemia index (RHI) was determined before and after mental stress tests. Also, concentrations of endothelin 1 (ET-1) and numbers of circulating endothelial cells (CEC) were measured after a two-year follow-up of TS patients.Results During the acute period of disease, all TS patients (n=45) had ED: RHI was below the threshold level of 1.67; furthermore, 42 (93.3 %) patients retained a lower RHI following mental stress. At one year (n=40), 16 (40%) patients showed ED at rest along with a significantly increased mean RHI. Mental stress produced at one year was associated with ED in 28 (70 %) TS patients. At two years (n=44), resting RHI was lower than normal in 19 (43.2 %) patients. Mental stress tests performed at two years were associated with ED in 29 (65.9 %) patients (RHI ≤1.67). Only 10% of CG subjects had a lower-than-normal RHI, which was significantly less than in the main group of TS patients during the acute and long-term periods (p&lt;0.05). Mean values of laboratory markers for ED also were significantly different between TS patients during the long-term period of disease (n=41) and CG subjects (n=40; p&lt;0.01).Conclusion During acute and long-term periods of disease, most of TS patients had impaired vascular reactivity both at rest and during mental stress. The laboratory markers of ED, ET-1 and CEC can be used in clinical practice for evaluation of the risk for TS.

The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes

ObjectiveBasal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been fully elucidated. In this context, we sought to evaluate the vascular function effects of adding the GLP1-RA exenatide or meal insulin lispro to basal glargine therapy in early T2DM.MethodsIn this 20-week trial, adults with T2DM of < 7-years duration were randomized to 8-weeks treatment with (i) insulin glargine (Glar), (ii) glargine + thrice-daily lispro (Glar/Lispro), or (iii) glargine + twice-daily exenatide (Glar/Exenatide), followed by 12-weeks washout. At baseline, 8-weeks, and washout, fasting endothelial function was assessed with reactive hyperemia index (RHI) measurement by peripheral arterial tonometry.ResultsAt baseline, there were no differences in blood pressure (BP), heart rate (HR) or RHI between participants randomized to Glar (n = 24), Glar/Lispro (n = 24), and Glar/Exenatide (n = 25). At 8-weeks, Glar/Exenatide decreased systolic BP (mean − 8.1 mmHg [95%CI − 13.9 to − 2.4], p = 0.008) and diastolic BP (mean − 5.1 mmHg [− 9.0 to − 1.3], p = 0.012) compared to baseline, with no significant changes in HR or RHI. Notably, baseline-adjusted RHI (mean ± SE) did not differ between the groups at 8-weeks (Glar 2.07 ± 0.10; Glar/Lispro 2.00 ± 0.10; Glar/Exenatide 1.81 ± 0.10; p = 0.19), nor did baseline-adjusted BP or HR. There were no differences between the groups in baseline-adjusted RHI, BP or HR after 12-weeks washout.ConclusionAdding either exenatide or lispro to basal insulin therapy does not appear to affect fasting endothelial function in early T2DM.Trial Registration: ClinicalTrials.Gov NCT02194595.

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease.

Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction. In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure. Reactive hyperemia index and flow-mediated dilation were used to measure microvascular and endothelial function, respectively, before and 30 minutes after a public-speaking mental stress task. Survival models for recurrent events were used to examine the association between vascular response to stress (difference between poststress and resting values) and MACE. Reactive hyperemia index and flow-mediated dilation were standardized in analyses. Of 263 patients (the mean age was 51 years; range, 25-61), 48% were women, and 65% were Black. During a median follow-up of 4.3 years, 64 patients had 141 adverse cardiovascular events (first and repeated). Worse microvascular response to stress (for each SD decrease in the reactive hyperemia index) was associated with 50% greater risk of MACE (hazard ratio, 1.50 [95% CI, 1.05-2.13]; P=0.03) among women only (sex interaction: P=0.03). Worse transient endothelial dysfunction in response to stress (for each SD decrease in flow-mediated dilation) was associated with a 35% greater risk of MACE (hazard ratio, 1.35 [95% CI, 1.07-1.71]; P=0.01), and the association was similar in women and men. Peripheral microvascular dysfunction with mental stress was associated with adverse events among women but not men. In contrast, endothelial dysfunction was similarly related to MACE among both men and women. These results suggest a female-specific mechanism linking psychological stress to adverse outcomes.