Peripheral Endothelial Function Research Articles

Cerebral blood flow in relation to peripheral endothelial function in youth bipolar disorder

IntroductionAnomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD. MethodsParticipants included 113 youth, 13–20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3 T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses. ResultsROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC. ConclusionWe found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.

Peripheral Endothelial and Microvascular Function with Repeated Far-infrared Sauna in Adults with Obesity

Obesity can lead to vascular dysfunction and elevated cardiovascular risk. Repeated far-infrared sauna bathing has improved cardiovascular function in cardiac patients. It is unknown if repeated far-infrared sauna bathing improves vascular function in adults with obesity. Purpose: We hypothesized that brachial artery flow-mediated dilation (FMD) and post-occlusion reactive hyperemia would be improved after 30 far-infrared sauna sessions in adults with obesity. Methods: Five adults with obesity (4 men, 1 woman; age: 33 ± 11; BMI: 36.3 ± 4.2 kg/m2) were assigned to a heat therapy (n=3) or time-control group (n=2). The heat therapy group completed 30 sessions of far-infrared sauna bathing (43 ± 4 min at 54 ± 2°C) at 3-4 times/week for 9 weeks. Peripheral vascular function was assessed before (PRE) and after (POST) the intervention. Brachial artery diameter and blood velocity were recorded via Doppler ultrasound for 1 min of baseline, 5 min of forearm occlusion, and 3 min of post-occlusion. FMD was calculated as the percent change from baseline diameter to peak diameter during post-occlusion. Relevant shear rate was calculated as the area under the curve (AUC) to peak dilation. Peak post-occlusion reactive hyperemia was defined as the peak blood flow during post-occlusion. Total post-occlusion reactive hyperemia was calculated as the AUC for blood flow above baseline for 3 min. Results: Baseline diameter did not differ at PRE vs. POST or between Control (3.76 ± 0.08 vs. 3.78 ± 0.09 mm) and Heat (4.25 ± 0.03 vs. 4.25 ± 0.02 mm) (all p &gt; 0.3977). FMD did not differ at PRE vs. POST and between Control (11.2 ± 5.2 vs. 10.6 ± 10.2%) or Heat (2.8 ± 2.4 vs. 6.2 ± 4.2%) (all p &gt; 0.2684). Relevant shear rate AUC did not differ at PRE vs. POST or between Control (27,412 ± 7,506 vs. 31,251 ± 20,608 a.u.) and Heat (16,538 ± 11,617 vs. 24,952 ± 10,639 a.u.) (all p &gt; 0.2577). Peak post-occlusion reactive hyperemia did not differ at PRE vs. POST or between Control (396 ± 42 vs. 387 ± 17 ml/min) and Heat (464 ± 40 vs. 441 ± 32 ml/min) (all p &gt; 0.1049). Total post-occlusion reactive hyperemia AUC was lower in Heat (140 ± 7 ml) vs Control (262 ± 12 ml) at PRE but did not differ across time or between groups at POST for Heat (212 ± 35 ml) vs Control (246 ± 66 ml). Conclusions: These preliminary data suggest there is no effect of 30 sessions of far-infrared sauna bathing on peripheral endothelial and microvascular function in adults with obesity. This may be due to the duration, frequency, and intensity of the far-infrared sauna compared to other passive heating modalities that have generated beneficial vascular adaptations in other studies. AHA 19TPA34890033. This is the full abstract presented at the American Physiology Summit 2024 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.

Home-Based Heat Therapy and Vascular Function of Adults Living with Type 2 Diabetes: Preliminary Analyses of a Randomized Controlled Trial

Background: Several studies indicate that various heat exposure interventions improve peripheral endothelial function and microvascular reactivity, as well as reduce central arterial stiffness and blood pressure in various populations. Nonetheless, few studies have considered the potential therapeutic effects of heat exposure for people living with type 2 diabetes mellitus (T2DM), who are at high cardiovascular risk. In addition, all heat therapy interventions investigated to date have been laboratory-based, which may limit long-term adherence. HYPOTHESES: This study aims is to determine the effects of a 12-week home-based heat therapy intervention on markers of vascular function in adults living with T2DM. The primary hypothesis is that heat therapy improves peripheral endothelial function relative to a sham intervention. Secondary hypotheses include improved microvascular reactivity, central arterial stiffness, and 24h blood pressure. METHODS: Thirteen adults (66 ± 10 years, 28.9 ± 6.0 kg/m2, 9 men/ 4 women) living with TD2M were randomized to 12 weeks of home-based heat therapy (n=7, lower leg immersion in 42°C water) or a thermoneutral sham intervention (n=6, lower leg immersion in 36°C water). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), microvascular reactivity (post-occlusive reactive hyperemia), arterial stiffness (carotid-femoral pulse wave velocity), and 24h blood pressure (ambulatory blood pressure monitoring), were measured before and after the intervention. RESULTS: Brachial artery FMD changed by 1.72% [95%CI, 0.06; 3.37] in response to heat therapy compared to 0.41% [-1.38; +2.20] in response to the sham intervention. Peak and total reactive hyperemia changed by 0.79 mL/min/mmHg [-0.27; 1.86] and by 1.77 mL/mmHg [0.73; 2.81], respectively, in response to heat therapy compared with 0.76 mL/min/mmHg [-0.38; 1.91] and 1.68 mL/mmHg [0.56; 2.80] in response to the sham intervention. Arterial stiffness changed by 0.55 m/s [-1.62; 2.71] in response to heat therapy compared with -1.60 m/s [-3.75; 0.57] in response to the sham intervention. The 24h-systolic and diastolic blood pressure changed by 6 mmHg [-1; +12] and 2 mmHg [-3; +7], respectively, in response to heat therapy compared with -2 mmHg [-10; +6] and -3 mmHg [-9; +3] in response to the sham intervention. CONCLUSION: These preliminary results suggest that 12 weeks of home-based lower leg hot water immersion improves brachial artery FMD in adults with T2DM. In contrast, the heat therapy intervention does not appear to improve microvascular reactivity, central arterial stiffness, or 24h blood pressure. Cardiometabolic Health Diabetes and Obesity Research Network and Diabète Quebec. This is the full abstract presented at the American Physiology Summit 2024 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.

Vascular responses during handgrip exercise in healthy postmenopausal females and older males

Introduction: Aerobic exercise interventions improve peripheral endothelial function in healthy older males. However, this effect is not always observed in healthy postmenopausal females and possible mechanisms underlying this sex-related difference remain unknown. Greater vascular shear stress during acute exercise is a key stimulus mediating longer-term improvements in vascular function. It remains unknown if postmenopausal females display a reduced endothelial sensitivity to exercise-induced shear stress relative to males of similar age. Objective and hypothesis: The objective of this study is to test the hypothesis that healthy postmenopausal females exhibit a lower endothelial sensitivity to exercise-induced shear stress relative to males. Methods: Fourteen healthy postmenopausal females (67 ± 8 years) not under hormone replacement therapy and 9 males of similar age (65 ± 7 years) performed handgrip exercise for 4 minutes at 20%, 40%, 60%, and 80% of their maximal voluntary contraction. Each exercise bout was separated by a 10-min recovery period. Brachial artery diameter and blood velocity were continuously measured using high-resolution ultrasound and analyzed using edge-detection software. Endothelial sensitivity to shear rate was quantified as the slope of the linear regression between brachial artery dilation (% change from baseline) and shear stress and compared between groups with an independent t-test. Workload, vascular conductance, diameter dilation, and shear stress were analyzed with mixed-effects models. Results: Males exercised at greater workloads relative to females across all exercise bouts (M: 17 ± 11 vs. F: 9 ± 5 kg, p&lt;0.01). Forearm vascular conductance was greater in males throughout each exercise intensity (M: 2.23 ± 1.70 vs. F: 1.03 ± 0.51 ml/min/mmHg, p=0.02). Despite these differences, arterial dilation (M: 5.32 ± 5.55 vs. F: 5.20 ± 4.80%, p=0.96) and shear stress (M: 142 ± 80 vs. F: 171 ± 86 s−1, p=0.27) did not differ between groups across exercise intensities. Endothelial sensitivity to exercise-induced shear stress did not differ between males (0.02 ± 0.05%/s−1) and females (0.03 ± 0.01%/s−1, p=0.67). Conclusion: These data suggest that a reduced endothelial sensitivity to exercise-induced shear stress may not explain why aerobic exercise interventions do not consistently improve peripheral endothelial function in healthy postmenopausal females. Montreal Heart Institute Foundation. This is the full abstract presented at the American Physiology Summit 2024 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.

Impact of Insulin-Induced Relative Hypoglycemia on Vascular Insulin Sensitivity and Central Hemodynamics in Prediabetes.

Relative hypoglycemia (RH) is linked to sympathetic responses that can alter vascular function in individuals with type 2 diabetes. However, less is known about the role of RH on hemodynamics or metabolic insulin sensitivity in prediabetes. Determine if RH alters peripheral endothelial function or central hemodynamics to a greater extent in those with prediabetes (PD) versus normoglycemia (NG). Seventy adults with obesity were classified using ADA criteria as PD (n=34 (28F); HbA1c=6.02±0.1%) or NG (n=36 (30F); HbA1c=5.4±0.0%). Brachial artery endothelial function, skeletal muscle capillary perfusion, and aortic waveforms were assessed at 0 and 120min of a euglycemic clamp (40 mU/m2/min, 90 mg/dl). Plasma nitrate/nitrite and endothelin-1 (ET-1) were measured as surrogates of nitric oxide-mediated vasodilation and vasoconstriction, respectively. RH was defined as the drop in glucose (%) from fasting to clamp steady state. There were no differences in age, weight, or VO2max between groups. PD had higher HbA1c (P<0.01) and a greater drop in glucose in response to insulin (14 vs. 8%; P=0.03). Further, heart rate (HR) increased in NG compared to PD (P<0.01), while forward wave (Pf) decreased in PD (P=0.04). Insulin also tended to reduce arterial stiffness (cfPWV) in NG versus PD (P=0.07), despite similar increases in pre-occlusion diameter (P=0.02), blood flow (P=0.02), and lower augmentation index (AIx75) (P≤0.05). Compared with NG, insulin-induced RH corresponded with a blunted rise in HR and drop in Pf during insulin infusion in adults with PD, independent of changes in peripheral endothelial function.

Effects of pre-exercise intake of plant- and animal-based foods on arterial function and aerobic exercise capacity in healthy young men: a randomized cross-over trial.

The purpose of this study was to examine the effects of plant- versus animal-based food intake before exercise on arterial function and subsequent aerobic exercise capacity. Eleven healthy adult males (mean age, 22.6±1.8 years) participated in this study. A plant- or animal-based randomized meal type crossover comparison was conducted on separate days with a uniform protein, fat, and carbohydrate balance. Both carotid-femoral pulse wave velocity (cfPWV), femoral-ankle pulse wave velocity (faPWV), and brachial artery flow-mediated dilatation (FMD) were measured as indexes of aortic and peripheral arterial stiffness and vascular endothelial function, respectively, before and at 120min after the meal. After these measurements, maximal oxygen uptake was assessed using a graded power test on an electronically braked cycle ergometer. The results revealed that cfPWV was significantly lower, whereas FMD was significantly higher, at 120min after compared with before the plant-based meal (p=0.01 and 0.02, respectively). By contrast, cfPWV and FMD did not change at 120min after compared with before the animal-based meal. In addition, faPWV did not change at 120min after compared with before the meal for either meal type. Maximal oxygen uptake was higher in the plant- than in the animal-based meal type (p=0.02). These results suggest that pre-exercise plant-based food intake may improve central arterial stiffness and vascular endothelial function, which may have favorable implications for aerobic exercise capacity.

Association between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease.

Endothelial dysfunction is a systemic disorder and risk factor for atherosclerosis. Our aim was to assess whether there is a relation between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease (CAD). We prospectively studied 54 patients, who had a positive result for obstructive CAD in coronary CT angiography. Myocardial perfusion (15O)H2O positron emission tomography was imaged at rest and during adenosine-induced maximal vasodilation. Peripheral endothelial function was assessed by measuring flow-mediated dilation (FMD) with ultrasound from the left brachial artery. There was a statistically significant correlation between FMD and global hyperaemic myocardial blood flow (MBF; r = 0.308, P = 0.023). The correlation remained statistically significant when controlling for gender, height, and diastolic blood pressure at rest (r = 0.367, P = 0.008). Receiver operating character analysis, however, yielded an area under curve of only 0.559 (P = 0.492) when FMD was used to predict reduced MBF (below 2.3 mL/g/min). Patients with significantly decreased MBF (n = 14) underwent invasive coronary angiography. FMD showed an inverse correlation with the severity of the most significant stenosis (r = -0.687, P = 0.007). Peripheral endothelial function is related with hyperaemic MBF and with the severity of CAD in invasive coronary angiography. Due to insufficient sensitivity and specificity in the identification of reduced MBF, FMD is not suitable for clinical practice at the individual level. However, it works at the population level as a research tool when assessing endothelial dysfunction in patients with CAD.

Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia

Background and aimsMicrovascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). MethodsFour groups of asymptomatic individuals aged 30–59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. ResultsThe groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. ConclusionsCoronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.

Acute aerobic exercise enhances cerebrovascular shear-mediated dilation in young adults: the role of cerebral shear.

Exercise-induced increases in shear rate (SR) acutely improve peripheral endothelial function, but the presence of this mechanism in cerebral arteries remains unclear. Thus, we evaluated shear-mediated dilation of the internal carotid artery (ICA), which is an index of cerebrovascular endothelial function, before and after exercise. Shear-mediated dilation was measured with 30 s of hypercapnia in 16 young adults before and 10 min after 30 min of sitting rest (CON) or three cycling exercises on four separate days. The target exercise intensity was 80% of oxygen uptake at the ventilatory threshold. To manipulate the ICA SR during exercise, participants breathed spontaneously (ExSB, SR increase) or hyperventilated without (ExHV, no increase in SR) or with ([Formula: see text], restoration of SR increase) addition of CO2 to inspiratory air. Shear-mediated dilation was calculated as a percent increase in diameter from baseline. Doppler ultrasound measures ICA velocity and diameter. The CON trial revealed that 30 min of sitting did not alter shear-mediated dilation (4.34 ± 1.37% to 3.44 ± 1.23%, P = 0.052). ICA dilation after exercise compared with preexercise levels increased in the ExSB trial (3.32 ± 1.37% to 4.74 ± 1.84%, P < 0.01), remained unchanged in the ExHV trial (4.07 ± 1.55% to 3.21 ± 1.48%, P = 0.07), but was elevated in the [Formula: see text] trial (3.35 ± 1.15% to 4.33 ± 2.12%, P = 0.04). Our results indicate that exercise-induced increases in cerebral shear may play a crucial role in improving cerebrovascular endothelial function after acute exercise in young adults.NEW & NOTEWORTHY We found that 30-min cycling (target intensity was 80% of the ventilatory threshold) with increasing shear of the internal carotid artery (ICA) enhanced transient hypercapnia-induced shear-mediated dilation of the ICA, reflecting improved cerebrovascular endothelial function. This enhancement of ICA dilation was diminished by suppressing the exercise-induced increase in ICA shear via hyperventilation. Our results indicate that increases in cerebral shear may be a key stimulus for improving cerebrovascular endothelial function after exercise in young adults.

Correlation between peripheral endothelial function, oxygen consumption and ventilatory efficiency in heart transplantation recipients

Endothelial dysfunction and peak oxygen uptake (VO2peak) are also predictors of increased risk of cardiovascular events in heart transplantation (HTx) recipients. The preservation of endothelial function may contribute to exercise tolerance. To investigate the correlation between peripheral endothelial function and exercise tolerance through VO2peak and ventilation to carbon dioxide production slope (VE / VCO2 slope) in HTx recipients. A pilot cross-sectional study was conducted with adult individuals aged 18-65 years, HTx ≥ six months after surgery, who had a stable medical condition and no changes over the last three months of immunosuppressive treatment. The patients underwent an assessment of endothelial function through PAT (EndoPAT-2000®) and performed a cardiopulmonary exercise test (CPET). A total of 41% of the studied population presented endothelial dysfunction. The individuals were divided into two groups: the endothelial dysfunction (GED; n=9) group and the normal endothelial function (GNEF; n=13) group according to the logarithm of the reactive hyperemia index (LnRHI). There was a positive and moderate correlation between the LnRHI and VO2 peak (r=0.659, p=0.013) and a negative and moderate correlation between the LnRHI and VE/VCO2 slope (r= -0.686, p= 0.009) in the GNEF. However, no significant correlations were found in the GED. The results showed that the preservation of peripheral endothelial function is significantly correlated with an increase in exercise tolerance in individuals after HTx. These findings bring important considerations for cardiovascular risk prevention and emphasize that therapeutic strategies with physical training programs must be implemented early.

Netarsudil-Associated Reticular Epithelial Edema Directly Influenced by Endothelial Dysfunction in a Post-Endothelial Keratoplasty Patient

Purpose: The purpose of this report was to describe a case in which reticular epithelial edema secondary to topical netarsudil ophthalmic solution 0.2% occurred directly in relation to focal endothelial dysfunction in a post-endothelial keratoplasty eye. Methods: This was a case report. Results: A 76-year-old man with a complex ocular history was diagnosed with pseudophakic bullous keratopathy of the left eye. Topical netarsudil was prescribed to treat his glaucoma and to attempt improvement of his corneal edema. The corneal examination remained stable for many months, but the patient eventually underwent a Descemet stripping automated endothelial keratoplasty (DSAEK) for worsening corneal edema. One week later, the patient was observed to have 360-degree reticular epithelial edema around the periphery of the DSAEK graft. Given the lack of visual significance and need for continued glaucoma treatment, the patient was continued on netarsudil. The reticular epithelial edema later became restricted to areas outside the graft zone as the peripheral DSAEK graft endothelial cell function improved. Two months post-DSAEK, the patient developed a partial inferior endothelial graft rejection related to inadvertent cessation of topical steroid, with keratic precipitates, stromal edema, and new overlying reticular epithelial edema. On treatment and resolution of the DSAEK graft rejection, the overlying reticular epithelial edema also resolved. Conclusions: This case clearly demonstrates that netarsudil-associated reticular epithelial edema is highly likely to be related to endothelial cell dysfunction and that if endothelial cell dysfunction improves, the reticular epithelial edema will also improve, despite the continuation of netarsudil.

Myocardial microvascular dysfunction in asymptomatic patients with hereditary dyslipidemia

Abstract Introduction Microvascular dysfunction underlies the pathophysiology of many cardiovascular disease (CVD) conditions and is strongly associated with future cardiovascular events. Hereditary forms of dyslipidaemia such as familial hypercholesterolemia (FH) and high levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerotic CVD but the degree of microvascular dysfunction in asymptomatic individuals is not fully explored. Purpose To evaluate the presence of microvascular dysfunction in asymptomatic individuals with the hereditary dyslipidaemias FH and high Lp(a). Methods Asymptomatic individuals without manifest CVD were recruited to four groups with 30 subjects in each; 1) controls with Lp(a)&amp;lt;30 nmol/L, 2) FH+Lp(a)&amp;lt;30 nmol/L, 3) FH+Lp(a)&amp;gt;125 nmol/L, and 4) isolated Lp(a)&amp;gt;125 nmol/L without FH. FH diagnoses were confirmed by genetic analysis. Transthoracic doppler echocardiography was used to record coronary flow in the distal part of the left anterior descending artery at rest and during hyperaemia induced by intravenous infusion of adenosine. Coronary flow reserve (CFR) was calculated by dividing hyperaemic to basal flow. Peripheral microvascular endothelial function was determined by recording reactive hyperaemia index (RHI) by peripheral arterial tonometry in the index fingers of both hands. CFR and RHI were considered impaired if values were &amp;lt;2.5 and &amp;lt;1.67, respectively. Results The four groups were balanced in age (mean 42.6±8.4 years), sex (50% females), BMI (mean 25.0±4.7 kg/m2), and smoking status (5.0% current smokers). Low-density lipoprotein cholesterol was also similar across the four groups (mean 2.8±1.1 mmol/L) with the two FH groups being on cholesterol lowering treatment while the other two were pharmacologically naïve. The three groups with hereditary dyslipidaemia had a higher proportion of subjects with impaired CFR, 30.0% in each group compared to 6.6% in controls (p=0.014) (Figure 1A). The FH+Lp(a)&amp;lt;30 nmol/L and FH+Lp(a)&amp;gt;125 nmol/L groups had received cholesterol lowering treatment for a median (inter quartile range, IQR) of 4.0 (8.0) and 11.0 (11.0) years respectively (p&amp;lt;0.001). In the FH+Lp(a)&amp;gt;125 nmol/L group individuals with normal CFR had received significantly longer treatment (p=0.006) but not in the FH+Lp(a)&amp;lt;30 nmol/L group (p=0.568) (Figure 1B). There were no major differences in median CFR (p=0.550) (Figure 2A) or median RHI (p=0.341) (Figure 2B) levels between the four groups. Conclusion Asymptomatic individuals with the hereditary dyslipidaemias FH and/or high Lp(a) have a higher degree of coronary microvascular dysfunction compared to healthy controls. For individuals with combined traits FH and high Lp(a), the total treatment years of cholesterol lowering is associated with preserved coronary microvascular function suggesting CFR as a potential useful non-invasive tool for cardiovascular risk-stratification in patients with hereditary dyslipidaemias.Figure 1Figure 2

Abstract 18949: Bariatric Surgery is Associated With Improved Coronary Microvascular Function and Cardiorespiratory Fitness in Patients With Ischemia and Non-Obstructive Coronary Arteries (INOCA)

Introduction - Severe obesity is associated with cardiometabolic disease and coronary microvascular dysfunction, as reflected by impaired coronary flow reserve (CFR). Bariatric surgery promotes sustained weight loss and lower incidence of diabetic microvascular complications, but its effect on the coronary microcirculation is unclear. In this ongoing pilot study, we aimed to investigate the impact of bariatric surgery on CFR, endothelial function, and cardiorespiratory fitness in patients with severe obesity and INOCA. Methods - Consecutive patients (N=19) with severe obesity (BMI≥35 kg/m 2 ), exertional dyspnea and planned bariatric surgery were enrolled. Patients underwent cardiac stress positron emission tomography (PET), peripheral arterial tonometry (PAT), echocardiogram and cardiopulmonary exercise testing (CPET) at baseline and after a median of 6.2 months post-surgery (N=9 completed to date). CFR was quantified as stress/rest myocardial blood flow (MBF) from PET. Reactive hyperemia index (RHI), a marker of endothelial function, was calculated as the ratio between PAT signal post and pre-occlusion in the corresponding arm. Results - Median age was 50 (Q1-Q3 42-54) years and 63% were female. At baseline, median BMI was 43 (40-54), LVEF was 0.62, and %LV visual ischemia was 0. Higher BMI inversely correlated with CFR (r= -0.53, p=0.02). As compared to baseline, patients post-surgery (78% sleeve gastrectomy, 22% gastric bypass) had significantly decreased BMI (45.2 vs. 34.3, p=0.008) and improved stress MBF [1.8 (1.3-2.2) vs. 2.4 (1.8-2.8), p&lt;0.02], CFR [2.3 (1.9-2.6) vs. 3.1 (2.4-3.6), p&lt;0.02] and peripheral endothelial function [RHI 1.5 (1.4-1.8) vs. 2.4 (1.8-2.8) vs. p=0.04]. These changes were accompanied on CPET by significantly higher exercise workload [112 (84.2-146) vs. 124.5 (90.5-149) W, p=0.046] and relative peak VO 2 [12.5 (11.9-14) vs. 15.2 (12.6-17) mL/kg/min, p=0.028]. Higher stress MBF directly correlated with relative peak VO 2 (r=0.53, p=0.04). Conclusion - In this pilot clinical study, bariatric surgery was associated with significant improvements in coronary microvascular function, peripheral endothelial function, and cardiorespiratory fitness in symptomatic patients with severe obesity after six months.

Abstract 11582: The Fingertip Artery is Better Than the Brachial Artery in Evaluating Vascular Endothelial Function for Coronary Artery Disease in Diabetic Patients

Introduction: Several studies demonstrated that endothelial function is impaired in diabetic patients, but no study evaluated vascular parameters in diabetic patients trough a combined analysis of macro and micro-endothelial function. In addition, the difference in vascular parameters between diabetes patients with coronary artery disease (CAD) and without CAD remains unknown. We assessed whether CAD is related to macro or micro vascular endothelial function in diabetic patients. Hypothesis: We measured vascular function in 219 diabetic patients (age 68±10 years), including 147 patients with CAD (CAD group) and 72 patients without CAD (control group). Flow mediated vasodilatation (FMD)indicating macro-endothelial function in the brachial artery was measured by ultrasound using a semi-automatic device: UNEXEF18G (UNEX Co. Nagoya, Japan). Reactive hyperemia index (RHI) indicating micro-endothelial function in the fingertip artery was measured by peripheral arterial tonometry (EndoPAT 2000). Vascular function tests were measured on the same day. Results: RHI was significantly impaired in CAD group (RHI: 2.0±0.7 vs.1.7±0.5 P=0.012), however FMD had no deference in the two groups. Logistic regression analysis revealed that RHI (odds ratio: 0.44, 95% confidence interval: 0.21-0.94) was an independent predictor for CAD in diabetic patients. Conclusions: RHI, an acknowledged marker of micro-endothelial function was a more sensitive method than FMD in evaluating the risk assessment of CAD in diabetic patients. more peripheral vascular endothelial function was associated with CAD in diabetic patients.

Abstract 17170: Association of Plasma Homocysteine Levels in Cancer Survivors - Data From Framingham Heart Study Offspring Cohort

Introduction: Cancer survivors experience a high prevalence of vascular remodeling from their anti-cancer therapies, which can lead to arterial stiffness. High plasma homocysteine (Hcy) is associated with increased cardiovascular disease risk via its role in decreasing nitric oxide bioavailability and impairing vascular function. However, there is limited work on its role in cancer survivorship. We, therefore, hypothesized that survivors of breast, gastrointestinal, and prostate cancer with elevated plasma Hcy values have higher arterial stiffness and lower endothelial function compared to those with low plasma Hcy. Methods: We evaluated cardiovascular disease-free cancer survivors in the Framingham Heart Study Offspring Cohort (n=196, 66±8 years old, 55.1% women, 26.4±1.2 years from cancer diagnosis, Range: [23.8 - 29.6 years]) with plasma Hcy measurements. The cohort median plasma Hcy was used to define low (&lt;8.16 μmol/L) and high Hcy (≥8.16 μmol/L) groups. Arterial stiffness was assessed via carotid-femoral pulse wave velocity (cfPWV). Peripheral vascular endothelial function was assessed via endothelium-dependent brachial artery flow-mediated dilation (FMD). Differences in cfPWV, FMD, and cardiovascular risk factors were assessed via independent sample t-test or chi-square test. Differences in cfPWV and FMD were further assessed via one-way ANCOVA with age, sex, and cardiovascular medications included as covariates. Results: cfPWV was significantly higher in the high Hcy (9.9±1.5m/s) vs. low Hcy group (8.5±1.9m/s, p=0.005); however, there were no differences in FMD between groups (2.4±1.7 vs. 2.7±2.0%, p=0.42). After controlling for our covariates, cfPWV was still significantly higher in the high Hcy group (Mean[95% CI]): (9.8[9.0-10.61]) compared to the low Hcy group (8.5[8-9.1]) (p=0.015). Conclusions: Our findings suggest an association between elevated Hcy and an increase in arterial stiffness in cancer survivors. This supports the potential adverse consequences of vascular stiffening following cancer diagnosis and treatment which could have long-term cardiovascular health implications.

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.

Intermittent vs. Continuous Handgrip Exercise and Peripheral Endothelial Function: Impact of Shear Rate Fluctuations.

Sustained exercise-induced elevations in shear rate (SR) has been well established as beneficial for improving endothelial function. However, the impact of intermittent fluctuations in SR is not understood. We investigated the effect of intermittent SR elevations compared to sustained elevations on peripheral endothelial function. Brachial artery flow-mediated dilation (FMD) was assessed in thirteen adults (9M/4F; 22±4 yr) before and after 30 min of handgrip exercise. Three different rhythmic forearm exercise interventions were performed at a rate of 20 contractions/min. Intermittent exercises (6 x 3 min exercise interspersed by 2 min of rest) were performed at 25% (INT-25%) and 15% (INT-15%) maximum voluntary contraction (MVC), and continuous exercise was completed at 15% MVC. Brachial artery diameter and velocity were measured using Doppler ultrasound. The total increase in SR above baseline throughout exercise was greater during INT-25% (4441±516·s-1) and continuous (4070±407 s-1) compared with INT-15% (2811±342 s-1, P<0.05). %FMD increased following all exercises (INT-25%: 5.7±1.2% to 8.1±1.2%; INT-15%: 5.2±1.2% to 7.0±1.1%; continuous: 5.5±1.3% to 6.8±1.3%, P<0.05 for all). The increase following INT-25% was significantly greater than INT-15% and continuous (P<0.05 for both). Normalized FMD to shear rate area under the curve increased with intermittent exercise (INT-25%: 2.2±0.2% to 3.4±0.3%; INT-15%: 2.1±0.2% to 3.2±0.2%, P<0.05 for both) but did not following continuous (2.1±0.2% to 2.5±0.1%, P=0.06). The increase in normalized FMD with intermittent exercises were greater than continuous (P<0.05 for both). These findings suggest intermittent fluctuations in SR during handgrip exercise may be more beneficial than sustained elevations on improving peripheral endothelial function.

Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study.

Mild cognitive impairment (MCI) is a prodromal stage to dementia, affecting up to 20% of the aging population worldwide. Patients with MCI have an annual conversion rate to dementia of 15-20%. Thus, conditions that increase the conversion from MCI to dementia are of the utmost public health concern. The COVID-19 pandemic poses a significant impact on our aging population with cognitive decline as one of the leading complications following recovery from acute infection. Recent findings suggest that COVID-19 increases the conversion rate from MCI to dementia in older adults. Hence, we aim to uncover a mechanism for COVID-19 induced cognitive impairment and progression to dementia to pave the way for future therapeutic targets that may mitigate COVID-19 induced cognitive decline. A prospective longitudinal study is conducted at the University of Oklahoma Health Sciences Center. Patients are screened in the Department of Neurology and must have a formal diagnosis of MCI, and MRI imaging prior to study enrollment. Patients who meet the inclusion criteria are enrolled and followed-up at 18-months after their first visit. Visit one and 18-month follow-up will include an integrated and cohesive battery of vascular and cognitive measurements, including peripheral endothelial function (flow-mediated dilation, laser speckle contrast imaging), retinal and cerebrovascular hemodynamics (dynamic vessel retinal analysis, functional near-infrared spectroscopy), and fluid and crystalized intelligence (NIH-Toolbox, n-back). Multiple logistic regression will be used for primary longitudinal data analysis to determine whether COVID-19 related impairment in neurovascular coupling and increases in white matter hyperintensity burden contribute to progression to dementia.

Prognostic value of peripheral endothelial function on major adverse cardiovascular events above traditional risk factors.

This study aims to identify whether adding peripheral microvascular dysfunction (PMED), a marker of atherosclerosis to established risk scores has an incremental prognostic value for major adverse cardiovascular events (MACE). This is a retrospective study of patients who underwent measuring peripheral arterial tonometry from 2006 to 2020. The optimal cut-off value of the reactive hyperaemia index (RHI) that had maximal prognostic value associated with MACE was calculated. Peripheral microvascular endothelial dysfunction was defined as the RHI lower than the cut-off. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, and vascular disease were determined to calculate the CHA2DS2-Vasc score. The outcome was MACE defined as myocardial infarction, heart failure hospitalization, cerebrovascular events, and all-cause mortality. A total of 1460 patients were enrolled (average age 51.4 ± 13.6, 64.1% female). The optimal cut-off value of the RHI was 1.83 in the overall population and in females and males was 1.61 and 1.8, respectively. The risk of MACE during 7 [interquartile range (IQR): 5,11] years of follow-up was 11.2%. Kaplan-Meier analysis showed that lower RHI is associated with worse MACE-free survival (P < 0.001). Multivariate Cox proportional hazard analysis, controlling for classic cardiovascular risk factors or risk scores such as CHA2DS2-Vasc and Framingham risk score revealed that PMED is an independent predictor of MACE. Peripheral microvascular dysfunction predicts cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

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.