Measure Of 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 3T 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.

Enhancing flow-mediated dilation analysis by optimizing an open-source software with automated edge detection.

Flow-mediated dilation (FMD) is a common measure of endothelial function and an indicator of vascular health. Automated software methods exist to improve the speed and accuracy of FMD analysis. Compared with commercial software, open-source software offers similar capabilities at a much lower cost while allowing for increased customization specific to users' needs. We introduced modifications to an existing open-source software, FloWave.us to better meet FMD analysis needs. The purpose of this study was to compare the repeatability and reliability of the modified FloWave.us software to the original software and to manual measurements. To assess these outcomes, duplex ultrasound imaging data from the popliteal artery in older adults were analyzed. The average percent FMD for the modified software was 6.98 ± 3.68% and 7.27 ± 3.81% for observer 1 and 2 respectively, compared with 9.17 ± 4.91% and 10.70 ± 4.47% with manual measurements and 5.07 ± 31.79% with the original software for observer 1. The modified software and manual methods demonstrated higher intraobserver intraclass correlation coefficients (ICCs) for repeated measures for baseline diameter, peak diameter, and percent FMD compared with the original software. For percent FMD, the interobserver ICC was 0.593 for manual measurements and 0.723 for the modified software. With the modified method, an average of 97.7 ± 2.4% of FMD videos frames were read, compared with only 17.9 ± 15.0% frames read with the original method when analyzed by the same observer. Overall, this work further establishes open-source software as a robust and viable tool for FMD analysis and demonstrates improved reliability compared with the original software.NEW & NOTEWORTHY This study improves edge detection capabilities and implements noise reduction strategies to optimize an existing open-source software's suitability for flow-mediated dilation (FMD) analysis. The modified software improves the precision and reliability of FMD analysis compared with the original software algorithm. We demonstrate that this modified open-source software is a robust tool for FMD analysis.

Advanced age and reduced hyaluronan synthesis impair glycocalyx integrity resulting in endothelial dysfunction

The glycocalyx (GC) is a densely structured, gel-like matrix that coats the inner lining of the vascular endothelium. The GC plays a pivotal role in regulating the integrity of the vascular endothelium, primarily through mechano-sensing and -transducing shear stress, while also preserving endothelial barrier function. With advancing age, the GC deteriorates concomitantly with its essential constituent, hyaluronan (HA), which may lead to endothelial dysfunction. Therefore, we hypothesized that advanced age and reduced HA synthesis alone or together will impair GC integrity resulting in endothelial dysfunction. We have generated a tamoxifen-inducible, endothelial cell-specific, knockout mouse model of a hyaluronan producing enzyme, hyaluronan synthase 2 (HAS2), in young (4-6 mo) and old (22-23 mo, n=9-12/group). HAS2 mRNA expression in carotid endothelial cell lysates were reduced by ~47% in endothelial cell HAS2 knockout (ecHAS2KO) vs wildtype (ecHAS2WT, p=0.004) after tamoxifen treatment. The perfused boundary region (PBR), indicative of GC barrier function, was evaluated in vivo in the mesenteric microcirculation. The PBR was significantly impaired with aging (young vs old ecHAS2WT, p=0.047) and genotype (young ecHAS2WT vs KO, p=0.012) but there was no additive effect of aging and genotype (old ecHAS2WT vs KO, p=0.989). Subsequently, GC thickness was determined by measuring the depth of GC collapsed by leukocyte passage through the mesenteric segments. GC thickness was diminished by ~53% with aging (young vs old ecHAS2WT, p&lt;0.0001) and ~59% with genotype (young ecHAS2WT vs KO, p&lt;0.0001) but there was no synergistic effect of aging and genotype (old ecHAS2WT vs KO, p=0.893). Mechano-sensing and -transducing properties of the GC were assessed using ex vivo flow-induced vasodilation in isolated carotid arteries with and without the intra-luminal infusion of HA degrading enzyme, hyaluronidase (HYAL). Flow-induced vasodilation was diminished with aging (young vs old ecHAS2WT, p&lt;0.0001) but this age-related decline was dampened with HYAL (p=0.212). The vasodilatory response to flow was reduced with genotype (young ecHAS2WT vs KO, p&lt;0.0001) but this effect was weakened with HYAL (p=0.953). There was no augmentative effect of aging and genotype with and without HYAL (all p≥0.883). Acetylcholine induced endothelium-dependent dilation (EDD), a measure of endothelial function, was examined ex vivo in isolated mesenteric arteries. The maximal EDD was diminished by ~23% with aging (young vs old ecHAS2WT, p=0.04) but not genotype (young ecHAS2WT vs KO, p=0.962). There was an additive reduction in maximal EDD by ~46% with aging and genotype (old ecHAS2KO vs WT, p=0.021). Endothelium-independent dilation in response to sodium nitroprusside, an exogenous nitric oxide donor, was not different across groups with either aging, genotype, or both (ALL p&gt;0.05). In conclusion, aging and reduced HA synthesis independently impaired GC integrity. As a result, mechano-sensing and -transducing property of GC was disturbed and further diminished by HYAL activity. In addition, endothelial function was impaired with aging and further exacerbated after a reduction in HA synthesis. Funded in part by awards from National Institutes of Health Awards R01 AG060395, R01 AG077751, R01 AG076748, T32 HL007576, T32 HL139451, Veteran's Affairs Merit Review Award I01 BX004492 and Nora Eccles Treadwell 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.

Age-Related Vascular Mitochondrial Dysfunction Is Ameliorated by Time-Restricted Feeding Intervention

Endothelial dysfunction constitutes a hallmark of vascular aging that can have serious implications for disease risk. In addition, aging is associated with mitochondrial dysfunction, which can lead to increased oxidative stress and create associated damages. Time-restricted feeding (TRF) is a dietary intervention known to have many benefits on age-related disease risk. The objective of this study is to elucidate the effects of TRF upon endothelial mitochondrial function of aorta during aging. We hypothesized that TRF protects the aorta from age-related endothelial mitochondrial dysfunction. Adult C57BL/6 mice underwent TRF regimen, including six hours of ad libitum feeding daily. Young and age-matched control mice were fed ad libitum. After 12 months of TRF, wire myography was performed on aorta tissue as a measure of endothelial function. The aorta received pharmacological treatments to induce contraction, and dose-dependent dilation was quantified. For the first time, simultaneous measurement of reactive oxygen species (ROS) and oxygen consumption were completed in aorta tissue using Oroboros O2K Fluorespirometry. Dihydroethidium (DHE) fluorescent staining of ROS in aorta tissue was used to validate ROS measurements from O2K. Serum ketone body levels related to metabolic switching and relevant to mitochondrial biogenesis were determined. TRF improved endothelial-dependent dilation of aorta tissue, representing the intervention’s protection of endothelial function in aging. Aged TRF mice had greater oxygen consumption and less ROS in aorta tissue than age-matched control mice, indicating improved vascular mitochondrial function after TRF intervention. Aged TRF mice had elevated serum levels of ketone bodies involved in mitochondrial biogenesis. This supports the hypothesis that age-related changes in vascular mitochondrial health are alleviated by TRF. The knowledge gained from this study is relevant to understanding the mechanisms of age-related vascular dysfunction. Stephenson Cancer Center, National Institute of Aging R03 AG070479, American Heart Association. 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.

The Influence of Resting Retrograde Shear Rate on Endothelial Function as Assessed by Flow Mediated Dilation

Shear stress profiles are an important determinant of endothelial function. Unidirectional blood flow enhances mean shear and protects endothelial function, whereas increased retrograde and oscillatory shear favors a proatherogenic environment. In this regard, acutely increasing retrograde shear has been shown to impair endothelial function. Also, previous studies have reported an elevation in retrograde shear in older adults that has been suggested to contribute to impaired endothelial function with age. However, the impact of having elevated retrograde shear at rest on endothelial function remains unclear. Therefore, we aimed to assess the associations between resting shear patterns and endothelial function, as measured by flow-mediated dilation (FMD) in a cohort of young and older adults. We hypothesized that higher retrograde shear rate and oscillatory shear index at rest would be related to a lower FMD value. Method: A total of 60 participants, 30 young adults (24 ± 5 years) and 30 older adults (62 ± 9 years), were studied. Resting brachial artery blood flow was measured using duplex Doppler ultrasound and retrograde shear rate and oscillatory shear index were calculated. Brachial artery FMD was used as a measure of endothelial function. Pearson correlations were used to investigate the associations between FMD, resting shear patterns, and age. Result: FMD was significantly lower in older compared to young adults (4.9 ± 2.7% vs. 7.6 ± 3.2%, p &lt; 0.01). Both retrograde shear rate and oscillatory shear index tended to be greater in older adults (-20.7 ± 15.1 s−1 vs. -15.2 ± 17 s−1, p = 0.062, and 10.7 ± 8% vs. 7.9 ± 8.0%, p = 0.056, respectively). FMD was not correlated with retrograde shear rate (r = -0.18, p = 0.17), or oscillatory shear index (r = -0.21, p = 0.11) in the entire cohort or in the young and older group alone. However, FMD, retrograde shear rate, and oscillatory index were moderately correlated with age: FMD (r = -0.45, p &lt; 0.01), retrograde shear rate (r = -0.32, p = 0.012), and oscillatory shear index (r = 0.33, p &lt; 0.01). Conclusion: These preliminary results suggest that resting retrograde shear and oscillatory shear index are not associated with reduced endothelial function in a cohort of young and old adults. Nevertheless, age-associated reductions in endothelial function and elevated retrograde shear were observed. This project was supported by the College of Nursing and Health Innovation. 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.

Acute and Chronic Endothelial Responses to Home-based High Intensity Interval Training in Healthy Older Adults

Advancing age is associated with endothelial dysfunction, a key early event in atherosclerosis development. Endurance exercise is recommended for cardiovascular disease prevention and some studies report endurance exercise training has beneficial effects on endothelial function in older adults. We have recently developed a supervised home-based exercise intervention using high intensity interval training on an all-extremity non-weight-bearing ergometer (HIIT-ANE). We tested the hypotheses that in healthy older adults: 1) endothelial function is improved in response to chronic HIIT-ANE, 2) the acute endothelial responses to HIIT-ANE are different in the trained and untrained states, and 3) the acute and chronic endothelial responses to HIIT-ANE are related. We assessed flow-mediated dilation (FMD), a measure of endothelial function, using brachial artery ultrasonography in twenty healthy sedentary older adults (age: 66±1, means ± SE; 11 postmenopausal women and 9 men). FMD was assessed: 1) in response to chronic HIIT-ANE (at baseline, after 8 weeks of normal lifestyle (control condition), and after 8 weeks of home-based HIIT-ANE) and 2) in response to a single session of HIIT-ANE (at pre-exercise, end of exercise and 1-hr and 24-hrs post-exercise), in the untrained and trained states. Following 8 weeks of HIIT-ANE, FMD was improved compared with baseline (3.39±0.30 vs. 4.18±0.46 %, P=0.005), but was not significantly changed from pre- to post-HIIT-ANE (3.68±0.44 vs. 4.18±0.46 %, P=0.3) or from baseline to post-control (3.39±0.30 vs. 3.68±0.44 %, P=0.4). In the untrained state, FMD was attenuated in response to a single bout of HIIT-ANE from pre- to 1-hr post-exercise (4.15±0.35 vs. 2.92±0.36 %, P=0.0004) and returned to pre-exercise level in 24-hrs post-exercise (4.15±0.35 vs. 3.98±0.40 %, P=1). In the trained state, the acute FMD response to HIIT-ANE was similar to the untrained state (P=0.6 for training state × time). The chronic change in FMD was inversely related with the acute change in FMD in the trained state (ρ=-0.70; p&lt;0.001), but not in the untrained state (ρ=-0.12; P=0.6). Biological sex did not significantly influence the acute or chronic FMD responses to HIIT-ANE (P≥0.1). In healthy older adults: 1) FMD is improved following 8-weeks of home-based remotely supervised HIIT-ANE compared to baseline, 2) FMD is attenuated and normalized within 24 hours of a single session of HIIT-ANE, and 3) chronic changes in FMD are related to acute changes in FMD. This work was supported by the National Institute of Aging grant AG063143. 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 health years after a hypertensive disorder of pregnancy: The EPOCH study

Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86). Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.

Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system.

Functional assessment of endothelium serves as an important indicator of vascular health and is compromised in vascular disorders including hypertension, atherosclerosis, and preeclampsia. Endothelial dysfunction in these cases is linked to dysregulation of the immune system involving both changes to immune cells and increased secretion of inflammatory cytokines. Herein, we utilize a well-established microfluidic device to generate a 3-dimensional vascular microphysiological system (MPS) consisting of a tubular blood vessel lined with human umbilical vein endothelial cells (HUVECs) to evaluate endothelial function measured via endothelial permeability and Ca2+ signaling. We evaluated the effect of a mixture of factors associated with inflammation and cardiovascular disease (TNFα, VEGF-A, IL-6 at 10 ng ml-1 each) on vascular MPS and inferred that inflammatory mediators contribute to endothelial dysfunction by disrupting the endothelial barrier over a 48 hour treatment and by diminishing coordinated Ca2+ activity over a 1 hour treatment. We also evaluated the effect of peripheral blood mononuclear cells (PBMCs) on endothelial permeability and Ca2+ signaling in the HUVEC MPS. HUVECs were co-cultured with PBMCs either directly wherein PBMCs passed through the lumen or indirectly with PBMCs embedded in the supporting collagen hydrogel. We revealed that phytohemagglutinin (PHA)-M activated PBMCs cause endothelial dysfunction in MPS both through increased permeability and decreased coordinated Ca2+ activity compared to non-activated PBMCs. Our MPS has potential applications in modeling cardiovascular disorders and screening for potential treatments using measures of endothelial function.

Biological sex does not influence the peak cardiac output response to twelve weeks of sprint interval training

Sprint interval training (SIT) increases peak oxygen uptake (V̇O2peak) but the mechanistic basis is unclear. We have reported that 12 wk of SIT increased V̇O2peak and peak cardiac output (Q̇peak) and the changes in these variables were correlated. An exploratory analysis suggested that Q̇peak increased in males but not females. The present study incorporated best practices to examine the potential influence of biological sex on the Q̇peak response to SIT. Male and female participants (n = 10 each; 21 ± 4 y) performed 33 ± 2 sessions of SIT over 12 wk. Each 10-min session involved 3 × 20-s ‘all-out’ sprints on an ergometer. V̇O2peak increased after SIT (3.16 ± 1.0 vs. 2.89 ± 1.0 L/min, η2p = 0.53, p < 0.001) with no sex × time interaction (p = 0.61). Q̇peak was unchanged after training (15.2 ± 3.3 vs. 15.1 ± 3.0 L/min, p = 0.85), in contrast to our previous study. The peak estimated arteriovenous oxygen difference increased after training (204 ± 30 vs. 187 ± 36 ml/L, p = 0.006). There was no effect of training or sex on measures of endothelial function. We conclude that 12 wk of SIT increases V̇O2peak but the mechanistic basis remains unclear. The capacity of inert gas rebreathing to assess changes in Q̇peak may be limited and invasive studies that use more direct measures are needed.

Serum Angiopoietin-like Protein 3 Levels Are Associated with Endothelial Function in Patients with Maintenance Hemodialysis.

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = -0.187, p = 0.045) and log-ANGPTL3 (r = -0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.

Association of number of siblings with preclinical markers of cardiovascular disease. The cardiovascular risk in Young Finns study

To investigate the association of number of siblings with preclinical cardiovascular disease (CVD) markers in adulthood.The sample comprised 2776 participants (54 % female) from the Cardiovascular Risk in Young Finns Study who had CVD risk factor data measured in childhood in 1980 (aged 3–18 years) and markers of preclinical CVD measured in adulthood. Echocardiography was performed in 2011, and carotid intima-media thickness, carotid distensibility, brachial flow-mediated dilatation, and arterial pulse wave velocity were measured in 2001 or 2007. The association between the number of siblings and preclinical CVD was assessed using generalized linear and logistic regression models. Analyses were stratified by sex as associations differed between sexes.Women with 1 sibling had lower E/e’-ratio (4.9, [95%CI 4.8–5.0]) in echocardiography compared with those without siblings (5.1[4.9–5.2]) and those with ≥2 more siblings (5.1[5.0–5.2]) (P for trend 0.01). Men without siblings had the lowest E/A-ratio (1.4[1.3–1.5]) compared with those with 1 sibling (1.5[1.5–1.5]), or ≥2 siblings (1.5[1.5–1.5]) (P for trend 0.01). Women without siblings had highest left ventricular ejection fraction (59.2 %[58.6–59.7 %]) compared with those with 1 sibling (59.1 %[58.8–59.4 %]), or ≥2 siblings (58.4 %[58.1–58.8 %])(P for trend 0.01). In women, brachial flow-mediated dilatation, a measure of endothelial function, was the lowest among participants with ≥2 siblings (9.4 %[9.0–9.8 %]) compared with those with 1 sibling (10.0 %[9.6–10.3 %]) and those without siblings (10.4 %[9.7–11.0 %])(P for trend 0.03).We observed that number of siblings may be associated with increased risk of heart failure in women. As the associations were somewhat inconsistent in males and females, further research is warranted.

Associations of mid‐life cardiovascular function with late‐life Alzheimer’s disease pathology burden in the Heart SCORE study

AbstractBackgroundCardiovascular (CV) disease is associated with dementia and Alzheimer’s disease (AD), but its relationship with AD pathology remains elusive. We examined whether mid‐life arterial stiffness, endothelial function, and blood pressure are associated with late‐life beta‐amyloid (Aß) and tau burden.MethodParticipants in the Heart Strategies Concentrating on Risk (SCORE) study completed cardiovascular phenotyping between 2003‐2005 (midlife; 45‐59 years) and up to three brain PET sessions between 2018‐2022 (late‐life; &gt;65 years). Mid‐life assessments included augmentation index (AI75; N = 134) as a measure of arterial stiffness, Framingham reactive hyperemia index (fRHI; N = 130) as a measure of endothelial function, and systolic‐blood pressure (SBP; N = 141); late‐life measures were global [11C]Pittsburgh Compound‐B (PiB) standardized uptake value ratio (SUVR) and regional (medial temporal, entorhinal, inferior temporal, amygdala) [18F]flortaucipir (FTP) SUVR as indices of Aß and tau deposition, respectively. In individual linear regression models, we tested associations of mid‐life AI75, RHI, and SBP with late‐life PiB and FTP SUVRs. We used mixed effects models to examine these relationships longitudinally. All models were adjusted for time between CV and PET measurements, baseline age, sex, racialization, apolipoprotein‐E4, BMI, and history of hypertension, high cholesterol, smoking, and diabetes.ResultIn multivariable models, higher mid‐life SBP was associated with lower late‐life FTP SUVR in the medial temporal lobe (β = ‐0.20, p = 0.04) and inferior temporal gyrus (β = ‐0.23, p = 0.01; Table 1); higher mid‐life SBP was also negatively associated with FTP SUVR trajectories in these regions (medial temporal lobe: β = ‐0.0004, p = 0.02; inferior temporal gyrus: β = ‐0.001, p = 0.01; Table 2). We did not detect significant relationships of mid‐life AI75 or RHI with late‐life FTP SUVRs (p≥0.05) or between any mid‐life cardiovascular measures and late‐life PiB SUVR (p≥0.08).ConclusionIn this dementia‐free, community‐based cohort, higher mid‐life SBP was associated with lower late‐life regional tau deposition and accumulation. Though counterintuitive, our findings are consistent with results of cross‐sectional studies, which suggest that CV risk factors may be followed by an initial brain arteriole response that is protective against tau accumulation through early years of late‐adulthood1,2. Future studies should interrogate the potential mechanisms and age‐modifying effects that may underlie the relationship between mid‐life CV risk factors and late‐life tau deposition.

Effect of Yoga on Endothelial Function: A Systematic Review and Meta-Analysis.

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau2 = 0.70, χ2 = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

Association of Vitamin D and Endothelial Function in a Subsample of the Participants in the Longitudinal Study of Adult Health (ELSA-BRASIL)

The Longitudinal Study of Adult Health (ELSA-BRASIL) is a multicentric and multidisciplinary cohort study aimed at investigating the incidence and risk factors of chronic diseases. Vitamin D deficiency has been associated with several comorbidities. In this context, the need to assess the impact of vitamin D on endothelial dysfunction in a large-scale study is justified. Thus, in this study, serum levels of vitamin D were determined by HPLC in 509 participants of the ELSA-BRASIL, and its association with endothelial function parameters by Peripheral Arterial Tonometry (BPA and PATratio). Reduced levels of vitamin D were shown to be associated with indicative measures of worse endothelial function. In the logistic regression model, the variables male sex, white color, increase in age, BMI, triglycerides, and vitamin D&lt;30ng/mL were also indicative of worse endothelial function. In summary, vitamin D has presented an association with endothelial function, which may indicate a protective action of vitamin D to the vascular endothelium.

Reduction of double-strand DNA break repair exacerbates vascular aging.

Advanced age is the greatest risk factor for cardiovascular disease (CVD), the leading cause of death. Arterial function is impaired in advanced age which contributes to the development of CVD. One underexplored hypothesis is that DNA damage within arteries leads to this dysfunction, yet evidence demonstrating the incidence and physiological consequences of DNA damage in arteries, and in particular, in the microvasculature, in advanced age is limited. In the present study, we began by assessing the abundance of DNA damage in human and mouse lung microvascular endothelial cells and found that aging increases the percentage of cells with DNA damage. To explore the physiological consequences of increases in arterial DNA damage, we evaluated measures of endothelial function, microvascular and glycocalyx properties, and arterial stiffness in mice that were lacking or heterozygous for the double-strand DNA break repair protein ATM kinase. Surprisingly, in young mice, vascular function remained unchanged which led us to rationalize that perhaps aging is required to accumulate DNA damage. Indeed, in comparison to wild type littermate controls, mice heterozygous for ATM that were aged to ~18 mo (Old ATM +/-) displayed an accelerated vascular aging phenotype characterized by increases in arterial DNA damage, senescence signaling, and impairments in endothelium-dependent dilation due to elevated oxidative stress. Furthermore, old ATM +/- mice had reduced microvascular density and glycocalyx thickness as well as increased arterial stiffness. Collectively, these data demonstrate that DNA damage that accumulates in arteries in advanced age contributes to arterial dysfunction that is known to drive CVD.

Acute Effect of Night Shift Work on Endothelial Function with and without Naps: A Scoping Review.

We examined the breadth and depth of the current evidence investigating napping/sleeping during night shift work and its impact on non-invasive measures of endothelial function. We used a scoping review study design and searched five databases: Ovid Medline, EMBASE, Ovid APA PsycInfo, Web of Science Core Collection, and EBSCO CINAHL. We limited our search to English language and publications from January 1980 to September 2022. Our reporting adhered to the PRISMA-ScR guidance for scoping reviews. Our search strategy yielded 1949 records (titles and abstracts) after deduplication, of which 36 were retained for full-text review. Five articles were retained, describing three observational and two experimental research studies with a total sample of 110 individuals, which examined the non-invasive indicators of endothelial function in relation to the exposure to night shift work. While there is some evidence of an effect of night shift work on the non-invasive indicators of endothelial function, this evidence is incomplete, limited to a small samples of shift workers, and is mostly restricted to one measurement technique for assessing endothelial function with diverse protocols. In addition, there is no identifiable research investigating the potential benefits of napping during night shift work on non-invasive measures of endothelial function.

The utility of the reperfusion rate of tissue oxygen saturation as a measure of vascular endothelial function in adolescents: reliability, validity and sensitivity.

Introduction: The near-infrared spectroscopy (NIRS)-derived reperfusion rate of tissue oxygen saturation (slope 2 StO2) may provide a surrogate measure of vascular function, however, this has yet to be examined in a paediatric population. This study investigated in adolescents: 1) the between-day reliability of NIRS-derived measurements; 2) the relationship between slope 2 StO2 and macro- (flow-mediated dilation, FMD) and microvascular (peak reactive hyperaemia, PRH) function; and 3) the effect of high-intensity interval exercise (HIIE) on slope 2 StO2, FMD, and PRH. Methods: Nineteen boys (13.3 ± 0.5 y) visited the laboratory on two occasions, separated by ∼ 1week. On visit 1, participants underwent simultaneous assessment of brachial artery FMD and slope 2 StO2 and PRH on the internal face of the forearm. On visit 2, participants completed a bout of HIIE with slope 2 StO2, FMD and PRH measured pre-, immediately post- and 1.5h post-exercise. Results: Slope 2 StO2 showed no mean bias (p = 0.18) and an intraclass correlation coefficient of 0.67 (p = 0.003) between visits. No significant correlation between slope 2 StO2 and FMD or PRH was observed on visit 1 (r = -0.04, p = 0.89 and r = -0.30, p = 0.23, respectively) or visit 2 pre-exercise (r = -0.28, p = 0.25 and r = -0.31, p = 0.20, respectively). Compared to pre-exercise, FMD decreased immediately post-exercise (p < 0.001) and then increased 1.5h post-exercise (p < 0.001). No significant change was detected for slope 2 StO2 (p = 0.30) or PRH (p = 0.55) following HIIE. Conclusion: In adolescents, slope 2 StO2 can be measured reliably, however, it is not correlated with FMD or PRH and does not follow the acute time course of changes in FMD post-exercise. Hence, the use of slope 2 StO2 as a surrogate measure of vascular function in youth must be refuted.

Acute exposure to simulated nocturnal traffic noise and cardiovascular complications and sleep disturbance—results from a pooled analysis of human field studies

ObjectivesA series of human field studies demonstrated that acute exposure to simulated nocturnal traffic noise is associated with cardiovascular complications and sleep disturbance, including endothelial dysfunction, increased blood pressure, and impaired sleep quality. A pooled analysis of these results remains to be established and is of tremendous interest to consolidate scientific knowledge.MethodsWe analyzed data from four randomized crossover studies (published between 2013 to 2021 and conducted at the University Medical Center Mainz, Germany). A total of 275 subjects (40.4% women, mean age 43.03 years) were each exposed to one control scenario (regular background noise) and at least to one traffic noise scenario (60 aircraft or train noise events) in their homes during nighttime. After each night, the subjects visited the study center for comprehensive cardiovascular function assessment, including the measurement of endothelial function and hemodynamic and biochemical parameters, as well as sleep-related variables.ResultsThe pooled analysis revealed a significantly impaired endothelial function when comparing the two different noise sequences (0–60 vs. 60–0 simulated noise events, mean difference in flow-mediated dilation −2.00%, 95% CI −2.32; −1.68, p < 0.0001). In concordance, mean arterial pressure was significantly increased after traffic noise exposure (mean difference 2.50 mmHg, 95% CI 0.54; 4.45, p = 0.013). Self-reported sleep quality, the restfulness of sleep, and feeling in the morning were significantly impaired after traffic noise exposure (all p < 0.0001).DiscussionAcute exposure to simulated nocturnal traffic noise is associated with endothelial dysfunction, increased mean arterial pressure, and sleep disturbance.

Associations between neurovascular coupling and cerebral small vessel disease: A systematic review and meta-analysis.

The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial cerebrovascular dysfunction. Neurovascular coupling (NVC) may be a practical alternative measure of endothelial function. We performed a systematic review of reported associations between NVC and cSVD. EMBASE and PubMed were searched for studies reporting an association between any STRIVE-defined marker of cSVD and a measure of NVC during functional magnetic resonance imaging, transcranial Doppler, positron emission tomography, near-infrared spectroscopy or single-photon emission computed tomography, from inception to November 3rd, 2022. Where quantitative data was available from studies using consistent tests and analyses, results were combined by inverse-variance weighted random effects meta-analysis. Of 29 studies (19 case-controls; 10 cohorts), 26 reported decreased NVC with increasing severity of cSVD, of which 18 were individually significant. In 28 studies reporting associations with increasing WMH, 25 reported reduced NVC. Other markers of cSVD were associated with reduced NVC in: eight of nine studies with cerebral microbleeds (six showing a significant effect); three of five studies with lacunar stroke; no studies reported an association with enlarged perivascular spaces. Specific SVD diseases were particularly associated with reduced NVC, including six out of seven studies in cerebral amyloid angiopathy and all four studies in CADASIL. In limited meta-analyses, %BOLD occipital change to a visual stimulus was consistently reduced with more severe WMH (seven studies, SMD -1.51, p < 0.01) and increasing microbleeds (seven studies, SMD -1.31, p < 0.01). In multiple, small studies, neurovascular coupling was reduced in patients with increasing severity of all markers of cSVD in sporadic disease, CAA and CADASIL. Cerebrovascular endothelial dysfunction, manifest as impaired NVC, may be a common marker of physiological dysfunction due to small vessel injury that can be easily measured in large studies and clinical practice.

Abstract P427: Effects Of Sedentary Activity In Pregnancy

Introduction: Preeclampsia is a multi-organ syndrome of late pregnancy characterized by gestational hypertension and proteinuria. There is strong evidence that maternal vascular dysfunction may be involved in the pathogenesis of this disorder. Regular physical activity during pregnancy has the potential to reduce this risk. Although physical activity during pregnancy is recommended, patient adherence is low. Therefore, the aim of this study was to determine the extent to which physical activity was associated with cardiovascular function throughout pregnancy in order to serve as an important intervention to prevent adverse pregnancy outcomes. Methods: Pregnant patients in their first trimester were recruited from obstetric outpatient clinics at the University of Iowa. Once consented, research participants completed a study visit during each trimester of pregnancy. Participants were administered the Pregnancy Physical Activity Questionnaire, a 36-item survey that asked about the amount of physical activity performed within the past 12 weeks. Participants’ vitals, BMI, and measures of vascular endothelial function and aortic stiffness were obtained at each visit. Results: Physical activity was measured in MET hours per week in each trimester of pregnancy. Pregnant women engaged in less physical activity by the end of their pregnancy, with an average of 193.6 MET hrs/week during the first trimester compared to 166.9 MET hrs/week during the third trimester. Sedentary time was found to be positively correlated with BMI during the second (β = .114, 95% CI [.020, .209], p-value = .018) and third trimesters of pregnancy (β = .212, 95% CI [.083, .340], p-value = .001). In addition, sedentary time positively correlated with aortic stiffness during the third trimester (ρ = .192, p-value = .014). Conclusion: Excess gestational weight gain is associated with short- and long-term pregnancy complications, including the development of preeclampsia. We found that women were less active later in pregnancy, and that increased sedentary time was associated with higher BMI in the second and third trimesters. Therefore, it is imperative that physical activity be highly encouraged throughout pregnancy to help prevent adverse health outcomes.