Measures Of Vascular Function Research Articles

Homocysteine, blood pressure and gene–diet interactions in relation to vascular function measures of black South Africans

Background and AimsWe investigated circulating homocysteine (Hcy), a cardiovascular disease (CVD) risk factor, examining its dietary associations to provide personalized nutrition advice. This study addressed the inadequacy of current dietary interventions to ultimately address the disproportionately high incidence of CVD in Black populations. Methods and Results: Cross-sectional analyses of 1,867 Black individuals of the PURE-SA study allowed the identification of dietary intake and cardiovascular measure interactions on three sub-categories: (1) normal blood pressure (BP), hypertension or Hcy-related hypertension (H-type), (2) low, normal or high Hcy concentrations, and (3) Hcy-related genetic combinations. Favorable body composition, but adverse dietary intake and cardiovascular determinants, were observed in higher Hcy categories. H-types, compared to regular hypertensives, had higher alcohol and lower macronutrient and micronutrient consumption. Inverse associations with carotid-radial pulse wave velocity were evident between monounsaturated fatty acid (FA) consumption and H-type hypertension as well as polyunsaturated FA and CBS883/ins68 TT carriers. Energy intake was positively associated with vascular cell adhesion molecule-1 (VCAM-1) in variant CBST883C/ins68 and CBS9276 GG carriers. VCAM-1 was also positively associated with plant protein intake in CBS9276 GG and MTR2756 AA carriers and negatively with total protein intake and CBS9276 GG carriers. Alcohol intake was positively associated with intercellular adhesion molecule-1 in MTR2756 minor allele carriers. Conclusion: Because Hcy gene-diet interactions are evident, personalized nutrition, by adjusting diets based on genetic profiles (e.g., CBS and MTR variations) and dietary interactions (e.g., FAs and proteins), can enhance cardiovascular outcomes by managing Hcy and related hypertension in genetically susceptible individuals.

Peripheral whole blood microRNA expression in relation to vascular function: a population-based study

BackgroundAs key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis.MethodsPeripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module’s expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis.ResultsFour modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion.ConclusionsWe identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.

Application of Principal Component Analysis to Heterogenous Fontan Registry Data Identifies Independent Contributing Factors to Decline.

Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that ultimately requires heart transplant. Our observational cohort study goal was to determine if principal component analysis (PCA) applied to data collected from a substantial Fontan cohort can predict functional decline (N=140). Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO2max), lymphatic biomarkers, and blood biomarkers were collected over 11 years at a single site; in that time, 16 events occurred that are considered here in a composite outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Our main findings suggest that the 6th PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by blood serum biomarkers and superior vena cava flow, is a superior measure of proportional hazard compared to EF, and displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and lymphatic dysfunction (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Our findings support our hypothesis that a multifactorial model must be considered to improve prognosis in the Fontan population.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.

Relationships among Gonadotropins, Sex Hormones, and Vascular Function in Adolescents with Normal Weight or Obesity

Objective: Childhood obesity may lead to premature cardiovascular disease in adulthood. Excess adiposity suppresses gonadotropin [luteinizing hormone (LH), follicle-stimulating hormone (FSH)] production in both adolescent males and females, which act upon the gonads, leading to the release of the sex hormones (estrogen and testosterone). Both estrogen and testosterone have been linked to vascular function. Relationships among gonadotropins, sex hormones, and vascular function are not completely understood in male and female adolescents across the weight-status spectrum. We, therefore, sought to examine associations among gonadotropins, sex hormones, and vascular health in adolescents with normal weight or obesity. We hypothesized that increased levels of gonadotropins would be associated with worsened vascular function, and higher levels of estrogen would be associated with favorable vascular function. Methods and Data: Adolescents (n=58; 12– <18-years of age) were stratified according to body mass index (BMI) percentile into normal weight (5th – <85th BMI percentile; n=25) and obesity (³95th BMI percentile; n=33) categories. Fasting blood samples were collected to measure FSH, LH, testosterone, estradiol, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), very-low-density lipoprotein cholesterol (VLDL), high-density lipoprotein cholesterol (HDL), glucose, and insulin. Insulin resistance was calculated using the homeostatic model assessment (HOMA-IR). Vascular function was measured via ultrasonography for measures of carotid artery compliance and distensibility [i.e., diameter compliance (cDC), incremental elastic modulus (cIEM)], and brachial artery flow mediated dilation (FMD). Results: Female adolescents with obesity had a significantly greater ( p=0.009) FMD compared to females with normal weight. Triglycerides, VLDL, total cholesterol-to-HDL ratio, HOMA-IR, and insulin were also significantly greater (all p<0.05) in adolescents with obesity compared to those with normal weight, while HDL was significantly lower ( p<0.0001). FSH, LH, testosterone, and estradiol did not statistically significantly differ between the normal weight and obesity groups in either sex. After adjusting for age, multiple comparisons, and stratifying by sex, higher testosterone was associated with decreased cDC (p=0.018) in females. Additionally in females, higher testosterone was associated with increased cIEM ( p=0.002). In adolescent males, higher estrogen was associated with decreased cDC ( p=0.006) and increased cIEM ( p=0.003). Conclusion: Adding to previous research showing relationships between sex hormones and vascular health in adults, the current study shows associations between sex hormones and cDC and cIEM in adolescents. That said, we found no associations between gonadotropins and measures of vascular function in adolescents with normal weight or obesity. Future studies are needed to confirm these results in a larger cohort and among those with BMI in the overweight (85th - <95th BMI percentile) category and differentiating severe obesity (>120% of the 95th percentile, or >35 kg/m2). Dr. Kelly serves as an unpaid investigator, consultant, and educator for Eli Lilly, Novo Nordisk, and Vivus; an unpaid consultant for Boehringer Ingelheim; receives donated study medication from Novo Nordisk and Vivus for NIDDK-funded clinical trials. Dr. Bomberg has served as a site principal investigator and site co-investigator for Novo Nordisk. His research program is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award number K23DK125668. The content is solely the responsibility of the authors and does not necessarily represent the offcial views of the NIH. 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.

357 Effects of Dietary Nitrate Supplementation on Vascular Function in Individuals with Prediabetes

OBJECTIVES/GOALS: Impaired vascular function, a subclinical marker of cardiovascular disease, has been identified in prediabetes. Dietary nitrate supplementation has been shown to improve vascular function. However, this has not been studied in prediabetes. The purpose was to determine the effects of dietary nitrate on vascular function in prediabetes. METHODS/STUDY POPULATION: Five individuals with prediabetes (4 men, 1 woman; 55 ± 17 yr; HbA1c = 5.8 ± 0.2) participated in a double-blind, placebo-controlled, repeated measures study. Participants were randomly assigned to a 3-day nitrate supplementation (nitrate-rich beetroot juice, 12.9 mmol, 140 mL), or a placebo supplementation (nitrate-depleted beetroot juice, 0.05 mmol, 140 mL). Following supplementation, participants reported to the lab for measures of vascular function in the lower limb. Doppler ultrasonography was used to measure flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (RH) of the superficial femoral artery in response to a 5-min bout of leg ischemia. RESULTS/ANTICIPATED RESULTS: FMD did not differ between the nitrate-rich (2.87 ± 2.01%) and placebo (2.24 ± 1.69%) conditions (p = 0.48; d = 0.35). Furthermore, peak RH did not differ between the nitrate-rich (1503 ± 443 ml/min) and placebo (1762 ± 414 ml/min) conditions (p = 0.36; d = 0.46). DISCUSSION/SIGNIFICANCE: These preliminary results suggest that dietary nitrate supplementation in the form of beetroot juice does not improve vascular function in individuals with prediabetes.

PFAS alters placental arterial vasculature in term human placentae: A prospective pregnancy cohort study

IntroductionPerfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. ObjectivesThe objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. MethodsUsing data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. ResultsIn both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (β = −0.23, 95% CI: −0.41, −0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (β = −0.19, 95% CI: −0.34, −0.051). There were no reliable differences in effect by fetal sex. DiscussionThe findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.

The Association Between Testosterone and Vascular Function in Reproductive-Aged Females With Chronic Kidney Disease

Cardiovascular disease is the leading cause of death in women, and women with chronic kidney disease (CKD) experience especially elevated risk. This study examined the association between testosterone and vascular function in 61 reproductive-aged females with CKD. Testosterone levels and measures of vascular function were assessed, including pulse wave velocity, aortic augmentation, flow-mediated dilation (FMD), and velocity time integral. Multivariable linear regression analyses assessed the relationship between testosterone and each measure of vascular function. No associations were observed between testosterone and vascular function outcomes, although a significant positive association between testosterone-to-estradiol ratio and FMD was demonstrated. Although testosterone levels were not independently predictive of vascular function, the level of testosterone relative to estradiol was associated with FMD and may therefore influence endothelial function in the high-risk population of reproductive-aged female patients with CKD.

Skin Carotenoid Score as an Important Prognostic Factor for Predicting Type 2 Diabetes Mellitus in Middle-Aged Subjects

This study aimed at identifying middle-aged subjects at risk for developing type 2 diabetes mellitus using noninvasive skin carotenoid and vascular function measurements. To this end, 61 subjects (40–65 years of age) without type 2 diabetes mellitus (Group A, Hemoglobin A1c < 6.5%) and 69 subjects (40–65 years of age) with type 2 diabetes mellitus (Group B, Hemoglobin A1c ≥ 6.5%) were recruited (Table 1). The skin carotenoid score was recorded using spectroscopy-based skin carotenoid measurements that approximate dietary fruit and vegetable intake. Endothelial function and heart rate variability were measured for the two groups and correlated with skin carotenoids scores. The daily vegetable and fruit intake was positively correlated with the skin carotenoids score in both groups (Group A, r = 0.598, p < 0.001; Group B, r = 0.449, p < 0.001). There were also significant differences in skin carotenoids score, indices of endothelial function, and heart rate variability between the subjects in group A and group B. There was a negative correlation between skin carotenoids score and individual determinants of metabolic syndrome, including high-density lipoprotein (r = −0.361, p = 0.009), waist circumference (r = −0.450, p < 0.001), fasting blood sugar (r = −0.713, p < 0.001), and Hemoglobin A1c (r = −0.808, p < 0.001); however, systolic blood pressure showed no significant correlation (p = 0.06). In conclusion, carotenoids and cardiovascular parameters are reliable predictive factors of type 2 diabetes mellitus in middle-aged subjects.

The effect of exercise on vascular health in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. This increased risk cannot be fully explained by traditional risk factors such as hypertension. Endothelial dysfunction and arterial stiffness have been suggested as factors that explain some of the increased risk and are independently associated with important cardiovascular outcomes in patients with CKD. Studies in other disease populations have shown the positive effects of exercise on vascular dysfunction. The aim of this review was to determine whether exercise training interventions improve measures of vascular function and morphology in patients across the spectrum of CKD and which exercise training interventions are most efficacious. A systematic search of Medline, Embase, and the Cochrane Central Register identified 25 randomized controlled trials. Only randomized control trials using an exercise intervention with a nonexercising control group and at least one measure of vascular function or morphology were included. Participants were patients with nondialysis CKD or transplant patients or those requiring dialysis therapy. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was completed for pulse wave velocity, augmentation index, and measures of endothelium-dependent vasodilation. Data from 25 studies with 872 participants showed that exercise training reduced pulse wave velocity and augmentation index but had no effect on endothelium-dependent vasodilation. Subgroup analyses suggested that exercise interventions of at least moderate intensity were more likely to be effective. Limitations included the absence of observational studies or other interventions aimed at increasing habitual physical activity. Further studies are warranted to investigate which are the most effective exercise interventions.NEW & NOTEWORTHY A thorough systematic review and meta-analysis of the effects of exercise training on measures of vascular function in patients with chronic kidney disease, including arterial stiffness and endothelial function, were conducted. Subgroup analyses investigated how differences in exercise training, according to frequency, intensity, type, and timing, have an impact on the efficacy of the intervention.

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.

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.

Abstract 018: Overexpression Of ERα In Adipose Tissue Contributes To The Anti-contractile Effect Of Mesenteric PVAT By NOX4-induced H 2 O 2

Perivascular adipose tissue (PVAT) induces a significant anti-contractile effect on vasculature, secreting relaxing and constricting factors. It is well established that the PVAT anti-contractile function is lost in cardiometabolic diseases, including obesity. Estrogen receptor alpha (ERα) is known to play a crucial role in the function of adipose tissues and its activation has been associated with adipogenesis by redox balance. In addition, NADPH oxidase 4 (NOX4) is an enzyme that contribute to adipose tissue differentiation and intracellular H 2 O 2 generation. While ERα are expressed in adipose tissue, but their potential role in PVAT function is unknown. To test the hypothesis, adipose tissue specific ERα overexpressing female mice at 30 weeks old were used. We aimed to determine whether the overexpression of ERα would enhance the anti-contractile effect of PVAT by NOX4-induced H 2 O 2 . The high-fat diet (40% fat) was administered for 20 weeks and mesenteric resistance arteries, with and without PVAT, were isolated and used for measurements of vascular function, protein levels (Western blot) and redox signaling (Amplex Red). The higher-fat diet increases the weigh in ~ 80% in Wild Type (WT) and ERα (p&gt;0.05). The anti-contractile effect of PVAT was exacerbated in arteries of ERα mice than WT [Area under the curve (AUC): WT 369±2 vs. ERα 230±1 p&lt;0.05). NOX1/4 inhibitor (GSK136901) increased the vasoconstriction only in arteries from ERα mice (WT 348 ±4 vs. ERα 580±5 p&lt;0.05). NOX4 (0.19±0.01 vs 2.3±0.6) and H 2 O 2 (&gt; 70%) levels were higher in PVAT from ERα mice than WT. In addition, 6 uM of H 2 O 2 , concentration corresponding to the observed in PVAT from ERα mice, induced vasodilatation in arteries from WT. On the other hand, a high-fat diet abrogates the anti-contractile effect of PVAT (WT with PVAT 233±1 vs. without PVAT 241±4) and has partially restored in the ERα, analyzing LogEC 50 (with PVAT 5±0.7 and without PVAT 6±0.8 M). In addition, H 2 O 2 levels (&gt;50%) were higher in PVAT from the high fat diet fed ERα mice, but NOX4 levels did not change. In summary, overexpression of ERα increases H 2 O 2 levels derived from NOX4, contributing to the anti-contractile effect of PVAT in healthy animals. This effect is partially restored in mice on a high-fat diet with overexpressed ERα.

The relationships between acetylcholine-induced chest pain, objective measures of coronary vascular function and symptom status.

Acetylcholine-induced chest pain is routinely measured during the assessment of microvascular function. The aim was to determine the relationships between acetylcholine-induced chest pain and both symptom burden and objective measures of vascular function. In patients with angina but no obstructive coronary artery disease, invasive studies determined the presence or absence of chest pain during both acetylcholine and adenosine infusion. Thermodilution-derived coronary blood flow (CBF) and index of microvascular resistance (IMR) was determined at rest and during both acetylcholine and adenosine infusion. Patients with epicardial spasm (>90%) were excluded; vasoconstriction between 20% and 90% was considered endothelial dysfunction. Eighty-seven patients met the inclusion criteria. Of these 52 patients (60%) experienced chest pain during acetylcholine while 35 (40%) did not. Those with acetylcholine-induced chest pain demonstrated: (1) Increased CBF at rest (1.6 ± 0.7 vs. 1.2 ± 0.4, p = 0.004) (2) Decreased IMR with acetylcholine (acetylcholine-IMR = 29.7 ± 16.3 vs. 40.4 ± 17.1, p = 0.004), (3) Equivalent IMR following adenosine (Adenosine-IMR: 21.1 ± 10.7 vs. 21.8 ± 8.2, p = 0.76), (4) Increased adenosine-induced chest pain (40/52 = 77% vs. 7/35 = 20%, p < 0.0001), (5) Increased chest pain during exercise testing (30/46 = 63% vs. 4/29 = 12%, p < 0.00001) with no differences in exercise duration or electrocardiographic changes, and (6) Increased prevalence of epicardial endothelial dysfunction (33/52 = 63% vs. 14/35 = 40%, p = 0.03). After excluding epicardial spasm, acetylcholine-induced chest pain is associated with increased pain during exercise and adenosine infusion, increased coronary blood flow at rest, decreased microvascular resistance in response to acetylcholine and increased prevalence of epicardial endothelial dysfunction. These findings raise questions about the mechanisms underlying acetylcholine-induced chest pain.

Trends among platelet function, arterial calcium, and vascular function measures

Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p < 2.22e-04). The diameter trends were consistent with lower shear environments invoking less platelet reactivity. The vessel calcium trends were consistent with subclinical atherosclerosis and platelet activation being inter-related.

Examining changes in vascular function, arterial stiffness and systemic inflammation during hospitalization and recovery from an acute exacerbation of chronic obstructive pulmonary disease

An acute exacerbation of COPD (AECOPD) is associated with increased risk of cardiovascular (CV) events. The elevated risk during an AECOPD may be related to changes in vascular function, arterial stiffness, and systemic inflammation; the time course of these measures and their corresponding recovery are poorly understood. Further, physical activity is reduced during an AECOPD, and physical activity may influence the cardiovascular responses to an AECOPD. The purpose of the study was to examine the acute impact of an AECOPD requiring hospitalization on vascular function, arterial stiffness, and systemic inflammation and examine whether physical activity modulates these variables during recovery. Patients hospitalized for an AECOPD were prospectively recruited and compared to control patients with stable COPD. Vascular function, arterial stiffness, and systemic inflammation (CRP, IL-6) were measured at hospital admission, hospital discharge and within 14 days of discharge. Physical activity was electronically tracked daily while in hospital and for 7 days following discharge using a Fitbit. One hundred and twenty-one patients with an AECOPD requiring hospitalization and 33 control patients with stable COPD were enrolled in the study. Vascular function was significantly lower, and systemic inflammation higher at hospital admission in patients with an AECOPD compared to stable COPD. Significant improvements in vascular function and inflammation were observed within 14 days of hospital discharge; however, vascular function remained lower than stable COPD. Physical activity was low at admission and increased following discharge; however, physical activity was unrelated to measures of vascular function or inflammation at any time point. An AECOPD requiring hospitalization is associated with impaired vascular function that persists during recovery. These findings provide a mechanistic link to help explain the enduring increase in CV risk and mortality following a severe AECOPD event.Clinical trial registration: ClinicalTrials.gov #NCT01949727; Registered: 09/20/2013.

Body composition affects blood lipids and vascular function in metabolically unhealthy or metabolically healthy older adult women with obesity: A multi-group path analysis/impact verification following latent profile analysis.

This study aimed to perform latent profile analysis (LPA) in older adult women with metabolic syndrome to extract a group according to their characteristics while controlling for body composition, blood lipid levels, and vascular function. The study also examined the relationship between different variables. The participants were 35 women aged ≥65 years, who met the Korean female standards for metabolic syndrome. Blood collection, blood pressure measurements, and vascular function measurements were performed. LPA and multigroup path analysis (MGPA) were performed to statistically analyze the effects of body composition on blood lipid levels and vascular function in older adult women with metabolic syndrome. Mplus 8.3 and jamovi 2.0.0 were used for the analyses, and the control significance level was set at .05. The participants were divided into the following three groups: (G1) metabolically unhealthy participants with normal weight, (G2) normal-weight participants with arteriosclerosis, and (G3) obese but metabolically healthy participants (G3). The effect of body composition on blood lipid levels showed a significant difference only in G1. The effect of body composition on vascular function was influenced by various variables in G1 and G3, while G1 showed a higher explanatory power. The MGPA results showed that the relationship between variables differs depending on the group. Therefore, the metabolic syndrome should be studied by subdividing it and confirming the characteristics of the classified groups, such as normal-weight but metabolically unhealthy individuals and obese but metabolically healthy individuals.

Transcatheter aortic valve implantation improves endothelial and autonomic function

Abstract Funding Acknowledgements Type of funding sources: None. Background Degenerative aortic stenosis is the leading native valve pathology in developed countries. Its degeneration process is affected by aging, common cardiovascular risk factors and an atherosclerotic-like process preceded by endothelial and autonomic dysfunction. With the increasing integration of transcatheter aortic valve implantation (TAVI) in the treatment of aortic stenosis in the elderly, research is being intensively oriented into its beneficial effect on the cardiovascular system. Measurements of vascular function with flow mediated dilatation (FMD) and autonomic cardiac function using heart rate variability parameters represent a validated method for treatment evaluation at different time-points. Purpose The purpose of our study was to assess whether haemodynamic and structural changes after TAVI will have a positive impact on endothelial and autonomic cardiac function on early and late follow-up. Methods 50 patients with severe aortic stenosis destinated to TAVI were prospectively included. Data was collected at baseline (24 hours before the procedure), on early follow-up (48 hours after the procedure) and on late follow-up (6 months after the procedure). While different heart rate variability parameters were obtained using a high-resolution electrocardiogram, FMD was assessed using a standardized ultrasound-based process with induced forearm hyperaemia. Results 43 patients completed the study (mean age 81 (75-85); 60% women). FMD measurements significantly changed from baseline to early follow-up (2.8 ± 1.5 % to 4.7 ± 2.7 %, p &amp;lt; 0.001). Improvement was persistent on late follow up (4.8 ± 2.7 %, p = 0.936). Moreover, heart rate variability parameters remained unchanged on early follow-up and improved 6 months after. Late follow-up statistical significance was reached by HF, a frequency-domain parameter (5231 ± 1783 to 6507 ± 1789 ms2; p = 0.029) and two Poincare diagram parameters: RR ecc (682 to 906 ms2; p &amp;lt; 0.001) and SDRR (9.6 to 23.9 ms; p = 0.001). Significant predictors of FMD change were as following: baseline maximal aortic valve velocity (R = 0.415; p = 0.011), mean aortic gradient (R = 0.373; p = 0.018), indexed stroke volume (R = 0.503; p = 0.006) and NT-proBNP (R = 0.491; p = 0.001). Conclusions Both endothelial and autonomic function improved after TAVI. While FMD seems to change early due to acute haemodynamic changes attributed to aortic valve stenosis resolution, autonomic cardiac functions remain stable and ameliorate late after procedure, likely reflecting left ventricular reverse remodelling.

Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease.

The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue-level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross-sectional case-control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation. Plasma biomarkers GDF-15, IL-6, NT-proBNP, and cTNI were significantly elevated in patients compared to HVs, as were several clinical chemistry and hematology markers. No differences between groups were found for mitochondrial membrane potential, mitochondrial reactive oxygen production, oxygen consumption rate, or extracellular acidification rate in PBMCs. Imaging revealed significantly higher nicotinamide-adenine-dinucleotide-hydrogen (NADH) content in skin as well as reduced passive leg movement-induced hyperemia in patients. This study confirmed results of earlier studies regarding plasma biomarkers in mitochondrial disease and identified several imaging techniques that could detect functional differences at the tissue level between participants with mitochondrial disease and HVs. However, assays of mitochondrial function in PBMCs did not show differences between participants with mitochondrial disease and HVs, possibly reflecting compensatory mechanisms and heterogeneity in mutational load. In future clinical trials, using a mix of imaging and blood-based biomarkers may be advisable, as well as combining these with an in vivo challenge to disturb homeostasis.

Higher levels of vigorous physical activity are associated with enhanced nocturnal blood pressure dipping

Introduction: Nocturnal blood pressure (BP) dipping determined from 24-hour ambulatory blood pressure monitoring (ABPM) is associated with reduced cardiovascular disease (CVD) risk. Physical activity lowers the risk of CVD related, in part, to preserved endothelial function and lower aortic stiffness, however the relation between physical activity and nocturnal dipping remains unclear. The objective of our cross-sectional retrospective analysis was to assess the relation between physical activity and nocturnal BP dipping, and whether this relation was confounded by measures of vascular function. We hypothesized that higher levels of physical activity would be associated with greater nocturnal BP dipping. Methods: Healthy adults (n=172, age 19 to 65 years, 55% female) had 24-hour ABPM measured. BP recordings were taken every 30 min during the daytime and every 60 min during the nighttime. Nocturnal “dippers” had a 10-20% difference between their mean daytime and nighttime systolic BP and “non-dippers/inverse dippers” had &lt;10% difference. The modifiable activity questionnaire was used to assess physical activity levels via self-reported days/week with greater than 30 min of moderate activity (3.0-6.0 METs) and vigorous activity (&gt;6.0 METs). Endothelial function (brachial artery flow-mediated dilation, FMD), and aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) were also assessed. Results: Nocturnal BP dippers performed more days/week of moderate and vigorous physical activity compared to non-dippers (P=0.007 and P=0.008, respectively). Both moderate (B=0.386, P=0.042) and vigorous physical activity (B=0.604, P=0.002) were associated with nocturnal BP dipping in univariate linear regression analyses. However, only vigorous activity (B=0.926, P=0.001) remained associated with nocturnal BP dipping after adjustment for age, BMI, 24-hr systolic BP and diastolic BP, brachial FMD and cfPWV. Conclusion: Vigorous physical activity may attenuate CVD risk in part from enhanced nocturnal BP dipping. Future studies should investigate additional mechanisms by which vigorous physical activity may enhance nocturnal BP dipping. This study was supported by grants from the National Institutes of Health (AG063790; HL014388, HL07121; AG043722). Dr. Pierce is supported by the Russell B. Day and Florence D. Day Endowed Chair in Liberal Arts and Sciences, University of Iowa. 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.