Carotid Artery Distensibility Research Articles

Association between arterial health and cognition in adolescents: The PANIC study.

We investigated the associations of the measures of arterial health with cognition in adolescents and whether physical activity (PA) or sedentary time (ST) confounds these associations. One hundred sixteen adolescents (71 boys) aged 15.9 ± 0.4 participated in the study. PA and ST were assessed using a combined accelerometer/heart rate monitor. Overall cognition was computed from the results of psychomotor function, attention, working memory, and paired-associate learning tests. Pulse wave velocity was measured by impedance cardiography, carotid intima-media thickness, and carotid artery distensibility by carotid ultrasonography. Systolic and diastolic blood pressure (SBP and DBP) were measured using an aneroid sphygmomanometer. SBP was inversely associated with overall cognition (standardized regression coefficient [β] = -0.216, 95% confidence interval (CI) -0.406 to -0.027, p = 0.025). Pulse wave velocity (β = -0.199, 95% CI -0.382 to -0.017, p = 0.033) was inversely associated with working memory task accuracy. SBP was directly associated with reaction time in the attention (β = 0.256, 95% CI 0.069 to 0.443, p = 0.008) and errors in the paired-associate learning tasks (β = 0.308, 95% CI 0.126 to 0.489, p = 0.001). Blood pressure was inversely associated with overall cognition. PA or ST did not confound the associations. Results suggest that preventing high blood pressure is important for promoting cognition in adolescents.

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.

Abstract 64: Risk Factors for Carotid Artery Lipid Deposition Measured by Gray Scale Median of the Intima-Media in Children and Young Adults Over the Life Course

Introduction: Echogenicity of the carotid arterial wall, measured by gray scale median of the intima-media (GSM-IM), is a unitless measure that reflects lipid deposition in the arterial wall, with lower values indicating greater lipid deposition and atherosclerosis. Due to the relative novelty of GSM-IM, its progression and associated risk factors are incompletely understood. This study investigated the GSM profile in childhood and young adulthood using a longitudinal cohort of individuals followed over time, and conducted a priori analysis on the behavioral, psychosocial, and health risk factors for GSM. Methods: Data were collected as part of the Meta-Air2 follow-up study of participants enrolled in the Southern California Children’s Health Study. A total of 240 study participants underwent a carotid artery ultrasound examination in 2008 (mean age±standard deviation [ SD] : 11.2±0.6 years), and again between 2018 and 2023 (24.2±1.6 years) to assess changes in carotid artery health, including GSM-IM, carotid artery intima-media thickness (CIMT), and carotid artery distensibility. Participants self-reported lifestyle behaviors, psychosocial health, and underwent anthropometric and blood pressure measures at both time points. Mixed effects models were used to predict GSM-IM changes with repeated measurements of lifestyle behaviors, perceived stress, BMI, and blood pressure. Results: Means and SDs of GSM-IM were 110.0±27.4 in childhood, and 75.6±15.8 in adulthood, with an annual change rate of -2.6 per year. Individuals of Hispanic ethnicity, and those with lower parental education levels had significantly lower GSM-IM in both childhood and adulthood. GSM-IM was significantly correlated with other measures of carotid artery atherosclerosis, including CIMT (r=0.28; p <0.001) and carotid artery distensibility (r=0.36; p <0.001). Results of mixed effects models adjusting for covariates, indicated that higher BMI (β=-1.35; 95% confidence interval [CI], -1.70, -0.99; p <0.001) and systolic blood pressure (β=-0.32, 95% CI, -0.55, -0.09; p=0.007) were significantly associated with lower GSM-IM. A significant interaction between BMI and age (β difference=0.14; 95% CI, 0.09, 0.20; p <0.001) suggested that a per-unit change in BMI has a greater effect on GSM-IM among adolescents compared to young adults. Health compromising behaviors, including less sleeping time, smoking, drug use, and higher perceived stress were significantly associated with lower GSM-IM in unadjusted models. However, these associations were attenuated after adjustment for covariates. Conclusion: Our study highlights the influence of BMI, particularly during childhood, blood pressure and lifestyle behaviors on adverse changes in GSM-IM, indicative of greater lipid deposition. These risk factors may be key targets for early prevention for atherosclerosis.

The associations of depressive symptoms and perceived stress with arterial health in adolescents.

Cardiovascular and mental diseases are among the most important global health problems, but little is known on the associations between mental and arterial health in adolescents. Therefore, we investigated the associations of arterial health with depressive symptoms and perceived stress in adolescents. A total of 277 adolescents, 151 boys, 126 girls, aged 15-17 years participated in the study. Depressive symptoms were assessed using the Beck Depression Inventory and perceived stress by the Cohen Perceived Stress Scale. Arterial health was assessed by measures from carotid ultrasonography (carotid intima-media thickness, Young's Elastic Modulus, carotid artery distensibility, stiffness index), impedance cardiography (pulse wave velocity, cardio-ankle vascular index), and pulse contour analysis (reflection index, stiffness index). The data were analyzed using linear regression models adjusted for age and sex. Depressive symptoms or perceived stress were not associated with indices of arterial health in the whole study group (β = -0.08 to 0.09, p > 0.05), in boys (β = -0.13 to 0.10, p > 0.05) or in girls (standardized regression coefficient β = -0.16 to 0.08, p > 0.05). We found no associations of depressive symptoms and perceived stress with arterial health in adolescents. These observations suggest that the association between mental and arterial health problems develop in later life.

Carotid wave analysis in young adults with a history of adolescent anorexia nervosa: a case control study

BackgroundAnorexia nervosa (AN) is associated with abnormalities that may increase the risk of future cardiovascular disease. This study assessed the cardiovascular health of individuals who recovered from AN during adolescence by conducting wave power analysis.MethodsFormer AN patients discharged from the Royal Children’s and Monash Children’s Hospitals (N = 17) in Melbourne, Australia underwent ultrasound imaging of the right carotid artery. Wave power analysis was conducted to assess biomechanical interactions of the cardiovascular system. Patient measures were compared to healthy controls (N = 51).ResultsEighty-eight percent of the former AN patients and controls were female, aged approximately 25 years, with a healthy body mass index. Mean carotid flow and pulsatility index were not different between groups. Carotid arterial strain and distensibility were lower, and the wave speed and beta stiffness index higher in the former AN patients. Characteristic impedance was not different nor were the forward and backward wave amplitudes. However, wave reflection indices (ratios of backward-to-forward compression wave area, and wave-related effect on pressure and hydraulic power) were 12–18% lower in the former AN patients (p < 0.05).ConclusionsIncreased carotid artery stiffness and reduced wave reflection are evident in young adults who recovered from adolescent AN. This may relate to an adaptive process that helps to maintain or restore flow and characteristic impedance despite increased vessel stiffness, with this warranting future investigation.

Rapid, Low-Cost Measurement of Carotid Artery Distensibility in Children with Sickle Cell Disease Using Compact Point-of-Care Ultrasound

Introduction: Silent cerebral infarction (SCI) is common in children with sickle cell disease and is linked to cognitive decline, poor academic performance, and overt stroke (DeBaun, 2014). Currently, the only clinical approach to identify patients at risk of SCI involves MRI screening for school-age children (DeBaun, 2020). However, this method is costly, not easily accessible, and often requires sedation, making implementation difficult. Moreover, prophylactic therapies, such as chronic blood transfusion, have shown minimal success in preventing SCI progression. Arterial stiffening is tightly linked with the development of stroke and SCIs in heart disease and elderly populations (Mattace-Raso, 2006). However, prior work in sickle cell disease on central arterial stiffening is inconclusive and arterial stiffness of the cerebrovascular is largely unknown, especially in children (Pikilidou, 2015). Therefore, the goal of this work was to determine the feasibility of compact, point of care ultrasound in the assessment of arterial stiffening of the carotid arteries and establish normative values in children with sickle cell disease. Methods: All studies were performed with IRB approval and with informed consent. The study population included 16 pediatric patients (14.75 ± 4.54 years, 11 Male, hemoglobin 9.72± 1.78 g/dL) recruited from the Blood and Cancer Center at Dell Children's Hospital in Austin, TX. All participants had their vitals taken and their right common carotid artery imaged in supine position following at least 10 minutes rest. Imaging was performed by an experienced imaging professional (AB, 10 years experience) using a Butterfly IQ + ultrasound probe (Burlington, MA) and an Apple smartphone (Cupertino, CA) in the B-mode vascular setting. Three to ten second recordings of the carotid artery were recorded at a rate of approximately 20 frames per second. In house MATLAB scripts were developed for semiautomated cross sectional area segmentation across the cardiac cycle to calculate vessel lumen area (Figure 1). Strain was calculated using the ratio of change in systolic and diastolic area over diastolic area, and distensibility (1/stiffness) was calculated as strain/ln[SBP/DBP] (Godia, 2007). Univariate and stepwise multiple analysis was performed to determine the correlates of arterial distensibility. Results: We measured an average distensibility of 0.23 ± 0.10 (a.u) across patients. A statistically significant inverse relationship between systolic pressure and distensibility (p=0.039, R 2=0.53) was measured. Upon multivariate analysis, systolic blood pressure was the only predictor of carotid distensibility. All other factors (sex, age, height, weight, hemoglobin concentration, and diastolic blood pressure) showed a statistically insignificant relationship (p&amp;gt;0.05). Further Applications: Our study shows it is possible to rapidly and inexpensively measure a metric of cerebral arterial stiffness in children with sickle cell disease and that arterial stiffness is linked with systolic blood pressure. Silent cerebral infarcts in children are known to be linked with systolic blood pressure, male gender and increase with age during adolescence (DeBaun, 2012). Whether arterial stiffening predicts the prevalence and progression of SCI and the role of point of care ultrasound is an ongoing area of research.

Determinants of vascular structure and function in at-risk children born to mothers managed for pre-eclampsia (FINNCARE study).

Pre-eclampsia (PE) is related to elevated blood pressure (BP) in children. The study aims to investigate if elevated BP is reflected in child arterial health and how anthropometrics, body composition, and gestational and perinatal factors influenced this. In this prospective cohort study, we assessed the arteries of 182 children exposed (46 had an early onset, with a diagnosis before 34 gestational weeks, and 136 had a late onset) and 85 children unexposed (non-PE) to PE at 8-12 years from delivery using ultra-high-frequency ultrasound in addition to ambulatory and central BPs, body composition and anthropometrics, and tonometry-derived pulse wave velocity (PWV). No differences were found in intima-media thickness (IMT), adventitia thickness (AT), lumen diameter (LD), local carotid artery stiffness, distensibility, or wall stress between PE-exposed and non-PE-exposed children. All children's brachial, radial, and femoral artery IMTs were associated with 24-h systolic BP (SBP) and pulse pressure, carotid-femoral PWV, and anthropometric measures. The 24-h SBP and anthropometrics, notably lean body mass, were independent predictors of peripheral artery IMTs (brachial R2 = 0.217, radial R2 = 0.208, femoral R2 = 0.214; p < 0.001). Head circumference predicted carotid artery IMT and LD (β = 0.163, p = 0.009; β = 0.417, p < 0.001, respectively), but carotid artery IMT was not associated with BP. No independent associations were found for peripheral artery ATs. Local carotid artery stiffness, distensibility, and wall stress were independently associated with adiposity. No significant associations were found between gestational or perinatal factors and child vascular health parameters. The peripheral artery IMT of PE-exposed children is identical to that of non-PE-exposed children, but associated with BP. Adiposity is related to local carotid artery stiffness. These adverse associations in arterial health may reflect the early progression of cardiovascular disease in PE-exposed children.

Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children.

Severe childhood infection has a dose-dependent association with adult cardiovascular events and with adverse cardiometabolic phenotypes. The relationship between cardiovascular outcomes and less severe childhood infections is unclear. To investigate the relationship between common, non-hospitalised infections, antibiotic exposure, and preclinical vascular phenotypes in young children. A Dutch prospective population-derived birth cohort study. Participants were from the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort. We collected data from birth to 5 years on antibiotic prescriptions, general practitioner (GP)-diagnosed infections, and monthly parent-reported febrile illnesses (0-1 years). At 5 years, carotid intima-media thickness (CIMT), carotid artery distensibility, and blood pressure (BP) were measured. General linear regression models were adjusted for age, sex, smoke exposure, birth weight z-score, body mass index, and socioeconomic status. Recent antibiotic exposure was associated with adverse cardiovascular phenotypes; each antibiotic prescription in the 3 and 6 months prior to vascular assessment was associated with an 18.1 μm (95% confidence interval, 4.5-31.6, p = 0.01) and 10.7 μm (0.8-20.5, p = 0.03) increase in CIMT, respectively. Each additional antibiotic prescription in the preceding 6 months was associated with an 8.3 mPa-1 decrease in carotid distensibility (-15.6- -1.1, p = 0.02). Any parent-reported febrile episode (compared to none) showed weak evidence of association with diastolic BP (1.6 mmHg increase, 0.04-3.1, p = 0.04). GP-diagnosed infections were not associated with vascular phenotypes. Recent antibiotics are associated with adverse vascular phenotypes in early childhood. Mechanistic studies may differentiate antibiotic-related from infection-related effects and inform preventative strategies.

VASCULAR REMODELING AND FIBROSIS INDEXES IN NAFLD SUBJECTS

Objective: Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem and is related to an increased burden of cardiovascular disease. Aim of the study: to assess the relation between non-invasive scoring systems for liver fibrosis (Fibrosis-4 Index and NAFLD Fibrosis Score) and structural and functional vascular properties in NAFLD patients. Design and method: The study enrolled 30 consecutive patients (mean age 64±13, BMI 29.3±6.1 kg/m2, male 60%) who underwent hepatological evaluation in our department. Atherosclerotic burden was evaluated by B-mode ultrasound in each carotid artery segment (common, bulb, internal), bilaterally, and expressed as mean of carotid intima-media thickness (mean-IMT) and mean of maximum IMT (M-MAX), right common carotid artery distensibility and stiffness (CardioVascular Suite 4, Quipu, Italy). Aortic stiffness was measured by applanation tonometry (PulsePen DiaTecne, Italy) and was expressed as carotid-femoral pulse wave velocity (PWV). Results: In our cohort vascular properties were: carotid mean-IMT 0.83±0.15 mm, M-MAX 0.98±0.17 mm, carotid distensibility 18.8±8.3 10-3/kPa, and carotid compliance CC 0.88±0.40 mm2/kPa. We found a significant correlation between NAFLD Fibrosis Score and PWV (mean PWV = 10.9±2.9m/s; Fibrosis Score = -0.97±1.80; R = 0.422, p = 0.020), which remained significant after adjustment for mean arterial blood pressure and sex (p = 0.017). No correlation was found between carotid ultrasound parameters and fibrosis scores. Conclusions: In NAFLD patients, our preliminary observation shows a correlation between a liver fibrosis score and PWV, an established marker of aortic stiffness, while no correlation was observed with carotid atherosclerosis markers. This vascular remodeling phenotype needs to be confirmed in a larger population.

Barosensory vessel mechanics and the vascular sympathetic baroreflex: Impact on blood pressure homeostasis.

What is the topic of this review? We review barosensory vessel mechanics and their role in blood pressure regulation across the lifespan. What advances does it highlight? In young normotensive men, aortic unloading mechanics contribute to the resting operating point of the vascular sympathetic baroreflex; however, with advancing age, this contribution is removed. This suggests that barosensory vessel unloading mechanics are not driving the well-documented age-related increase in resting muscle sympathetic nerve activity. An age-associated increase in arterial blood pressure is evident for apparently healthy humans. This is frequently attributed to stiffening of the central arteries and a concurrent increase in sympathetic outflow, potentially mediated by a reduced ability of the baroreceptive vessels to distend. This is supported, in part, by a reduced mechanical component of the vascular sympathetic baroreflex (i.e., a reduction in distension for a given pressure). Previous characterization of the mechanical component has assessed only carotid artery distension; however, evidence suggests that both the aortic and carotid baroreflexes are integral to blood pressure regulation. In addition, given that baroreceptors are located in the vessel wall, the change in wall tension, comprising diameter, pressure and vessel wall thickness, and the mechanics of this change might provide a better index of the baroreceptor stimulus than the previous method used to characterize the mechanical component that relies on diameter alone. This brief review summarizes the data using this new method of assessing barosensory vessel mechanics and their influence on the vascular sympathetic baroreflex across the lifespan.

Comparison between Carotid Distensibility-Based Vascular Age and Risk-Based Vascular Age in Middle-Aged Population Free of Cardiovascular Disease.

The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.

Menopausal Hormone Therapy and Subclinical Cardiovascular Disease in Women With and Without Human Immunodeficiency Virus.

Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI}, .40-.80]; P < .01), 2.51 µm less progression of CIMT per year (95% CI, -4.60, to -.41; P = .02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI, .14-1.03; P = .06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.

Heart rate reactivity to acute mental stress is associated with adiposity, carotid distensibility, sleep efficiency, and autonomic modulation in young men

Acute mental stress (AMS) increases heart rate (HR) and blood pressure. Since obesity can impair the cardiovascular reactivity to AMS, a better understanding of the mechanisms involved in this response is needed. We aimed to evaluate the cardiovascular reactivity to AMS in young men with normal or excess body fat. We also assessed the association between cardiovascular reactivity to AMS and cardiovascular risk factors, including autonomic modulation, carotid artery distensibility, physical activity levels, and sleep efficiency. Sixty-six young men (26.1 ± 4.1 years old) underwent anthropometric and body fat assessment (dual-energy X-ray absorptiometry) and had right-carotid artery ultrasonography. Accelerometers assessed physical activity levels and sleep efficiency. AMS was induced through the Stroop color-word test while blood pressure, HR, and cardiac interval were measured. Analyses were performed in Normal and Excess fat groups divided by fat mass index (FMI). Continuous data was used for multiple linear regression analyses. An interaction between FMI and time for HR reactivity was observed. Cardiac interval variability analysis showed that only participants with normal fat displayed parasympathetic withdrawal during AMS (P < 0.05). Multiple linear regression analysis supported the role of adiposity and autonomic modulation in the HR reactivity to AMS and showed involvement of carotid distensibility and sleep efficiency (P < 0.05). Carotid distensibility was the only predictor for blood pressure reactivity (P < 0.05). Physical activity was not associated with AMS's cardiovascular reactivity. We conclude that increased adiposity is associated with reduced HR reactivity to AMS, which is possibly linked to an impaired parasympathetic withdrawal. Carotid distension and sleep efficiency seem to contribute to this response.

Association of Vascular Properties With the Brain White Matter Hyperintensity in Middle-Aged Population.

BackgroundThe periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation.Methods and ResultsA total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold.ConclusionsWe show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.

Abstract 14367: Elevated Creatinine Levels Are Associated With Vascular Dysfunction in Liver Transplant Recipients

Introduction: Liver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. The physiological mechanisms driving LT-related CVD are not fully understood. Renal impairment post-transplant may contribute to CVD risk in LT recipients. The aim of this study was to investigate the relationship between plasma creatinine levels and vascular function in LT patients. Methods: Conduit artery endothelial function was measured via flow-mediated dilation of the brachial artery (FMD BA ) with duplex ultrasound in 13 LT patients (7 Male, 6 Female; Median [IQR]: Age 59 [56 - 64] years). Parameters of carotid artery function (distension, distensibility, compliance and stiffness) were assessed using B mode ultrasound and central aortic pressure waves that were synthesized from radial artery waveforms acquired by applanation tonometry in 13 LT patients (6 Male, 7 Female; Age 57 [56 - 64] years). Blood samples were analyzed for plasma creatinine by nuclear magnetic resonance spectroscopy. Results: Conduit artery endothelial function via FMD BA (4.07 [3.52 - 6.40] %) was negatively associated with plasma creatinine levels (1.30 [1.08 - 1.56] mg/dL; r = -0.63, p = 0.03). Plasma creatinine levels were also inversely associated with carotid artery distension (0.53 [0.35 - 0.61] mm, r = -0.74, p = 0.006), distensibility (25.62 [20.65 - 33.03] 10 -3 ·kPa -1 , r = -0.59, p = 0.04), and compliance (1.19 [0.82 - 1.41] 10 -6 ·m 2 ·kPa -1 , r = -0.66, p = 0.02), and positively associated with carotid stiffness (6.07 [5.35 - 6.76] m·s -1 , r = 0.59, p = 0.04) as shown in Figure 1. Conclusions: Our results indicate that LT patients with higher levels of creatinine have impaired conduit artery endothelial function and compromised carotid artery function, making these individuals more susceptible to the development of atherosclerosis and stroke. The presence of renal dysfunction after LT may contribute to CVD risk and warrants investigation in future trials.

Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study

BackgroundHypertension and atherosclerosis may partly originate in early life. Altered epigenetic aging may be a mechanism underlying associations of early-life exposures and the development of cardiovascular risk factors in childhood. A discrepancy between chronological age and age predicted from neonatal DNA methylation data is referred to as age acceleration. It may either be positive, if DNA methylation age is older than clinical age, or negative, if DNA methylation age is younger than chronological age. We examined associations of age acceleration at birth (‘gestational age acceleration’), and of age acceleration at school-age, with blood pressure and with intima-media thickness and distensibility of the common carotid artery, as markers of vascular structure and function, respectively, measured at age 10 years.ResultsThis study was embedded in the Generation R Study, a population-based prospective cohort study. We included 1115 children with information on cord blood DNA methylation and blood pressure, carotid intima-media thickness or carotid distensibility. Gestational age acceleration was calculated using the Bohlin epigenetic clock, which was developed specifically for cord blood DNA methylation data. It predicts gestational age based on methylation levels of 96 CpGs from HumanMethylation450 BeadChip. We observed no associations of gestational age acceleration with blood pressure, carotid intima-media thickness or carotid distensibility at age 10 years. In analyses among children with peripheral blood DNA methylation measured at age 6 (n = 470) and 10 (n = 449) years, we also observed no associations of age acceleration at these ages with the same cardiovascular outcomes, using the ‘skin and blood clock,’ which predicts age based on methylation levels at 391 CpGs from HumanMethylation450 BeadChip.ConclusionsOur findings do not provide support for the hypothesis that altered epigenetic aging during the earliest phase of life is involved in the development of cardiovascular risk factors in childhood.

Relationship between life-time exposure to ambient fine particulate matter and carotid artery intima-media thickness in Australian children aged 11–12 years

Long-term exposure to air pollutants, especially particulates, in adulthood is related to cardiovascular diseases and vascular markers of atherosclerosis. However, whether vascular changes in children is related to exposure to air pollutants remains unknown. This study examined whether childhood exposure to air pollutants was related to a marker of cardiovascular risk, carotid intima–media thickness (CIMT) in children aged 11–12 years old. Longitudinal Study of Australian Children (LSAC) recruited parents and their children born in 2003–4. Among the participants, CheckPoint examination was conducted when the children were 11–12 years old. Ultrasound of the right carotid artery was performed using standardized protocols. Average and maximum far-wall CIMT, carotid artery distensibility, and elasticity were quantified using semiautomated software. Annual and life-time exposure to air pollutants was estimated using satellite-based land-use regression by residential postcodes. A total of 1063 children (50.4% girls) with CIMT data, serum cholesterol, and modeled estimates of NO2 and PM2.5 exposure for the period 2003 to 2015 were included. The average and maximum CIMT, carotid distensibility, and elasticity were 497 μm (standard deviation, SD 58), 580 μm (SD 44), 17.4% (SD 3.2), and 0.48%/mmHg (SD 0.09), respectively. The life-time average concentrations of PM2.5 and NO2 were 6.4 μg/m3 (SD 1.4) and 6.4 ppb (SD 2.4), respectively. Both average and maximum CIMT were significantly associated with average ambient PM2.5 concentration (average CIMT: +5.5 μm per μg/m3, 95% confidence interval, CI 2.4 to 8.5, and maximum CIMT: +4.9 μm per μg/m3, CI 2.3 to 7.6), estimated using linear regression, adjusting for potential confounders. CIMT was not significantly related to NO2 exposure. Carotid artery diameter, distensibility, and elasticity were not significantly associated with air pollutants. We conclude that life-time exposure to low levels of PM2.5 in children might have measurable adverse impacts on vascular structure by age 11–12 years.

Vitamin B12, folate and homocysteine concentrations during pregnancy and early signs of atherosclerosis at school-age

SummaryBackground & aimsSuboptimal circulating vitamin B12, folate and homocysteine concentrations during fetal life seem to be associated with cardiometabolic health at school-age. We examined whether fetal exposure to lower circulating vitamin B12 and folate concentrations and higher circulating homocysteine concentrations is also associated with early signs of atherosclerosis at school-age.MethodsThis study among 3826 school-age children and their mothers was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We examined the associations of early-pregnancy and cord blood serum total and active B12 and plasma folate and homocysteine concentrations with common carotid artery intima-media thickness and distensibility in the children aged ten years.ResultsAs compared to normal early-pregnancy serum total B12 concentrations (≥145 pmol/L), low serum total B12 concentrations (<145 pmol/L) were associated with higher carotid intima-media thickness in the children at school-age (difference 0.09 standard deviations score (SDS); 95% confidence interval (CI): 0.01, 0.16). As compared to normal early-pregnancy plasma folate concentrations (≥8 nmol/L), low plasma folate concentrations (<8 nmol/L) were associated with lower carotid disten-sibility in the children at school-age (difference −0.16 SDS; 95% CI: −0.28, −0.04). Early-pregnancy circulating total and active B12, folate and homocysteine concentrations measured continuously were not associated with carotid intima-media thickness or carotid distensibility in the children at school-age. One SDS higher plasma homocysteine concentrations measured in cord blood at birth was associated with a −0.05 SDS (95% CI: −0.09, −0.02) lower carotid distensibility at school-age. Cord blood total and active B12 and folate concentrations were not associated with carotid intima-media thickness or carotid distensibility at school-age.ConclusionsCirculating total B12, folate and homocysteine concentrations during fetal life seem to be associated with markers of subclinical atherosclerosis at school-age. Further studies need to examine the causality and mechanisms underlying these associations.

Ultrasonography to detect cardiovascular damage in children with essential hypertension

BackgroundEssential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography.MethodsAll patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid–femoral pulse wave velocity (cfPWV), intimal–medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography.ResultsThe cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E’ among three groups.ConclusionChildren and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Prenatal Exercise and Cardiovascular Health (PEACH) Study: Impact on the Vascular System.

Healthy pregnancy is typically associated with favorable vascular adaptations to both structure and function of the peripheral arteries. Exercise is independently associated with improvements in peripheral vascular health; however, the impact of exercise on prenatal adaptations is unclear. Therefore, we hypothesized that a structured aerobic exercise intervention between the second and third trimesters (TM2 and TM3, respectively) of pregnancy would augment the already-positive changes in vascular outcomes. We recruited 59 inactive pregnant women (<20 wk of gestation) and randomized them into control (standard care; n = 28) or exercise (moderate-intensity aerobic exercise, 3-4 d·wk-1, 25-40 min, 14 ± 1 wk; n = 31) conditions. Before and after the intervention, all women completed the comprehensive peripheral vascular assessment, which included blood markers of vascular health, carotid distensibility metrics, measures of arterial stiffness (pulse wave velocity), and [superficial] femoral artery reactivity during cold pressor test. Carotid artery diameter increased from 6.5 to 6.9 mm (P < 0.001), and strain (%) decreased from 9.9% to 8.4% (P < 0.001). Carotid artery blood flow, compliance and distensibility coefficients, stiffness (β), distensibility (1/β), and elastic modulus were not different across gestation. Pulse wave velocity was not different across gestation. Superficial femoral artery diameter was increased from 5.4 to 5.6 mm (P = 0.004), whereas blood flow, conductance, and resistance at rest and during the cold pressor test were not different across gestation. None of our measures of vascular health were impacted by exercise. We did not observe an impact of aerobic exercise on altering the changes across pregnancy in blood vessel health. However, the present study was conducted in women who were overall at low risk for developing gestational hypertension and should be interpreted with caution. Future work in high-risk women is needed.