Measures Of Vascular Function Research Articles

Abstract 12000: Altered Vascular Elasticity Reflected Vascular Endothelial Dysfunction and Elevated Galectin-3 Using Novel Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometric Approach

Introduction: Simple vascular function measurements are desirable for atherosclerosis risk assessments. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery’s vascular elastic modulus (V E ) and reported that V E is uninfluenced by blood pressure. Galectin-3 (Gal-3) expressed in endothelial cells regulates vascular fibrosis and is a molecular determinant of vascular stiffness. Hypothesis: We aimed to clarify whether V E selectively correlates with marker of vascular stiffness in chronic kidney disease (CKD). Methods: 12 moderate-to-severe CKD pts (mean eGFR 25.9±23.5 mL/min/1.73m 2 ) and 15 controls were studied. Rest V E in brachial artery was measured by new automated oscillometric detector. V E was defined as follows [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery diameter at rest and during reactive hyperemia [flow mediated dilatation (FMD) with endothelial-dependent dilatation] was measured. Gal-3 and interleukin-6 (IL-6), a representative inflammatory marker, were measured by enzyme-linked immune assay. Results: CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and had attenuated V E than control (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). CKD had higher IL-6 (0.67±0.29 vs 0.29±0.33 pg/mL, P=0.003) and higher Gal-3 (20.0±12.4 vs. 5.84±2.83 pg/mL, P<0.001). V E was negatively correlated with %FMD (r=-0.46, P=0.015) and correlated with Gal-3 (r=0.40, P=0.036) but not in IL-6 (r=0.21, P=0.28). Conclusions: Attenuated vascular elasticity detected by this novel approach closely correlated with increase in Gal-3 and reduced FMD in CKD. This may indicate that the attenuated vascular elasticity selectively reflects vascular fibrosis as evidenced by Gal-3 and subsequent endothelial responses to vascular stiffness. Thus, this oscillometric measurement may be useful for detecting vascular fibrosis information and dysfunction in endothelium level.

ADMA and arginine derivatives in relation to non-invasive vascular function in the general population

ObjectiveNitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population. Approach and resultsIn 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations were observed between all measured arginine derivatives and vascular function measures, except of l-arginine and FMD and SDMA and PAT ratio. In multivariate adjusted linear regression analyses we could show statistically significant relationships between arginine derivatives and vascular function measures, which were influenced by age, sex and body mass index (BMI). Thus, a negative relationship between ADMA and FMD in females who were normal (beta: −0.095, P < 0.001) to overweight (beta: −0.071, P < 0.001) and a negative association of SDMA and FMD for middle-aged females was seen. The relationship between ADMA and PAT was negative for males who were normal (beta: −0.089, P < 0.001) to overweight (beta: −0.051, P = 0.007) and positive for obese females (beta: 0.073, P = 0.021). ConclusionsWe showed small but significant correlations between ADMA and related arginine derivatives and non-invasive vascular function measures representative of different vascular regions. The associations were markedly influenced by age, sex and BMI. These findings support a complex interplay of arginine metabolism and vascular function.

Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation, Carotid Intima-Media Thickness, and Arterial Stiffness in Children

To determine the associations of adiposity and insulin resistance with measures of vascular structure and function in children. A cross-sectional study included 252 children (age 15.1 ± 2.4 years; body mass index percentile 68.2 ± 26.5%; Tanner 2-5). Measurements of body fat percentage were obtained with dual-energy X-ray absorptiometry and visceral adipose tissue (VAT) with computed tomography. Insulin resistance was measured with hyperinsulinemic euglycemic clamp. Vascular measurements for endothelial function (brachial artery flow-mediated dilation [FMD]), vascular structure (carotid intima-media thickness [cIMT]), vascular stiffness (carotid incremental elastic modulus), and pulse wave velocity were analyzed by tertiles of adiposity and insulin resistance. Additional analyses with ANCOVA and linear regression were adjusted for Tanner, sex, race, and family relationship; FMD was also adjusted for baseline artery diameter. FMD was positively associated with high adiposity (body mass index, body fat percentage, and VAT) (P < .01 all). Insulin resistance was not associated with FMD. cIMT was significantly, positively related to obesity, VAT, and insulin resistance (P < .05 all). No differences in carotid incremental elastic modulus and pulse wave velocity were observed in relation to adiposity or insulin resistance. The findings suggest that adiposity is associated with higher FMD, and insulin resistance and VAT are associated with higher cIMT in children. Further research is needed to clarify the progression of these relations.

Vascular and Microvascular Endothelial Function in Heart Failure With Preserved Ejection Fraction

BackgroundAssessment of vascular endothelial function lacks consistency, and microvascular endothelial function has been only partly assessed in heart failure with preserved ejection fraction (HFpEF). MethodsThe study population consisted of 90 patients: 45 had well documented HFpEF, and 45 had hypertension and no history or evidence of heart failure. Patients with hypertension but no heart failure were matched with HFpEF patients for age, sex, and diabetes. They served as control subjects. All patients underwent 2-dimensional Doppler echocardiography and vascular function measurements, including assessment of arterial wave reflections and arterial stiffness, brachial artery flow-mediated dilation (FMD), and forearm cutaneous blood flow with the use of a laser Doppler flow probe at rest and after release of arterial occlusion for 5 minutes. ResultsBrachial artery FMD was lower in HFpEF than in control subjects (median (IQR) 3.6 (0.4-7.4) vs 7.2 (3.2-17.2)%, P = .001). Forearm cutaneous blood flow at rest was similar in HFpEF and control subjects (P = .68). After release of arterial occlusion, forearm cutaneous peak blood flow was lower in HFpEF than in control subjects (P = .03). Estimated aortic systolic and mean blood pressures were similar in HFpEF and control subjects, whereas pulse pressure and pressure augmentation were greater in HFPEF than in control subjects (both P < .05). ConclusionCompared with hypertensive control subjects, patients with HFpEF had a depressed endothelial function in the forearm vasculature and microvasculature.

Abstract P124: Human Small Artery MicroRNA Expression Profiles: Changes in Type 2 Diabetes and Associations with Endothelial Function

Background: Studies of experimental models and human blood samples support an important role of microRNAs (miRNAs) in the development of vascular dysfunction in hypertension and diabetes mellitus (DM). Information on miRNA expression in clinically directly relevant tissues such as human small arteries and its relationship with impaired vascular endothelial function is currently lacking. Methods and Results: 38 subjects (18 type 2 DM, 20 controls) underwent gluteal adipose pad biopsy to obtain small arteries for miRNA expression profiling by small RNA deep sequencing. In vivo conduit artery endothelial function was measured by brachial artery reactivity. In vitro microvascular endothelium dependent vasodilation was measured by videomicroscopy. Correlations between miRNA expression and measurements of endothelial function were calculated using generalized linear models. Several miRNAs correlated with measurements of vascular structure and function. Endothelium dependent vasodilation was impaired in type 2 DM subjects compared to controls based on both the vasodilatory response to peak dose acetylcholine (44±25 vs. 69±18 %, P=0.04) and by analyses of the entire acetylcholine dose-response curve. Several miRNAs were differentially expressed in small arteries from type 2 DM subjects, two of which were verified by real-time PCR. Cross-referencing the top 30 miRNAs (P&lt;0.015) with prior studies of plasma miRNA expression in DM subjects identified 7 miRNAs differentially expressed in both human small arteries and plasma, all of which have some reported role in vascular regulation. Conclusions: Multiple miRNAs are differentially expressed in human small arteries in DM patients and correlated with in vivo or in vitro measurements of endothelial function, suggesting an important role of microvascular miRNAs in the development of endothelial dysfunction in humans.

The Role of Femoral Artery Ultrasound Measurements in Predicting Restenosis following Endovascular Intervention

Background Although endovascular interventions for peripheral artery disease (PAD) have become increasingly common, they are associated with a significant rate of restenosis. An improved understanding of the risk factors for restenosis is needed to guide the management of patients with PAD. Methods We performed a cross-sectional analysis of 101 patients with PAD, to determine the association between clinical predictors, novel imaging measures of vascular function of the femoral artery [intima-media thickness, diameter, and intima-media cross-sectional area, change in diameter (delta diameter), average expansion and average contraction], and risk of reintervention. Univariable and multivariable associations between clinical and imaging measures and the need for reintervention were assessed using logistic regression. The predictive accuracy of the selected regression model and added predictive value of imaging measures were assessed using the area under the Receiver operating characteristic curve (AUC). The added predictive value of ultrasound was assessed by comparing AUC of the selected model with clinical parameters alone with that of the same model with additional ultrasound parameters. Results Of the 101 patients with PAD, 20 underwent recent multiple reinterventions. Vessel diameter was statistically significantly smaller in the group who underwent multiple reinterventions, p = 0.0170. Univariate logistic regression revealed that smoking status, hypertension, hypercholesterolemia, and chronic renal insufficiency were clinical parameters that met the statistical cut point of p ≤ 0.20. In the multivariable model, chronic renal insufficiency status (odds ratio (OR) = 8.27, 1.17–58.25), hypertension (OR = 0.145, 0.020–1.062), and femoral artery diameter (OR = 0.375, 0.136–1.031) remained important predictors for reintervention. The AUC for the clinical multivariable logistic regression model was 0.7481 while that for the model additionally including the ultrasound parameters was 0.8325 ( p = 0.044). Conclusions Including ultrasound parameters in the risk prediction model for restenosis improved the ability to predict restenosis in this group of patients with known PAD. Further study is needed to define its utility in preoperative assessment and risk stratification before revascularization.

Abnormalities of vascular structure and function in pediatric hypertension.

Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima-media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage.

Association between retinal vasculature and muscle mass in older people

Sarcopenia in older people is a major health issue and its early detection could help target interventions and improve health. Evidence suggests that poor muscle mass is associated with greater arterial stiffness and cardiovascular risk. Arterial stiffness in turn is associated with smaller retinal artery width. This study examined the association of muscle mass in older people with retinal vascular width, a non-invasive measure of vascular function. MethodsParticipants >65 years were recruited to a cross-sectional study. Exclusions: Inability to walk independently; diabetes mellitus; stroke (within 6 months), severe macular degeneration, glaucoma, retinal dystrophy; advanced cataract. Digital Retinal images of both eyes were analysed using the VAMPIRE software suite. Central Retinal Artery and Vein Equivalents (CRVE and CRAE) were measured. Body composition was measured using Dual Energy X ray Absorptimetry (DXA). Appendicular Skeletal Muscle Mass/Height2 was calculated. Physical function was measured: 6-min walk distance, Short Physical performance battery, handgrip strength and quadriceps strength. Results79 participants with mean age 72 (SD 6) years were recruited. 44% were female. Digital Retinal images of sufficient quality for measuring CRAE and CRVE were available for 51/75 (68%) of participants. Regression analysis showed significant association between larger ASMM/H2 and smaller CRAE (β=−0.20, p=0.001) and CRVE (β=−0.12, p=0.05). Handgrip strength, body mass index and sex combined with CRAE explained 88% and with CRVE explained 86% of the variance in ASMM/H2. ConclusionLarger muscle mass was significantly associated with smaller retinal artery size in older people. This unexpected finding needs further investigation.

Using aortic distensibility index to detect coronary stenosis

Objective The aortic distensibility index, as a measure of vascular function, can serve as a marker of coronary artery disease severity. This study explores the feasibility of using the non-invasively measured index as an indicator of severity of coronary stenosis.Methods One hundred patients with normal left ventricular systolic function were prospectively enrolled. They were subjected to assessment of aortic distensibility using computed tomographic angiography and transthoracic echocardiography. Coronary artery disease severity and coronary artery calcium score were assessed.Results The mean age of the whole study cohort was 58 ± 9 years, 63 (63%) being males. A signifi cant inverse correlation was found between aortic distensibility measured using computed tomographic angiography and patients’ age, systolic blood pressure, coronary artery calcium score and severity of coronary artery disease (percent luminal stenosis). However, there was no statistical correlation with the number of diseased coronary arteries. A strong direct correlation was recorded upon comparing aortic distensibility index values obtained using computed tomographic angiography and transthoracic echocardiography (r = 0.325, P= 0.004). Receiver operating characteristic curve analysis revealed that an echocardiography-derived aortic distensibility index value of ≤ 6.65% is associated with signifi cant (≥ 50% luminal stenosis) coronary artery disease with a sensitivity of 83%, specifi city of 93%, positive predictive value of 97% and negative predictive value of 65%.Conclusion Non-invasive assessment of aortic distensibility indices is a feasible procedure to predict signifi cant atherosclerotic coronary artery disease. Lower values are associated with signifi cant obstructive coronary artery disease and high coronary artery calcium score.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. We investigated the substitution of 9.5-9.6%TE dietary SFAs with either monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on vascular function and other CVD risk factors. In a randomized, controlled, single-blind, parallel-group dietary intervention, 195 men and women aged 21-60 y from the United Kingdom with moderate CVD risk (≥50% above the population mean) followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA) that were rich in SFAs (36:17:11:4, n = 65), MUFAs (36:9:19:4, n = 64), or n-6 PUFAs (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation; secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation, and endothelial activation. Replacing SFAs with MUFAs or n-6 PUFAs did not affect the percentage of flow-mediated dilatation (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFAs with MUFAs attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFAs or n-6 PUFAs lowered fasting serum total cholesterol (-8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%), and total cholesterol to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Taking steps in the workplace to improve vascular function.

Taking steps in the workplace to improve vascular function.

Effects of overfeeding in breastfeeding period on blood pressure and vascular endothelial dilation function of rats

Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats, and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding. Methods Male Sprague-Dawley rats were randomly divided into normal feeding group (10/litter) and overfeeding group (3/litter) on postnatal day 3 with a random number table. After weaning at postnatal week 3, the rats were randomly given standard chow or high-fat (HF) diet until week 16. Hence four groups were analyzed, namely normal feeding group, breastfed overfeeding group, post-weaning overfeeding group, and continuous overfeeding group. Body weight was continuously monitored in each week. Visceral fat pad(retroperitoneal and perigenital), systolic pressure, and heart rate were observed at week 3 and week 16. Thoracic aorta was sampled for measurement of vascular endothelial dilation function. Histological morphology was observed with HE staining, nitric oxide content of thoracic aorta was detected with nitrate reductase method. The mRNA expression of endothelial nitric oxide synthase (eNOS) in thoracic aorta was determined by real-time polymerase chain reaction. The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot. Results At week 3, breastfed overfeeding rats displayed significantly larger body weight [(77.80±0.57) g vs. (62.80±0.85)g, t=14.576, P<0.01] and visceral fat [retroperitoneal: (8.19±0.49)mg/g vs. (4.92±0.31)mg/g, t=5.629, P<0.01; perigenital: (3.50±0.29)mg/g vs. (2.08±0.13)mg/g, t=4.552, P<0.01] compared with normal feedindg rats, and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 (F=15.215, P<0.01); high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats. At week 16, continuous overfeeding rats showed hypertension [(149±1.94)mmHg (1 mmHg=0.133 kPa), F=22.834, P<0.01], impaired vascular endothelial dilation function (F=7.648, P<0.05), and reduced protein expression of phosphorylated eNOS(F=15.215, P<0.01), while the post-weaning overfeeding group only had elevated blood pressure. Conclusions Overfeeding in breastfeeding period and high-fat diet after weaning leads to hypertension. The continuous decrease in phosphorylated eNOS in vascular tissues may be an important molecular process participating in the occurrence of vascular endothelial dysfunction in adults induced by postnatal overfeeding. Key words: Early postnatal overfeeding; Vascular endothelial dilation function; Hypertension; Nitric oxide; Phosphorylated endothelial nitric oxide synthase

The effect of a low-fat spread with added plant sterols on vascular function markers: Results of the investigating vascular function effects of plant sterols (invest) study

Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. Objectives: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. Design: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. Results: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: −0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: −0.40, −0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively. Conclusions: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as {type:clinical-trial,attrs:{text:NCT01803178,term_id:NCT01803178}}NCT01803178.

Exercise training improves cardiopulmonary and endothelial function in women with breast cancer: findings from the Diana-5 dietary intervention study.

To investigate whether exercise training (ET) improves cardiopulmonary and endothelial function in women with breast cancer (BC). Fifty-one female patients (aged between 39 and 72years) with a history of primary invasive BC within the previous 5years and enrolled in the Mediterranean diet-based DIANA (diet and androgens)-5 Trial were subdivided into 2 groups: an ET group (n=25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60-70% VO2peak for 3months, followed by one session/week until 1-year follow-up), while a control group (n=26) did not perform any formal ET. At baseline and at 1-year follow-up, all patients underwent cardiopulmonary exercise stress test (CPET) and measurements of vascular endothelial function by peripheral artery tonometry (Reactive Hyperemia Index, RHI). There were no significant differences between the groups in baseline anthropometrical, BC characteristics, and metabolic profile. No differences in baseline CPET and RHI parameters were found. Peak oxygen consumption (VO2peak) significantly increased in ET group (from 12.4±2.9 to 14.3±3.3mL/kg/min, p<0.001) compared to the control group (from 12.8±2.5 to 12.6±2.8mL/kg/min, p=0.55; p<0.001 between groups). Compared to the control group (from 2.0±0.4 to 1.9±0.4, p=0.62), the ET group showed a significant improvement of RHI after 1year (from 2.1±0.7 to 2.5±0.8, p<0.001). Changes in VO2peak were correlated with changes in RHI (ΔVO2peak vs. ΔRHI: r=0.47, p=0.017). In BC survivors, ET program improves cardiopulmonary functional capacity and vascular endothelial function after 12months. Whether these changes may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution should be investigated.

Inverse Relationship between Cardio-Ankle Vascular Index and Body Mass Index in Healthy Children

To establish reference scores for cardio-ankle vascular index (CAVI), a noninvasive measure of vascular function, which reflects the stiffness of arteries, in healthy children, to test for racial and ethnic differences, and to compare CAVI scores between overweight and normal weight children. Subjects included 292 children aged 10-18 years: 100 non-Hispanic whites, 89 non-Hispanic blacks, and 103 Hispanics. Subjects were grouped as normal weight (body mass index [BMI] <85th percentile for age) and overweight (BMI >85th percentile for age). Blood pressure (BP) and CAVI scores were measured in all subjects. After controlling for age, sex, and BMI, normal weight black males had a higher CAVI score (indicating stiffer arteries) in comparison with Hispanic males and white males (5.53 ± 0.15 vs 5.13 ± 0.15 vs 5.02 ± 0.15, P = .04). BMI had an inverse association on the CAVI score (r = -0.335, P < .0001). In multivariable analysis, BMI and average CAVI scores were significant predictors of each other (R(2) = 0.37, P < .0001, R(2) = 0.21, P < .0001). There was no significant correlation between CAVI scores and resting BP values, confirming that CAVI scores were independent of concurrent BP values. Significant differences in vascular function exist among ethnic groups of children. Overweight children had lower CAVI scores, suggestive of vascular adaptation to obesity in early life. CAVI, by providing a noninvasive measure of vascular health, may help identify children at increased risk for cardiovascular disease.

Severe Obesity in Adolescents and Young Adults Is Associated With Subclinical Cardiac and Vascular Changes.

Severe obesity is the fastest growing subgroup of obesity in youth. We sought to explore the association between severe obesity and subclinical measures of cardiac and vascular structure and function in adolescents and young adults. This was a cross-sectional comparison of 265 adolescents and young adults with severe obesity (defined as body mass index [BMI] ≥120% of the 95th percentile) to 182 adolescents and young adults with obesity (defined as BMI ≥100-119th of the 95th percentile) at tertiary medical center. Noninvasive measures of cardiac and vascular structure and function were assessed. Participants were a mean age of 17.9 years, 62% were non-Caucasian, and 68% were female. Systolic blood pressure, fasting insulin, C-reactive protein, IL-6, and frequency of type 2 diabetes were higher in participants with severe obesity (all P < .05). Arterial thickness and stiffness, cardiac structure, and diastolic function were also significantly worse in youth with severe obesity as measured by higher left ventricular mass index, worse diastolic function, higher carotid intima media thickness, and pulse wave velocity and lower brachial distensibility (all P < .05). Regression modeling showed that severe obesity (compared with obesity) was independently associated with each of the above outcomes after adjustment for age, race, sex, blood pressure, lipids, and inflammatory markers (P < .05). Adolescents and young adults with severe obesity have a more adverse cardiovascular risk profile and worse cardiac and vascular structure and function. More importantly, severe obesity is independently associated with these subclinical cardiac and vascular changes.

Plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women.

ObjectivesTo investigate the associations of the plasma homocysteine levels with the alterations in arterial stiffness in a community-based cohort. The gender differences in these associations were examined.MethodsWe evaluated the relationship between plasma homocysteine levels to three measures of vascular function [carotid-femoral pulse wave velocity (CF-PWV), carotid-ankle PWV (CA-PWV) and heart rate corrected augmentation index (AI)] in 1680 participants (mean age: 61.5 years; 709 men, 971 women) from communities of Beijing, China.ResultsIn univariate analysis, plasma homocysteine levels was positively related to the CF-PWV (r = 0.211, P < 0.0001) and CA-PWV (r = 0.148, P < 0.0001), whereas inversely associated with AI (r = −0.052, P = 0.016). In multiple linear regression models adjusting for covariants, plasma homocysteine remained positively related to the CF-PWV (standardized β = 0.065, P = 0.007) in total cases. When the groups of men and women were examined separately, plasma homocysteine remained positively associated with the CF-PWV (standardized β = 0.082, P = 0.023) in men, whereas the relations between homocysteine and any of the arterial stiffness indices were not further present in women.ConclusionsIn Chinese population, plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women.

Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study.

Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk of cardiovascular disease; however, it is not known whether NAFLD contributes to cardiovascular disease independent of established risk factors. We examined the association between NAFLD and vascular function. We conducted a cross-sectional study of 2284 Framingham Heart Study participants without overt cardiovascular disease who had liver fat attenuation measured on computed tomography and who had measurements of vascular function and covariates. We evaluated the association between NAFLD and vascular function using multivariable partial correlations adjusting for age, sex, cohort, smoking, diabetes mellitus, hyperlipidemia, hypertension, body mass index, and visceral adipose tissue. The prevalence of NAFLD in our sample (mean age, 52±12 years; 51.4% women) was 15.3%. In age-, sex-, and cohort-adjusted analyses, greater liver fat was modestly associated with lower flow-mediated dilation (r=-0.05; P=0.02), lower peripheral arterial tonometry ratio (r=-0.20; P<0.0001), higher carotid-femoral pulse wave velocity (r=0.13; P<0.0001), and higher mean arterial pressure (r=0.11; P<0.0001). In multivariable-adjusted models, NAFLD remained associated with higher mean arterial pressure (r=0.06; P=0.005) and lower peripheral arterial tonometry ratio (r=-0.12; P<0.0001). The association between NAFLD and peripheral arterial tonometry ratio persisted after further adjustment for body mass index and visceral adipose tissue. For multiple measures of vascular function, the relationship with NAFLD appeared largely determined by shared cardiometabolic risk factors. The persistent relationship with reduced peripheral arterial tonometry response beyond established risk factors suggests that NAFLD may contribute to microvascular dysfunction.

Abstract 278: Vascular Anatomic and Physiologic Relationships with Local Adipose Phenotype in Chronic Kidney Disease Patients

Introduction: Local adipose biomarkers have recently been shown to correlate with outward remodeling (adiponectin, IL-8, MCP-1, resistin and TNF) and flow volume (adiponectin, MCP-1) after human hemodialysis AVF creation. As a potential mechanism underlying this observation, we hypothesized that vascular anatomy and physiologic function is dependent on local adipose phenotype. Methods: During AVF creation surgery, adipose tissue contiguous to the proximal anastomosis was obtained from patients at two institutions participating in the NIDDK Hemodialysis Fistula Maturation (HFM) Study (n=112). Nine adipose-associated biologic mediators (adiponectin, IL-1 beta, IL-6, IL-8, leptin, MCP-1, PAI-1, resistin, and TNF) were quantified. Levels of adipose biomarkers were correlated to measurements obtained from comprehensive pre-operative non-invasive vascular anatomic and functional studies performed as part of the HFM Study protocol using Spearman correlation (before logarithmic transformation) and Pearson correlation (after transformation). Bonferroni correction was performed for multiple testing (alpha/9=0.006) Results: Smaller brachial arterial diameter correlated with higher IL-8 (r=-0.23, 95% CI -0.41 to -0.03, p=0.02), MCP-1 (r=-0.24, 95% CI -0.42 to -0.05, p=0.01), and PAI-1 (r=-0.25, 95% CI -0.42 to -0.05, p=0.01) levels and lower brachial arterial flow velocity correlated with higher MCP-1 (r=-0.22, 95% CI -0.40 to -0.02, p =0.03), but the associations were not significant after Bonferroni adjustment. Brachial artery flow- and nitroglycerin-mediated dilation (FMD and NMD), carotid-radial and -femoral pulse wave velocity (PWV), augmentation index, and the slope of the venous volume-pressure relationship did not correlate with adipose mediator levels. Conclusions: While there was suggestion of a relationship between local adipose mediator levels and baseline brachial artery characteristics, relationships with vascular function as assessed by FMD, NMD, PWV and venous capacitance slope were not evident using tests of monotonic associations. Processes not reflected in these measures of vascular characteristics and function may underlie relationships between adipose phenotype and vascular remodeling in human AVFs.

The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study

Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage.Objectives: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD.Design: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed.Results: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: −0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: −0.40, −0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 μmol/L and 13.9 μmol/L (expressed as geometric means), respectively.Conclusions: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.