Brachial Artery Reactivity Testing Research Articles

Association of hepatokines with markers of endothelial dysfunction and vascular reactivity in obese adolescents.

Obesity-induced insulin resistance (IR) is known to influence hepatic cytokines (hepatokines), including fibroblast growth factor (FGF-21), fetuin-A, and chemerin. This study aimed to investigate the association between hepatokines and markers of endothelial dysfunction and vascular reactivity in obese adolescents. A total of 45 obese adolescents were categorized into three groups based on glucose tolerance: normal glucose tolerance (NGT), prediabetes (PD), and type 2 diabetes (T2D). We examined the relationships between FGF-21, fetuin-A, and chemerin with endothelial markers (plasminogen activator inhibitor-1 [PAI-1], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion marker-1 [VCAM-1]) and vascular surrogates (brachial artery reactivity testing [BART] and peak reactive hyperemia [PRH]). Obese adolescents (age 16.2±1.2 years; 62 % female, 65 % Hispanic) with NGT (n=20), PD (n=14), and T2D (n=11) had significant differences between groups in BMI; waist-hip ratio (p=0.05), systolic BP (p=0.008), LDL-C (p=0.02), PAI-1 (p<0.001). FGF-21 pg/mL (mean±SD: NGT vs. PD vs. T2D 54±42; 266±286; 160±126 p=0.006) and fetuin-A ng/mL (266±80; 253±66; 313±50 p=0.018), were significantly different while chemerin ng/mL (26±5; 31±10; 28±2) did not significantly differ between the groups. Positive correlations were found between chemerin and both PAI-1 (r=0.6; p=0.05) and ICAM-1 (r=0.6; p=0.05), FGF-21 and PAI-1 (r=0.6; p<0.001), and fetuin-A with TNFα (r=-0.4; p=0.05). Negative correlations were found between chemerin and PRH (r= -0.5; p=0.017) and fetuin-A and PRH (r=-0.4; p=0.05). In our cohort, IR predicted higher FGF-21 levels suggesting a linear relationship may exist between the two parameters. Hepatokines can augment alterations in the microvascular milieu in obese adolescents as demonstrated by their associations with the markers PAI-1, ICAM-1, and PRH.

Vascular endothelium as a target for perfluroalkyl substances (PFAs)

IntroductionPerfluoroalkyl substances (PFAs) are ubiquitous, anthropogenic organic compounds that have been linked with cardiovascular disease and cardiovascular risk factors. Older, long-chain PFAs have been phased out due to adverse cardiometabolic health effect and replaced by newer short-chain PFAs. However, emerging research suggests that short-chain PFAs may also have adverse cardiovascular effects. Non-invasive measures of vascular function can detect preclinical cardiovascular disease and serve as a useful surrogate for early CVD risk. We hypothesized that serum concentrations of PFAs would be associated with noninvasive measures of vascular function, carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART), in adults with non-occupational exposure to PFAs. MethodsWe measured serum concentrations of 14 PFAs with hybrid solid-phase extraction and ultrahigh-performance liquid chromatography–tandem mass spectrometry in 94 adult outpatients with no known cardiovascular disease. We collected clinical and demographic data; and measured vascular function, PWV and BART, using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. ResultsTen PFAs were measured above the limit of detection in >50% of participants. Each standard deviation increase in concentration of perfluoroheptanoic acid (PFHpA) was associated with 15% decrease in BART (95% CI: −28.5, −0.17). The weighted index of a mixture of PFAs with correlated concentrations was inversely associated with BART: each tertile increase in the weighted PFA mixture was associated with 25% lower BART, with 73% of the effect driven by PFHpA. In contrast, no PFAs or mixtures were associated with PWV. ConclusionsSerum concentration of PFHpA, a new, short-chain PFA, was associated with impaired vascular function among outpatients without CVD. Our findings support a potential adverse cardiovascular effect of newer, short-chain PFAs.

Abstract 12258: Associations Between Serum Perfluoroalkyl Substances and Vascular Function

Introduction: Perfluoroalkyl substances (PFA)s are ubiquitous synthetic organic compounds used in packaging, flame retardants and stain resistant fabric. The use of older, long-chain, persistent PFAs in the U.S. has been phased out due to cardiometabolic health effects and replaced with short-chain, less persistent, alternative PFAs for which little data on cardiotoxicity exists. We evaluated the relationships between serum PFAs and noninvasive measures of vascular function by carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART). Methods: We measured 14 serum PFAs using hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients without CVD from an urban medical center. Using medical records and questionnaires, we collected demographic and clinical data; and measured PWV and BART using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. Results: Of the 14 measured PFAs, 10 were detectable in &gt;50% of samples, and were included for analysis. Each standard deviation increase in perfluroheptanoic acid (PFHpA) was associated with -0.17 (-0.34, -0.002) decrease in log BART. The weighted index of PFAs in mixture 1 (Table) was significantly and inversely associated with log BART; each tertile increase in the weighted index of mixture 1 was associated with a -0.29 (-0.52, -0.06) decrease in log BART, with PFHpA having the greatest weight (0.73) in the mixture. In contrast, neither individual PFAs nor PFA mixtures were associated with PWV. Conclusions: Increasing concentrations of a new, short-chain PFA, PFHpA, are associated with impaired vascular function among outpatients without CVD. Our findings contribute evidence of potential adverse cardiovascular effects of currently used PFAs.

Hydroxychloroquine is associated with lower platelet activity and improved vascular health in systemic lupus erythematosus

ObjectiveHydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use...

Metabolomics reveals the impact of Type 2 diabetes on local muscle and vascular responses to ischemic stress.

Type 2 diabetes mellitus (T2DM) reduces exercise capacity, but the mechanisms are incompletely understood. We probed the impact of ischemic stress on skeletal muscle metabolite signatures and T2DM-related vascular dysfunction. we recruited 38 subjects (18 healthy, 20 T2DM), placed an antecubital intravenous catheter, and performed ipsilateral brachial artery reactivity testing. Blood samples for plasma metabolite profiling were obtained at baseline and immediately upon cuff release after 5 min of ischemia. Brachial artery diameter was measured at baseline and 1 min after cuff release. as expected, flow-mediated vasodilation was attenuated in subjects with T2DM (P<0.01). We confirmed known T2DM-associated baseline differences in plasma metabolites, including homocysteine, dimethylguanidino valeric acid and β-alanine (all P<0.05). Ischemia-induced metabolite changes that differed between groups included 5-hydroxyindoleacetic acid (healthy: -27%; DM +14%), orotic acid (healthy: +5%; DM -7%), trimethylamine-N-oxide (healthy: -51%; DM +0.2%), and glyoxylic acid (healthy: +19%; DM -6%) (all P<0.05). Levels of serine, betaine, β-aminoisobutyric acid and anthranilic acid were associated with vessel diameter at baseline, but only in T2DM (all P<0.05). Metabolite responses to ischemia were significantly associated with vasodilation extent, but primarily observed in T2DM, and included enrichment in phospholipid metabolism (P<0.05). our study highlights impairments in muscle and vascular signaling at rest and during ischemic stress in T2DM. While metabolites change in both healthy and T2DM subjects in response to ischemia, the relationship between muscle metabolism and vascular function is modified in T2DM, suggesting that dysregulated muscle metabolism in T2DM may have direct effects on vascular function.

Vascular Aging Is Accelerated in Flight Attendants With Occupational Secondhand Smoke Exposure.

To determine whether early vascular aging may be present in flight attendants with remote in-cabin secondhand smoke (SHS) exposure. Twenty-six flight attendants with a history of in-cabin SHS exposure prior to the airline smoking bans were recruited. Pulse wave analysis, peripheral arterial tonometry, and brachial artery reactivity testing evaluated their arterial compliance and endothelial function. Flight attendants with remote in-cabin SHS exposure have normal blood pressure, pulse wave velocity, and reactive hyperemia index, but abnormal pulse pressure, augmentation index, flow-mediated dilation, and hyperemic mean flow ratio. These preliminary findings suggest that flight attendants with remote in-cabin SHS exposure have preclinical signs of accelerated vascular aging and raise new questions about the relationship between remote SHS exposure and vascular health.

Abstract 256: The Direct Characterization of Endothelial Inflammation in Patients with Psoriasis

Objective: Psoriasis, an inflammatory autoimmune disease, increases the risk of cardiovascular disease (CVD). Active psoriatic disease is linked to systemic vascular inflammation, yet how this contributes to CVD is unknown. Using in vivo and ex-vivo measures of the vascular endothelium our study investigates the vascular health of psoriasis patients to better understand the mechanism(s) that predispose psoriatics to CVD. Methods: Ten patients with active psoriasis (average age 46 years, 50% male (5 of 10), 6% [3.5% – 90%] body surface area involvement) were compared to age- and sex- matched controls. In vivo vascular endothelial function was assessed by brachial artery reactivity testing (BART, %) with high resolution ultrasonography. Venous endothelial cells were collected from the brachial vein using guidewires inserted through an angiocatheter and isolated with magnetic beads directed against CD146. Following collection, endothelial RNA was isolated, converted to cDNA and inflammatory gene profiling performed by RT-qPCR with Taqman probes and primers. Results: Transcriptomic profiling of venous endothelial cells revealed upregulation of genes associated with inflammatory cytokines and chemokines ( lymphotoxin beta [2.5 - fold], CCL3 [3.5 - fold], and IL-1 β [2.8 - fold], P &lt; 0.05 for all) and genes related to intracellular adhesion and inflammation ( ICAM1 [2.3 – fold] and COX-2 [1.4 – fold], P &lt; 0.05 for both) in psoriatics vs. controls. Unexpectedly, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (higher levels indicate healthy endothelial NO production) were upregulated (2 - 3 fold) in psoriatics vs. controls (p = 0.24, p = 0.14 respectively). BART was also higher in psoriatics when compared to controls (7.1 ± 1% vs. 3.9 ± 2.7%, P = 0.03). Conclusion: This cross-sectional study is the first to directly examine the vascular endothelium of psoriatic patients. Compared to controls, active psoriatic disease was associated with upregulation of cytokines, chemokines and genes regulating intracellular adhesion as well as increased expression of eNOS, and increased BART. These findings suggest potential mechanisms to explain the increased prevalence of atherosclerosis and CVD risk seen in those with psoriasis.

Abstract 333: Dynamic Limb-specific Metabolomics Reveals the Impact of Diabetes on Muscle and Vascular Responses to Ischemic Stress

Background: Type 2 Diabetes Mellitus (T2DM) increases cardiovascular risk, but the mechanisms are incompletely understood. Blood metabolomic signatures are altered in T2DM, but the impact of ischemic stress on the local skeletal muscle signature and T2DM-related vascular dysfunction is unknown. Methods: We recruited 38 subjects (18 healthy, 20 T2DM), placed an antecubital intravenous catheter, and performed ipsilateral brachial artery reactivity testing. Blood samples for plasma metabolite profiling were obtained at baseline and upon cuff release after 5 minutes of ischemia. Brachial artery diameter was measured at baseline and 1 minute after cuff release. Results: As expected, flow-mediated vasodilation was attenuated in subjects with T2DM (p&lt;0.01). We confirmed known T2DM-associated baseline differences in plasma metabolites, including homocysteine, dimethylguanidino valeric acid and β-alanine (all p&lt;0.05). Metabolites were significantly altered in response to experimental ischemia. Ischemia-induced metabolite changes that differed between groups included 5-hydroxyindoleacetic acid (Healthy: -27%; T2DM +14%), orotic acid (Healthy: +5%; T2DM -7%), trimethylamine-N-oxide (Healthy: -51%; T2DM +0.2%), and glyoxylic acid (Healthy: +19%; T2DM -6%) (all p&lt;0.05). Serine, betaine, aminoisobutyric acid and anthranilic acid associated with vessel diameter at baseline, but only in T2DM (all p&lt;0.05). Metabolite responses to ischemia were significantly associated with vasodilation extent, but primarily observed in T2DM. Within T2DM subjects, metabolite changes predicting change in vessel diameter included enrichment in amino acid, glycerophospholipid and propanoate metabolism (all p&lt;0.05). Conclusion: Our study highlights potential impairments in muscle and vascular signaling at rest and during ischemic stress in T2DM. While metabolites change in both healthy and T2DM subjects in response to ischemia, a relationship between muscle metabolism and vascular function is modified in T2DM, suggesting that dysregulated muscle metabolism in T2DM may have direct effects on vascular function.

The relationship between insulin resistance and endothelial dysfunction in obese adolescents.

Insulin resistance and endothelial dysfunction share a reciprocal relationship that links the metabolic and cardiovascular sequelae of obesity. We characterized the brachial artery reactivity testing (BART) and carotid artery-intima media thickness (CIMT) in adolescents categorized as obese insulin resistant (OIR) and obese not insulin resistant (ONIR). Lipoprotein particle (p) analysis and inflammatory cytokines in OIR and ONIR groups were also analyzed. Obese adolescents (n=40; mean body mass index [BMI] 35.6) were categorized as ONIR and OIR based on their homeostatic model assessment of insulin resistance (HOMA-IR) calculation (≤or> than 3.4). Ultrasound measured conduit arterial function BART, microvascular function (post-ischemic hyperemia) and conduit artery structure CIMT. BART did not differ according to IR status (mean±SD: 7.0±4.3% vs. 5.9±3.4% in ONIR and OIR, respectively, p=0.3, but post-ischemic hyperemia was significantly greater in the ONIR group (4.5±2.2 vs. 3.5±3, p=0.04). Atherogenic lipoprotein particles; large VLDL particles and small LDL particles were higher in the OIR compared to ONIR group. OIR adolescents demonstrate an inflamed atherogenic milieu compared to the ONIR adolescents. Microvascular function, but not conduit vessel structure or function, was impaired in association with IR.

Feed-forward active contour analysis for improved brachial artery reactivity testing.

The object of this study was to utilize a novel feed-forward active contour (FFAC) algorithm to find a reproducible technique for analysis of brachial artery reactivity. Flow-mediated dilation (FMD) is an important marker of vascular endothelial function but has not been adopted for widespread clinical use given its technical limitations, including inter-observer variability and differences in technique across clinical sites. We developed a novel FFAC algorithm with the goal of validating a more reliable standard. Forty-six healthy volunteers underwent FMD measurement according to the standard technique. Ultrasound videos lasting 5-10 seconds each were obtained pre-cuff inflation and at minutes 1 through 5 post-cuff deflation in longitudinal and transverse views. Automated segmentation using the FFAC algorithm with initial boundary definition from three different observers was used to analyze the images to measure diameter/cross-sectional area over the cardiac cycle. The %FMD was calculated for average, minimum, and maximum diameters/areas. Using the FFAC algorithm, the population-specific coefficient of variation (CV) at end-diastole was 3.24% for transverse compared to 9.96% for longitudinal measurements; the subject-specific CV was 15.03% compared to 57.41%, respectively. For longitudinal measurements made via the conventional method, the population-specific CV was 4.77% and subject-specific CV was 117.79%. The intraclass correlation coefficient (ICC) for transverse measurements was 0.97 (95% CI: 0.95-0.98) compared to 0.90 (95% CI: 0.84-0.94) for longitudinal measurements with FFAC and 0.72 (95% CI: 0.51-0.84) for conventional measurements. In conclusion, transverse views using the novel FFAC method provide less inter-observer variability than traditional longitudinal views. Improved reproducibility may allow adoption of FMD testing in a clinical setting. The FFAC algorithm is a robust technique that should be evaluated further for its ability to replace the more limited conventional technique for measurement of FMD.

Treatment of Obstructive Sleep Apnea in Young and Middle-Aged Adults: Effects of Positive Airway Pressure and Compliance on Arterial Stiffness, Endothelial Function, and Cardiac Hemodynamics.

BackgroundThe cardiovascular effects of positive airway pressure (PAP) therapy in obstructive sleep apnea (OSA) patients are not clear because of confounding by comorbid conditions.Methods and ResultsProspective interventional study of PAP therapy and withdrawal. Apnea Hypopnea Index (AHI; events/hour of sleep) was determined from polysomnography. Central aortic blood pressures (BPs), Aortic Augmentation Index (AAIx), and central (PWV c‐f) and peripheral pulse wave (PWV c‐r) velocities were determined by applanation tonometry. Echocardiography and brachial artery reactivity testing were performed at baseline, after 4 and 12 weeks of PAP therapy, and 1 week after PAP withdrawal. The 84 participants were mean (SD) 41.1 (7.6) years old and had 39.8 (24.5) AHI events/hour. After 4 weeks post‐PAP initiation and sustained after 12 weeks, subjects experienced decreases in central systolic BP (P=0.008), diastolic BP, mean BP, AAIx, and PWV c‐r, and brachial artery dilation (all P<0.001), as well as improvements in left ventricular diastolic function and systemic and pulmonary vascular resistance. In adjusted models, PAP use (hours/night) predicted reductions in diastolic BP (β=−0.65 [SE, 0.32] mm Hg/hour; P=0.045), AAIx (β=−0.53 [0.27] %/hour; P=0.049) and PWV c‐r (β=−0.13 [0.05] m·s−1/hour; P=0.007), and improved brachial artery flow‐mediated dilation (β=0.31 [0.14] %/hour use; P=0.015). After 1 week of PAP withdrawal, brachial diameter, diastolic BP, mean BP, AAIx, and heart rate increased (P≤0.05).Conclusions PAP therapy reduces arterial tone and improves endothelial and diastolic function in young to middle‐aged adults. This positive effect is observed after 4 weeks and depends on hours of use, but reverts quickly with PAP withdrawal.Clinical Trial RegistrationURL: https://clinicaltrials.gov/. Unique identifier: NCT01317329.

Cardiovascular Magnetic Resonance Imaging-Based Computational Fluid Dynamics/Fluid–Structure Interaction Pilot Study to Detect Early Vascular Changes in Pediatric Patients with Type 1 Diabetes

We hypothesized that pediatric patients with type 1 diabetes have cardiac magnetic resonance (CMR) detectable differences in thoracic aortic wall properties and hemodynamics leading to significant local differences in indices of wall shear stress, when compared with age-matched control subjects without diabetes. Pediatric patients with type 1 diabetes were recruited from Children's Hospital of Wisconsin and compared with controls. All underwent morning CMR scanning, 4-limb blood pressure, brachial artery reactivity testing, and venipuncture. Patient-specific computational fluid dynamics modeling with fluid-structure interaction, based on CMR data, determined regional time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI). Twenty type 1 diabetic subjects, median age 15.8 years (11.6-18.4) and 8 controls 15.4 years (10.3-18.2) were similar except for higher glucose, hemoglobin A1c, and triglycerides for type 1 diabetic subjects. Lower flow-mediated dilation was seen for those with type 1 diabetes (6.5) versus controls (7.8), p = 0.036. For type 1 diabetic subjects, the aorta had more regions with high TAWSS when compared to controls. OSI maps appeared similar. Flow-mediated dilation positively correlated with age at diabetes diagnosis (r = 0.468, p = 0.038) and hemoglobin A1c (r = 0.472, p = 0.036), but did not correlate with aortic distensibility, TAWSS, or OSI. TAWSS did not correlate with any clinical parameter for either group. CMR shows regional differences in aortic wall properties for young diabetic patients. Some local differences in wall shear stress indices were also observed, but a longitudinal study is now warranted.

Vascular endothelial function and blood pressure regulation in afferent autonomic failure.

Familial dysautonomia (FD) is a rare hereditary disease characterized by loss of afferent autonomic neural fiber signaling and consequent profound impairment of arterial baroreflex function and blood pressure regulation. Whether vascular endothelial dysfunction contributes to defective vasomotor control in this form of afferent autonomic failure is not known. We assessed blood pressure response to orthostatic stress and vascular endothelial function with brachial artery reactivity testing in 34 FD subjects with afferent autonomic failure and 34 healthy control subjects. Forty-four percent of the afferent autonomic failure subjects had uncontrolled hypertension at supine rest (median systolic blood pressure = 148mm Hg, interquartile range (IQR) = 144-155mm Hg; median diastolic blood pressure = 83mm Hg, IQR = 78-105mm Hg), and 88% had abnormal response to orthostatic stress (median decrease in systolic blood pressure after upright tilt = 48mm Hg, IQR = 29-61mm Hg). Flow-mediated brachial artery reactivity did not differ in subjects with afferent autonomic failure vs. healthy control subjects (median = 6.00%, IQR = 1.86-11.77%; vs. median = 6.27%, IQR = 4.65-9.34%; P = 0.75). In afferent autonomic failure subjects, brachial artery reactivity was not associated with resting blood pressure or the magnitude of orthostatic hypotension but was decreased in association with reduced glomerular filtration rate (r = 0.62; P < 0.001). Brachial artery reactivity was preserved in subjects with afferent autonomic failure despite the presence of marked blood pressure dysregulation. Comorbid renal dysfunction was associated with reduced brachial artery reactivity.

Endothelial function and left ventricular diastolic functional reserve in type 2 diabetes mellitus

BackgroundEndothelial dysfunction is an early feature of vascular disease. Left ventricular (LV) diastolic reserve is the ability of the left ventricle to augment diastolic function with exercise and may be...

Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment.

Brachial artery constriction during brachial artery reactivity testing predicts major adverse clinical outcomes in women with suspected myocardial ischemia: results from the NHLBI-sponsored women's ischemia Syndrome Evaluation (WISE) Study.

BackgroundLimited brachial artery (BA) flow-mediated dilation during brachial artery reactivity testing (BART) has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC) following hyperemia.ObjectivesTo determine whether BAC predicts adverse CV outcomes and/or mortality in the women’s ischemic Syndrome Evaluation Study (WISE). Further, as a secondary objective we sought to determine the risk factors associated with BAC.MethodsWe performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure.ResultsBA diameter change ranged from -20.6% to +44.9%, and 41 (11%) women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004). In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018) when adjusting for obstructive CAD and traditional risk factors.ConclusionsBAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women.

Preoperative Microvascular Dysfunction: A Prospective, Observational Study Expanding Risk Assessment Strategies in Major Thoracic Surgery

Brachial artery reactivity testing (BART)--a surrogate test of microvascular function--predicts cardiac risk in the nonsurgical population and associates it with adverse outcome after vascular surgery. This pilot study investigated BART-derived variables, including flow-mediated dilation (FMD), in preoperative risk stratification for major thoracic surgery. After institutional review board approval, BART was performed in 63 patients before major thoracic surgery. Ultrasonography recorded two-dimensional images and Doppler flow signals of the brachial artery preoperatively at baseline and after induced reactive hyperemia. Variables derived using BART were correlated with preoperative risk factors, established risk scores, and postoperative complications. The median preoperative FMD value in patients without postoperative complications was 11.5%. This value was used to delineate all patients into two groups: low (FMD < 11.5%) and high (FMD ≥ 11.5%) FMD cohorts. Patients in the low FMD group experienced more postoperative complications: 54% versus 30% had one or more adverse postoperative event, and 11% versus 0% had three or more adverse postoperative events (p < 0.001), respectively. The low FMD group required longer intensive care unit (3.9 ± 2.0 days versus 0.9 ± 0.3 days; p = 0.015) and hospital (14.0 ± 3.3 days versus 6.8 ± 0.6 days; p = 0.007) stays. This cutoff point for FMD accurately predicted 71% of the patients with adverse postoperative events, achieving 71.4% (95% confidence interval, 54.7 to 88.2) sensitivity and 48.6% (95% confidence interval, 32.0 to 65.1) specificity. Using BART, preoperative microvascular dysfunction can be identified in patients at increased risk for postoperative complications. These data suggest that larger observational studies and studies exploring preoperative optimization strategies aimed at improving microvascular function are warranted.

Reduced cardiovascular risk after bariatric surgery is linked to plasma ceramides, apolipoprotein-B100, and ApoB100/A1 ratio

Obesity-associated hyperlipidemia and hyperlipoproteinemia are risk factors for cardiovascular disease (CVD). Recently, ceramide-derived sphingolipids were identified as a novel independent CVD risk factor. We hypothesized that the beneficial effect of Roux-en-Y gastric bypass (RYGB) on CVD risk is related to ceramide-mediated improvement in lipoprotein profile. A prospective study of patients undergoing RYGB was conducted. The patients' clinical data and biochemical markers related to cardiovascular risk were documented. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1), apolipoprotein (Apo)B100 and ApoA1 were quantified preoperatively and 3 and 6 months after RYGB, as was the Framingham risk score. Brachial artery reactivity testing was performed before and 6 months after RYGB. Ten patients (9 women; age 48.6 ± 9.6 yr; body mass index, 48.5 ± 5.8 kg/m(2)) were included in the present study. At 6 months postoperatively, the mean body mass index had decreased to 35.7 ± 5.0 kg/m(2), corresponding to 51.3% ± 10.0% excess weight loss. The fasting total cholesterol, triglycerides, low-density lipoprotein, free fatty acids, ApoB100, ApoB100/ApoA1 ratio and insulin resistance estimated from Homeostasis Model of Assessment of Insulin Resistance were significantly reduced compared with the preoperative values. The ApoB100/ApoA1 ratio correlated with a reduction in ceramide subspecies (C18:0, C18:1, C20:0, C24:0, and C24:1; P < .05). ApoB100 and the ApoB100/ApoA1 ratio also correlated positively with the reduction in triglycerides, low-density lipoprotein, and Homeostasis Model of Assessment of Insulin Resistance (P < .05). Brachial artery reactivity testing correlated inversely with ApoB100 and total ceramide (P = .05). Furthermore, the change in brachial artery reactivity testing correlated with the decrease in C16:0 (P < .03). Our data suggest that improvements in lipid profiles and CVD risk factors after gastric bypass surgery could be linked to changes in ceramide lipids. Mechanistic studies are needed to determine whether this link is causative or purely correlative.

Early effects of gastric bypass on endothelial function, inflammation, and cardiovascular risk in obese patients

Obesity is associated with a chronic low-grade inflammatory state, insulin resistance, and endothelial dysfunction, all of which contribute to increased risk of cardiovascular disease. We hypothesized that gastric bypass would produce rapid improvements in endothelial function, reduce inflammation, and lead to a decrease in cardiovascular risk. We performed a prospective study of morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB). Clinical data, biochemical markers of inflammation, and parameters indicative of cardiovascular risk were collected preoperatively and at 3 and 6 months postoperatively. Metabolic and inflammatory mediators that were quantified included C-reactive protein, fibrinogen, PAI-1, IL-6, IL-10, IL-1Ra, adiponectin, leptin, triglycerides, total cholesterol, HDL, LDL, glucose, insulin, and HbA1c. Brachial artery reactivity testing (BART) was performed to assess peripheral arterial endothelial function, and Framingham cardiovascular risk score (FRS) was calculated on all study participants pre- and postoperatively. Fifteen patients (11 female) were enrolled (age = 49.2 ± 10.4 years; BMI = 48.1 ± 5.3 kg/m(2)). Six months post RYGB, mean BMI decreased to 35.4 ± 4.5, corresponding to 51.7% excess weight loss (P < 0.001). Mean waist circumference decreased significantly from 132 cm at baseline to 110 cm at 3 months (P = 0.003) and 107 cm at 6 months (P < 0.001). Six months after RYGB, weight loss led to significant improvements in clinical parameters indicative of cardiovascular disease or risk, including brachial artery diameter, endothelial independent vasodilation, and FRS. Favorable improvements in the proinflammatory markers CRP (P = 0.01) and leptin (P = 0.005), the anti-inflammatory mediator adiponectin (P = 0.002), and insulin sensitivity (HOMA-IR, P = 0.007) were evident at 3 months. At 6 months, improvements in CRP, leptin, and fasting insulin were maintained and fibrinogen levels also decreased (P = 0.047). Adiponectin continued to increase at 6 months (P = 0.004). Gastric bypass is associated with early reversal of endothelial dysfunction, a more favorable inflammatory milieu, and, most importantly, a reduction in cardiovascular risk.

Cardiac magnetic resonance imaging can detect early vascular changes in children with type 1 diabetes (T1DM)

Adult studies have shown that cardiac magnetic resonance (CMR) can image vascular changes including altered aortic compliance and early plaque which correlates well with Framingham risk score and endothelial function. Impaired endothelial function, measured with brachial artery reactivity testing, is recognized as an early and modulating process in the pathophysiology of atherosclerotic plaque development. No CMR imaging studies of early atherosclerosis and vascular health exist in diabetic pediatric populations. This prospective pilot CMR proof of concept study hypothesized that children with T1DM will have thoracic aortic wall characteristics, as well as CMR-derived aortic computational fluid dynamic (CFD) models, different from age-matched control subjects. Furthermore, a positive correlation was sought between key CMR data and brachial artery reactivity measures, as well as cardiac venous biomarkers in T1DM. 7 control and 8 T1DM pediatric subjects had same-day fasting CMR scan, brachial artery testing, and venous blood draw (for lipid panel, HgbA1c, glucose, high sensitivity c-reactive protein (hs-cRP), fibrinogen, and homocysteine). Enrolled T1DM and control subjects were similar: age (14.5 ±1.7 versus (vs.) 15.2 ± 2.7 years), sex (4 male and 4 female T1DM vs. 5 male and 2 female controls), weight (55.7 ± 14.8 vs. 67.6 ± 23.5 kg), body mass index (20.8 ± 4.3 vs. 23.1 ± 5.7 kg/m2) and systolic blood pressure (113 ± 11.4 vs. 116 ± 8.8). They had no significant differences in lipid values, fibrinogen, or hs-cRP, but did differ with regard to glucose (182.1 ± 100.8 vs. 85.4 ± 5.7, p < 0.02), HgbA1c (9.0 ± 2.2 vs. 5.2 ± 0.3, p < 0.001), and homocysteine (4.3 ± 0.6 vs. 5.7 ± 1.0, p < 0.04). While brachial artery reactivity did not change with age, CMR determined ascending aortic (AAo) compliance decreased with increasing age in T1DM (R2 = 0.54, p < 0.09), but not for controls. In T1DM, CMR determined ascending aortic (AAo) compliance declined, as hs-cRP increased (R2 = 0.66, p < 0.05).No other significant correlations existed between AAo compliance and venous biomarkers. Preliminary qualitative analyses of aortic CFD models show different patterns of aortic wall shear stress and oscillatory shear index (OSI) for T1DM versus age-matched control pediatric subjects (Figure ​(Figure1).1). In conclusion, this pilot CMR study of T1DM and control pediatric subjects illustrates that early differences in vascular characteristics can be detected by MRI and correlate with age and with select venous biomarkers. Figure 1