Brachial Artery Pulse Research Articles

The Relation between Immune Cell Mitochondrial Respiration and Brachial Artery Pulse Pressure in Humans

Elevated pulse pressure (PP) occurs with advancing age due to stiffening of the elastic arteries and is an important risk factor for cardiovascular disease (CVD), even among normotensive adults. Mitochondrial function declines with aging and may contribute to the increase in PP through a mechanism involving oxidative stress and chronic inflammation; two important hallmarks of arterial aging. Emerging evidence indicates that mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) is negatively associated with risk factors for CVD in heart failure; however, the role of impaired mitochondrial function on cardiovascular function in healthy adults is not known. We hypothesized that mitochondrial function would be negatively associated with brachial PP. Twenty‐two healthy adults free of overt CVD (12 M/10 F; age: 56 ± 21 years; age range: 22–78 years; blood pressure, BP: 123 ± 15/72 ± 10 mmHg; PP: 51 ± 11 mmHg) were included in this analysis. PP was determined from brachial artery BP assessed in triplicate in the non‐dominant arm using an automated BP monitor. PBMCs were isolated by density dependent centrifugation and used to assess mitochondrial function by respirometry using an Agilent Seahorse XFp Analyzer. Primary outcome measures included the oxygen consumption rate (OCR) at baseline (basal respiration; BASERESP) and following three serial injections of oligomycin, FCCP and rotenone/antimycin A into the respirometer to determine maximal respiration (MAXRESP). Spare respiratory capacity (SRC), an indicator of how well the cell can respond to an increased energetic demand, ATP‐linked oxygen consumption (ATPO2), and coupling efficiency, which is how well ATPO2 is matched to BASERESP, were also measured. The associations between mitochondrial function and PP were analyzed using multi‐linear regressions correcting for age. PP was not associated with BASERESP (p=0.89, R2=0.10, β=0.01), coupling efficiency (p=0.20, R2=0.18, β= −8.5), or ATPO2 (p=0.33, R2=0.15, β= −0.10). However, PP was inversely associated with MAXRESP (p=0.05, R2=0.28, β= − 0.03) and SRC (PP; p=0.02, R2=0.33, β=−0.04). These data suggest that the impaired mitochondrial respiration may be an important contributor to CVD risk through increases in pulse pressure. Future studies should explore whether these associations are mediated by increases in oxidative stress and inflammatory cytokines.Support or Funding InformationFunding Sources: P20GM113125, K01AG054731

The effect of ivabradine as part of standard therapy on vascular endothelial function and cardiac electrical instability in patients with post-infarction cardiosclerosis and heart failure

Aim. To reveal the equivalence of nebivolol replacement with ivabradine in the prevention of endothelial dysfunction and cardiac electrical instability in patients with heart failure with reduced ejection fraction (HFrEF).Material and methods. In current observational study, 126 patients with HFrEF in the postinfarction period were randomized into two groups for six-month treatment: group 1 (n=62) — standard therapy (acetylsalicylic acid 0,1 g/day, clopidogrel 75 mg/day, veroshpiron 50 mg/day, nebivolol 5 mg/day, perindopril 5 mg/day and rosuvastatin 20 mg/day; group 2 (n=66) — the same therapy with nebivolol replacement with ivabradine 10 mg/day. Initially and after 6 months, 24-hour Holter monitoring was performed, heart rate variability was determined. We also investigated endothelial dysfunction using the photoplethysmographic technique with post-occlusive reactive hyperemia (PORH) test.Results. The heart rate, the number of episodes and the duration of symptomatic and silent myocardial ischemia, total myocardial ischemia were significantly decreased in both groups (p<0,001). The decrease of supraventricular extrasystole frequency in both groups had not statistical significance (p>0,05). In both groups, after therapy, parameters of heart rate variability were improved with the parasympathetic predominance (p<0,01). In both groups, the PORH test revealed the increase of brachial artery diameter (group 1 — 5,90Ѓ}3,15% and group 2 — 5,88Ѓ}1,82%) and pulse wave amplitude (group 1 — 1,81Ѓ}0,78 and group 2 — 1,73Ѓ}0,90 times), which indicates a trend towards an improvement in endothelial function. Intergroup comparisons did not reveal significant differences.Conclusion. Ivabradine is equivalent to nebivolol in preventing ventricular extrasystole and reducing heart rate, number of episodes of symptomatic and silent ischemia and the duration of total myocardial ischemia in patients with HFrEF. Ivabradine equivalently to nebivolol improves endothelial function and heart rate variability with reducing the sympathetic activity.

Restless legs syndrome is associated with arterial stiffness and clinical outcome in stroke patients

ObjectiveRestless legs syndrome (RLS) has been associated with vascular diseases, including cerebrovascular and cardiovascular diseases. Among the various mechanisms in RLS, peripheral vascular endothelial dysfunction in patients with RLS has recently been proposed as a vascular pathophysiology of RLS. This study investigated arterial stiffness related to RLS in acute ischemic stroke patients and its influence on stroke outcome. MethodsRLS in patients with acute ischemic stroke was assessed based on the four essential criteria of the International Restless Legs Syndrome Study Group described in 2003. The patients’ clinical and laboratory characteristics, arterial stiffness, small vessel disease occurrence, and burden on brain MRI were recorded. Stroke severity was determined using the National Institute of Health Stroke Scale (NIHSS), and clinical outcomes were determined using the modified Rankin Scale. ResultsOf 296 patients with acute ischemic stroke, 16 (5.4%) were diagnosed with restless legs syndrome. Logistic regression analysis showed that a 1 m/s increase in brachial arterial pulse wave velocity was associated with the diagnosis of RLS (odds ratio, 1.092; 95% confidence interval, 1.019–1.170, p = 0.012). Diagnosis of RLS in patients with acute ischemic stroke was associated with poor clinical outcome three months after stroke (modified Rankin Scale 3–6) (odds ratio, 4.263; 95% confidence interval, 1.229–14.792, p = 0.022) along with initial NIHSS score. ConclusionRLS in patients with acute ischemic stroke is associated with increased arterial stiffness and poor clinical outcomes.

Arterial stiffness as a risk factor for cardiovascular events and all-cause mortality in people with Type 2 diabetes.

AimTo quantify the risk of different non‐invasive arterial stiffness measurements with macrovascular disease and all‐cause mortality in high‐risk people with Type 2 diabetes.MethodsWe conducted a prospective cohort study of 1910 people with Type 2 diabetes included in the Second Manifestations of ARTerial disease (SMART) study. Arterial stiffness was assessed by brachial artery pulse pressure, normal range (≥0.9) ankle–brachial index and carotid artery distension. Cox regression was used to evaluate the effects of arterial stiffness on risk of cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all‐cause mortality.ResultsA total of 380 new cardiovascular events and 436 deaths occurred during a median (interquartile range) follow‐up of 7.5 (4.1–11.0) years. A 10‐mmHg higher brachial pulse pressure was related to higher hazard of cardiovascular events (hazard ratio 1.09, 95% CI 1.02 to 1.16) and all‐cause mortality (hazard ratio 1.10, 95% CI 1.03 to 1.16). A 0.1‐point lower ankle–brachial index within the normal range was related to a higher hazard of cardiovascular events (hazard ratio 1.13, 95% CI 1.01 to 1.27) and all‐cause mortality (hazard ratio 1.17, 95% CI 1.04 to 1.31). A one‐unit (10−3×kPa−1) lower carotid artery distensibility coefficient was related to a higher hazard of vascular mortality (hazard ratio 1.04, 95% CI 1.00 to 1.09) and all‐cause mortality (hazard ratio 1.04, 95% CI 1.00 to 1.07).ConclusionIncreased arterial stiffness, as measured by either increased pulse pressure, normal‐range ankle–brachial index or carotid artery distensibility coefficient, is related to increased hazard of cardiovascular events and all‐cause mortality in people with Type 2 diabetes.

Pulse wave velocity: Dependence on contemporaneous and historical blood pressure components

BackgroundArterial stiffness as measured by PWV along the aorta is an important determinant of cardiovascular risk. PWV is known to be dependent on contemporaneous blood pressure (BP) but its dependence on long-term BP has not been established.MethodsSubjects from Twins UK who had tonometric measures of carotid-femoral PWV with previous longitudinal measures of blood pressure (n = 2094) and, in a sub-sample, PWV (n = 956) were studied. Brachial artery pulse pressure (PP) and mean arterial pressure (MAP) were averaged over the period of longitudinal follow-up to obtain measures of historical PP and MAP (PPH and MAPH). The relationship of PWV to contemporaneous PP and MAP (PPC and MAPC) was compared with that to PPH and MAPH.ResultsThe average duration of blood pressure measurement was 14.0 ± 4.3 years.PWV correlated strongly with PPC (r = 0.542, p < 0.001), PPH (r = 0.474, p < 0.001), MAPC (r = 0.462, p < 0.001) and MAPH (r = 0.360, p < 0.001). In multiple regression analysis incorporating historical and contemporaneous values of PP and MAP as well as age and heart rate, PWV was significantly associated with PPC, MAPC and PPH but not with MAPH. In the sub-study in which historical values of PWV were available, PWV increased by 0.75 ± 1.42 m/s, over an average of 5.5 ± 1.7 years. The change in PWV was associated with MAPC and with PPH (β = 0.144, p < 0.001).ConclusionsThese results are consistent with strong dependence of PWV on contemporaneous BP but also historical values of pulse pressure which may drive arterial stiffening.

Abstract P200: Elevated Triacylglycerols and Diacylglycerols Had Association With Increased Carotid Arterial Stiffness, Independent of Cvd Risk Factors, in Women With or at High Risk of HIV Infection

Background: Metabolomics has provided new insights into mechanistic knowledge of CVD. However, this approach has limited use for studying arterial disease in high-risk women with and without HIV infection. Methods: Using liquid chromatography-tandem mass spectrometry, we profiled plasma levels of 114 cationic polar and 211 nonpolar lipid metabolites among 411 women (72% HIV+; 60% Black and 31% Hispanic) aged 35-50 from the Women’s Interagency HIV Study. Carotid arterial distensibility, a direct measure of carotid stiffness, was calculated from ultrasound measurements of the right common carotid artery diameter at systole and diastole and brachial artery pulse pressure measured. We performed partial least squares discriminant analysis (PLS-DA) to identify metabolite clusters associated with carotid stiffness (lowest vs. the other 3 quartiles of distensibility index). We used multivariate linear regression models to examine associations of individual metabolites with the distensibility index. Results: PLS-DA identified two major metabolite clusters associated with carotid stiffness. In the lipid metabolite cluster, triacylglycerols (TAGs 52:3, 52:4, 54:4), diacylglycerols (DAGs 36:2, 36:3) and sphingomyelins (16:1, 18:1, 18:2) were associated with decreased distensibility, while lysophosphatidylcholines (18:2, 20:5) were associated with increased distensibility. In the cationic polar metabolite cluster, urate, C4-OH carnitine, C5-DC carnitine, pseudouridine and 1-methyladenosine were associated with decreased distensibility. The associations of TAGs 52:3, 52:4, 54:4 and DAG 36:3 with carotid stiffness remained significant after further adjustment for conventional CVD risk factors ( Table ). No interaction by HIV infection was found. Conclusions: Among women with or at risk of HIV infection from predominantly race-ethnic minority groups, plasma TAGs and DAG of higher carbon number and double bond content are associated with carotid stiffness independent of conventional CVD risk factors.

Effects of circuit exercise training on vascular health and blood pressure.

As the global burden of cardiovascular disease (CVD) rises, public health-related interventions aimed at prevention of heart disease have gained medical attention. Clinical research reports that exercise is a protective risk factor associated with CVD and that clinicians need to provide exercise recommendations to patients. Nevertheless, physical inactivity remains a public health problem. In certain populations, like firefighters (FF), increased risk of CVD is especially concerning. The workload FF face is extreme, 50% of line-of-duty deaths (LODD) in FF are cardiac-related, and research on the volunteer FF population is scarce. Government regulations do not require volunteer FF companies to have fitness testing or programming, so exercise intervention studies are necessary to improve the burden of CVD risk in this population. Therefore, this study examined the effects of a 4-week exercise circuit training (CT) intervention on vascular health and fitness in volunteer FF (N = 27) from the Philadelphia PA area compared to a control group of Non-FF (N = 25). Carotid artery intima-media thickness (IMT), brachial artery flow-mediated dilation (FMD), augmentation index, and pulse pressure (PP), brachial and central blood pressure (BP) and fitness were measured pre- and post- intervention. Overall, volunteer FF had more significant improvements (p < 0.05) in vascular health measures (FMD, IMT, and PP). In both groups, we also found that brachial and central BP decreased with exercise. We show that a 4 week CT program can improve vascular structure and function in the volunteer FF population, suggesting that clinicians may be able to reduce or prevent cardiac LODD by exercise.

Comparison of laboratory and ambulatory measures of central blood pressure and pulse wave reflection: hitting the target or missing the mark?

Prior studies demonstrating clinical significance of noninvasive estimates of central blood pressure (BP) and pulse wave reflection have relied primarily on discrete resting measures. The aim of this study was to compare central BP and pulse wave reflection measures sampled during a single resting laboratory visit against those obtained under ambulatory conditions. The secondary aim was to investigate the reproducibility of ambulatory central BP and pulse wave reflection measurements. Forty healthy participants (21 males; 24 ± 3 years) completed three measurements of brachial artery pulse wave analysis (Oscar 2 with SphygmoCor Inside) in the laboratory followed by 24 hours of ambulatory monitoring. Seventeen participants repeated the 24-hour ambulatory monitoring visit after at least 1 week. Ambulatory measures were divided into daytime (9 AM–9 PM), nighttime (1 AM–6 AM), and 24-hour periods. Compared with laboratory measurements, central systolic BP, augmentation pressure, and augmentation index (with and without heart rate normalization) were higher (all P < .01) during daytime and 24-hour periods but lower during the nighttime period (all P < .001). The drop in nighttime brachial systolic BP was larger than central systolic pressure (Δ −20 ± 6 vs. −15 ± 6 mm Hg; P < .0001). Repeat ambulatory measurements of central BP and pulse wave reflection displayed good-to-excellent intraclass correlation coefficients (r = 0.58–0.86; all P < .01), although measures of pulse wave reflection had higher coefficients of variation (14%–41%). The results highlight absolute differences in central BP and pulse wave reflection between discrete laboratory and ambulatory conditions. The use of ambulatory measures of central BP and pulse wave reflection warrant further investigation for clinical prognostic value.

The correlation of brachial ankle pulse wave velocity with arterosclerosis at different estimated levels of glomerular filtration rate

To explore the relationship between brachial ankle artery pulse wave velocity of the (baPWV) in different estimation GFR (eGFR) groups and atherosclerosis.In 2010, 2012 and 2014, eGFR and baPWV were detected in 1 427 healthy persons.As eGFR level decreased, baPWV increased accordingly with higher proportion of baPWV ≥1 400 cm/s.The percentage of eGFR lower than 60 ml·min-1·1.73 m-2 was similar in subgroups with different baPWV.However, the proportion of eGFR reduction≥30% decreased according to the elevation of baPWV.Multivariate logistic regression analysis indicated the lower the eGFR, the higher the risk of atherosclerosis.Low eGFR is an independent risk factor for atherosclerosis.

Abstract 164: The Effects of Resveratrol Treatment on Vascular Function in Type 2 Diabetes Mellitus

Patients with diabetes mellitus (DM) have abnormal vascular function characterized by premature aging and aortic stiffness. In animal models of metabolic disease, the plant-derived polyphenol, resveratrol, decreases arterial stiffness through SirT1 activation. Therefore, we hypothesized that resveratrol would improve vascular function and activate SirT1 in patients with DM. We performed a randomized, double-blind, placebo-controlled crossover study of resveratrol supplementation in 57 patients with DM (age 56±8 years, female 52%, African-American 67%, BMI 31.7±4.4 kg/m 2 ). Patients consumed resveratrol 100 mg/d for 2 weeks followed by 300 mg/d for 2 weeks or a matched placebo containing no polyphenols with a two-week wash-out period between treatments. In the overall study group, there was a trend toward lower carotid-femoral pulse wave velocity (CFPWV) with resveratrol treatment (P=0.18). In a subset of patients with high arterial stiffness at baseline, resveratrol treatment lowered CFPWV without a change in systemic blood pressure consistent with reduced central aortic stiffness (Figure). Brachial artery flow-mediated dilation, reactive hyperemia, and pulse amplitude tonometry did not change. In a subset of 7 patients, we collected venous endothelial cells by J-wire biopsy and observed a trend toward increased SirT1 activity with resveratrol treatment. Our findings suggest that resveratrol supplementation may reverse arterial stiffening in patients with DM potentially through activation of endothelial SirT1 activity.

Cine-CMR partial voxel segmentation demonstrates increased aortic stiffness among patients with Marfan syndrome.

Standard cine-cardiac magnetic resonance (CMR) imaging is commonly used to evaluate cardiac structure, geometry and function. Prior studies have shown that automated segmentation via partial voxel interpolation (PVI) accurately quantifies phantom-based cardiac chamber volumes and necropsy left ventricular myocardial mass. Despite this, the applicability and usefulness of PVI in the determination of physiologic parameters of the aorta such as aortic stiffness has yet to be investigated. Routine CMR was conducted with a 1.5T (GE) scanner with pulse sequences similar to that of standard CMR (parameters: TR 3.4 msec, TE 1.14 msec, flip angle 60°, temporal resolution ~30-40 msec). Views were obtained in standard cardiac-oriented longitudinal or axial views (2, 3 and 4 chambers). Within non-dilated regions of the descending thoracic aorta, aortic area was quantified via a novel PVI automated process (LV-METRIC), which discerns relative amounts of blood pool in each voxel. Aortic stiffness, as calculated from brachial artery pulse pressure and aortic area at maximal and minimal dimensions, was evaluated in 60 total segments (one segment per patient). All segments were in the descending aorta and were not aneurysmal. Sixty patients in total were studied, including 50 that had genetically-related aortic disorder [35 bicuspid aortic valve (BAV), 15 Marfan syndrome (MFS)]. Ten normal controls without aortic disease were included for comparison purposes. All patients (n=60) had evaluable CMR images for assessment of the descending aorta with use of automated segmentation. Patients with BAV and MFS were similar to controls in age, systolic blood pressure, brachial artery pulse pressure, smoking status or hypercholesterolemia (all P=NS). There were more women (P<0.001), lower body mass index (P=0.008), and greater height (P<0.001) in the MFS cohort compared to BAV and controls. Descending aortic area in either systole (maximal) or diastole (minimal) was similar among all three cohorts. However, change in aortic area (ΔArea) throughout the cardiac cycle was substantially lower in MFS than control subjects (P<0.001). In contrast, change in aortic area throughout the cardiac cycle was not significantly different between BAV vs. controls (P=0.62). Aortic stiffness was increased among MFS patients versus control subjects (P=0.014). When comparing MFS to BAV subjects, a comparable trend was observed (P=0.09). No statistical difference was evident in aortic stiffness in patients with BAV versus control subjects (P=0.29). The application of PVI to standard CMR imaging can assess abnormal descending aorta functional indices in normal caliber segments in MFS subjects. Future prospective studies with larger subject populations are warranted to further determine the overall utility of automated aortic segmentation as a possible early biomarker of aortic dysfunction before overt dilatation.

Heritability of Vascular Structure and Function: A Parent-Child Study.

BackgroundUnderstanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring.Methods and ResultsHigh‐resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow‐mediated dilation were measured in the brachial artery. Intima‐media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross‐sectional distensibility were measured, and carotid cross‐sectional compliance was measured in the carotid artery. Carotid–radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body–mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P<0.001), intima‐media thickness (h2=29±13%, P=0.014), diameter distensibility (h2=28±7%, P<0.001), cross‐sectional distensibility (h2=27±7%, P<0.001), and pulse wave velocity (h2=26±9%, P<0.001) were significantly heritable. Flow‐mediated dilation and incremental elastic modulus were not significantly heritable. Similar associations were observed in analysis restricted to siblings and complete Trios (mother, father, and child).ConclusionsThese data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.

Fibulin Levels in Autosomal Dominant Polycystic Kidney Disease and Its Relationship to Arterial Stiffness.

The objective of the present study was to evaluate fibulin 1 levels in different stages of patients with autosomal dominant polycystic kidney disease (ADPKD) and investigate possible connections between fibulin-1 and arterial stiffness. For this cross-sectional study, we included 74 patients with ADPKD (mean age, 50.92 ± 15.70 years) and 32 healthy controls (mean age, 49.53 ± 7.32 years). Patients with ADPKD were classified based on CKD epidemiology collaboration (CKD-EPI) equation assessments of estimated glomerular filtration rate (eGFR). Blood levels of fibulin 1 and creatinine levels were analyzed. We measured brachial artery PWV (baPWV), augmentation index (AIx), and pulse pressure (PP) for the assessment of arterial stiffness and systolic and diastolic blood pressures (SBP and DBP, respectively). Fibulin 1 was significantly higher in the patient group (p < 0.001). SBP, DBP, MAP, PP, and baPWV levels were also significantly higher in the patient group. A statistically significant positive correlation was found between fibulin 1 and creatinine (r = 0.377, p = 0.001). No significant correlation was found between the fibulin 1 levels and age, SBP, DBP, MAP, baPWV, and AIx. Plasma concentrations of fibulin 1 increased in patients with ADPKD. Arterial stiffness measured by baPWV increased in patients with ADPKD, but it was not related to fibulin 1 levels.

Enhancement of arterial pulsation during flow-mediated dilation is impaired in the presence of ischemic heart disease.

Purpose The aim of this study is to investigate the relationship between arterial pulse amplitude change under increased shear stress and the presence of ischemic heart disease (IHD).Methods This study comprised 31 subjects, including 14 subjects with IHD. We investigated the change in brachial artery pulse amplitude during flow-mediated dilation (FMD) using ultrasonography.ResultsThe arterial pulse amplitude increased during FMD in 19 subjects, whereas it decreased in 12 subjects. There was a marked difference in the change in arterial pulse amplitude (the maximum amplitude of the arterial pulse amplitude during FMD/the arterial pulse amplitude at baseline) between subjects with and without IHD (0.98 ± 0.53 and 1.37 ± 0.53, p = 0.028). Furthermore, decreased arterial pulse amplitude during FMD was a significant predictor of IHD after adjustment of age, blood pressure, the presence of each type of coronary risks, the value of FMD and sex (p = 0.0001).ConclusionsThe decrease of arterial pulsation amplitude during FMD was a useful predictive parameter for IHD.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2794-0) contains supplementary material, which is available to authorized users.

Serial assessment of arterial structure and function in patients with coarctation of the aorta undergoing stenting

Stenting for CoA has become an acceptable treatment modality in the last 20years. However little is known about arterial changes after this procedure. To assess arterial structure and function including peripheral reactivity and stiffness and intima-media thickness (IMT) pre and post stenting for coarctation of the aorta (CoA). Twenty-one patients [median age: 15years (8-39)] were studied at baseline, 1day, 6months and 1year after stenting. Twenty-one healthy subjects (1:1 matched) were used as controls. Left ventricular (LV) mass, ejection fraction, flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of left brachial artery, common carotid (CC) and right subclavian artery (RSCA) IMT and pulse wave velocity (PWV) were assessed by echocardiography and vascular ultrasound. CoA patients had higher LV indexed mass (p<0.0001), impaired FMD (p<0.0001) and NMD (p<0.0001), increased PWV (p<0.0001), carotid and RSCA IMT (both p<0.0001). All procedures were successful and resulted in significant gradient reduction (p<0.001). One year after stenting there was improvement in LV function (p=0.034) and although there was significant reduction of LV mass (103.29±24.77 vs. 74.39±22.07g/m(2), p<0.0001) values did not normalize. There was no significant change in FMD, NMD, PWV and CC or RSCA IMT. In patients with CoA, arterial reactivity is impaired and LV mass, arterial stiffness and thickness are increased. Although stenting is successful to relieve the obstruction resulting in better LV function and mass reduction, arterial structure and function remains abnormal after 1year of follow-up.

Chemerin is not associated with subclinical atherosclerosis markers in prediabetes and diabetes.

Objective:Chemerin is a novel adipokine that is correlated with adipocyte differentiation, glucose metabolism, and inflammation. We aimed to investigate the relation between serum chemerin level and subclinical atherosclerosis markers as exemplified by brachial artery pulse wave velocity (baPWV), carotid intima–media thickness (CIMT), epicardial fat thickness (EFT), and carotid plaque presence in diabetes and prediabetes.Methods:Age-, body mass index (BMI)-, and gender-matched patients with type 2 DM (n=30), prediabetes (n=25), and normal glucose tolerance (n=25) were included in this cross-sectional study. Serum chemerin level, lipid parameters, glucose metabolism marker, baPWV, CIMT, EFT, and anthropometric were recorded. The independent risk factors for atherosclerosis markers were determined by linear and/or multiple logistic regression analysis.Results:baPWV and carotid plaque presence were higher in the diabetes group than in prediabetes and control groups (p=0.039 and p=0.035 respectively), whereas serum chemerin levels were similar among groups (p=0.338). Chemerin levels were not correlated with PWV, CIMT, and epicardial fat thickness overall or in the subgroups. Overall and in the diabetes group, chemerin levels were positively correlated with the key components of metabolic syndrome as BMI, total body fat percentage, waist circumference, triglyceride, and systolic and diastolic blood pressure (BP). After adjusting for age, gender, and BMI, only the association between chemerin and systolic BP remained significant. Chemerin was not found as an independent risk factor for predicting atherosclerosis in diabetes and prediabetes.Conclusion:Chemerin is not a predictive marker for atherosclerosis in diabetes and prediabetes, but correlates well with key aspects of the metabolic syndrome particularly in diabetes.

Abstract 13444: Longer Telomere Length is Associated With More Distensible Carotid Arteries in a Healthy Adult Population

Introduction: Chronological age is associated with loss of arterial distensibility leading to greater cardiac afterload and inefficient systemic perfusion. It is not known if cellular aging, marked by a loss of telomeres, underlies vascular aging. We thus examined the association of leukocyte telomere length (LTL) with common carotid distensibility (CD) in a healthy adult population. Methods: We analyzed data from 119 adults free of clinical cardiovascular disease (ages 21-80 years, 39% African American, 60% women, from 99 families) with familial history of early onset coronary artery disease (30x coverage, Illumina HiSeq) for both 4 (LTL4) and 7 (LTL7) contiguous telomere motif repeats (TTAGGG or CCCTAA) using the approach of Ding et al (2014). Mean CD of both carotid arteries was calculated from systolic and diastolic carotid diameters measured using B-mode ultrasound and simultaneous measurement of brachial artery pulse pressure (follow-up time 0-5 years from the LTL visit). We used mixed model regression to account for non-independence of data in families. Results: The mean (SD) of LTL4 was 94851 (16370) and of LTL7 was 80666 (15001) repeats. Adjusting for age at LTL measurement, follow-up time to carotid measurement, sex, race, systolic and diastolic blood pressure, LDL- and HDL-cholesterol levels, current smoking and diabetes, 1 SD higher level of LTL4 was associated with 2.0 х 10 -4 (p = 0.027), and 1 SD higher level of LTL7 with 1.8 х 10 -4 mmHg -1 (p = 0.048) higher CD, which is equivalent to CD at a chronological age that is lower by 4.4 and 4.0 years, respectively. Hypertension is not significantly associated with CD (p = 0.49) when added to this model. Conclusions: Greater LTL is associated with more distensible carotid arteries independent of cardiac risk factors including chronological age and blood pressure. Preserved telomere length represents healthy cellular aging in terms of fewer cell divisions, and thus greater vascular reparative reserve, which may lead to preserved arterial distensibility. This mechanism may partly explain the reported association of greater telomere length with lower risk of vascular events including coronary disease, heart failure and stroke.

Cardiovascular function in healthy Himalayan high-altitude dwellers

BackgroundResidents of the Himalayan valleys uniquely adapted to their hypoxic environment in terms of pulmonary vasculature, but their systemic vascular function is still largely unexplored. The aim of the study was to investigate vascular function and structure in rural Sherpa population, permanently living at high altitude in Nepal (HA), in comparison with control Caucasian subjects (C) living at sea level. Methods and results95 HA and 64 C were enrolled. Cardiac ultrasound, flow-mediated dilation (FMD) of the brachial artery, carotid geometry and stiffness, and aortic pulse wave velocity (PWV) were performed. The same protocol was repeated in 11 HA with reduced FMD, after 1-h 100% O2 administration.HA presented lower FMD (5.18 ± 3.10 vs. 6.44 ± 2.91%, p = 0.02) and hyperemic velocity than C (0.61 ± 0.24 vs. 0.75 ± 0.28 m/s, p = 0.008), while systolic pulmonary pressure was higher (29.4 ± 5.5 vs. 23.6 ± 4.8 mmHg, p < 0.0001). In multiple regression analysis performed in HA, hyperemic velocity remained an independent predictor of FMD, after adjustment for baseline brachial artery diameter, room temperature and pulse pressure, explaining 8.7% of its variance. On the contrary, in C brachial artery diameter remained the only independent predictor of FMD, after adjustment for confounders. HA presented also lower carotid IMT than C (0.509 ± 0.121 vs. 0.576 ± 0.122 mm, p < 0.0001), higher diameter (6.98 ± 1.07 vs. 6.81 ± 0.85 mm, p = 0.004 adjusted for body surface area) and circumferential wall stress (67.6 ± 13.1 vs. 56.4 ± 16.0 kPa, p < 0.0001), while PWV was similar. O2 administration did not modify vascular variables. ConclusionsHA exhibit reduced NO-mediated dilation in the brachial artery, which is associated to reduced hyperemic response, indicating microcirculatory dysfunction. A peculiar carotid phenotype, characterized by reduced IMT and enlarged diameter, was also found.

The combined assessment of flow-mediated dilation of the brachial artery and brachial-ankle pulse wave velocity improves the prediction of future coronary events in patients with chronic coronary artery disease

Background and purposeMeasurement of either flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery, brachial-ankle pulse wave velocity (baPWV), or intima-media thickness (IMT) of the carotid artery is useful for risk assessment of future cardiovascular events. This study examined whether combination of these vascular parameters may have an additive effect on the ability of traditional risk factors to predict coronary events in patients with chronic coronary artery disease (CAD). MethodsPatients (n=923) with stable CAD had measurements of FMD, baPWV, and maximum IMT (maxIMT), and were prospectively followed up for <8.5 years or until a coronary event – cardiac death, non-fatal myocardial infarction (MI) or unstable angina pectoris (uAP) requiring unplanned coronary revascularization. ResultsDuring the follow-up period, 116 events occurred (29 cardiac deaths, 46 non-fatal MIs and 41 cases of uAP). A multivariate Cox proportional hazards analysis showed that FMD (HR 0.50, 95% CI 0.38–0.66) and baPWV (HR 1.52, 95% CI 1.27–1.82) but not maxIMT were significant predictors of coronary events. Based on the concordance statistics, the predictive value of traditional risk factors [area under the receiver operating characteristic curve (AUC), 0.67] was increased more by the addition of FMD and baPWV combined (AUC, 0.75) compared with the addition of either maxIMT, FMD, or baPWV alone, or the combination of maxIMT and FMD or maxIMT and baPWV (AUC, 0.67, 0.71, 0.71, 0.71 and 0.71, respectively). ConclusionsThe combined addition of FMD and baPWV to the risk assessment algorithms may be useful for risk stratification of chronic CAD patients.

Effect of Platelet Reactivity, Endothelial Function, and Inflammatory Status on Outcomes in Patients With Stable Angina Pectoris on Clopidogrel Therapy

Although high on-treatment platelet reactivity (HTPR) is an important predictor of clinical outcomes in patients undergoing coronary stenting, it is unknown whether endothelial dysfunction and HTPR are associated. We examined the platelet function, peripheral vascular function, endothelial progenitor cell (EPC) number, platelet activation markers, high-sensitivity C-reactive protein (hs-CRP) level, and clinical outcomes in patients receiving chronic clopidogrel therapy. We consecutively enrolled 91 patients who underwent follow-up angiography because of chest discomfort. All patients took aspirin and clopidogrel for an average of 498 ± 138 days. Platelet reactivity was assessed by light transmittance aggregometry (maximal platelet aggregation by 5 μmol/L of adenosine diphosphate ≤50% in group 1 [optimal response] and >50% as group 2 [HTPR]). Flow-mediated dilation of the brachial artery and brachial-ankle pulse wave velocity (PWV), numbers of EPCs isolated from peripheral blood, platelet activation markers (soluble CD40 ligand and soluble P-selectin), and hs-CRP levels were assessed before follow-up angiography. There were no significant differences in baseline characteristics and previous percutaneous coronary intervention (PCI) data between groups 1 (n = 59) and 2 (n = 32). Group 2 showed poorer flow-mediated dilation (6.1 ± 4.1% vs 12.9 ± 6.2%, p <0.001), pulse wave velocity (1925.4 ± 362.2 vs 1571.0 ± 306.5 ms, p <0.001), and lower circulating EPCs by flow cytometry (21.9 ± 14.7 vs 65.2 ± 30.1 per 10 fields, p <0.001) compared with group 1. Significantly higher levels of soluble CD40 ligand, soluble P-selectin, and hs-CRP were observed in group 2. In multivariate analysis, elevated hs-CRP level, but not HTPR, was independently associated with repeated PCI. In patients with angina, HTPR was associated endothelial dysfunction and elevated hs-CRP, although elevated hs-CRP level was significantly associated with poorer outcomes.