Brachial Artery Vasoreactivity Research Articles

Androgen receptor gene CAG-trinucleotide repeat length affects function of endothelium in men with hypogonadism and type 2 diabetes mellitus

Introduction. The influence of the length of the number of CAG repeats in the androgen receptor gene (nCAG AR) on endothelial dysfunction (EnD) is currently understudied.Objective. The study aimed to evaluate the relationship between the nCAG AR and the dynamics of biochemical and ultrasound markers of EnD in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) receiving testosterone replacement therapy (TRT).Materials & methods. This study included 45 hypogonadal men with T2DM, receiving TRT for 1 year. Patients were assessed for carbohydrate and lipid metabolism parameters; total and free T; sex hormone-binding globulin; biochemical markers of EnD (NO, eNOS3, endothelin) and the nCAG AR; brachial artery (BA) vasoreactivity. Patients were divided into 3 groups: group I — 9 men with nCAG AR < 19; group II — 27 men with nCAG AR > 19 – 24; and group III — 9 men with nCAG AR >24.Results. Patients with nCAG AR < 19 exhibited a 2-fold greater and faster increase in BA vasoreactivity on TRT compared to patients with nCAG AR 19-24 and 3-fold greater than men with nCAG AR >24 (p < 0.05). Patients with nCAG AR < 19 also demonstrated the most pronounced rise in NO and eNOS3 on TRT compared to men with nCAG AR > 24. Patients with nCAG AR < 19 experienced the most pronounced decreases in weight, waist circumference, and HbA1c on TRT compared to other patients (p < 0.05).Conclusion. The nCAG AR length significantly affects the response to TRT in men with hypogonadism and T2DM. The most significant improvements are seen in patients with short nCAG AR.

Comparison of Adiposomal Lipids between Obese and Non-Obese Individuals.

Our recent findings revealed that human adipose tissues (AT)-derived extracellular vesicles (adiposomes) vary in cargo among obese and lean individuals. The main objective of this study was to investigate the adiposomal lipid profiles and their correlation with cardiometabolic risk factors. AT samples were collected from obese subjects and lean controls and analyzed for their characteristics and lipid content. In addition, we measured the correlation between adiposomal lipid profiles and body composition, glucose and lipid metabolic profiles, brachial artery vasoreactivity, AT arteriolar flow-induced dilation, and circulating markers such as IL-6, C-reactive protein, and nitric oxide (NO). Compared to lean controls, adiposomes isolated from obese subjects were higher in number after normalization to AT volume. The two major lipid classes differentially expressed were lysophosphatidylcholine/phosphatidylcholine (LPC/PC) and ceramides (Cer). All lipids in the LPC/PC class were several-fold lower in adiposomes from obese subjects compared to lean controls, on top of which were PC 18:2, PC 18:1, and PC 36:3. Most ceramides were markedly upregulated in the obese group, especially Cer d37:0, Cer d18:0, and Cer d39:0. Regression analyses revealed associations between adiposomal lipid profiles and several cardiometabolic risk factors such as body mass index (BMI), fat percentage, insulin resistance, arteriolar and brachial artery vasoreactivity, NO bioavailability, and high-density lipoproteins (HDL-C). We conclude that the ability of adiposomes from obese subjects to disrupt cardiometabolic function could be partly attributed to the dysregulated lipid cargo.

Improved endothelial function after short-term therapy with evolocumab

The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test. Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2months of therapy with evolocumab 140mg twice in a month. Mean brachial artery diameter, velocity time integral, flow-mediated dilation (FMD) and low-density lipoprotein (LDL) cholesterol levels were also evaluated. After 2months of treatment with evolocumab, mean total cholesterol levels decreased from 245±41 to 128±30mg/dL (P<.001, -48%), and LDL levels from 176±43 to 71±26mg/dL (P=.001, -59%); FMD conversely increased from 6.3±4.1% to 8.8±6.3% (P=.004,+40%). Improvement in FMD was proportional to reduction of LDL levels (r=0.69, P=.006). Therapy with evolocumab increased brachial artery diameter during vasoreactivity test (peak values 0.39±0.09 vs 0.36±0.11cm, P=.010; final values 0.36±0.10 vs 0.34±0.10cm, P=.001), and velocity time integral (peak levels 96±1 vs 85±9cm, P=.045). Two months of treatment with evolocumab 140mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.

ENDOTHELIAL DYSFUNCTIONS AND THEIR CORRECTION IN WOMEN WITH EARLY POSTMENOPAUSE

Aim. To evaluate the nature of the dysfunction of the endothelium in postmenopausal women with climacteric syndrome, peculiarities of its changes during long-term use of a fixed low-dose combination of 17β-estradiol 1 mg/drosperidone 2 mg daily (Е2 1 mg/DRSP 2 mg). Material and methods. A non-randomized, uncontrolled study included 162 women in early postmenopausal period with climacteric syndrome. Patients were divided into 2 groups. Patients of the main group (n=84) received menopausal hormone therapy (MHT) with the fixed combination of Е2 1 mg/DRSP 2 mg. Patients of the control group (n=78) did not receive MHT. The duration of the follow-up was 5.2 years. The endothelium dependent vasodilation (EDVD) of brachial artery was assessed by reactive hyperemia. Endothelial dysfunction (ED) markers - plasma levels of endothelin-1 (ET-1), NO metabolites, asymmetric dimethylarginine (ADMA) and von Willebrand factor antigen (vWF:Ag) - were studied by a highly sensitive quantitative enzyme-linked immunosorbent assay. Results. The examined postmenopausal women with climacteric syndrome had significant increase in the concentration of ET-1 up to 1.0 (0.7-1.3) fmol/ml, increased levels of vWF:Ag up to 0.835 (0.760-0.990) U/ml and reduction in the level of the total content of stable metabolites of nitric oxide (NOx) to 39.2 (35.4-43.7) μmol/l. Disorders of EDVD of the brachial artery were observed in 50 (59.5%) women of the main group and in 45 (57.6%) women of the control group (p=0.7). The relationships between EDVD parameters and levels of ADMA (r=-0.31, p=0.029) and NOx (r=0.31, p=0.002) were revealed. In patients with impaired EDVD, a significant decrease in the level of stable NO metabolites and an increase in ADMA and ET-1 levels were detected. A significant increase in the EDVD of the brachial artery was observed throughout the follow-up period. Besides an increase in NO metabolites level, and decrease in the ET-1 and ADMA levels were found by the 12th month of MHT. Conclusions. Disorders of endothelial function were found in the majority of women in early postmenopausal period, the most marked changes were in patients with impaired vasoreactivity of brachial artery. Favorable changes in vascular endothelium function were observed during long-term MHT with the fixed combination of Е2 1 mg/DRSP 2 mg.

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.

Comparison of Brachial Artery Vasoreactivity in Elite Power Athletes and Age-Matched Controls

Elite endurance athletes typically have larger arteries contributing to greater skeletal muscle blood flow, oxygen and nutrient delivery and improved physical performance. Few studies have examined structural and functional properties of arteries in power athletes.PurposeTo compare the size and vasoreactivity of the brachial artery of elite power athletes to age-matched controls. It was hypothesized brachial artery diameters of athletes would be larger, have less vasodilation in response to cuff occlusion, but more constriction after a cold pressor test than age-matched controls.MethodsEight elite power athletes (age = 23±2 years) and ten controls (age = 22±1 yrs) were studied. High-resolution ultrasonography was used to assess brachial artery diameters at rest and following 5 minutes of forearm occlusion (Brachial Artery Flow Mediated Dilation = BAFMD) and a cold pressor test (CPT). Basic fitness measures included a handgrip test and 3-minute step test.ResultsBrachial arteries of athletes were larger (Athletes 5.39±1.51 vs. Controls: 3.73±0.71 mm, p<0.05), had greater vasodilatory (BAFMD%: Athletes: 8.21±1.78 vs. Controls: 5.69±1.56%) and constrictor (CPT %: Athletes: -2.95±1.07 vs. Controls: −1.20±0.48%) responses, compared to controls. Vascular operating range (VOR = Peak dilation+Peak Constriction) was also greater in athletes (VOR: Athletes: 0.55±0.15 vs. Controls: 0.25±0.18 mm, p<0.05). Athletes had superior handgrip strength (Athletes: 55.92±17.06 vs. Controls: 36.77±17.06 kg, p<0.05) but similar heart rate responses at peak (Athletes: 123±16 vs. Controls: 130±25 bpm, p>0.05) and 1 minute recovery (Athletes: 88±21 vs. Controls: 98±26 bpm, p>0.05) following the step test.ConclusionElite power athletes have larger brachial arteries, and greater vasoreactivity (greater vasodilatory and constrictor responses) than age-matched controls, contributing to a significantly greater VOR. These data extend the existence of an ‘athlete’s artery’ as previously shown for elite endurance athletes to elite power athletes, and presents a hypothetical explanation for the functional significance of the ‘power athlete’s artery’.

Endothelial Function Predicts Positive Arterial-Venous Fistula Remodeling in Subjects with Stage IV and V Chronic Kidney Disease

The maturation of an arteriovenous fistula (AVF) requires remodeling of the arterial inflow and the venous outflow limbs to sustain flows sufficient to support hemodialysis. However, factors influencing remodeling of AVF are poorly understood. We hypothesized that AVF remodeling was an endothelium-dependent process. This is a prospective cohort study of patients (n=25) undergoing autologous AVF formation. Brachial artery vasoreactivity studies were performed pre-operatively to assess endothelium-dependent, flow-mediated vasodilation (FMD). High-resolution ultrasound was used to assess venous and arterial diameters intraoperatively, and at 3 months. The mean age was 64.5 ± 13.6 yrs. Twelve patients (48%) had diabetes. The mean FMD for the entire cohort was (mean ± SEM) 5.82 ± 0.9%, (range) 0-17.3%. The vein increased in size 3.19 ± .28 to 6.11 ± .41 mm, 108.4 ± 17.9%, p=.0001, while the artery increased from 3.29 ± .14 to 4.48 ± .30 mm, 20.47 ± 10.8%, p=.013. There was a significant positive correlation between the degree of arterial and venous remodeling, r=.52, p=.023. Brachial artery FMD most strongly correlated with the magnitude of arterial remodeling, r=.47, p=.038. Patients with diabetes failed to undergo venous remodeling to the same extent as did those without diabetes, 59.2 ± 24.4% vs. 141.5 ± 25.4%, p=.04. Impairment of endothelial function is associated with decreased arterial remodeling and final venous lumen diameter attained at 3 months. Further investigation is needed to determine whether modulation of endothelial function in this cohort can improve AVF maturation.

Comparison of Brachial Artery Vasoreactivity in Elite Athletes and Age-Matched Controls

Comparison of Brachial Artery Vasoreactivity in Elite Athletes and Age-Matched Controls

Abstract: P1197 METABOLIC CONTROL AND ARTERIAL VASOREACTIVITY IN CHILDREN WITH TYPE I DIABETES USING INSULIN PUMP

P1197 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2 METABOLIC CONTROL AND ARTERIAL VASOREACTIVITY IN CHILDREN WITH TYPE I DIABETES USING INSULIN PUMP M Sebestjen, N Battelino, T Battelino, I Keber Department of Angiology, University Clinical Centre Ljubljana, Ljubljana; University Children's Hospital, University Clinical Centre Ljubljana, Ljubljana Children with type I diabetes mellitus have impaired endothelial function which is the first change in atheroslcerotic process. The aim of our study was to find out whether arterial vasoreactivity in children with type I diabetes mellitus using insulin pump is depending on the intensitivity of metabolic control. We studied 97 children with type I diabetes, aged between 7 and 18 years. The children were classified into two groups according to HbA1c below (Group 1) or more than (Group 2) 8,0%. In all participants physical examination, measurements of serum lipids, glucose, HbA1c and ultrasonographic studies of brachial artery vasoreactivity were performed. Children in group 1 were significantly younger than those in group 2 (10,3 ±1,9 and 15,6 ± 1,9 years; respectively (p<0,0001)). The mean values of blood glucose were 8,1 ± 3,2 mmol/l and 9,3 ± 4,0 mmol/l (p=ns), while mean values of HbA1c were 7,4 ± 0,4% and 9,3 ± 1,7%; respetivly (p<0,0001). Total (4,0 ± 0,6 mmol/l and 4,5 ± 0,7 mmol/l (p= 0,007)) and LDL cholesterol (2,0 ± 0,5 mmol/l and 2,4 ± 0,7 mmol/l (p= 0,04)) were lower in group 1 than in group 2. No difference were found in HDL cholesterol, and systolic and diastolic blood pressure. The flow mediated dilatation (FMD) was 6,7 ± 4,5% and 3,2 ± 5,4% (p= 0,02) in group 1 and group 2; respectively. Only HbA1c emerged as independed predictor of FMD. The value of HbA1c is the most important predictor of FMD in children with type I diabetes mellitus using insulin pump. Lifestyle modifications and strickt control of HbA1c early in childhood are important to prevent early atherosclerostic changes in these population.

Brachial artery vasoreactivity is associated with cross-sectional and longitudinal anatomical measures of atherosclerosis in postmenopausal women with coronary artery disease

Background The diagnostic and prognostic importance of brachial artery flow-mediated dilation (BFMD) for cardiovascular disease (CVD) is not certain and associations between BFMD and recognized measures of atherosclerosis have not been well established. Methods We investigated cross-sectional and longitudinal correlations between repeated measures of BFMD and quantitative coronary artery angiographic (QCA) measurements of average percent diameter stenosis, number of lesions and minimum luminal diameter (MLD), and ultrasonographic measurement of carotid artery intima-media thickness (CIMT) in an ethnically diverse cohort of postmenopausal women ( n = 132) with coronary artery disease (CAD). Subjects were participants in a 3-year randomized, placebo-controlled clinical trial, testing the efficacy of hormone therapy on atherosclerosis progression. Associations between BFMD and QCA measures, and between BFMD and CIMT were examined using measurements from the same study visit. Results BFMD was significantly inversely correlated with coronary artery stenosis at baseline ( β = −1.21% [S.E.( β) = 0.38], p = 0.002). BFMD levels significantly predicted rate of change in CIMT over the trial period ( β = −0.76 μm/year [S.E.( β) = 0.29], p = 0.008). Conclusions Physiological and anatomical measures of atherosclerosis are correlated among postmenopausal women with CAD, which provides some validation of BFMD as a measure of atherosclerosis in high-risk populations.

Long-Term Prognostic Role of Flow-Mediated Dilatation of the Brachial Artery After Acute Coronary Syndromes Without ST Elevation

Coronary endothelial vasodilator dysfunction is associated with increased cardiac events; the close relation between coronary vasomotor dysfunction and brachial artery vasoreactivity has been previously described. This study assessed the prognostic value of noninvasively assessed brachial artery vasoreactivity in survivors of acute coronary syndromes without ST-segment elevation. We examined 98 men (63.1 +/- 10.8 years) who were referred to our hospital for acute coronary syndromes without ST-segment elevation. Brachial artery endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitrate-mediated dilation were examined in all patients using high-resolution echocardiographic Doppler ultrasound within 24 hours of admission. Plasma malondialdehyde, a marker of oxidative stress, and left ventricular ejection fraction were also assessed. Twenty-seven patients underwent coronary revascularization. Patients were followed for 24.8 +/- 5.9 months. Cardiovascular death, myocardial infarction, stroke, and unstable angina were designated as cardiovascular events (CEs). Twenty CEs were recorded. Kaplan-Meyer analysis showed that patients with FMD <1.9% (tertile 1 of FMD values) were more likely to have CEs than those with FMD >1.9% (log rank 5.29, p = 0.021). Multivariate Cox regression analysis showed that FMD <1.9% predicted CEs with an adjusted hazard ratio of 3.035 (95% confidence interval 1.148 to 8.023, p = 0.025) after adjustment for age, risk factors, troponin T, ejection fraction, revascularization procedures, number of diseased vessels, and medication. In conclusion, endothelium-dependent dilation of the brachial artery is a strong independent predictor of adverse outcome in survivors of acute coronary syndromes without ST-segment elevation.

Tu-P7:130 PUlse pressure is a predictor of endothelial function assesed by brachial artery vasoreactivity testing in healthy volunteers

Tu-P7:130 PUlse pressure is a predictor of endothelial function assesed by brachial artery vasoreactivity testing in healthy volunteers

Evaluation of Macrocirculatory Endothelium-Dependent and Endothelium-Independent Vasoreactivity in Vascular Disease

Macrocirculatory endothelium-dependent and independent vasodilatation is integral to tissue-bed oxygen delivery and homeostasis. Dysfunction of macrocirculatory vasoreactivity is a precursor to atherosclerosis and occurs in a similar fashion in multiple tissue beds long before the onset of symptoms. Impaired macrocirculatory vasodilatation has been shown to occur in certain disease states including diabetes mellitus, hypercholesterolemia, chronic renal failure, peripheral arterial atherosclerosis, and abdominal aortic aneurysms, as well as secondary to smoking, advanced age, menopause, high-fat diet, and sedentary lifestyle. Brachial artery vasoreactivity is a noninvasive means of assessing macrocirculatory vasodilatory capacity that may help identify patients at increased risk for peripheral and cardiovascular disease and allow for objective assessment and monitoring of treatment. Endothelium-dependent vasoreactivity, or flow-mediated dilatation, is measured after brachial artery occlusion with a pneumatic blood pressure cuff, and endothelium-independent vasoreactivity is measured after the administration of sublingual nitroglycerin. The accuracy of brachial artery vasoreactivity is dependent on hematologic variables, as well as diurnal, day-to-day, ultrasound operator, and reader variations; however, the overall coefficient of variation is only 1.8%. We discuss the importance of the macrocirculation, investigative methods for evaluating macrocirculatory vasoreactivity, and review the literature of vasoreactivity in these different states.

The long-term effects of tibolone on aortic stiffness and endothelial function

Objective To investigate the effect of 10 years of treatment with tibolone on aortic stiffness and endothelial function.Design Cross-sectional study of women currently participating in an open-label, non-randomized study of the long-term efficacy of tibolone. A total of 113 recently postmenopausal women were recruited in 1988. Fifty-eight agreed to take tibolone 2.5 mg daily and 55 were followed during the study as matched controls (who chose not to take any form of hormone replacement therapy (HRT) for the duration of the study). The groups were matched for age, weight and time since last menstrual period.Setting A Central London Teaching Hospital.Subjects After 10 years, 60 women remained in the study, 32 in the tibolone group and 28 in the control group. All of these women were invited to participate in this pilot study and attend the Menopause Research Unit. Fourteen women from each group agreed to attend. The main outcome measures were aortic stiffness, measured by pulse wave velocity, and endothelial function, as assessed by flow-mediated dilatation of the brachial artery.Results Pulse wave velocity was significantly lower in the tibolone group (10.4 ± 1.2) than in the control group (11.6 ± 1.2), p = 0.042. The flow-mediated dilatations were similar in both groups.Conclusion In this study, long-term use of tibolone over 10 years has a beneficial effect on aortic stiffness. The differences seen in brachial artery vasoreactivity failed to reach statistical significance. Whether this is a true indication of the effects of long-term tibolone on brachial artery vasoreactivity will only be determined by performing a larger, placebo-controlled, randomized study.

The Effects of Exercise on Endothelial Function in Patients with Coronary Artery Disease

1657 Although there is no direct link between endothelial dysfunction and coronary artery disease, there is evidence that the loss of normal endothelial function may contribute to the pathophysiology of coronary ischemia and the development of atherosclerosis. Despite the clear association between exercise and the reduction of coronary artery disease, the mechanism responsible for the reduction has not been elucidated. PURPOSE: The purpose of this study was to determine the effect of exercise typical to most cardiac rehabilitation programs, on endothelial-dependent vasodilatation in patients with coronary artery disease. METHODS: Participants completing this study were 14 males and 2 females (mean age 59 yrs, range 44–79 yrs) with no prior history of regular exercise. Each of the participants began this 12-week study after undergoing an angiogram that confirmed the presence of coronary artery disease. Following recruitment, participants came to the testing site for determination of their baseline endothelial function. Endothelial function was determined by measuring the brachial artery vasoreactivity following 5 min of upper arm ischemia. This measurement was done non-invasively using ultrasound. Vasodilation following upper arm occlusion was expressed relative to the average of three measurements at rest. Subjects began a monitored exercise program following their baseline measurements in which they were encouraged to exercise 3 times per week. Subjects had exercise prescribed each day they trained that was equal to a RPE of 3 (moderate) on the modified Borg RPE scale. Modalities used were treadmills, bikes, and recumbent stepping machines. Exercise was continuously monitored by exercise technicians trained in cardiac rehabilitation. RESULTS: To test the hypothesis that endothelial function improves with exercise a one-way repeated measures ANOVA was conducted. For this analysis, maximum percent change in brachial artery diameter post blood pressure cuff release following 5 min upper arm occlusion served as the dependent variable and exercise served as the independent variable. Time served as the within subjects' factor. No significant difference in the change in the brachial artery diameter was observed. CONCLUSION: These results suggest that brachial artery reactivity to increased blood flow was not altered by exercise as typically prescribed in cardiac rehabilitation programs.

Effects of cilostazol in patients with Raynaud's syndrome

Raynaud's syndrome (RS), which is characterized by recurrent episodes of vasospasm with exposure to cold, may occur alone (primary RS) or in association with connective tissue diseases or other underlying conditions (secondary RS). We investigated the effect of cilostazol on vessel wall responses in RS. Patients were diagnosed (primary or secondary RS associated with connective tissue diseases) and randomized to placebo or cilostazol 100 mg twice daily for 6 weeks in a double-blind manner. Brachial artery vasoreactivity, laser Doppler fluxmetry, and cold pressor testing (CPT) were performed at study initiation and completion. Symptoms were assessed using standardized questionnaires. Forty subjects completed the study (19 with primary RS and 21 with secondary RS). Cilostazol significantly increased the mean brachial artery diameter at 6 weeks (primary RS, p = 0.006; secondary RS, p = 0.06). There was no change in median flow-mediated dilation (FMD) with cilostazol in primary RS (25th, 75th percentiles) (4.06% [2.5, 6.1] to −0.77% [−2.4, 3.4] or secondary RS (2.2% [0.05, 6.3] to 2.95% [1.7, 7.4]). There were no changes in nitroglycerin-mediated dilation or microvascular flow indexes in either cohort. In patients with primary RS, cilostazol treatment yielded a positive change in the slope of brachial responsiveness to CPT (increase of 0.32 mm/min; p = 0.002 vs placebo). Cilostazol treatment remained significantly associated with increased brachial artery diameter when controlling for baseline values (p = 0.018). Cilostazol increased conduit vessel diameter in patients with primary and secondary RS, with a favorable impact on conduit vessel responsiveness to cold in patients with primary RS without affecting microvascular flow or symptoms.

Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease

ObjectivesThe aim of this study was to determine whether selective cyclooxygenase-2 (COX-2) inhibition with rofecoxib can modulate endothelial dysfunction and levels of circulating inflammatory markers in patients with established coronary artery disease (CAD). BackgroundExpression of COX-2 is upregulated in atherosclerosis. Thus, it has been hypothesized that COX-2 may contribute to atherogenesis by producing eicosanoids, which mediate vascular inflammation and endothelial dysfunction. MethodsIn a randomized, double-blind, placebo-controlled, parallel-design trial, we studied the vascular effects of rofecoxib on brachial artery vasoreactivity and inflammatory markers in 60 patients with angiographically proven CAD who were taking concomitant low-dose aspirin. Patients were randomly assigned to receive either rofecoxib (25 mg/day; n = 30) or placebo (n = 30) for eight weeks. Brachial artery endothelium-dependent flow-mediated dilation (FMD), endothelium-independent nitroglycerin-mediated dilation (NMD), and inflammatory markers (i.e., high-sensitivity C-reactive protein [CRP], soluble intercellular adhesion molecule-1 [sICAM-1], and soluble interleukin-6 receptor [sIL-6r]) were measured at baseline and after eight-week follow-up. ResultsBaseline clinical characteristics were similar in the two groups. After eight weeks of treatment, FMD did not significantly change in either the rofecoxib or placebo group (4.0 ± 3.0% to 4.0 ± 3.8% vs. 2.7 ± 2.7% to 3.1 ± 2.7%, respectively; p = 0.6 by two-way analysis of variance). Similarly, NMD remained unchanged in both groups. Levels of CRP, sICAM-1, and sIL-6r were not significantly altered in either the rofecoxib or placebo group. ConclusionsThe addition of selective COX-2 inhibition with rofecoxib did not appear to have any favorable or adverse effects on endothelial dysfunction or vascular inflammation in patients with CAD using concomitant low-dose aspirin.

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The metabolic syndrome: a practical guide to origins and treatment: Part II.

The metabolic syndrome (MetS), a cluster of metabolic abnormalities with insulin resistance as a major characteristic, has gone by several names over the past two decades. The diagnostic criteria proposed by the Adult Treatment Program III (ATP III) of the National Cholesterol Education Program (NCEP) have led to greater awareness of the components and treatment strategies.1 Five diagnostic traits are listed in the ATP III version of the MetS (Table; referred to as the “metabolic syndrome”), and the presence of any 3 of these factors is considered sufficient for diagnosis. This practical review will consider each in turn, providing advice for cardiologists, internists, and other health care providers who are diagnosing and treating persons with the syndrome in an effort to prevent a variety of clinical outcomes. View this table: Diagnostic Criteria for the Metabolic Syndrome The major adverse consequence of the MetS is cardiovascular disease (CVD). Several of the metabolic abnormalities associated with the syndrome, in fact, are CVD risk factors. One of these abnormalities, insulin resistance, also predisposes to the development of type 2 diabetes mellitus (T2DM). In age-adjusted estimates from the National Health and Nutrition Examination Survey III in 1998 to 1994, approximately 24% of adult Americans had ≥3 of the 5 MetS criteria. Key determinants of greater prevalence were age and ethnicity. Prevalence rates were highest in Mexican Americans and were successively lower in white, African American and other racial groups.2 These published estimates included persons with diabetes mellitus who had met the 1998 fasting glucose criteria (≥126 mg/dL [8.0 mmol/L]) of the American Diabetes Association.3 This article will focus on the features of the MetS in persons without diabetes mellitus, although most persons with T2DM also have the MetS. Moreover, the therapeutic approaches to metabolic risk factors described here also can be applied to …

ASSOCIATION OF BRACHIAL ARTERY SIZE WITH CARDIOVASCULAR RISK FACTORS

Non-invasive assessment of brachial artery vasoreactivity is used as a surrogate marker for coronary heart disease (CHD). Recent data suggests baseline brachial artery size is an independent predictor of CHD in women. PURPOSE To examine the influence of CHD risk factors on brachial artery size in men and women (n = 301, Age: 55 ± 5y). METHODS Following a fast and supine rest, brachial artery diameters were imaged before and after 5min of forearm occlusion. Still images of the artery in diastole were analyzed. CHD risk scores were calculated from hematologic and hemodynamic measures and the Framingham prediction algorithm. RESULTS Average lipid profiles (HDL: Women: 64 ± 13; Men: 48 ± 9mg/dl, p = 0.001; LDL: Women: 132 ± 25; Men: 137 ± 23mg/dl, p = 0.07), diastolic pressure (Women: 76 ± 7; Men: 78 ± 8mmHg, p = 0.02) and glucose (Women: 97 ± 9; Men: 101 ± 9mg/dl, p = 0.02) were more favorable in women. Brachial artery size was associated with LDL (r = 0.18, p = 0.003), glucose (r = 0.27, p = 0.001), diastolic pressure (r = 0.21, p = 0.001) and HDL (Women: r = −0.24, p = 0.01; Men: r = −0.24, p = 0.05). The 10y predicted CHD risk score indicates both women (6.08 ± 3.42) and men (10.29 ± 5.99) were at average risk for CHD. Moreover, the risk score was related to brachial artery size (r = 0.33, p = 0.001). Finally, baseline vessel size was inversely related to vasoreactivity following occlusion (r = −0.263, p = 0.001). After adjusting for vessel size, vasoreactivity was significantly lower in women (Women: 4.67%, CI: 4.10 to 5.25; Men: 6.73%, CI: 5.85 to 7.61, p = 0.001). CONCLUSION Independent CHD risk factors and profiles are associated with brachial artery size in men and women. Vessel size is inversely related to vasoreactivity. After correcting for vessel size women have lower reactivity than men. The association between CHD risk factors and vessel size warrants careful consideration in interpretation of vasoreactivity and should be included as an independent outcome measure in trials. Supported in part by a Grant from the National Dairy Council