Baseline Brachial Artery Diameter Research Articles

Effect of a Single 20-mg Tablet of Atorvastatin on Brachial Artery Blood Flow in Normolipidemic Male Smokers Versus Nonsmokers

This study evaluated the acute effect of statin administration in smokers. We conducted a prospective study to determine the acute effect (24 hours) of single-dose atorvastatin (20 mg) on brachial artery endothelial function using vascular ultrasonography (flow-mediated vasodilation [FMD]) and blood flow in normolipidemic smokers (10 men, 42 +/- 9 years of age) and healthy nonsmokers (10 men, 39 +/- 7 years of age). Atorvastatin increased brachial artery percent FMD in smokers from 4.1 +/- 1.4% to 5.7 +/- 1.7% (p <0.0005), whereas we found no significant change after atorvastatin in nonsmokers (from 5.8 +/- 1.2% to 5.9 +/- 1.2%, p = NS). The velocity time integral also showed a significant increase as percent FMD in smokers 24 hours after taking atorvastatin (from 19 +/- 11 to 25 +/- 12 cm, p <0.05), whereas no significant change occurred in nonsmokers (from 18 +/- 9 to 19 +/- 10 cm, p = NS). Baseline brachial artery diameter significantly dilated in smokers after taking atorvastatin compared with before taking atorvastatin (from 4.23 +/- 0.5 to 4.35 +/- 0.4 mm, p <0.05), but did not change in nonsmokers (from 4.26 +/- 0.6 to 4.31 +/- 0.6 mm, p = NS). In conclusion, single-dose atorvastatin restores endothelial function and increases brachial artery blood flow in normolipidemic men smokers within 24 hours. These findings suggest early benefits of statin therapy on endothelial function in smokers.

Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing’s Syndrome

Cushing's Syndrome (CS) is associated with excess and premature cardiovascular disease. Endothelial dysfunction is the initiating event in the development of atherosclerosis. Endothelial function is assessed by flow-mediated dilatation (FMD) of brachial artery. The aim of this study was to assess FMD in patients with CS. We prospectively evaluated 22 patients with CS (12 women, 10 men; aged 42 +/- 11 years, serum cortisol 28.2 +/- 14 microg/dl, 24-h urinary free cortisol (UFC) 269 +/- 92 microg/day), and 23 control subjects (13 women, 10 men; aged 43 +/- 10 years, serum cortisol 14 +/- 4 microg/dl, 24 h cortisol 60 +/- 22 microg/day). Endothelial function, measured as FMD of the brachial artery using ultrasound, was calculated in two groups. Endothelial function was evaluated by assessing 1-min postischemic FMD of the brachial artery. FMD was lower in patients with CS than that in those without (11.7 +/- 4.8% vs. 15.8 +/- 3.2%, P = 0.0001, respectively). There was no significant difference between two groups regarding baseline diameter of brachial artery. But, hyperemia diameter was lower in patients with CS than without CS (3.6 +/- 0.22 mm vs. 3.9 +/- 0.19 mm, P = 0.04, respectively). Endothelium-dependent FMD may impair in patients with CS compared to controls. Measurement of endothelial function may identify high-risk individuals early and therapy to reduce or retard endothelial dysfunction in patients with CS may lead to decreased cardiovascular morbidity and mortality.

Genetic contribution to brachial artery flow-mediated dilation: The Northern Manhattan Family Study

Background Brachial artery flow-mediated dilation (FMD) is a non-invasive measure of endothelial function. Endothelial dysfunction has been associated with traditional vascular risk factors and increased risk of cardiovascular disease. The importance of genetic contribution to FMD and baseline brachial artery diameter has not been shown in Hispanic populations. The purpose of this study was to estimate the heritability of FMD. Methods Flow mediated dilation and brachial artery diameter were measured in a subset of Caribbean Hispanic families from the ongoing Northern Manhattan Family Study (NOMAFS), which studies the contribution of genetics to stroke and cardiovascular risk factors. The age- and sex-adjusted heritability of FMD was estimated using variance component methods. Results The current data include 620 subjects (97 probands and 523 relatives) from 97 families. The age and sex-adjusted heritability of brachial artery diameter was 0.57 ( p < 0.01). The age- and sex-adjusted heritability of FMD was 0.20 ( p = 0.01). After additional adjustment for systolic and diastolic blood pressure, body mass index, smoking, lipid, diabetes mellitus, medication, and baseline brachial artery diameter, the heritability of FMD was 0.17 ( p = 0.01). Conclusions We found modest heritability of FMD. FMD might be a reasonable phenotype for further investigation of genetic contribution to atherosclerosis.

The association of homocysteine and related factors to brachial artery diameter and flow-mediated dilation

Brachial artery flow-mediated dilation (BAFMD) has been proposed as a measurement of the degree and severity of cardiovascular disease. The purpose of this study was to (1) evaluate the associations between BAFMD and homocysteine, folate, vitamin B 12, vitamin B 6; (2) examine the influence of 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes on homocysteine levels and BAFMD; and (3) evaluate the effect of homocysteine on the baseline diameter of the vessel vs BAFMD. A total of 174 healthy research subjects were examined for BAFMD, homocysteine, folate, vitamin B 12, vitamin B 6, and MTHFR genotype, nucleotide 677 C→T. The data indicated a significant inverse correlation between homocysteine and BAFMD ( r = −0.1763, P = .02). There was a significant difference in BAFMD between MTHFR genotype groups ( P = .01) (T/T vs C/C, P = .042; C/C vs C/T, P = .13; T/T vs C/T, P = .003). Homocysteine was significantly associated with the baseline brachial artery diameter ( r = 0.1878, P = .013). The data confirmed a significant inverse correlation between baseline diameter and BAFMD ( r = −0.3321, P = .0001). Regression analysis indicated that the MTHFR genotype, homocysteine, and age were significant predictors of BAFMD ( P = .0001, r 2 = 0.118). When the baseline brachial diameter was incorporated into the model, the effect of homocysteine on BAFMD disappeared. The present data indicate an association between homocysteine and BAFMD and reduced BAFMD in individuals with the MTHFR nucleotide 677 T/T genotype, despite similar blood values for folate and homocysteine. Finally, the data suggest that the effect of homocysteine on vascular reactivity is in part a consequence of its influence on baseline brachial artery diameter.

The Effects of Acute Passive Smoke Exposure on Endothelium-Dependent Brachial Artery Dilation in Healthy Individuals

Passive smoking has both short-term and long-term vascular effects. It is not clear whether impairment of endothelial function reflects the acute effects of passive smoke exposure or the chronic effects. The purpose of this study was to assess the hypothesis that short-term exposure to passive smoke impairs endothelium-dependent vasodilation in healthy nonsmokers. Eighteen healthy young never smokers (12 men, 6 women) 21 to 55 years old (mean +/- SD: 34 +/-9 years) underwent ultrasonography measuring baseline brachial-artery diameter and brachial-artery diameter during hyperemia and after sublingual administration of nitroglycerin, twice: in a smoke-free environment, and then in the same environment polluted by 30 to 35 ppm carbon monoxide. Each subject served as his/her control. Carboxyhemoglobin was measured in blood samples of subjects tested. Mean value of carboxyhemoglobin was 0.6 +/-0.5% in a smoke-free environment and 1.4 +/- 0.5% in a smoking environment (p <0.02). Mean values of flow-mediated dilation (FMD) were 12.6% +/- 7.8% in a smoke-free environment versus 6.8 +/- 7.8% in a smoking environment (p <0.01). On the contrary, nitroglycerin-induced vasodilation did not show any statistical difference (21 +/- 9.8% versus 23 +/-1.4%). Finally, the increase of carboxyhemoglobin was related statistically to the impairment of flow-mediated dilation (r = 0.51; p <0.002). Passive smoking impaired flow-mediated vasodilation in healthy never smokers in a smoking environment. The impairment was strongly related to carboxyhemoglobin level.

Nox2 Is Determinant for Ischemia-Induced Oxidative Stress and Arterial Vasodilatation: A Pilot Study in Patients With Hereditary Nox2 Deficiency

To the Editor: Reactive oxidant species (ROS) are a family of molecules that are involved in the modulation of arterial tone via rapid degradation of nitric oxide (NO).1 NADPH oxidase is a predominant cellular source of O2−-producing enzymes.1 Four homologs of gp91phox (Nox 2) named Nox1, Nox3, Nox4, and Nox5 have been identified as components of nonphagocyte-type NADPH oxidase.2 Recent studies performed in Nox1 and Nox2 knock-out animals suggested that these Nox isoforms may be implicated in controlling vascular function via modulation of NO bioactivity.3,4 X-chronic granulomatous disease (X-CGD) is a rare primary immunodeficiency affecting the innate immunologic system; it is caused by mutations in any of the 4 genes encoding subunits of the O2− generating NADPH oxidase, resulting in defective O2− generation and intracellular killing.5 We speculated that in patients with downregulation of NADPH oxidase the …

Microcirculatory Hemodynamics and Endothelial Dysfunction in Systemic Lupus Erythematosus

Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P<0.001). DSS (dyne/cm2) was significantly reduced in SLE patients (median, 18.5; range, 3.9 to 34.0 versus median 21.8; range, 14.1 to 58.7; P=0.037). A strong correlation between FMD and DSS, r(s)=0.65, P=0.01 was found. Postischemic RI was not significantly different between the 2 groups; however, there were significant differences in the power-frequency spectrums of the Doppler velocity envelopes (P<0.05). These data suggest that in SLE, altered structure and function of the forearm microcirculation contributes to impaired FMD through a reduction in shear stress stimulus.

Determinants of short-term variation in arterial flow-mediated dilatation in healthy young men

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

Effects of estradiol and medroxyprogesterone acetate on flow mediated dilation in young women

These preliminary data examine the acute affects of medroxyprogesterone acetate (MPA) alone and in combination with estradiol (E2) on conduit vessel responsiveness in young women. We suppressed endogenous estrogens and progesterone in three subjects using a gonadotropin - releasing hormone antagonist (GnRHa) for 14 days. On day 5 of GnRHa, two subjects were administered 0.2 mg E2 for 5 days (GnRH + E2), and on day 10 added 200 mg MPA for 5 days (GnRH + E2 + MPA). One subject was given MPA beginning on day 5 (GnRH + MPA) and added E2 on day 10 (GnRH + MPA + E2). On days 4, 9, and 14 of GnRHa administration, wall tracking of high resolution ultrasound images of the brachial artery were used during flow mediated dilation (FMD) and nitroglycerin (NTG) administration to test endothelial dependent and independent vasodilation, respectively. There was no difference in baseline brachial artery diameter, shear rate, or dilation to NTG between hormone treatments (p>0.05). During treatment with GnRHa + E2, FMD was greater than GnRHa alone (9.87 ± 2.81% vs. 5.65 ± 1.85%; p=.039). FMD decreased with GnRHa + E2 + MPA and was not significantly different from GnRHa alone (4.24 ± 0.02% vs. 5.65 ± 1.85%; p>0.05). In the subject treated with GnRHa + MPA, FMD was similar to GnRHa treatment alone. These preliminary data support previous evidence that E2 increases endothelial dependent vasodilation, and expand upon this finding to suggest that acute MPA administration attenuates the affects of E2 on the vasculature. Supported by the Medical Research Foundation of Oregon

Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function

Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers (representing these pathways) to brachial artery vasodilator function. We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P=0.001 and P=0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P=0.01). None of the other biomarkers was significantly related to the vascular function measures studied. In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.

Effect of acute sympathetic nervous system activation on flow-mediated dilation of brachial artery

We tested the hypothesis that flow-mediated dilation (FMD) of the brachial artery would be impaired by acute increases in sympathetic nervous system activity (SNA) in models where similar peak shear stress stimulus was achieved by varying the duration of forearm muscle ischemia. Eleven healthy young men were studied under four different conditions, each with its own control: lower body suction (LBS), cold pressor test (CPT), mental arithmetic task (MAT), and activation of muscle chemoreflex (MCR). The duration of ischemia before observation of FMD by ultrasound imaging was 5 min each for control, LBS, and CPT; 3 min for MAT; and 2-min for MCR. Peak shear rate was not different between control and any of the SNA conditions, although total shear in the first minute was reduced in MAT. MCR was the only condition in which brachial artery vasoconstriction was observed before forearm occlusion [4.38 (SD 0.53) vs. control 4.60 (SD 0.53) mm, P < 0.05]; however, diameter increased to the same absolute value as that of the control, so the percent FMD was greater for MCR [9.85 (SD 2.33) vs. control 5.29 (SD 1.50)%]. Blunting of the FMD response occurred only in the CPT model [1.51 (SD 1.20)%]. During SNA, the increase in plasma cortisol from baseline was significant only for MCR; the increase in plasma norepinephrine was significant for MCR, LBS, and CPT; and the increase in epinephrine was significant only for MCR. These results showed that the four models employed to achieve increases in SNA had different effects on baseline brachial artery diameter and that blunted FMD is not a general response to increased SNA.

ENDOTHELIAL DYSFUNCTION IN TRAUMA PATIENTS: A PRELIMINARY COMMUNICATION

Global ischemia, followed by reperfusion during resuscitation, leads to cellular damage by generating toxic reactive metabolites that includes, but is not exclusive to, superoxide radical. Superoxide decreases the bioavailability of nitric oxide (NO) via its reaction that yields peroxynitrite. The observation of decreased bioavailability of NO, and attenuated endothelium-dependent relaxation have been observed in animal models of trauma and resuscitation. However, it remains unknown whether endothelium-mediated vasodilation is impaired in humans after traumatic hemorrhage followed by crystalloid resuscitation. Based on these previously established precepts, we hypothesized that endothelium-dependent relaxation is impaired in trauma patients despite adequate fluid resuscitation with crystalloid solutions. Baseline characteristics such as age, body mass index, and blood pressure being similar in both groups, NO-mediated, endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was examined in resuscitated trauma victims (n = 13) and compared in normal controls (n = 12). Baseline brachial artery diameter, endothelium-dependent FMD induced by reactive hyperemia and endothelium-independent dilation induced by administration of sublingual nitroglycerin were measured. Brachial artery diameter measured at baseline in trauma patients and in control subjects were not dissimilar. In conclusion, brachial artery FMD, a surrogate for NO-mediated endothelial function, was significantly impaired in trauma patients despite fluid resuscitation resulting in stable hemodynamics (0.8 +/- 1.7 mm vs. 5.7 +/- 0.8 mm, respectively; P < 0.05) However, endothelium-independent dilation induced by nitroglycerin was not significantly different between trauma patients and controls.

Improvement in Endothelial Structure and Function after Metformin Treatment in Young Normal-Weight Women with Polycystic Ovary Syndrome: Results of a 6-Month Study

Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients. The objective of this study was to evaluate the effects of 6 months of metformin administration on endothelial structure and function in women with PCOS. This was a prospective, baseline-controlled, clinical study. The study was performed at University Federico II (Naples, Italy). Thirty young normal-weight women with PCOS without additional metabolic or cardiovascular diseases were studied. Metformin (850 mg daily) was administered for 6 months. The main outcome measures were complete hormonal profile, including total testosterone, SHBG, dehydroepiandrosterone sulfate, prolactin, and gonadotropin levels; serum insulin and glucose levels during a 75-g 2-h oral glucose tolerance test; plasma endothelin-1 concentrations (picomoles per liter +/- sd); serum lipid profile; brachial artery baseline diameter (millimeters +/- sd), diameter after reactive hyperemia (millimeters +/- sd), and flow-mediated dilation (percentage +/- sd); and the intima media thickness (millimeters +/- sd) on both common carotid arteries. After treatment, SHBG levels and the free androgen index changed significantly (P < 0.001). High-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly (P < 0.001) increased, whereas low-density lipoproteins and plasma endothelin-1 levels were significantly (P < 0.001) reduced. No other change was found in any of the biochemical parameters evaluated. A significant difference was observed in brachial artery baseline diameter (3.24 +/- 0.30 vs. 3.0 +/- 0.30), flow-mediated dilation (14.30 +/- 1.90 vs. 15.70 +/- 1.50) (P < 0.01, each), diameter after reactive hyperemia (3.70 +/- 0.30 vs. 3.55 +/- 0.10) (P < 0.05), and intima media thickness (0.53 +/- 0.09 vs. 0.40 +/- 0.07) (P < 0.001) after metformin treatment in comparison with baseline values. A 6-month course of metformin improves endothelial structure and function in young, normal-weight women with PCOS.

Improved Endothelium Dependent Vasodilation in Endurance Athletes and Its Relation With ACE I/D Polymorphism

Aerobic exercise enhances endothelium-dependent vasodilation in healthy individuals. It is thought that exercise increases nitric oxide (NO) production and decreases NO inactivation, leading to an increase in NO bioavailability. Angiotensin II and NO have important roles in maintaining vascular tone. There are polymorphisms of the angiotensin converting enzyme (ACE) gene and the presence of the deletion (D) allele has been associated with higher concentrations of circulating and tissue ACE. In this study, the relationship between endothelial function and ACE gene polymorphisms was investigated in athletes and sedentary subjects. The study group comprised 56 endurance athletes and 46 sedentary subjects who underwent brachial artery ultrasonographic examination. ACE insertion (I) and D allele frequencies were analyzed in all patients. Baseline brachial artery diameter and resting blood flow were similar in athletes and controls (p > 0.05). The flow-mediated dilation (FMD) was 8.48+/-3.65% in athletes and 5.16+/-2.5% in controls (p = 0.0001). FMD was significantly different between ACE genotypes in the athletes (p < 0.0001): it was higher in ACE II (10.5+/-1.6%) subjects than in the DI (8.4+/-2.3%) or DD (7+/-1.2%) subgroups. Regular isotonic exercise can improve endothelium-dependent vasodilation especially in those with the ACE II genotype.

Peripheral Vascular Endothelial Function in Essential Hyperhidrosis

Essential hyperhidrosis, a disorder of the eccrine sweat glands, is associated with sympathetic overactivity and the aim of the present study was to determine endothelium-dependent vasodilator function in patients with this condition. Using high-resolution ultrasound, the diameter of the brachial artery at rest and during reactive hyperemia (flow-mediated dilatation, %FMD endothelial-dependent stimulus to vasodilatation), as well as after sublingual administration of nitroglycerin (%NTG endothelium-independent vasodilatation) was measured in 18 subjects (mean age 27+/-5 years) with essential hyperhidrosis and 24 healthy control subjects (mean age 29+/-5 years). Baseline brachial artery diameter and FMD were comparable in both groups (BAD: 4.1+/-0.7 mm vs 4.3+/-0.5 mm (control), p = 0.8; FMD: 5.6+/-1.9% vs 6.7+/-2.2%, p=0.1). The time-averaged flow velocity during peak reactive hyperemia was similar in the 2 groups (75+/-11 cm/s vs 72+/-10 cm/s, p = 0.5), nor did NTG-induced dilatation in the patients with essential hyperhidrosis differ significantly from that in healthy control subjects (12.8+/-2.7% vs 14.0+/-3.6%, p = 0.3). These findings suggest that endothelium-dependent dilatation of large conduit arteries is preserved in essential hyperhidrosis and it seems to be a localized disorder of the eccrine sweat glands rather than a generalized disorder involving vascular endothelium.

Continuous Therapy with Nitroglycerin Impairs Endothelium-Dependent Vasodilation but Does Not Cause Tolerance in Conductance Arteries

We investigated in healthy humans whether continuous therapy with organic nitrates impairs conduit artery responses to nitroglycerin (GTN) as well as its effects on endothelium-dependent vasodilation. Sixteen young male volunteers were randomized to continuous treatment with either transdermal GTN (0.6 mg/h/24 hrs for 6 days) or no therapy. Endothelium-dependent (flow-mediated) dilatation (FMD) and endothelium-independent (GTN-mediated) dilatation (GMD) of the brachial artery were evaluated before randomization (session 1), after six days of transdermal GTN treatment (session 2), and three hours after withdrawal of transdermal GTN (session 3). In the GTN group, on session 1, 0.4 mg sublingual GTN increased resting brachial artery diameter from 0.40 +/- 0.03 to 0.45 +/- 0.03 cm (P < 0.01). At the time of session 2, this GTN-mediated vasodilation remained unchanged at baseline (0.47 +/- 0.04 cm), with no further significant dilatation in response to either stimulus. On session 3, three hours after patch removal, baseline brachial artery diameter and GMD returned to pretreatment values, but FMD remained blunted (session 1: 8.7 +/- 2.5; session 3: 4.1 +/- 1.7%, P < 0.05). There was no change in these variables in the control group. Our data demonstrate that continuous GTN therapy impairs endothelium-dependent vasodilation in conduit arteries yet does not induce nitrate tolerance.

Comparison of B-mode and echo tracking methods of assessing flow-mediated dilation

The aim of this study was to compare B-mode and echo tracking methods to assess endothelium-dependent flow-mediated dilation (FMD). Baseline brachial artery diameter, 60-s post cuff release diameter and FMD percent were assessed in 17 normal, healthy individuals using both techniques. Mean values for baseline diameter, 60-s diameter and FMD for M-mode were 3.83 ± 0.69 mm, 4.06 ± 0.66 mm and 6.35 ± 3.98%, respectively. Mean values for baseline diameter, 60-s diameter and FMD for B-mode were 3.75 ± 0.65 mm, 4.00 ± 0.63 mm and 6.91 ± 2.85%, respectively. Results, as displayed by Bland-Altman graphs, indicate a strong agreement between B-mode and echo tracking methods of assessing brachial artery diameter changes via FMD. (E-mail: akelly@stphc.com)

Endothelial Dysfunction in Young Women with Polycystic Ovary Syndrome: Relationship with Insulin Resistance and Low-Grade Chronic Inflammation

Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors. Cardiovascular morbidity is elevated even in young women with PCOS. Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP) and endothelial dysfunction have recently been linked to development of atherosclerosis. We compared high-sensitivity (hs)CRP concentrations and endothelium dysfunction in 37 women with PCOS and 25 control subjects matched as a group for age and body mass index (BMI). Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli. Serum LH, testosterone, androstenedione, and fasting insulin levels were significantly higher in the PCOS group than the control group. The PCOS group was more insulin resistant than age- and BMI-matched control women. CRP concentrations were higher in PCOS women than the healthy control group (0.25 vs. 0.09 mg/dl). hsCRP concentrations were correlated with BMI, insulin sensitivity indices (homeostasis model assessment and quantitative insulin sensitivity check index), and endothelium-dependent vasodilation. The groups were well matched for baseline brachial artery diameter. There was a significant difference in endothelium-dependent (flow- mediated dilation) and endothelium-independent (sublingual nitroglycerin) vascular responses between the women with PCOS and the normal healthy control group (P = 0.002 and P = 0.01, respectively). Endothelium-dependent vasodilation was correlated with hsCRP concentrations and insulin resistance. In conclusion, this study is the first to demonstrate increased levels of hsCRP, endothelial dysfunction, and the relation with insulin resistance in young and normal-weight women with PCOS. Clinical strategies aimed at reducing insulin resistance may prevent early atherosclerosis in women with PCOS.

Effect of Smoking on Endothelial Function and Wall Thickness of Brachial Artery

Impaired flow mediated dilatation (FMD) and increased wall thickness (WT) of the brachial artery have been associated with atherosclerosis and its risk factors. In this study we sought to determine brachial artery wall thickness in chronic smokers and the instantaneous effect of smoking on brachial artery endothelium dependent vasodilator function in smokers and non-smokers. Using a high-resolution ultrasound, WT of posterior brachial artery wall, the diameter of brachial artery at rest and during reactive hyperemia (FMD %), as well as after sublingual administration of nitroglycerine (nitroglycerine mediated dilatation (NMD) %) was measured in 20 smokers and 20 non-smokers. Wall thickness (WT) of the posterior brachial artery wall and the wall index (WI) were greater in smokers than non-smokers. The baseline brachial artery diameter was comparable in smokers and non-smokers. Flow mediated dilation (FMD) was found to be less in smokers than non-smokers. The NMD in smokers also did not differ significantly from that in non-smokers. Flow mediated dilation significantly reduced after smoking compared to baseline in both groups. However, NMD remained unchanged after smoking in both groups. Increased WT and impaired endothelium-dependent dilatation of brachial artery suggests that cigarette smoking disrupts vessel wall morphology long before atherosclerosis is manifest.

Comparative effects of ramipril, sildenafil, or both on endothelial function in patients with chronic heart failure

Endothelial dysfunction may contribute to the pathogenesis of hypertension and heart failure. Angiotensin converting enzyme (ACE) inhibitors and phosphodiesterase type 5 (PDE5) inhibitors have been reported to individually enhance endothelium-dependent vasodilation in chronic heart failure (CHF). ACE inhibitors increase bioavailability of endothelium-derived nitric oxide whereas PDE5 inhibitors augment nitric oxide-mediated cGMP signaling in vascular smooth muscle. We hypothesized that these 2 classes of agents may have additive effects in CHF. 64 patients with NYHA Class 2-3 CHF (mean age 56 yrs, LVEF 23%) were enrolled in a prospective, randomized, double-blind trial to compare the effects of a single oral dose of ramipril 10 mg, sildenafil 50 mg, their combination or placebo on flow-mediated dilation (FMD, %) determined by high-resolution ultrasonography of the brachial artery over 4-hours. Background ACE inhibitors were stopped 72 hours before the study. Baseline clinical characteristics, baseline brachial artery diameter, and baseline FMD of the 4 treatment groups were similar. Responses to study drug shown in Figure. Placebo did not change FMD over 4 hours. Ramipril tended to increase FMD when compared with placebo at 4 hours (p=0.11). Sildenafil significantly increased FMD when compared with placebo at 1 and 2 hours (p<0.05). The combination of ramipril and sildenafil had additive effects which significantly increased FMD at 1, 2, and 4 hours when compared with placebo (p<0.05). Sildenafil did not augment the acute blood pressure lowering effects of ramipril. All study drugs were well-tolerated. Combined administration of an ACE inhibitor and a PDE5 inhibitor had additive effects on FMD but not blood pressure. These agents were well-tolerated and significantly improved endothelial function over a 4 hour period in patients with CHF.