Brachial Artery Responses Research Articles

Impaired endothelial function in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) patients suffer from excess cardiac deaths due to accelerated atherosclerosis. Endothelial dysfunction is a marker of early atherosclerosis. We tested the hypothesis that SLE patients have impaired endothelial function and assessed the relationship between endothelial function and clinical outcome over the subsequent five years. Thirty-six female SLE patients were compared with 22 healthy age and sex matched controls. Endothelial dependent vasodilatation (EDD) was assessed at the brachial artery in response to shear stress. Endothelium-independent dilatation induced by glyceryl trinitrate was also measured. Patients were followed for up to five years and the development of damage in the cardiovascular and other systems recorded. SLE patients showed significantly impaired endothelial function (median EDD 5.6%, IQR 3.1-7.2%) compared with healthy controls (median EDD 8.0%, IQR 6.3-9.3%; P = 0.001). Endothelium independent dilatation did not differ between the two groups. Endothelial function was significantly worse in postmenopausal compared with premenopausal women (median EDD 6.6%, IQR 3.9-7.8% versus 3.1%, IQR 2.6-5.1%; P = 0.016). Total cholesterol was inversely correlated with endothelial function in SLE patients (Spearman correlation r = -0.422, P = 0.025). There was no relationship between endothelial function and the development of damage in any organ system, including the cardiovascular system during patient follow-up. Patients with SLE have impaired endothelial Lupus (2007) 16, 84-88.

Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults

In the present study, we investigated whether measures of brachial artery reactivity were associated with the presence and extent of subclinical coronary atherosclerosis in asymptomatic adults. Electron beam computed tomography was employed to assess the presence and quantity of CAC (coronary artery calcium) in 441 participants (mean age, 61 years; 49% men) without prior history of CHD (coronary heart disease) or stroke, and CAC score was calculated using the method described by Agatston and co-workers [(1990) J. Am. Coll. Cardiol. 15, 827-832] High-resolution ultrasound was employed to measure BAD (brachial artery diameter), FMD (flow-mediated dilatation) and NMD (nitroglycerine-mediated dilatation). CAC score and FMD were log-transformed after adding 1 to reduce skewness. Multivariable logistic and linear regression models based on generalized estimating equations were used to assess whether BAD, FMD and NMD were each independently associated with the presence and quantity of CAC after adjustment for CHD risk factors and use of statin and hypertension medication. CAC was detectable in 64% of participants. After adjustment for age and sex, FMD was not correlated (r=-0.06; P=0.27), BAD was positively correlated (r=0.16; P=0.004) and NMD was inversely correlated in a borderline significant manner (r=-0.10; P=0.084) with log(CAC+1). In multivariable logistic regression analyses, FMD was not associated, whereas higher BAD (P=0.021) and lower NMD (P=0.030) were independently associated with the presence of CAC. In multivariable linear regression analyses, higher BAD (P=0.004) and lower NMD (P=0.016), but not FMD, were independently associated with log(CAC+1). We conclude that greater diameter of the brachial artery and lower vasodilator response to nitroglycerine, but not FMD, are associated with subclinical coronary atherosclerosis.

Effects of selective and non‐selective cyclo‐oxygenase inhibition on endothelial function in patients with rheumatoid arthritis

Objectives: Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk that has been attributed to endothelial dysfunction and inflammation. Non‐steroidal anti‐inflammatory drugs (NSAIDs) and cyclo‐oxygenase (COX)‐2 inhibitors have been shown in some studies to improve endothelial function in subjects without RA. The aim of this study was to investigate the effects of COX inhibition on endothelial function in patients with RA.Methods: Patients with RA (n = 37) were randomized to receive a 2‐week course of either indomethacin (75 mg bd), rofecoxib (12.5 mg bd), or placebo in a double‐blind study. Endothelial function was measured using flow‐mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia. Arterial stiffness was also assessed using pulse wave analysis (PWA) through the measurement of the aortic augmentation index (AIx). Measurements of vascular function and inflammatory markers were taken before and at the end of the treatment period.Results: There were no significant differences in changes in FMD, AIx, blood pressure (BP), serum creatinine, erythrocyte sedimentation rate (ESR), or high‐sensitivity C‐reactive protein (hsCRP) between groups. However, compared with the other treatment groups, there was a tendency for systolic BP to decrease in the placebo group (p = 0.063) and for creatinine to increase in the indomethacin and rofecoxib groups after treatment (p = 0.054).Conclusions: This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA.

Residual adverse changes in arterial endothelial function and LDL oxidation after a mild systemic inflammation induced by influenza vaccination

Background. Several clinical studies have suggested possible increase in cardiovascular risk during and in the first weeks after an acute inflammatory disease. Using influenza vaccine as inflammatory stimulus, we investigated whether arterial endothelial dysfunction could persist beyond the inflammatory state, and whether amplified oxidative modification of low‐density lipoprotein (LDL) accompanies this vascular disturbance.Methods and subjects. The brachial artery responses to hyperemia (flow‐mediated dilatation (FMD), and to sublingual glyceryl trinitrate (GTN), and the carotid intima‐media thickness were assessed by external ultrasound in eight healthy male volunteers (age 17–30 y) before, and 2 and 14 days after intramuscular administration of influenza vaccine. Plasma levels of high‐sensitivity C‐reactive protein (CRP), fibrinogen, cyclic guanosine monophosphate (cGMP), and antibodies against oxidized LDL (oxLDL) were measured at each time point. Data are means±standard errors of the mean (SEM).Results. Influenza vaccination caused a slight elevation in CRP (from 0.5±0.1 at baseline, to 2±0.6 mg/L, P = 0.01) and fibrinogen (from 2.3±0.1 to 2.7±0.1 g/L, P = 0.01) at 2 days, which completely resolved at 14 days (CRP: 0.6±0.2 mg/L, P = 0.9, and fibrinogen: 2.3±0.1 g/L, P = 0.8 versus baseline). OxLDL antibody levels rose significantly at 2 days (from 1±0.1 at baseline to 2±0.4, P = 0.04), and remained elevated at 14 days (1.7±0.3, P = 0.1 versus baseline). FMD of the brachial artery decreased at 2 days (from 8.3±1.2% at baseline, to 5.4±1%, P = 0.05) with a further decrease at 14 days (4.9±0.8%, P = 0.03 versus baseline). The dilatory responses to GTN and the carotid IMT remained unchanged throughout the study period (P>0.5).Conclusion. Abnormalities in arterial function and LDL oxidation may persist for at least 2 weeks after a slight inflammatory reaction induced by influenza vaccination. These could explain in part the earlier reported increase in cardiovascular risk during the first weeks after an acute inflammatory disorder.

Cyclic guanosine monophosphate phosphodiesterase-5 inhibitor promotes an endothelium NO-dependent-like vasodilation in patients with refractory hypertension

The nitric oxide/cyclic-guanosine 3′,5′-monophosphate signaling cascade plays an essential role in cardiovascular homeostasis but its involvement in the pathophysiology of refractory hypertension is unclear. The acute vasodilatory effect of a single oral dose of a phosphodiesterase-5 inhibitor (sildenafil citrate) on the brachial artery dilatation was evaluated in 25 normal healthy volunteers (NL) and in 25 refractory hypertensive patients (RH). Endothelial and vascular smooth muscle functions were assessed two times. First, the brachial artery response to endothelium-dependent (flow-mediated dilatation [FMD]) and independent (glyceryl trinitrate [GTN]) stimuli was examined. The FMD in NL was 14.2 ± 3.2% compared to 10.3 ± 3.5% in RH ( P < 0.001) and the GTN-induced responses were 23.5 ± 6.3 in NL compared to 18.4 ± 5.7% in RH ( P < 0.001). Two weeks later, the brachial artery responses to FMD were determined before and after the administration of sildenafil citrate. Sildenafil caused a significant, slow and progressive dilatation of the brachial artery until 45 min after administration (4.7 ± 3.0%, 6.7 ± 3.0% and 9.4 ± 3.9% after 15′, 30′ and 45′, respectively, in RH and 3.7 ± 1.9%, 7.4 ± 2.7% and 10.1 ± 3.0%, respectively, in NL). A second FMD stimulus, applied 45 min after ingesting 50 mg of sildenafil resulted in an additional significant increase in the vasodilatory response (from 9.4 ± 3.9% to 13.0 ± 4.0% in RH; P < 0.001 and from 10.1 ± 3.0 to 14.6 ± 4.1 in NL; P < 0.001), but this was still significantly less than the response to GTN. Sildenafil citrate caused brachial artery vasodilatation similar to that caused by NO released during FMD in patients with refractory hypertension.

Effect of Postconditioning on Coronary Blood Flow Velocity and Endothelial Function and LV Recovery After Myocardial Infarction

Postconditioning is a novel approach to myocardial protection during ischemia reperfusion. Our study observed the effect of postconditioning on coronary blood flow velocity and endothelial function in patients who underwent emergency percutaneous coronary intervention (PCI). Ninety-four patients with their first acute myocardial infarction who underwent revascularization within 12 hours of onset by primary PCI were recruited in the study. All the patients were randomized to two groups, IR group (PCI without postconditioning) and Postcond group (PCI with postconditioning). Corrected TIMI frame count (CTFC) was used to evaluate velocity of coronary blood after PCI. Creatine phosphokinase (CK), CK-MB, and malondialdehyde (MDA) were measured before and after PCI. Arterial endothelial function was studied noninvasively by examination of brachial artery responses to endothelium-dependent and endothelium-independent stimuli by echo Doppler technique. Wall motion score index (WMSI) was assessed by two-dimensional echocardiography before and 8 weeks after angioplasty. There were no significant differences between the two groups with regard to age, sex, presence of angiographically visible collaterals, and elapsed time from the onset of symptoms until perfusion. Patients with postconditioning had much faster CTFC than patients without postconditioning (25.38 +/- 5.35 vs 29.23 +/- 5.54). After 8 weeks, the WMSI improved significantly in both groups, but the DeltaWMSI in Postcond group was significantly larger than that of IR group (1.20 +/- 0.30 vs 1.04 +/- 0.36, P < 0.05). There was a significant negative correlation between DeltaWMSI and CTFC in IR group and Postcond group (r = -0.9032, P < 0.01; r = -0.7884, P < 0.01). The peaks of CK and CK-MB of Postcond group were much lower than that of IR group (1236.57 +/- 813.21 U/L vs 1697.36 +/- 965.74 U/L; 116.92 +/- 75.83 U/L vs 172.41 +/- 92.64 U/L), and MDA-reactive products were significantly lower than that in the IR group at any same time after PCI. All patients with acute myocardial infarction had a depressed endothelium-dependent vasodilation function, while the endothelium-dependent vasodilation function was improved in Postcond group. Postconditioning is a simple, operative procedure for salvaging the coronary endothelial function and cardiomyocyte. It could be used widely in clinic and to better the prognosis of acute myocardial infarction.

Decreased nitrate-mediated dilatation in patients with coronary artery ectasia: an ultrasonographic evaluation of brachial artery

Coronary artery ectasia has been defined as localized or diffuse nonobstructive lesions of the epicardial coronary arteries with a luminal dilation exceeding the 1.5-fold of normal adjacent segment or vessel diameter. Although coronary artery disease is supposed to be responsible for more than 50% of coronary ectasia, the precise pathology of coronary artery ectasia is not clearly understood. The brachial artery ultrasound test for flow-mediated endothelial-dependent vasodilatory function includes administration of sublingual nitrates to examine the vasodilating effect of an exogenous source of nitric oxide. In the present study, we aimed to compare flow-mediated and nitrate-mediated responses of brachial artery in patients with coronary artery ectasia and patients with coronary artery disease. Thirty-six consecutive patients with coronary artery ectasia in combination with coronary artery disease and 42 age-matched and sex-matched patients with coronary artery disease alone were included in the study. Flow-mediated and nitrate-mediated dilatations were measured in all patients using a high-resolution B-mode ultrasonographic system. Baseline brachial artery diameters in patients with coronary artery ectasia were not statistically different from those in patients with coronary artery disease (4.2+/-0.6 vs. 4.0+/-0.6 mm, respectively, P=0.16). Although the forearm flow-mediated dilatation of the patients with coronary artery ectasia did not differ from that of patients with coronary artery disease alone (5.5+/-3.8 vs. 4.8+/-3.6%, respectively, P=0.41), nitrate-mediated dilatation was significantly lower than that of patients with coronary artery disease alone (7.9+/-5.2 vs. 10.9+/-5.4%, respectively, P=0.02). We have shown that patients with coronary artery ectasia have decreased nitrate-mediated response of brachial artery compared with patients with coronary artery disease alone, suggesting more severe dysfunction or, possibly, destruction of the media layer in coronary artery ectasia than in coronary artery disease.

Vascular Function in Individuals with a Predisposition for Type 2 Diabetes

Alterations in vascular endothelial function are correlated to cardiovascular disease and can be detected in individuals prior to the development of heart or vascular diseases. Reduced vascular function has been found in type 2 diabetics but has not been study in those who are at increased risk for disease due to family history. PURPOSE: To determine if young individuals with a family history of type 2 diabetes (FH+) have reduced vascular function compared to individuals who have no history of type 2 diabetes in their family (FH-). The FH+ group was defined as individuals who had a parent who was diagnosed with type 2 diabetes after the age of 35 years old (n = 12). Individuals who did not have a grandparent or parent with type 2 diabetes were placed in the control group (n = 13). METHODS: Male and females between the ages of 18–30 years old, who did not perform routine aerobic exercise, smoke, or who were obese (BMI < 32) were recruited to participate in this study. Vascular function was assessed by measuring flow mediated dilation (FMD) in the brachial artery in response to 5 minutes of cuff ischemia using quantitative Doppler Ultrasound. RESULTS: Comparisons between groups indicated that FMD trended (p = 0.100) towards being reduced in the FH+ group, however, there was a significant difference between groups on age (28 ± 4 vs. 23 ± 3 for FH+ vs. FH-, respectively; p = 0.003). Thus, an ANCO VA was used to compare differences between groups on FMD. There was no significant difference in FMD between genders, therefore, males and females were combined to determine differences between groups on FMD. FMD was not significantly different between groups after controlling for differences in age (6.6 ±3.7 vs. 9.0 ±3.6 for FH+ vs. FH-, respectively; p = 0.293). CONCLUSIONS: Significant reductions in FMD in healthy, young individuals with a family history of type 2 diabetes compared to those with no family history were not found. The data trends towards FH+ individuals having reduced vascular function; however, due to a small sample size, we may have limited power to detect these differences. Thus, further data collection is necessary to completely elucidate the effects of family history of type 2 diabetes on vascular function.

Is endothelial function impaired in erectile dysfunction patients?

Erectile dysfunction (ED) and vascular disease are thought to be linked at the level of the endothelium. Endothelial dysfunction, resulting in the inability of the smooth muscle cells lining the arterioles to relax, prevents vasodilatation. Likewise, penile erection depends on the relaxation of smooth muscle in the corpus cavernosum and the wall of small arteries. The aim was to assess the systemic vascular function in patients with ED. In all, 32 ED patients diagnosed with Doppler Ultrasound and the International Index of Erectile Function-5-item questionnaire and 25 healthy men as a control group enrolled to the study. They all underwent the tests including serum glucose and lipid levels. Echocardiography and exercise stress test was performed routinely. Baseline demographics (body mass index, heart rate and blood pressures), fasting glucose and lipid levels were not significantly different between ED and control groups. Endothelial-dependent brachial artery flow-mediated vasodilatation and brachial artery response to 0.4 mg nitroglycerine (NTG) were measured. Participants were negative on exercise stress test, and echocardiographic parameters including ejection fraction were similar. Endothelial-dependent brachial artery percent diameter change with flow-mediated dilatation (6.01+/-2.9 vs 12.3+/-3.5) and brachial artery response to NTG (12.8+/-4.2 vs 17.8+/-5.2) were significantly different between groups (P<0.001). We found that endothelial function was impaired in ED patients with no apparent cardiovascular disease and diabetes mellitus. This impaired function might be explained by the abnormality in systemic nitric oxide-cyclic guanosine monophosphate vasodilator system and suggest that ED and vascular disease may be linked at the level of the endothelium.

Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) exhibit elevated levels of serum C-reactive protein (CRP) and impaired endothelium dysfunction which are directly correlated with insulin resistance. Because rosiglitazone improves insulin sensitivity, we tested whether rosiglitazone treatment ameliorates high-sensitivity (hs)CRP levels and endothelial dysfunction in these patients. Thirty-one women with PCOS were recruited (mean age, 24.7+/-3.9 (s.e.) years; mean body mass index (BMI), 25.6+/-3.2 kg/m2). All women were treated with 4 mg rosiglitazone daily for 12 months. Serum levels of testosterone, LH, FSH, sex hormone-binding globulin (SHBG), insulin and hsCRP were measured. The BMI, hirsutism scores and insulin sensitivity indices were calculated before and after treatment. Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli before and after treatment. After treatment with rosigitazone there were significant decreases in serum testosterone (91.2+/-37.5 vs 56.1+/-21.8 ng/dl; P < 0.01) and fasting insulin concentrations (12.5+/-7.6 vs 8.75+/-4.03 microU/ml; P = 0.015). Insulin resistance indices were significantly improved after rosiglitazone treatment (P < 0.05). There were no significant changes in BMI, waist circumference, serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, FSH and LH levels. Hirsutism score was decreased significantly after treatment (10.8+/-1.8 vs 7.6+/-1.7; P < 0.05). Twenty-four of the women reverted to regular menstrual cycles. Levels of SHBG increased significantly after treatment (28.7+/-8.7 vs 48.4+/-11.2 nmol/l; P < 0.01). Serum hsCRP levels were decreased significantly after rosiglitazone treatment (0.25+/-0.1 vs 0.09+/-0.02 mg/dl; P = 0.006). There was also significant improvement in endothelium-dependent vascular responses after rosiglitazone treatment (9.9+/-3.9 vs 16.4+/-5.1%; P < 0.01). We conclude that rosiglitazone treatment improves insulin sensitivity in women with PCOS. It also decreases androgen production without significant weight gain. More importantly, it has beneficial effects on endothelial dysfunction and low-grade chronic inflammation in normal weight young women with PCOS.

Persistent endothelial dysfunction is related to elevated C-reactive protein (CRP) levels in Type II diabetic patients after acute myocardial infarction

The atherosclerotic process is an ongoing dynamic and progressive state arising from endothelial dysfunction and inflammation. Although suffering from an acute coronary artery disease, patients with Type II diabetes have a poor outcome compared with non-diabetic patients, which may only partly be explained by traditional risk factors. Our purpose was to compare non-traditional risk factors, such as endothelial function, C-reactive protein (CRP) and adiponectin, in Type II diabetic and non-diabetic patients following AMI (acute myocardial infarction). Twenty Type II diabetic patients were compared with 25 non-diabetic patients at baseline (1-3 days from the onset of chest pain) and at 60 days follow-up after an AMI. Using high-resolution ultrasound, brachial artery responses to FMD (flow-mediated vasodilatation; endothelium-dependent vasodilatation) and NTG (nitroglycerine-induced vasodilatation; endothelium-independent vasodilatation) were measured. Plasma levels of CRP and adiponectin were measured by ELISA. At baseline, FMD (1.9 compared with 3.2%; P=0.22) and CRP levels (6.95 compared with. 5.51 mg/l; P=0.40) did not differ between Type II diabetic and non-diabetic patients, whereas adiponectin levels were lower in Type II diabetic patients (2.8 compared with 5.0 ng/ml; P<0.05). At 60 days follow-up, there were significant differences in FMD (1.5 compared with 4.1%; P<0.02), CRP (4.23 compared with 1.46 mg/ml; P<0.01) and adiponectin (3.3 compared with 5.3 ng/ml; P<0.05) levels between Type II diabetic and non-diabetic patients. In contrast, NTG responses improved in both groups between baseline and follow-up (Type II diabetic patients, 9.7 compared with 13.2% respectively, P<0.05; non-diabetic patients, 7.9 compared with 12.4% respectively, P<0.01). These results show a persistent endothelium-dependent dysfunction and inflammatory activity in patients with Type II diabetes, but not in non-diabetic patients, after AMI. These findings may, in part explain, the poor outcome in coronary artery disease seen in Type II diabetes.

Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease†

Nonalcoholic fatty liver disease (NAFLD) is consistently associated with features of the metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the vasodilatory response of the brachial artery in response to ischemia (a test of endothelial function) (FMV) as well as cardiovascular risk profile in 52 NAFLD cases and 28 age- and sex-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33% +/- 5.93% in NAFLD versus 12.22% +/- 5.05% in controls (P < .0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%) (P = .010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r = -0.243; P = .030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (OR, 6.7; 95% CI, 1.26-36.1), after adjustment for age, sex, body mass index, and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted OR, 6.8; 95% CI, 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. In conclusion, our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well recognized in NAFLD patients, but the large majority of cases might experience cardiovascular disease in the long term, indirectly limiting the burden of liver failure.

Endothelial Dysfunction in Patients With Chronic Periodontitis and Its Improvement After Initial Periodontal Therapy

Recent epidemiological data suggested that there is a relationship between periodontal health and atherosclerotic coronary heart disease. Although hypothetical models were proposed, the exact mechanism of this association has not been clarified. The aim of this study is to investigate whether there is an endothelial dysfunction in patients with chronic periodontitis and, if present, whether recovery is possible with therapy. The study groups consisted of 28 patients (mean age: 45.5 +/- 8.6 years) with chronic periodontitis and without any atherosclerotic vascular disease, and 26 healthy controls (mean age: 43.7 +/- 6.8 years). Cardiovascular risk factors were investigated in both groups. Brachial artery responses to reactive hyperemia (endothelium-dependent dilatation [EDD]) and sublingual nitroglycerin (endothelium-independent dilatation [EID]) were measured using high-resolution vascular ultrasound in both groups. Measurements were taken before and after initial periodontal therapy in the periodontal patients. There was no significant difference between the groups with regard to cardiovascular risk factors. In the baseline measurements, EDD and EID were significantly impaired in patients with chronic periodontitis when compared with the controls (8.4% +/- 4.0% versus 19.4% +/- 8.1%, P<0.0001; 13.3% +/- 6.3% versus 29.5% +/- 10.0%, P<0.0001 for EDD and EID, respectively). After non-surgical periodontal therapy, EDD and EID improved significantly (from 8.4% +/- 4.0% to 17.7% +/- 5.7%, P<0.0001; and from 13.3% +/- 6.3% to 24.9% +/- 7.3%, P<0.0001 for FMD and EID, respectively). The EDD and EID changes in the controls were insignificant. This study showed that endothelial functions were impaired in patients with chronic periodontitis and that they improve following initial periodontal therapy.

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.

Impaired brachial endothelial function in patients with primary anti-phospholipid syndrome

Although the precise pathophysiology of thrombosis is unknown in primary anti-phospholipid syndrome (PAPS), it is assumed that autoantibodies developed against endothelial cells and platelets might be one of the primary mechanisms. However, whether interaction between autoantibodies and endothelium leads to an impaired vasodilator response has not been investigated yet. In this study, we aimed to investigate the endothelial functions in patients with PAPS. Thirty-one patients with PAPS (22 female, nine male, mean age: 34.6+/-8.9 years) and 27 age- and sex-matched, healthy controls were included in the study. Brachial artery responses to reactive hyperaemia (endothelium-dependent dilatation) [EDD] and sublingual nitroglycerine (endothelium-independent dilatation) [EID] were measured by using high-resolution vascular ultrasound both in patients with PAPS and in the controls. The results were expressed as percentage of change in baseline values. Regarding cardiovascular risk factors, there was no significant difference between the two groups. EDD in patients with PAPS was significantly lower than those of controls (6.9+/-4.9 vs. 14.8+/-4.1%; p<0.0001). EID measurements were not significantly different between the groups. In the PAPS group, EDD in patients with arterial involvement (17 patients) was significantly lower than those of patients with venous involvement (12 patients) (4.6+/-3.9 vs. 7.4+/-4.1%; p = 0.02). This study showed that endothelial functions determined by using brachial artery ultrasound were impaired in patients with PAPS, and this was more prominent in the subgroup of patients with arterial involvement compared to patients with venous involvement.

Noninvasive ultrasound assessment of maternal vascular reactivity during pregnancy: a longitudinal study.

To estimate the pattern of maternal vascular reactivity in normal and high-risk pregnancies using postocclusion brachial artery diameter. Prospective, longitudinal study of 44 low-risk singleton pregnancies and 28 high-risk pregnancies, defined as pregestational diabetes (n = 7), chronic hypertension (n = 4), twin gestation (n = 6), and a previous history of preeclampsia, fetal growth restriction, or vascular disease (n = 11). During each trimester, the brachial artery was ultrasonographically imaged above the antecubital crease. Brachial artery diameter was measured and then occluded for 5 minutes using an inflated blood pressure cuff. Changes in brachial artery diameter at 1 minute after occlusion were expressed as percent change from baseline and were compared across trimesters for both low-risk and high-risk groups, adjusting for potential confounders. Brachial artery diameters were increased after occlusion in every trimester for all groups. For low-risk women, the degree of postocclusion brachial artery dilatation was similar in the first and second trimesters, but was lower in the third trimester. In the first trimester, low-risk women had significantly greater brachial artery diameter increases at 1 minute compared with high-risk singleton pregnancies (19% compared with 12%; P <.001). Compared with low-risk women, pregnancies complicated by pregestational diabetes or chronic hypertension had significantly smaller 1-minute brachial artery diameter changes in the first trimester (7.0 +/- 0.5%, P <.001), whereas twin gestations had greater brachial artery responses (22.9 +/- 6.0%, P <.001). Women with previous preeclampsia or vascular disease had responses similar to low-risk women. Maternal vascular reactivity as assessed by postocclusion brachial artery dilatation decreases in the third trimester in both low-risk and high-risk women. In addition, singleton pregnancies at high risk for preeclampsia display decreased brachial artery reactivity compared with low-risk women.

Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations.

Our objective was to compare brachial artery endothelium dependent and independent vasodilation in lupus patients and healthy females, by means of high-resolution noninvasive brachial artery ultrasound. Endothelially mediated vasodilation was estimated noninvasively by examination of brachial artery responses to postischemic reactive hyperemia and endothelial independent vasodilation from response to sublingual glycerlynitrate (GTN) using high-resolution external vascular ultrasound. Five patients with known coronary artery disease (CAD), five with subclinical CAD, five with no CAD and five control subjects were assessed. Endothelium dependent vasodilation was significantly blunted in lupus patients with CAD as compared with healthy female controls (0.11 versus 11.1%, P = 0.018). Corresponding values for lupus patients with subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject, endothelium dependent vasodilation (EDV) was related to endothelium independent vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN in individual subjects. This ratio was markedly depressed in lupus patients with CAD as compared with control subjects (0.12 versus 1.15). The corresponding EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69 and 0.65, respectively. The conclusion was that flow mediated vasodilation in lupus patients with coronary artery disease is markedly depressed as compared to healthy subjects.

Systemic lupus erythematosus: an independent risk factor for endothelial dysfunction in women.

Systemic lupus erythematosus (SLE) patients have a significantly increased risk of coronary heart disease (CHD) that is not fully explained by classic risk factors. Endothelial dysfunction is an early stage in the process of atherogenesis. Our aim was to determine whether endothelial dysfunction occurs in SLE and whether it is associated with the occurrence of classic Framingham risk factors. We studied 62 women with SLE (1997 revised criteria) and 38 healthy women. Demographic and risk factor data were collected. In patients, disease activity and treatment-related parameters were also assessed. Endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery in response to reactive hyperemia. Carotid intima-media thickness (IMT) and the presence of carotid plaques were also assessed in SLE patients. FMD was impaired in SLE patients (median, 3.6%; range, -6.3% to 13.7%; versus median, 6.9%; range, -6.6% to 17.8%, P<0.01). Using multiple regression analysis that included all subjects in which we retained all the classic CHD risk factors, we found that systolic blood pressure (P=0.019) and SLE (P=0.017) were significantly associated with impaired FMD. Within SLE patients, IMT showed a negative correlation with percent FMD (r=-0.37, P<0.01). In stepwise multiple regression of SLE patients only that also included SLE factors and IMT, IMT alone was independently associated with FMD (P=0.037). Patients with SLE have endothelial dysfunction that remained significant even after adjustment for other classic CHD risk factors. Within SLE patients, endothelial dysfunction correlates negatively with IMT, another marker of early atherosclerosis. Understanding the mechanism(s) of endothelial dysfunction in SLE may suggest novel strategies for CHD prevention in this context.

Temporal Responses of the Brachial Artery Following Forearm Occlusion

0436 Measurement of flow-mediated dilation of the brachial artery in response to a sudden change in blood flow has emerged as a useful tool for atherosclerosis research. In the setting of cardiovascular disease risk factors flow-mediated dilation declines, perhaps suggesting a loss of normal endothelial function. Interestingly, little attention has been given to the temporal responses of the vessel's behavior following the occlusion period. PURPOSE: To examine the temporal response of the brachial artery following forearm occlusion. METHODS: Twelve healthy males (28 ± 5.47y) underwent highresolution ultrasonography of the brachial artery before and after 5 minutes of forearm occlusion. RESULTS: As show in the figure the average brachial artery diameter at rest was 3.52 ± 0.46mm. A significant decrease in brachial artery diameter was observed approx. 10 ± 4 sec after release of the occlusion (3.45 ± 0.47mm vs. baseline, p = 0.03), which was followed by a rapid increase in the diameter reaching a peak at approx. 49 ± 16sec (3.81 ± 0.48mm vs. baseline, p = 0.001). CONCLUSION: These results indicate a biphasic temporal pattern following 5 minutes of forearm occlusion. The mechanism for the initial decrease in diameter is uncertain, but may be a response to a change in fluid mechanics following cuff release or a myogenic influence. The subsequent increase in brachial diameter may in part be a reflection of endothelial mediated mechanisms. The temporal pattern may provide additional information regarding the structural and physiological status of the artery.Figure

Comparison of Temporal Responses of the Brachial Artery Following Forearm Occlusion In Younger Vs. Older Adults

2022 Measurement of flow-mediated dilation of the brachial artery in response to shear stress has emerged as a useful tool for atherosclerosis research. Brachial artery flowmediated dilation is typically defined as the absolute (mm) and percent change (%) in vessel diameter from rest to peak dilation following 5 min of forearm occlusion. Close observation of the temporal response of the vessel indicates a biphasic pattern, whereby an increase in vessel diameter is preceded by a decrease shortly after cuff release. It was hypothesized that the biphasic pattern would be less pronounced in older adults. PURPOSE: To compare temporal responses of the brachial artery following forearm occlusion in younger vs. older adults. METHODS: Twelve healthy young males (28 ± 5.5yrs) and six healthy older males (81 ± 13.1yrs) underwent high-resolution ultrasonography of the brachial artery before and after 5 minutes of forearm occlusion. RESULTS: Average baseline diameter for the young adults was smaller compared to the old (Y: 3.52 ± 0.46; O: 4.65 ± 0.51mm, p = 0.001). In both young and old a significant decrease in brachial artery diameter was observed at approximately 10 sec after release of the occlusion (p = 0.03). However, the magnitude of the drop appeared less in the older group (Y: 2.1 ± 2; O: 1.1 ± 0.7%, p = 0.11). Peak brachial artery flow-mediated dilation was observed in 11/12 young adults and only 2/6 older adults (Y: 8.19 ± 3.56; O: 2.16 ± 1.46%, p = 0.001), at approximately 45 seconds following occlusion. The magnitude of the drop following cuff release was significantly associated with peak brachial artery flow-mediated dilation, (r = −0.67, p = 0.002). CONCLUSIONS: These results suggest both phases of the temporal pattern of the brachial artery following occlusion are blunted in older adults. This further confirms that the vasculature is stiffer and less responsive in the elderly secondary to structural and physiological modifications associated with the aging process.