Independent Predictor Of Flow-mediated Dilation Research Articles

Determinants of Systemic Vascular Function in Patients with Stable Chronic Obstructive Pulmonary Disease

Impaired vascular reactivity is an important factor in the pathogenesis of cardiovascular disease. We sought to assess vascular reactivity in patients with chronic obstructive pulmonary disease (COPD) and respective control subjects, and to investigate the relation between vascular function and airflow obstruction and systemic inflammation. We studied 60 patients with stable COPD; 20 smokers with normal lung function matched for age, sex, and body weight; and 20 similarly matched nonsmokers. Patients with cardiovascular comorbidities were excluded. The endothelium-dependent and endothelium-independent function of the vasculature was measured using flow-mediated and nitrogen-mediated dilation of the brachial artery, respectively. Systemic inflammatory markers, including C-reactive protein, fibrinogen, and interleukin (IL)-6, were determined in serum. Both flow-mediated and nitrogen-mediated dilation of the brachial artery were significantly lower in patients with stable COPD than in smoking and nonsmoking control subjects. Levels of inflammatory mediators such as IL-6 and fibrinogen were higher in patients than they were in control subjects. In patients with COPD, stepwise multiple regression analysis showed that age, sex, baseline brachial artery diameter, C-reactive protein level, leukocyte count, blood glucose level, and percentage of predicted forced expiratory volume in 1 s were independent predictors of flow-mediated dilation. There was no relation between flow-mediated dilation and pack-years of smoking. Baseline brachial artery diameter was the only independent predictor of nitrogen-mediated dilation in patients with COPD. Both endothelium-dependent and endothelium-independent vasodilation is significantly impaired in patients with stable COPD. Airflow obstruction and systemic inflammation may increase the risk of cardiovascular disease in patients with COPD.

ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction

Asymmetric dimethyl-arginine (ADMA), a residue of the proteolysis of arginine-methylated proteins, is a potent inhibitor of nitric oxide synthesis. The increased protein turnover that accompanies proteinuric secondary amyloidosis may increase circulating levels of ADMA, and this may contribute to endothelial dysfunction. We performed a cross-sectional study of 121 nondiabetic proteinuric patients with normal GFR (including 39 patients with nephrotic-range proteinuria and secondary amyloidosis) and 50 age-, sex-, and BMI-matched healthy controls. The proteinuric patients had higher levels of serum ADMA, symmetric dimethyl-arginine (SDMA), high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment index) than controls. Compared with controls, brachial artery flow-mediated dilatation (FMD), serum L-Arginine, and the L-Arginine/ADMA ratio were significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA and SDMA levels and lower L-Arginine/ADMA ratios and FMD measurements (P < 0.001 for all). Finally, even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. We propose that ADMA synthesis may be increased in chronic kidney disease, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality.

The relative impact of different measures of adiposity on markers of early atherosclerosis

Background Although there are several methods available to assess adiposity, there is still controversy on the relative clinical utility of each of these methods. This study examines the relative impact of different measures of adiposity on markers of early atherosclerosis. In particular weight changes over time have been poorly assessed in this setting. Methods Eighty-six healthy individuals (31 men, age 36.5 ± 8.9 years) with a wide range of body-mass index (28.7 ± 7.0, 18.9–57.9 kg/m 2) without hypertension, diabetes or smoking were examined. In addition to waist circumference and waist-to-hip ratio self-reported weight change since adolescence was also calculated. Ultrasonography was used to measure abdominal fat layers and their ratio. Flow-mediated dilatation of the brachial artery, serum levels of intercellular adhesion molecule (sICAM-1) and mean intima-media thickness of the carotid artery were measured as markers of early atherosclerosis. Results Stepwise multivariate regression analysis showed waist circumference and waist-to-hip ratio as the only independent predictor of flow-mediated dilatation. Waist circumference and weight change but not current body-mass index were independent predictors of intima-media thickness. These correlations were not influenced by ultrasonographically measured fat layers, C-reactive protein and basal insulin resistance. Body-mass index and weight gain were associated with sICAM-1 but not independently of basal insulin resistance and C-reactive protein. Conclusions Waist circumference and weight gain were the strongest predictors of early atherosclerosis in a population of apparently healthy adults. The ultrasonographically measured fat layers did not provide additional information in this population.

Predictors of Endothelial Dysfunction in Young Women with Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) may be at increased risk for cardiovascular disease. Endothelial dysfunction is an early marker of atherosclerosis. The objectives of this study were to 1) compare endothelial function in young women with PCOS and regularly menstruating control women, and 2) to identify the determinants of endothelial function and investigate its relationship with body mass index in women with PCOS. This was a cross-sectional study. This study was conducted at a tertiary cardiovascular research center. Sixty-two young women with PCOS (mean age, 22.7 yr) and 17 control women, matched as a group for age and body mass index, were studied. Twenty-three women with PCOS were lean, 21 were overweight, and 18 were obese. Endothelium-dependent and -independent vascular function was assessed by measuring flow-mediated dilation (FMD) and nitrate-mediated dilation in the brachial artery (diameter change during hand hyperemia and after sublingual glyceryl trinitrate administration, respectively). FMD and nitrate-mediated dilation were significantly lower in PCOS than in control women (reduced by approximately 50 and 25%, respectively; both P < 0.0005). Insulin resistance, total testosterone, and total cholesterol were independent predictors of FMD, accounting for 21, 10, and 9% of the variance, respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to overweight and obese PCOS women was observed, but differences among groups were not statistically significant. Women with PCOS have significant endothelial dysfunction at an early age (i.e. early 20s), and largely independent of obesity. This suggests that women with PCOS are at increased risk for early onset cardiovascular disease and may gain particular benefit from measures to improve endothelial function.

Determinants of endothelial dysfunction and carotid intima???media thickness in combined hyperlipidemia

Early functional and morphological changes in the course of the atherosclerotic process are manifested as endothelial dysfunction and increased intima-media thickness (IMT) of the arterial wall. These are both associated with various atherosclerotic risk factors. We investigated whether the same factors are associated with functional and morphological changes of the arterial wall in men with combined hyperlipidemia. Flow-mediated dilatation (FMD) of the brachial artery and carotid IMT were measured in 72 male patients aged 46+/-5 years with combined hyperlipidemia. Serum lipoproteins, fibrinolytic and coagulation parameters, blood glucose, proinflammatory cytokines and C-reactive protein were also measured. Tumor necrosis factor-alpha, interleukin 6 and apolipoprotein (apo) B were found to be independent predictors of FMD, explaining 87% of FMD variability in multivariate analysis. On the other hand, total tissue factor pathway inhibitor and apo B were independent predictors of increased carotid IMT, explaining 82% of the variation in carotid IMT. Apo B, which is a marker for the presence of the atherogenic lipoproteins, is associated with both functional and morphological changes of the artery wall. In addition, in asymptomatic overweight middle-aged men with combined hyperlipidemia, functional changes are associated with proinflammatory cytokines, while morphological changes are associated with coagulation parameters.

Comparison of flow-mediated dilatation of the brachial artery in coronary patients with low-density lipoprotein cholesterol levels

Testing of peripheral vascular endothelial function was performed in subjects who had coronary artery disease and a low-density lipoprotein (LDL) cholesterol level <100 mg/dl. LDL cholesterol was an independent predictor of flow-mediated dilation of the brachial artery (p = 0.010). The 63 subjects who had an LDL cholesterol level <80 mg/dl had better endothelial function (flow-mediated dilation 8.4 +/- 3.8%) than did 47 subjects whose level of LDL cholesterol was 80 to 100 mg/dl (flow-mediated dilation 6.8 +/- 4.0%, p = 0.03). The beneficial effects of LDL cholesterol levels <80 mg/dl on endothelial function were more apparent in subjects who had low levels of high-density lipoprotein cholesterol than in those who had normal levels. These data support recent reports that decreasing levels of LDL cholesterol below those currently recommended provides additional benefits and suggest that this benefit may be due in part to increased endothelial function.

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 ± 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 ± 48, 47 ± 13, 108 ± 37 and 154 ± 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 ± 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 ± 3.6%) compared with those with an HDL cholesterol ≥40 mg/dl (11.0 ± 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.

Análisis de las diferencias encontradas en la dilatación mediada por flujo según la terapia seguida en pacientes con enfermedad coronaria

Flow-mediated dilation (FMD) is thought to be related to the development of coronary disease. We were interested in knowing the degree of FMD in a large sample of coronary patients in relation to the therapy they were given in clinical practice. We studied 1,081 coronary patients (age 68 +/- 12 years, 73% male) in which FMD was evaluated in the brachial artery. The patients were classified into 5 treatment groups (416 who receive 2 or more treatments were excluded): group A: 81 controls treated with aspirin, group B: 198 treated with ACE inhibitors, group C: 106 with calcium antagonists, group D: 145 with beta-blockers, and group E: 135 with lipid lowering medication (93% statins). ANOVA was used to analyze the differences between groups. With regard to the number of risk factors present in each group, the patients treated with ACE inhibitors (2.44 +/- 0.79 vs 2.14 +/- 0.89; p < 0.05) and statins (3.45 +/- 0.70 vs 2.14 +/- 0.89; p < 0.05) had more risk factors than GrA and higher levels of LDL-cholesterol (ACE inhibitors 145.0 +/- 33.5 vs 128.5 +/- 32.2 and statins 157.8 +/- 45.3 vs 128.5 +/- 32.2; p < 0.05). GrB had a higher glycemia than controls (123.4 +/- 32.2 vs 114.7 +/- 33.7; p < 0.05). The control group was younger than the therapeutic groups (p < 0.05). Compared with the control group, FMD was significantly higher only in the group treated with ACE inhibitors (3.42 +/- 6.01 vs 0.82 +/- 6.04; p < 0.05). Multivariate logistical regression showed that treatment with ACE inhibitors and statins (p < 0.05) were independent predictors of FMD > 4%. Treatment with ACE inhibitors or statins was predictive of the normalization of FMD in coronary patients in clinical practice.

Leukocyte count and vascular function in Type 2 diabetic subjects with treated hypertension

Background: Traditional cardiovascular risk factors may only partially explain abnormal vascular function in Type 2 diabetic patients. This study examined the associations between vascular function and markers of inflammation in Type 2 diabetic subjects with treated hypertension. Methods: Flow-mediated dilatation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) of the brachial artery were used to assess endothelium-dependent and -independent function, respectively, in 29 hypertensive Type 2 diabetic subjects (HbA1c <9%), and 17 healthy control subjects. Plasma C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leukocyte count were used as markers of inflammation. Soluble L-selectin, P-selectin, and von Willebrand factor (vWf) were measured to assess leukocyte, platelet and endothelial cell activation, respectively. Results: Compared with controls, diabetic subjects had impaired FMD (3.9±3.0 vs. 5.5±2.4%, P=0.07) and GTNMD (11.4±4.8% vs. 15.4±7.1%, P=0.04). They also had higher levels of CRP (2.7±2.6 vs. 1.4±1.1 mg/l, P=0.03), fibrinogen (3.4±0.7 vs. 2.7±0.3 g/l, P<0.001) and TNF-α (20.9±13.4 vs. 2.5±1.7 pg/l, P<0.001). In diabetic subjects, after adjustment for age and gender, leukocyte count was an independent predictor of FMD ( P=0.02), accounting for 17% of total variance. Similarly, leukocyte count ( P<0.001) accounted for 23% and IL-6 ( P=0.03) for 12% of the variance in GTNMD. vWf was correlated with leukocyte count ( r=0.38, P=0.04), FMD ( r=−0.35, P=0.06) and GTNMD ( r=−0.47, P=0.009), whilst P-selectin correlated with fibrinogen ( r=0.58, P=0.001). Conclusion: These cross-sectional observations are consistent with the hypothesis that reduced FMD and GTNMD in Type 2 diabetes is at least in part secondary to increased inflammation, with associated endothelial and platelet activation.

Endothelial dysfunction in type 2 diabetes mellitus subjects with peripheral artery disease

We strived to characterize the endothelial function status in type 2 diabetic patients with peripheral artery disease which was detected by ankle-brachial index by utilizing high frequency ultrasounds. Predictors of endothelial dysfunction were investigated. We chose 23 type 2 diabetic patients had ankle-brachial index <0.97 (0.15–0.95; mean=0.74±0.20), 31 diabetic patients had ankle-brachial index ≥1.0 and 28 non-diabetic subjects for study. Older age, a longer duration of diabetes, higher systolic blood pressure, higher prevalence of history of hypertension were observed in patients with peripheral vascular disease. Type 2 diabetic patients showed impaired flow-mediated dilatation than non-diabetic and it showed more impaired in patients with peripheral vascular disease. Nitroglyerin-induced dilatation showed a trend of impairment in patients with peripheral vascular disease but did not reach statistical significance. Age ( r=−0.259, P=0.019), baseline brachial artery diameter ( r=−0.321, P=0.003), ankle-brachial index ( r=0.259, P=0.002) and hypertension history ( P=0.01) were significantly associated with flow-mediated dilatation. However, after adjusting for age, only baseline diameter and ankle-brachial index were independent predictors of flow-mediated dilatation. In conclusion, we demonstrated flow-mediated dilatation was impaired in type 2 diabetic patients and it was further impaired in patients with peripheral vascular disease. Nitroglycerin-induced dilatation showed a trend of impairment but did not reach statistical significance.