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Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD.We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events.BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03).In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk.

It is established that low-density lipoprotein cholesterol is an independent risk factor for cardiovascular events. Recently, circulating triglycerides level has been focused on as a risk factor for cardiovascular events. In this study, we evaluated the associations between triglycerides and endothelial function in a general population.We analyzed data for 4887 subjects who were enrolled in the FMD-Japan registry. We investigated cross-sectional associations between serum triglyceride levels and endothelial function assessed by measurement of flow-mediated vasodilation (FMD).Serum triglyceride levels were correlated with FMD (r = -0.12, p 0.001). Subjects were divided into six groups based on serum triglyceride levels. FMD was significantly decreased with an increase in serum triglyceride levels (≤0.71 mmol/L, 7.0 ± 3.5%; 0.72-0.94 mmol/L, 6.3 ± 3.5%; 0.95-1.19 mmol/L, 6.0 ± 3.1%; 1.20-1.48 mmol/L, 5.8 ± 3.2%; 1.49-2.02 mmol/L, 5.7 ± 3.1%; ≥2.03 mmol/L, 5.5 ± 3.0%; p for trend0.001). After adjustment for age, sex, and cardiovascular risk factors, including high-density lipoprotein cholesterol, serum triglyceride levels of more than 1.20 mmol/L were independently associated with the low quartile of FMD (1.20-1.48 mmol/L, odds ratio (OR) 1.41, 95% confidence interval (CI) 1.09 to 1.82; 1.49-2.02 mmol/L, OR 1.31, 95% CI 1.00 to 1.70; ≥2.03 mmol/L, OR 1.48, 95% CI 1.13 to 1.95) using serum triglyceride levels of less than 0.71 mmol/L group as the reference.These findings suggest that triglycerides are an independent predictor of endothelial function. Lowering circulating triglyceride levels may improve endothelial function, leading to a decrease in cardiovascular events.URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409.

Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. It is clinically important to estimate the degree of ROCK activity in humans. The purpose of this study was to confirm the validity of a leukocyte ROCK parameter as an index of ROCK activity in comparison with vascular response to a ROCK inhibitor.We evaluated the ratio of phospho myosin-binding subunit (p-MBS) on myosin light-chain phosphatase to total MBS in peripheral leukocytes by Western blot analysis and forearm blood flow (FBF) response to the ROCK inhibitor fasudil using strain-gauge plethysmography in 36 healthy subjects and 39 patients with cardiovascular diseases. Fasudil (3, 10, 30μg/min) was infused intra-arterially for 5min at each dose. Leukocyte p-MBS/total-MBS was higher in cardiovascular diseases than in healthy subjects (0.97±0.37 vs. 0.51±0.14; P=0.002). Fasudil increased FBF from 4.9±1.2 to 14.5±5.7mL/min/100mL tissue (P0.0001) in patients with cardiovascular diseases, while fasudil did not alter FBF in healthy subjects. There was a significant relationship between leukocyte p-MBS/total-MBS and maximal FBF response to fasudil in all subjects (r=0.72, P0.0001). There was also a significant correlation between p-MBS/total-MBS and maximal FBF response to fasudil in patients with cardiovascular diseases (r=0.59, P0.0001). In healthy subjects, there was no significant correlation between the two parameters.These findings suggest that assessment of leukocyte ROCK activity is minimally invasive and does not require pharmacologic intervention using ROCK inhibitors. Leukocyte p-MBS/total-MBS may be useful for evaluating ROCK activity in a clinical setting.

Background The aim of this study was to determine pioglitazone treatment restores endothelial function in hypertensive patients with impaired glucose tolerance (IGT). Methods and results We evaluated the effects of pioglitazone treatment for 12 weeks on forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside in 34 hypertensive patients with IGT who were randomly divided into a pioglitazone group ( n =17) and an amlodipine monotherapy group ( n =17) and in 34 healthy subjects. Pioglitazone, but not amlodipine, increased the FBF response to acetylcholine and decreased urinary excretion of 8-hydroxy-2′-deoxyguanosine. Pioglitazone did not alter sodium nitroprusside-stimulated vasodilation. N G -monomethyl-l-arginine abolished the augmentation of FBF response to acetylcholine after pioglitazone treatment. The increase in maximal FBF response to acetylcholine correlated with the decrease in urinary excretion of 8-hydroxy-2′-deoxyguanosine. Conclusion Pioglitazone improved endothelial function in hypertensive patients with IGT through an increase in nitric oxide bioavailability by, in part, a decrease in oxidative stress.

Objective: Several studies have shown that periodontitis is a risk factor for cardiovascular diseases. There is an association between inflammation and endothelial dysfunction. The purpose of this study was to evaluate endothelial function in patients with coronary artery disease (CAD) who had periodontitis. Methods and results: We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in 101 CAD patients with periodontitis (37 men and 11 women, 63 +/- 12 yr) and without periodontitis (36 men and 17 women, 62 +/- 13 yr). FBF was measured by using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the non-periodontitis group. FBF response to ACh was significantly smaller in the periodontitis group than in the non-periodontitis group. SNP-stimulated vasodilation was similar in the two groups. Periodontal therapy reduced serum concentrations of C-reactive protein from 2.7 +/- 1.9 to 1.8 +/- 0.9 mg/L (P < 0.05) and interleukin-6 from 2.6 +/- 3.4 to 1.6 +/- 2.6 ng/L (P < 0.05) and augmented ACh-induced vasodilation from 14.7 +/- 5.2 to 20.1 +/- 6.1 mL/(min 100 mL) tissue (P < 0.05) in patients with periodontitis. The SNP-stimulated vasodilation was similar before and after treatment. After administration of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, FBF response to ACh was similar before and after treatment. Conclusion: These findings suggest that periodontitis is associated with endothelial dysfunction in patients with CAD through a decrease in nitric oxide bioavailability. Systemic inflammation may be, at least in part, a cause and predictor of progression of endothelial dysfunction.