Search

Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease. [ABSTRACT FROM AUTHOR]

Ankle-brachial index (ABI) has been used as a vascular marker of atherosclerosis for cardiovascular risk assessment. However, it is unclear whether there is a difference in cardiovascular risk between patients with low ABI (<1.00) in one leg (unilateral low ABI) and patients with low ABIs in both legs (bilateral low ABI). Therefore, we investigated the associations of cardiovascular disease (CVD) with unilateral low ABI and bilateral low ABI to determine whether cardiovascular risk is higher in patients with bilateral low ABI than in patients with unilateral low ABI. We measured ABI in 2226 subjects. The prevalence of CVD was higher in patients with bilateral low ABI than in individuals with normal ABI (1.00–1.40) and patients with unilateral low ABI (49.2%, 25.7% and 17.0%, respectively; p < 0.001). Multivariate analysis revealed that bilateral low ABI was significantly associated with an increased risk of CVD (OR, 2.30; 95% CI, 1.16 to 4.54; p = 0.02), whereas there was no significant association between unilateral low ABI and CVD (OR, 0.83; 95% CI, 0.47 to 1.46; p = 0.51). Propensity score matching analysis showed that the prevalence of CVD was significantly higher in patients with bilateral low ABI than in patients with unilateral low ABI (45.5% vs. 27.3%, p = 0.02). Cardiovascular risk may be higher in patients with bilateral low ABI than in patients with unilateral low ABI. More attention should be paid to whether a low ABI is present in one leg or in both legs for more precise cardiovascular risk assessment. [Display omitted] • ・Ankle-brachial index (ABI) has been used for cardiovascular risk assessment. • ・Bilateral low ABI is associated with an increased risk of concomitant cardiovascular (CV) disease. • ・Unilateral low ABI is not associated with an increased risk of CV disease. • ・Attention should be paid to whether a low ABI is present in one leg or in both legs. [ABSTRACT FROM AUTHOR]

A body shape index (ABSI) was proposed for estimation of abdominal adiposity. ABSI has been reported to have associations with cardiovascular risk factors and cardiovascular events. However, there is no information on the association between ABSI and endothelial function. We examined cross-sectional associations of ABSI with endothelial function in 8823 subjects (6773 men and 2050 women). Subjects with a lower quartile of flow-mediated vasodilation (FMD) were defined as subjects having endothelial dysfunction. Pearson's correlation coefficient analysis revealed that ABSI was negatively correlated with FMD (men, r = − 0.23, P = 0.003; women, r = − 0.32, P < 0.001). The areas under the curves of ABSI and body mass index to predict endothelial dysfunction were 0.64 (95% confidence interval [CI] 0.62–0.65) and 0.58 (95% CI 0.57–0.60) in men, and 0.68 (95% CI 0.66–0.71) and 0.59 (95% CI 0.56–0.61) in women, respectively. The cutoff values of ABSI for predicting subjects with endothelial dysfunction were 0.0796 (sensitivity, 55.2%; specificity, 65.5%) in men and 0.0823 (sensitivity, 56.2%; specificity, 73.4%) in women. Multivariate analysis revealed that an ABSI value higher than the cutoff value remained an independent predictor of endothelial dysfunction in both sexes. The results of our study suggest that ABSI calculation should be performed for evaluation of risk of cardiovascular events in both men and women. Clinical trial registration information URL for Clinical Trial: https://www.umin.ac.jp/ctr/index.htm; Registration Number for Clinical Trial: UMIN000012952 (01/05/2010). [ABSTRACT FROM AUTHOR]

Various therapeutic strategies for angiogenesis are performed to improve symptoms in patients with critical limb ischemia (CLI). Pre-clinical studies have shown that low-intensity pulsed ultrasound (LIPUS) exposure induces angiogenesis. LIPUS may be a new stratergy for treatment of CLI. The purpose of this pilot trial was to evaluate outcomes in patients with CLI who were treated with LIPUS. Fourteen patients with CLI, who were not candidates for angioplasty or surgical revascularization, were enrolled in this study. Historical control data were obtained from the Hiroshima University PAD database. The primary endpoints were major amputation and death. The outcomes were compared in 16 lower limbs of the 14 patients with CLI who were treated with LIPUS and in 14 lower limbs of 14 patients with CLI as historical controls. All patients were followed for after 5 years after treatment with LIPUS. The mean duration of LIPUS exposure in the LIPUS group was 381± 283 days. During the 5-year follow-up periods, there were 3 major amputations and 7 deaths in the LIPUS group and there were 14 major amputations and 7 deaths in the historical control group. The overall amputation-free survival rate was significantly higher in patients who were treated with LIPUS than in historical controls. There was no significant difference between overall mortality-free survival rates in the LIPUS group and historical control group. LIPUS is a noninvasive option for therapeutic angiogenesis with the potential to reduce the incidence of major amputations in patients with CLI. [ABSTRACT FROM AUTHOR]

The association of body weight with cardiovascular events is still controversial. We evaluated the relationship between body mass index (BMI) and endothelial function. We measured flow-mediated vasodilation (FMD) and BMI in 7682 men. All participants were divided into four groups by BMI: underweight (<18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight (25.0 to 29.9 kg/m2), and obesity (≥30.0 kg/m2). Multiple logistic regression analysis revealed that overweight (OR: 1.30, 95% CI: 1.14–1.47; P < 0.001) and obesity (OR: 1.40, 95% CI: 1.09–1.80; P = 0.009) were associated with an increased risk of a low quartile of FMD. In 5571 younger adults (<60 years), overweight (OR: 1.34, 95% CI: 1.16–1.55; P < 0.001) and obesity (OR: 1.37, 95% CI: 1.04–1.81; P = 0.03) were associated with an increased risk of a low quartile of FMD, and underweight (OR: 0.56, 95% CI: 0.35–0.89; P = 0.01) was associated with a reduced risk of a low quartile of FMD. In 2111 older adults (≥60 years), underweight (OR: 2.16, 95% CI: 1.22–3.80; P = 0.008) was associated with an increased risk of a low quartile of FMD, and overweight and obesity were not associated with a risk of a low quartile of FMD. In Asian men, endothelial function was impaired in the overweight and obesity groups compared with that in the normal weight group. The risk for endothelial dysfunction was higher in obese younger adults than in obese older adults. The association of BMI with endothelial function may be different in young and elderly men. Clinical Trial Registration Information: http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000012952). • The risk for endothelial dysfunction was higher in obese younger adults than in obese older adults. • Obesity paradox was seen in the endothelial function in the elderly. • Endothelial function was better in underweight younger adults than in the normal weight group. • Endothelial function was impaired in underweight older adults compared with that in normal weight group. • The association of BMI with endothelial function may be different by age. [ABSTRACT FROM AUTHOR]

Light to moderate alcohol consumption has protective effects on all-cause death and coronary artery disease in women. It is thought that light to moderate alcohol consumption has a beneficial effect on vascular function in women. We measured flow-mediated vasodilation (FMD) in 702 women aged 17–86 years who provided information on alcohol consumption. We divided the subjects into four groups: non-drinkers (0 g/week), light drinkers (>0 to 140 g/week), moderate drinkers (>140 to 280 g/week) and heavy drinkers (>280 g/week). There was no significant difference in FMD among the four groups. Multivariate regression analysis revealed that alcohol consumption in non-drinkers and light drinkers was not an independent predictor of FMD (β = −0.001, P = 0.98). We compared 50 moderate drinkers and 50 non-drinkers matched for age and medical histories and 22 heavy drinkers and 22 non-drinkers in matched pair analysis. There was no significant difference in FMD between moderate drinkers and non-drinkers (8.2±4.3% vs. 8.1±3.5, P = 0.91), while FMD in heavy drinkers was significantly lower than that in non-drinkers (5.9±2.5% vs. 8.9±3.5%, P = 0.002). These findings suggest that heavy alcohol consumption is associated with endothelial dysfunction but that light to moderate alcohol consumption is not associated with endothelial dysfunction in women. Clinical trial registration information This study was approved by principal authorities and ethical issues in Japan (University Hospital Medical Information Network UMIN000012952, 01/12/2009). www.umin.ac.jp/. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammation is associated with endothelial dysfunction and plays an important role in the pathogenesis and development of cardiovascular diseases. It has been shown that colchicine, an anti-inflammatory drug, improves the cardiovascular outcome in patients with cardiovascular disease. The purpose of this study was to evaluate the short-term effect of low-dose colchicine on endothelial function in patients with coronary artery disease (CAD). Methods This was a double-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 28 patients with CAD received low-dose colchicine (0.5 mg/day) or a placebo for 7 days with a washout period of at least 14 days. Flow-mediated vasodilation (FMD) and serum concentrations of high-sensitivity C-reactive protein (hs-CRP) were measured after the 7-day treatment with colchicine or the placebo. Results The serum concentration of hs-CRP was significantly decreased after administration of colchicine compared with that after administration of the placebo [median (interquartile range): 0.04 (0.02–0.08) mg/dL vs. 0.07 (0.04–0.11) mg/dL, P = 0.003], while there was no significant difference in FMD between the treatments [median (interquartile range): 3.1% (1.5–5.3%) vs. 3.3% (1.9–5.2%), P = 0.384]. Colchicine, however, significantly improved FMD in coronary artery disease patients with white blood cell (WBC) counts of ≥7500 WBC/mm3 [median (interquartile range): 3.3% (2.1–6.6%) vs. 2.0% (1.4–3.8%), P = 0.043]. Conclusions Administration of low-dose colchicine did not improve endothelial function in patients with CAD, but exploratory analysis suggested that endothelial function is significantly improved in patients with leukocyte activation. Highlights • This work is a double-blind, randomized, placebo-controlled, crossover trial. • The effect of colchicine (0.5 mg/day) on endothelial function was evaluated. • Administration of low-dose colchicine improved endothelial function. • Further studies are needed to assess effects of colchicine on vascular function. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. Methods: This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Results: Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. Conclusions: These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. Clinical Trial Registration: URL for Clinical Trial: https://upload.umin.ac.jp; Registration Number for Clinical Trial: UMIN000013283. [ABSTRACT FROM AUTHOR]

Background Measurement of flow-mediated vasodilation (FMD) is an established method for assessing endothelial function. Measurement of FMD is useful for showing the relationship between atherosclerosis and endothelial function, mechanisms of endothelial dysfunction, and clinical implications including effects of interventions and cardiovascular events. To shorten and simplify the measurement of FMD, we have developed a novel technique named short time FMD (stFMD). We investigated the validity of stFMD for assessment of endothelial function compared with conventional FMD. Methods and results We evaluated stFMD and conventional FMD in 82 subjects including patients with atherosclerotic risk factors and cardiovascular disease (66 men and 16 women, 57 ± 16 years). Both stFMD and conventional FMD were significantly correlated with age, systolic blood pressure, diastolic blood pressure and baseline brachial artery diameter. In addition, stFMD was significantly correlated with conventional FMD (r = 0.76, P < 0.001). Bland-Altman plot analysis showed good agreement b etween stFMD and conventional FMD. Moreover, stFMD in the at risk group and that in the cardiovascular disease group were significantly lower than that in the no risk group (4.6 ± 2.3% and 4.4 ± 2.2% vs. 7.3 ± 1.9%, P < 0.001, respectively). Optimal cutoff value of stFMD for diagnosing atherosclerosis was 7.0% (sensitivity of 71.0% and specificity of 85.0%). Conclusions These findings suggest that measurement of stFMD, a novel and simple method, is useful for assessing endothelial function. Measurement of stFMD may be suitable for screening of atherosclerosis when repeated measurements of vascular function are required and when performing a clinical trial using a large population. Clinical trial registration information URL for Clinical Trial: http://UMIN ; Registration Number for Clinical Trial: UMIN000025458. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function. Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512). [ABSTRACT FROM AUTHOR]

Background: Low-intensity pulsed ultrasound (LIPUS) irradiation has been shown to induce various responses in different cells. It has been shown that LIPUS activates extracellular signal–regulated kinase 1/2 (ERK1/2) through integrin. Purpose: To study the effects of LIPUS on myogenic regulatory factors and other related myogenesis elements in a volumetric skeletal muscle loss injury model. Study Design: Controlled laboratory study. Methods: C57BL/6J mice were subjected to full-thickness muscle defect injury of the quadriceps and treated with direct application of LIPUS 20 min/d or non-LIPUS treatment (control) for 3, 7, and 14 days. LIPUS was also applied to C2C12 cells in culture in the presence of low and high doses of lipopolysaccharides. The expression levels of myogenic regulatory factors and the expression levels of myokine-related and angiogenic-related proteins of the control and LIPUS groups were analyzed. Results: Muscle volume in the injury site was restored at day 14 with LIPUS treatment. Paired-box protein 7, myogenic factor 5, myogenin, and desmin expressions were significantly different between control and LIPUS groups at days 7 and 14. Myokine and angiogenic cytokine-related factors were significantly increased in the LIPUS group at day 3 and decreased with no significant difference between the groups by day 14. LIPUS induced different responses of myogenic regulatory factors in C2C12 cells with low and high doses of lipopolysaccharides. LIPUS promoted myogenesis through short-lived increase in interleukin-6 and heme oxygenase 1, together with activation of ERK1/2. Conclusion: LIPUS had a constant effect on the variables of tissue damage, from macrotrauma to microtrauma, leading to efficient muscle regeneration. Clinical Relevance: The focus of therapeutic strategies with LIPUS has been not only for microvascular regeneration but also for skeletal muscle and related local tissue recovery from acute or chronic damage. [ABSTRACT FROM AUTHOR]

Background Periodontal disease is associated with endothelial dysfunction, leading to cardiovascular disease. The effect of detailed tooth brushing behavior, not only frequency but also duration of tooth brushing, on endothelial function is unclear. The purpose of this study was to evaluate the relationships of detailed methods of tooth brushing with vascular function. Methods We evaluated flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and frequency and duration of tooth brushing in 896 subjects. We divided the subjects into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (< twice/day and < 2 min/procedure), low frequency or short duration group (< twice/day or < 2 min/procedure), non-low frequency and non-short duration group (≥ twice/day and ≥ 2 min/procedure). Results FMD in the low frequency and short duration group was significantly lower than FMD in the low frequency or short duration group and FMD in the non-low frequency and non-short duration group [3.1 (2.7)% vs. 4.2 (3.1)% and 4.7 (3.1)%, P = 0.001 and < 0.001, respectively]. Nitroglycerine-induced vasodilation was similar in the three groups. Using the non-low frequency and non-short duration group as the reference, the low frequency and short duration of tooth brushing group was significantly associated with an increased odds ratio of a low FMD tertile after adjustment for conventional risk factors (OR: 2.25, 95% CI: 1.39–3.59; P < 0.001). Conclusions These findings suggest that low frequency and short duration of tooth brushing are associated with endothelial dysfunction. Clinical trial registration information : URL for clinical trial: http://UMIN ; registration number for clinical trial: UMIN000003409. [ABSTRACT FROM AUTHOR]

Background Endothelial dysfunction and abnormal vascular structure may be involved in the pathogenesis of chronic heart failure (HF). The purpose of this study was to evaluate simultaneously vascular function and vascular structure in patients with heart failure with preserved ejection fraction (HFpEF). Methods We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of the brachial artery in 41 patients with HFpEF (23 men and 18 women; mean age, 66 ± 12 yr) and 165 patients without HF (95 men and 70 women; mean age, 54 ± 16 yr). Results FMD was significantly smaller in patients with HFpEF than in patients without HF (2.9 ± 2.1% versus 4.6 ± 2.7%, P = 0.0002). Nitroglycerine-induced vasodilation was significantly smaller in patients with HFpEF than in patients without HF (9.3 ± 4.1% versus 12.9 ± 4.9%, P < 0.0001). Brachial artery IMT was significantly larger in patients with HFpEF than in patients without HF (0.35 ± 0.06 mm versus 0.31 ± 0.07 mm, P = 0.0002). After adjustment for age, sex, hypertension, dyslipidemia, and diabetes mellitus, the associations remained significant between HFpEF and FMD (odds ratio, 0.79; 95% confidence interval, 0.66–0.92; P = 0.0032), nitroglycerine-induced vasodilation (odds ratio, 0.88; 95% confidence interval, 0.80–0.96; P = 0.0039), and brachial artery IMT (odds ratio, 1.08; 95% confidence interval, 1.01–1.17; P = 0.033). Conclusions These findings suggest that both endothelial dysfunction and abnormal vascular structure may contribute to the pathogenesis and maintenance of HFpEF. Endothelial function and vascular structure may be potential therapeutic targets for HFpEF. [ABSTRACT FROM AUTHOR]

Background Heavy drinking should be a predictor of endothelial dysfunction. However, there is little information on the effects of light to moderate alcohol consumption on endothelial function. The purpose of this study was to estimate the effects of dose-dependent alcohol consumption on endothelial function. Methods We measured flow-mediated vasodilation (FMD) in 2734 men aged 21–81 years who provided information on alcohol intake at 3 general hospitals. The subjects were divided into 5 groups; non-drinkers (0 g/week), light drinkers (> 0 to 140 g/week), moderate drinkers (> 140 to 280 g/week), heavy drinkers (> 280 to 420 g/week), and excessive heavy drinkers (> 420 g/week). Results FMD showed a gradual decrease in accordance with alcohol consumption in the entire study population (non-drinkers, 6.6 ± 3.4%; light drinkers, 6.2 ± 3.0%; moderate drinkers, 6.0 ± 3.0%; heavy drinkers, 5.5 ± 2.9%; excessive heavy drinkers, 5.3 ± 3.0%; P < 0.001). There was a significant difference in FMD between the light alcohol drinker group and the non-drinker group ( P = 0.015). After adjustment for other risk factors, the odds of having FMD in the lowest quartile was found to be significantly increased in the 4 drinker groups than in the non-drinker group: light (OR, 1.38; 95% CI, 1.10 to 1.75), moderate (OR, 1.36; 95% CI, 1.01 to 1.82), heavy (OR, 2.05; 95% CI, 1.46 to 2.87), excessive (OR, 2.04; 95% CI, 1.43 to 2.89). Conclusion These findings suggest that FMD is impaired in relation to alcohol consumption and that FMD is significantly smaller even in light alcohol drinkers than in non-drinkers. Alcohol intake per se may be harmful for vascular function. [ABSTRACT FROM AUTHOR]

Background Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. It is thought that PEDF plays a protective role against atherosclerosis. Clinical studies have shown that serum levels of PEDF are increased in subjects with cardiovascular risk factors. The role of PEDF in cardiovascular disease is still controversial. The purpose of this study was to evaluate the associations between serum levels of PEDF and vascular function and structure. Methods We measured serum levels of PEDF, assessed vascular function by measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in the brachial artery, and measured brachial artery intima-media thickness (IMT) in 150 subjects who underwent health examinations. Results and conclusions Univariate regression analysis revealed that serum level of PEDF was significantly correlated with body mass index, high-density lipoprotein cholesterol, glucose, FMD, nitroglycerine-induced vasodilation, and brachial artery IMT. Multivariate analysis revealed that serum levels of PEDF remained an independent predictor of nitroglycerine-induced vasodilation (β = − 0.20, P = 0.02) and brachial artery IMT (β = 0.14, P = 0.03) after adjustment of cardiovascular risk factors, while serum level of PEDF was not associated with FMD (β = − 0.02, P = 0.79). These findings suggest that PEDF may be a factor directly associated with atherosclerosis. The serum level of PEDF may be a new biochemical marker of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background Nitroglycerine-induced vasodilation, an index of endothelium-independent vasodilation, is measured for the assessment of vascular smooth muscle cell function or alterations of vascular structure. Both coronary and brachial artery responses to nitroglycerine have been demonstrated to be independent prognostic markers of cardiovascular events. The purpose of this study was to evaluate the nitroglycerine-induced vasodilation in coronary and brachial arteries in the same patients. Methods We measured nitroglycerine-induced vasodilation in coronary and brachial arteries in 30 subjects with suspected coronary artery disease who underwent coronary angiography (19 men and 11 women; mean age, 69.0 ± 8.8 years; age range, 42–85 years). Results and conclusions The mean values of nitroglycerine-induced vasodilation in the brachial artery, left anterior descending coronary artery, and left circumflex coronary artery were 12.6 ± 5.2%, 11.6 ± 10.3%, and 11.9 ± 11.0%, respectively. Nitroglycerine-induced vasodilation in the brachial artery correlated significantly with that in the left anterior descending coronary artery (r = 0.43, P = 0.02) and that in the left circumflex coronary artery (r = 0.49, P = 0.006). There was also a significant correlation between nitroglycerine-induced vasodilation in the left anterior descending coronary artery and that in the left circumflex coronary artery (r = 0.72, P < 0.001). These findings suggest that vascular smooth muscle cell dysfunction is a systemic disorder and thus impairment of endothelium-independent vasodilation in peripheral arteries and that in coronary arteries are simultaneously present. Nitroglycerine-induced vasodilation in the brachial artery could be used as a surrogate for that in a coronary artery and as a prognostic marker for cardiovascular events. [ABSTRACT FROM AUTHOR]

Background and aims 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. Methods 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). Results 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 trend <0.001). 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. Conclusions 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. Clinical trial registration information URL for Clinical Trial: http://UMIN ; Registration Number for Clinical Trial: UMIN000003409 [ABSTRACT FROM AUTHOR]

We measured upstroke time in 509 patients with diabetes who had a normal ankle-brachial index (ABI) (1.00 ≤ ABI ≤ 1.40) (443 men and 66 women; mean age: 67.6 ± 10.8 years). The prevalence of cardiovascular disease was significantly higher in patients with prolonged upstroke time at the ankle than in patients with normal upstroke time. The association between prolonged upstroke time and a higher risk of cardiovascular disease remained significant after adjusting for confounders. [ABSTRACT FROM AUTHOR]

It is well known that white blood cell (WBC) count is an independent predictor of cardiovascular events. However, associations of WBC count and WBC subtypes with endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) are unclear. The aim of this study was to determine the relationships of WBC count and WBC subtypes with vascular function assessed by FMD and NID. A total of 1351 subjects in whom FMD and NID had been measured were recruited from Hiroshima University Vascular Registry. Mean values were 3.7 ± 2.8% for FMD and 11.8 ± 5.9% for NID. WBC was not correlated with FMD or NID. NID was significantly correlated with lymphocytes in univariate analysis but not with other hematologic parameters. In multiple linear regression analyses, NID was not correlated with lymphocytes. In all subgroups including subgroups of age, gender, body mass index, hypertension, dyslipidemia, diabetes mellitus, smoking and tertile of WBC count, WBC count was not correlated with FMD or NID. WBC count and WBC subtypes were not associated with endothelial function assessed by FMD or vascular smooth muscle function assessed by NID. WBC count and vascular function assessed by FMD and NID may reflect different aspects of atherosclerosis. Clinical Trial Registration Information: URL for Clinical Trial: http://www.umin.ac.jp Registration Number for Clinical Trial: UMIN000039512. [ABSTRACT FROM AUTHOR]

An elevation of serum low-density lipoprotein cholesterol (LDL-C) levels has been associated with endothelial dysfunction in statin naïve subjects. However, there is no information on endothelial function in subjects with extremely low levels of LDL-C. The purpose of the present study was to determine the relationship of LDL-C levels, especially low levels of LDL-C, with endothelial function. Endothelial function assessed by flow-mediated vasodilation (FMD) measurement and LDL-C levels were evaluated in 7120 subjects without lipid-lowering therapy. We divided the subjects into five groups by LDL-C levels: <70 mg/dL, 70–99 mg/dL, 100–119 md/dL, 120–139 mg/dL, and ≥140 mg/dL. FMD values were significantly smaller in subjects with LDL-C levels of ≥140 mg/dL than in those with LDL-C levels of 70–99 mg/dL and 100–119 mg/dL (p < 0.001 and p = 0.004, respectively). The FMD values in the LDL-C of <70 mg/dL group were not significantly different from those in the other groups. To evaluate the relationship of extremely low LDL-C levels with endothelial function, we divided the subjects with LDL-C of <70 mg/dL into those with LDL-C levels of <50 mg/dL and 50–69 mg/dL. FMD values were similar in the LDL-C <50 mg/dL group and ≥50 mg/dL group in the propensity score-matched population (p = 0.570). A significant benefit was not found in subjects with low LDL-C levels from the aspect of endothelial function. [ABSTRACT FROM AUTHOR]

Cell therapy using intramuscular injections of autologous bone-marrow mononuclear cells (BM-MNCs) improves clinical symptoms and can prevent limb amputation in atherosclerotic peripheral arterial disease (PAD) patients with critical limb ischemia (CLI). The purpose of this study was to evaluate the effects of the number of implanted BM-MNCs on clinical outcomes in atherosclerotic PAD patients with CLI who underwent cell therapy. This study was a retrospective observational study with median follow-up period of 13.5 years (range, 6.8–15.5 years) from BM-MNC implantation procedure. The mean number of implanted cells was 1.2 ± 0.7 × 109 per limb. There was no significant difference in number of BM-MNCs implanted between the no major amputation group and major amputation group (1.1 ± 0.7 × 109 vs. 1.5 ± 0.8 × 109 per limb, P = 0.138). There was also no significant difference in number of BM-MNCs implanted between the no death group and death group (1.5 ± 0.9 × 109 vs. 1.8 ± 0.8 × 109 per patient, P = 0.404). Differences in the number of BM-MNCs (mean number, 1.2 ± 0.7 × 109 per limb) for cell therapy did not alter the major amputation-free survival rate or mortality rate in atherosclerotic PAD patients with CLI. A large number of BM-MNCs will not improve limb salvage outcome or mortality. [ABSTRACT FROM AUTHOR]

The effects of Covid-19 vaccines on vascular function are still controversial. We evaluated the effects of BNT162b2 vaccine (BioNTech and Pfizer) on endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID). This study was a prospective observational study. A total of 23 medical staff at Hiroshima University Hospital were enrolled in this study. FMD and NID were measured before vaccination and two weeks and six months after the 2nd dose of vaccination. FMD was significantly smaller two weeks after the 2nd dose of vaccination than before vaccination (6.5±2.4% and 8.2±2.6%, p = 0.03). FMD was significantly larger at six months than at two weeks after the 2nd dose of vaccination (8.2±3.0% and 6.5±2.4%, p = 0.03). There was no significant difference between FMD before vaccination and that at six months after the 2nd dose of vaccination (8.2±2.6% to 8.2±3.0%, p = 0.96). NID values were similar before vaccination and at two weeks, and six months after vaccination (p = 0.89). The BNT162b2 Covid-19 vaccine temporally impaired endothelial function but not vascular smooth muscle function, and the impaired endothelial function returned to the baseline level within six months after vaccination. [ABSTRACT FROM AUTHOR]

The dipeptidyl peptidase-4 inhibitor saxagliptin is a widely used antihyperglycemic agent in patients with type 2 diabetes. The purpose of this study was to evaluate the effects of saxagliptin on endothelial function in patients with type 2 diabetes. This was a prospective, multicenter, interventional study. A total of 34 patients with type 2 diabetes were enrolled at four university hospitals in Japan. Treatment of patients was initially started with saxagliptin at a dose of 5 mg daily. Assessment of endothelial function assessed by flow-mediated vasodilation (FMD) and measurement of stromal cell-derived factor-1α (SDF-1α) were conducted at baseline and at 3 months after treatment with saxagliptin. A total of 31 patients with type 2 diabetes were included in the analysis. Saxagliptin significantly increased FMD from 3.1 ± 3.1% to 4.2 ± 2.4% (P = 0.032) and significantly decreased total cholesterol from 190 ± 24 mg/dL to 181 ± 25 mg/dL (P = 0.002), glucose from 160 ± 53 mg/dL to 133 ± 25 mg/dL (P < 0.001), HbA1c from 7.5 ± 0.6% to 7.0 ± 0.6% (P < 0.001), urine albumin-to-creatinine ratio from 63.8 ± 134.2 mg/g to 40.9 ± 83.0 mg/g (P = 0.043), and total SDF-1α from 2108 ± 243 pg/mL to 1284 ± 345 pg/mL (P < 0.001). These findings suggest that saxagliptin is effective for improving endothelial function. [ABSTRACT FROM AUTHOR]

High and low hematocrit (Hct) and hemoglobin (Hb) levels are associated with the risk of cardiovascular disease. The purpose of this study was to determine the relationships of Hct, Hb and red blood cells (RBCs) with vascular function and structure. We measured flow-mediated vasodilation (FMD), nitroglycerin-induced vasodilation (NID), brachial intima media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in 807 men. The subjects were divided into six groups according to the levels of Hct, Hb and RBCs. NID was highest in the 46.0–48.9% Hct group among the six groups according to Hct levels. Brachial IMT was lowest in the 46.0–48.9% Hct group among the six groups. There were no significant differences in FMD and baPWV among the six groups. We used 46.0–48.9% Hct as a reference to define the lower tertile. The adjusted odds ratio of being in the low tertile of NID was significantly higher in the < 42.9% and ≥ 49.0% Hct groups. Adjusted odds ratio of being in the low tertile of brachial IMT was significantly lower in the < 39.9% Hct groups. Similar results were obtained for Hb and RBCs. Low and high levels of Hct, Hb and RBCs were associated with vascular smooth muscle dysfunction, and low Hct levels were associated with abnormal vascular structure. Increases in the levels of Hct, Hb and RBCs within normal ranges may have beneficial effects on the vasculature. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is associated with endothelial dysfunction. Vascular function per se plays an important role in cardiac function, whether it is a cause or consequence. However, there is no information on vascular function in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). The purpose of this study was to evaluate vascular function in patients with ATTRwt-CM. We measured flow-mediated vasodilation (FMD) as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function and brachial artery intima-media thickness (bIMT) and brachial-ankle pulse wave velocity (baPWV) as indices of arterial stiffness in 22 patients with ATTRwt-CM and in 22 one-by-one matched control patients using vascular function confounding factors. FMD was significantly greater in patients with ATTRwt-CM than in the controls (5.4 ± 3.4% versus 3.5 ± 2.4%, p = 0.038) and the N-terminal pro-brain natriuretic peptide (NT-proBNP) level was significantly greater in patients with ATTRwt-CM than in the controls (2202 ± 1478 versus 470 ± 677 pg/mL, p < 0.001). There were no significant differences in NID, bIMT or baPWV between the two groups. There was a significant relationship between NT-proBNP and FMD in patients with ATTRwt-CM (r = 0.485, p = 0.022). NT-proBNP showed no significant relationships with NID, bIMT or baPWV. Conclusions: Endothelial function was preserved in patients with ATTRwt-CM. Patients with ATTRwt-CM may have compensatory effects with respect to endothelial function through elevation of BNP. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Diabetes mellitus is associated with endothelial dysfunction. However, it is still controversial as to whether antidiabetic drug treatment affects endothelial function. The purpose of this study was to evaluate the relationships of the hemoglobin A1c (HbA1c) level with flow‐mediated vasodilation (FMD) and nitroglycerine‐induced vasodilation (NID) in patients with type 2 diabetes mellitus who are receiving antidiabetic drugs. Materials and Methods: The FMD was measured in 866 patients with type 2 diabetes mellitus who were receiving antidiabetic drugs (625 men and 241 women; mean age: 62 ± 10 years). The patients were divided into four groups according to HbA1c levels: <6.5, 6.5–6.9, 7.0–7.9, and ≥8.0%. Results: There was an inverted U‐shaped pattern of association of the HbA1c level with the FMD at an HbA1c level of about 7% of the peak of FMD in patients with type 2 diabetes mellitus who were receiving antidiabetic drugs. The FMD was significantly smaller in the HbA1c <6.5% group than in the HbA1c 6.5–6.9% group and the HbA1c 7.0–7.9% group (P < 0.001 and P < 0.001, respectively). The FMD values were similar in the HbA1c <6.5% group and HbA1c ≥8.0% group (P = 0.10). There were no significant differences in NID among the four groups (P = 0.98). Conclusions: These findings suggest that a low HbA1c <6.5% as well as a high HbA1c ≥8.0% is associated with endothelial dysfunction in patients with type 2 diabetes mellitus who are receiving antidiabetic drugs and that vascular smooth muscle function is similar in such patients regardless of the HbA1c level. [ABSTRACT FROM AUTHOR]

Hypoxia preconditioning enhances the paracrine abilities of mesenchymal stem cells (MSCs) for vascular regeneration and tissue healing. Implantation of hypoxia-induced mesenchymal stem cells (hi-MSCs) may further improve limb perfusion in a murine model of hindlimb ischemia. This study is aimed at determining whether implantation of hi-MSCs is an effective modality for improving outcomes of treatment of ischemic artery diseases. We evaluated the effects of human bone marrow-derived MSC implantation on limb blood flow in an ischemic hindlimb model. hi-MSCs were prepared by cell culture under 1% oxygen for 24 hours prior to implantation. A total of 1 × 10 5 MSCs and hi-MSCs and phosphate-buffered saline (PBS) were intramuscularly implanted into ischemic muscles at 36 hours after surgery. Restoration of blood flow and muscle perfusion was evaluated by laser Doppler perfusion imaging. Blood perfusion recovery, enhanced vessel densities, and improvement of function of the ischemia limb were significantly greater in the hi-MSC group than in the MSC or PBS group. Immunochemistry revealed that hi-MSCs had higher expression levels of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor A than those in MSCs. In addition, an endothelial cell-inducing medium showed high expression levels of vascular endothelial growth factor, platelet endothelial cell adhesion molecule-1, and von Willebrand factor in hi-MSCs compared to those in MSCs. These findings suggest that pretreatment of MSCs with a hypoxia condition and implantation of hi-MSCs advances neovascularization capability with enhanced therapeutic angiogenic effects in a murine hindlimb ischemia model. [ABSTRACT FROM AUTHOR]

Poor oral care is associated with cardiovascular disease. The aim of this study was to determine the impact of tooth brushing behavior on the incidences of future cardiovascular events in a general population including patients with cardiovascular disease. This was a prospective observational study which included 692 participants (437 men and 255 women, mean age, 63 ± 16 years). The participants were divided into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (

Abstract: Background: It is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Recently, we developed a new noninvasive method for measurement of vascular response to reactive hyperemia in the brachial artery, named enclosed zone flow-mediated vasodilation (ezFMD). The purpose of this study was to determine the validity of ezFMD for assessment of endothelial function. Methods and results: We measured ezFMD by a new device using an oscillometric method and conventional FMD using ultrasonography in 306 subjects, including patients with hypertension, dyslipidemia, and diabetes mellitus (218 men and 88 women, 30 ± 16 yr). Univariate regression analysis revealed that ezFMD significantly correlated with age (r = −0.42, P < 0.0001), body mass index (r = −0.13, P = 0.028), systolic blood pressure (r = −0.15, P = 0.009), diastolic blood pressure (r = −0.14, P = 0.011), fasting glucose level (r = −0.27, P = 0.006), smoking (r = −0.21, P = 0.007) and baseline pulse wave amplitude (r = −0.51, P < 0.0001). ezFMD significantly correlated with conventional FMD (r = 0.34, P < 0.0001). Multiple regression analysis revealed that age (P = 0.002), body mass index (P = 0.013), systolic blood pressure (P = 0.009), smoking (P = 0.004) and baseline pulse wave amplitude (P < 0.001) were independent predictors of ezFMD. Conclusions: These findings suggest that measurement of ezFMD, a novel noninvasive and simple method, may be useful for determination of vascular diameter response to reactive hyperemia. Since ezFMD is automatically measured by a device with an oscillometric method, measurement of ezFMD is easier and less biased than that of conventional FMD. [Copyright &y& Elsevier]

The purpose of this study was to evaluate whether heart failure with mildly reduced ejection fraction (HFmrEF) is associated with vascular dysfunction and whether vascular function predicts future deterioration of LVEF in patients with HFmrEF. We evaluated endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) in 69 patients with HFmrEF and 426 patients without HF and evaluated the future deterioration of LVEF, defined as a decrease in LVEF to <40%, in 39 patients with HFmrEF for up to 3 years. Both FMD and NID were significantly lower in patients with HFmrEF than in patients without HF. We categorized patients into two groups based on low tertiles of NID: a low group (NID of <7.0%) and an intermediate and high group (NID of ≥7.0%). There were significant differences between the Kaplan–Meier curves for the deterioration of LVEF in the two groups (p < 0.01). Multivariate Cox proportional hazard analysis revealed that NID of <7.0% was an independent predictor of future deterioration of LVEF in patients with HFmrEF. Both endothelial function and vascular smooth muscle function are impaired in patients with HFmrEF compared with those in patients without HF. In addition, low NID of <7.0% predicts future deterioration of LVEF. [ABSTRACT FROM AUTHOR]

Background: The ankle-brachial index measurement is used for screening and diagnosis of lower-extremity peripheral artery disease and cardiovascular risk assessment. However, the value is occasionally unreliable since the oscillometric ankle-brachial index can be elevated and falsely normalized despite the presence of lower-extremity peripheral artery disease because of the incompressibility of infrapopliteal arteries at the ankle, potentially leading to a missed diagnosis of lower-extremity peripheral artery disease or underestimation of cardiovascular risk.Case Presentation: We report two cases of lower extremity peripheral artery disease with normal ankle-brachial index (a 76-year-old Asian man and a 66-year-old Asian man). In both cases, the ankle-brachial index was within the normal range (1.00-1.40) despite the presence of lower-extremity peripheral artery disease, whereas upstroke time at the ankle calculated from the pulse volume waveform simultaneously obtained by plethysmography during the ankle-brachial index measurement was prolonged (≥ 180 milliseconds). Diagnostic imaging tests revealed the presence of occlusive arterial disease in the lower extremity and severe calcification of infrapopliteal arteries.Conclusions: In both cases, the oscillometric ankle-brachial index might have been falsely normalized despite the presence of lower-extremity peripheral artery disease because of calcified incompressible infrapopliteal arteries. Sole reliance on the ankle-brachial index value may lead to a missed diagnosis of lower-extremity peripheral artery disease or underestimation of cardiovascular risk. Upstroke time at the ankle was helpful for suspecting the presence of lower-extremity peripheral artery disease in both patients with normal ankle-brachial index. In addition to history-taking and vascular examination, upstroke time at the ankle should be carefully checked for accurate diagnosis of peripheral artery disease and cardiovascular risk assessment in patients with normal ankle-brachial index. [ABSTRACT FROM AUTHOR]

It is established that smoking is a major risk factor of atherosclerosis. Endothelial dysfunction occurs in the initial step in the pathogenesis of atherosclerosis and plays a critical role in the development of atherosclerosis. The purpose of this study was to evaluate the association between smoking status and endothelial function in detail in men. We measured flow-mediated vasodilation (FMD) in 2209 Japanese men including 1181 men who had never smoked and 1028 current smokers. All of the participants were divided into five groups by smoking pack-years: never smoker group (= 0), light smoker group (> 0 to 10), moderate smoker group (> 10 to 20), heavy smoker group (> 20 to 30) and excessive smoker group (> 30). FMD significantly decreased in relation to pack-years (6.6 ± 3.4% in the never smoker group, 6.8 ± 3.0% in the light smoker group, 6.5 ± 2.9% in the moderate smoker group, 5.9 ± 2.9% in the heavy smoker group, and 4.9 ± 2.7% in the excessive smoker group; P < 0.001). After adjustment for age (≥ 65 years), body mass index, systolic blood pressure, low-density lipoprotein cholesterol, glucose, and year of recruitment, FMD was significantly smaller in the excessive smoker group than in the never smoker group as a reference group (OR 1.95, 95% CI 1.42 to 2.67; P < 0.001). These findings suggest that FMD decreases with an increase in the number of cigarettes smoked and that excessive smoking is associated with endothelial dysfunction. Cigarette smoking is harmful to vascular function in men who are heavy smokers. [ABSTRACT FROM AUTHOR]

Introduction: The usefulness of vascular function tests for management of patients with a history of coronary artery disease (CAD) is not fully known. Methods: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with CAD for assessment of the predictive value of vascular function tests for future cardiovascular events in a prospective multicenter observational study. The primary outcome was coronary events, and the secondary outcome was a composite of coronary events, stroke, heart failure, and sudden death. Results: During a median follow-up period of 49.2 months, the primary outcome occurred in 56 patients and the secondary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the primary and secondary outcomes, was significantly associated with lower risk of the primary (hazard ratio, 0.27; 95% confidence interval [CI], 0.06-0.74; P=0.008) and secondary (hazard ratio, 0.32; 95% CI, 0.09-0.79; P=0.01) outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the primary (hazard ratio, 1.86; 95% CI, 1.01-3.44; P=0.04) and secondary (hazard ratio, 2.19; 95% CI, 1.23-3.90; P=0.008) outcomes. Among four groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the primary and secondary outcomes were observed. Conclusions: In patients with CAD, both FMD and baPWV were independent predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification. [ABSTRACT FROM AUTHOR]

Backgrounds Nitroglycerine-induced vasodilation (NID) is usually assessed as a control test for flow-mediated vasodilation (FMD). However, NID per se is impaired in patients with high cardiovascular risk. The purpose of this study was to investigate the associations of chronic kidney disease (CKD) with NID and FMD. Methods We measured NID and FMD in a total of 1567 adult subjects without end-stage renal disease (ESRD), 28% of whom had CKD as judged by measurements of estimated glomerular filtration rate (995 men and 572 women; mean age, 59.0 ± 16.9 years; age range, 18 to 92 years). Results NID was significantly smaller in patients with CKD than in those without CKD (10.8 ± 6.0% vs. 12.7 ± 5.7%, P < 0.001). The prevalence of vascular smooth muscle dysfunction, defined as NID of less than the division point for the lowest quartile, was significantly higher in patients with CKD than in those without CKD (37.5% vs. 21.5%, P < 0.001). Multivariate analysis revealed that CKD was independently associated with vascular smooth muscle dysfunction (OR: 1.36, 95% CI: 1.02 to 1.81, P = 0.04). FMD was significantly smaller in patients with CKD than in those without CKD (3.1 ± 2.8% vs. 4.0 ± 3.0%, P < 0.001). The prevalence of endothelial dysfunction, defined as FMD of less than the division point for the lowest quartile, was significantly higher in patients with CKD than in those without CKD (31.7% vs. 23.1%, P = 0.002). However, CKD was not independently associated with endothelial dysfunction in an age- and sex-adjusted model (OR: 0.95, 95% CI: 0.71 to 1.26, P = 0.72). Conclusions Non-ESRD CKD is independently associated with vascular smooth muscle dysfunction but not with endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Background and aims 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. Methods 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. Results 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). Conclusions In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Objective: Rho-associated kinase (ROCK) signaling pathway has been shown to mediate various cellular functions including cell proliferation, migration, adhesion, apoptosis, and contraction, all of which may be involved in pathogenesis of atherosclerosis. Endogenous nitric oxide (NO) is well known to have an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Methods: VSMCs migration was evaluated using a modified Boyden chamber assay. ROCK activities were measured by Western blot analysis in murine and human VSMCs and aorta of mice treated with or without angiotensin II (Ang II) and/or sodium nitroprusside (SNP), an NO donor. Results: Co-treatment with SNP inhibited the Ang II-induced cell migration and increases in ROCK activity in murine and human VSMCs. Similarly, the increased ROCK activity 2 weeks after Ang II infusion in the mouse aorta was substantially inhibited by subcutaneous injection of SNP. Conclusions: These findings suggest that administration of exogenous NO can inhibit ROCK activity in VSMCs in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Objective: Nitroglycerine-induced vasodilation is usually used as a control test for flow-mediated vasodilation (FMD). However, nitroglycerine-induced vasodilation per se has also been reported to be impaired in patients with atherosclerosis. The purpose of this study was to determine the relationship between nitroglycerine-induced vasodilation and the clinical severity of peripheral artery disease (PAD). Methods and results: We measured nitroglycerine-induced vasodilation and FMD in 144 subjects (mean age: 63.8 ± 15.1 years), including 32 PAD patients with critical limb ischemia (CLI group), 28 PAD patients without CLI (non-CLI group), 60 age- and sex-matched patients without established cardiovascular disease (at-risk group), and 24 healthy subjects (healthy group). Nitroglycerine-induced vasodilation was significantly impaired in the CLI group compared to that in the other three groups (healthy group, 16.0 ± 5.3%; at-risk group, 12.9 ± 3.8%; non-CLI group, 10.3 ± 5.1%; CLI group, 6.7 ± 3.9%; P < 0.05, respectively). Even after multivariate adjustment, the differences remained significant. On the other hand, FMD was significantly impaired in the at-risk, non-CLI, and CLI group compared with that in the healthy group (healthy group, 7.1 ± 2.9%; at-risk group, 3.4 ± 2.3%; non-CLI group, 3.5 ± 2.7%; CLI group, 3.0 ± 2.8%; P < 0.001, respectively), but the differences among the at-risk, non-CLI, and CLI groups were not significant. Multivariate analysis revealed that nitroglycerine-induced vasodilation (odds ratio: 0.77, 95% confidence interval [CI]: 0.61–0.97) and diabetes mellitus (odds ratio: 8.75, 95% CI: 1.74–44.2) were independent variables for CLI in PAD patients. Conclusions: There was no significant difference in FMD between PAD patients with and those without CLI, but nitroglycerine-induced vasodilation was significantly smaller in PAD patients with CLI compared with those without CLI. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model. Methods: We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20) or saline was injected as a control group (n = 20). LBF was measured using an electromagnetic flowmeter. A total of 106 MSCs were implanted into each ischemic limb. Results: Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. Conclusions: These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production. [ABSTRACT FROM AUTHOR]

Background--Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation. Methods and Results--This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P=0.01), the intra-arrest PCI was higher (88% versus 70%; P=0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25-51] versus 54 minutes [34-74 minutes]; P=0.002). Conclusions--Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed. [ABSTRACT FROM AUTHOR]

Background--Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors. Methods and Results--A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 versus 9.4±2.7 μmol/L; P

Backgrounds: Periodontal disease is independently associated with cardiovascular disease. Several lines of evidence have shown that intensive treatment for periodontal disease improves the systemic inflammation and vascular function. However, it is unclear whether tooth brushing behavior, which is basic oral care in daily life, improves cardiovascular outcome. The purpose of this study was to evaluate the impact of the detailed tooth brushing behavior on the incidence of cardiovascular events. Methods: A total of 682 subjects (423 men and 259 women, mean age of 62 years) including 197 subjects with cardiovascular disease were enrolled in the study from January 2012 to October 2016. We divided the patients into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (

Introduction: Lower urinary tract symptoms (LUTS) is common symptom and impairs quality of life in elderly men. Recently, atherosclerosis has been focused on as one of the mechanisms of LUTS. The objective of this study was to evaluate the relationships of vascular function and structure with LUTS in men and women. Methods: This was a single center cross-sectional study. A total of 583 subjects (379 men and 204 women, mean age of 64 years) including 176 subjects with cardiovascular disease were assessed vascular function by flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), and vascular structure by brachial-ankle pulse wave velocity (baPWV), and LUTS by International Prostate Symptom Score (IPSS). Results: IPSS was significantly correlated with conventional atherosclerotic factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS was independently associated with the prevalence of cardiovascular disease (OR: 1.79, 95% CI, 1.08-2.96; P=0.02) after adjusting for traditional cardiovascular risk factors. In men, FMD and NID were lower in the moderate to severe LUTS group than in the none to mild LUTS group (2.1±2.0% vs. 4.0±3.0% and 9.3±6.1% vs. 12.8±6.6%, P<0.001, respectively). baPWV was higher in the moderate to severe LUTS group than in the none to mild LUTS group (1722±386 cm/s vs. 1509±309 cm/s, P<0.001). After adjusting for confounding factors of LUTS, FMD was independently associated with decreasing IPSS (β=-0.15, P=0.01), storage subscore (β=-0.13, P=0.03) and voiding subscore (β=-0.13, P=0.04) in men, but not in women. NID and baPWV were not independently associated with IPSS in either men or women. Conclusions: In the present study, endothelial dysfunction was associated with LUTS in men. LUTS in men should be focused on as the early phenotype of atherosclerosis. Further studies are needed to determine whether LUTS can predict future cardiovascular events. [ABSTRACT FROM AUTHOR]