Background Diagnostic criteria of flow‐mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin‐induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no‐risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow‐Mediated Dilation Japan study and the Flow‐Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver‐operator characteristic curve analysis of FMD to discriminate subjects in the no‐risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no‐risk group was 7.1%. Receiver‐operator characteristic curve analysis of NID to discriminate subjects in the no‐risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no‐risk group was 15.6%. Conclusions We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects. Clinical Trial Registration www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409

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 brachialankle 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. Hematocrit (Hct), the volume percentage of red blood cells (RBCs) in total blood, and hemoglobin (Hb) are associated with a risk of cardiovascular disease. A high Hct level has been shown to be associated with an increased risk of cardiovascular disease 1-3. On the other hand, J-or U-shaped relations between Hct and morbidity and mortality from cardiovascular events have been shown 1. The relationship between a low Hct level and cardiovascular disease is controversial 1,3,4. It is well known that Hct and Hb levels are major determinants of blood viscosity and oxygen delivery dynamics. It is thought that changes in blood viscosity and oxygen delivery dynamics alter vascular function and structure. Indeed, Lee et al. showed that high blood viscosity was associated with increased carotid intima-media thickness (IMT) 5. However, there is no information on the associations of Hct, Hb and RBCs with vascular function and vascular structure. Endothelial dysfunction is the initial step of atherosclerosis and leading to the development and progression of this condition 6,7. Recently, flow-mediated vasodilation (FMD) as an index of endothelium-dependent

BACKGROUND: It is not clear whether a high level of high-density lipoprotein cholesterol (HDL-C) is associated with lower risk of atherosclerosis. It is likely that HDL-C is a double-edged sword for atherosclerosis. OBJECTIVE: The purpose of this study was to evaluate the relationship between HDL-C levels and endothelial function in men. METHODS: This was a cross-sectional study. We evaluated flow-mediated vasodilation (FMD) and serum levels of HDL-C in 5842 men aged 18 to 92 years who were not receiving lipid-lowering therapy. All participants were divided into four groups by HDL-C level: low HDL-C (,40 mg/dL),

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.

Objective: Primary aldosteronism is one of the most common cause of secondary hypertension. It is well known that the incidence of cardiovascular events is higher in patients with primary aldosteronism than in patients with essential hypertension. In a previous study, we showed that aldosterone-producing adenoma is associated with vascular function and structure. The aim of this study was to evaluate the effects of eplerenone on vascular function in the macrovasculature and microvasculature, arterial stiffness and Rho-associated kinase (ROCK) activity in patients with idiopathic hyperaldosteronism (IHA). Methods: Vascular function, including reactive hyperemia index (RHI), flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), arterial stiffness including brachial–ankle pulse wave velocity (baPWV) and brachial intima–media thickness (IMT) and ROCK activity in peripheral leukocytes were measured before and after 12 weeks of treatment with eplerenone in 50 patients with IHA. Results: After 12 weeks, eplerenone decreased the aldosterone renin ratio but did not alter SBP and DBP. Eplerenone treatment increased log RHI from 0.56 ± 0.25 to 0.69 ± 0.25 (P< 0.01) and NID from 12.8 ± 5.8 to 14.9 ± 6.9% (P = 0.02) and it decreased baPWV from 1540± 263 to 1505 ±281 (P = 0.04) and ROCK activity from 1.20 ± 0.54 to 0.89 ± 0.42 (P< 0.01), whereas there was no significant change in FMD (increase from 4.6 ± 3.4 to 4.6±3.6%, P = 0.99) or brachial IMT (decrease from 0.28±0.07 to 0.28±0.04mm, P = 0.14). Conclusion: Eplerenone improves microvascular endothelial function, vascular smooth muscle function, arterial stiffness and ROCK activity in patients with IHA.