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• Cumulative LDL-C exposure, calculated by age × LDL-C, had significant negative correlations with FMD value and NID value and significant positive correlations with mean CCA-IMT and maximum CCA-IMT in subjects not being treated with lipid-lowering drugs. • Endothelial dysfunction was found to be induced by cumulative LDL-C exposure of >4000 mg·year/dL, vascular smooth muscle damage >5000 mg·year/dL, and increase in IMT and plaque formation ≥6000 mg·year/dL. • Cumulative LDL-C calculated by age × LDL-C is useful for assessing the progression of atherosclerosis. The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain. The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA). This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg·year/dL, 4000–4999 mg·year/dL, 5000–5999 mg·year/dL, and ≥6000 mg·year/dL. The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg·year/dL group was significantly higher than the odds ratios in the other groups. The odds ratio of the lower quartile of NID in the <4000 mg·year/dL group was significantly higher than the odds ratios in the 5000–5999 mg·year/dL and ≥6000 mg·year/dL groups. The odds ratio of the prevalence of CCA plaque in the <4000 mg·year/dL group was significantly higher than that in the ≥6000 mg·year/dL group. Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg·year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg·year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg·year/dL. http://www.umin.ac.jp (UMIN000012950, UMIN000012951, and UMIN000012952, UMIN000003409) [Display omitted] [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]

• FMD values were highest in the group with extremely low levels of triglycerides. • Lower triglyceride levels are associated with better endothelial function. • The group with extremely low triglycerides had fewer atherosclerosis risk factors. • The odds ratio for a lower quartile of FMD remained independently lower. Increased serum triglyceride levels are independently associated with endothelial dysfunction. However, there is little evidence to define normal levels of triglycerides and there is little information on endothelial function in subjects with extremely low levels of triglycerides. The purpose of this study was to determine the relationship between triglycerides, especially low levels of triglycerides, and vascular function. We measured flow-mediated vasodilation (FMD) in 7047 subjects and nitroglycerine-induced vasodilation (NID) in 1017 subjects. We divided the subjects into eight groups by triglyceride levels: <50 mg/dL, 50-69 mg/dL, 70-89 mg/dL, 90-109 mg/dL, 110-129 mg/dL, 130-149 mg/dL, 150-199 mg/dL, and ≥200 mg/dL. FMD was significantly higher in subjects with triglyceride levels of <50 mg/dL than in subjects with triglyceride levels of 50-69 mg/dL, 70-89 mg/dL, 90-109 mg/dL, 110-129 mg/dL, 130-149 mg/dL, 150-199 mg/dL, and ≥200 mg/dL (p =0.002, p <0.001, p <0.001, p <0.001, p<0.001, p<0.001, and p <0.001, respectively). Using triglyceride levels of >200 mg/dL as a reference, the odds ratios for a lower quartile of FMD were significantly lower in the <50 mg/dL group, 50-69 mg/dL group, 70-89 mg/dL group, and 90-109 mg/dL group after adjustment for age, gender and other cardiovascular risk factors. There was a slight negative correlation between NID and triglycerides (r =-0.074; p =0.019). However, there was no significant differences in NID among the eight groups. FMD values were highest in subjects with extremely low levels of triglycerides (<50 mg/dL). Lower triglyceride levels were associated with better endothelial function. http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000012950) [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]

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]

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]

Summary: Background: Although the metabolic syndrome is associated with incident cardiovascular disease, low-density lipoprotein (LDL) cholesterol is a well-known risk factor for coronary atherosclerosis. The aim of this study was to clarify the clinical markers for coronary plaque vulnerability in acute coronary syndrome (ACS) patients (men) without the metabolic syndrome. Methods: Consecutive Japanese men with ACS (n =264) underwent emergent coronary angiography and B-mode carotid ultrasonography. Common carotid intima-media thickening and vascular dilatation were considered to indicate carotid artery remodeling. Patients were divided into two groups based on the number of complex plaques identified by coronary angiography. Results: Abdominal obesity and low high-density lipoprotein cholesterol levels were frequently observed in overall patients with multiple complex coronary lesions. Although the metabolic syndrome was a significant independent predictor of multiple complex coronary lesions in overall ACS patients, a high LDL cholesterol level was an independent predictor in ACS patients without the metabolic syndrome. Carotid artery remodeling was an independent predictor of multiple complex coronary lesions in both overall patients and patients without the metabolic syndrome. Conclusion: In ACS patients without the metabolic syndrome, high LDL cholesterol levels and carotid artery remodeling are important indicators for assessing the efficacy of aggressive treatments for secondary prevention of ACS. [Copyright &y& Elsevier]

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. The purpose of this study was to evaluate the relationship between HDL-C levels and endothelial function in men. 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), moderate HDL-C (40–59 mg/dL), high HDL-C (60–79 md/dL), and extremely high HDL-C (≥80 mg/dL). We were not able to evaluate the amount of alcohol intake because there was limited information on the amount of alcohol drinking in our database. FMD values were significantly smaller in the low group and the extremely high group than in the high group (P =.001 and P =.016, respectively). There was no significant difference in FMD between the low group and the extremely high group. Multiple logistic regression analysis revealed that extremely high HDL-C, but not low HDL-C, was independently associated with the lowest quartile of FMD (odds ratio: 1.39, 95% confidence interval: 1.09–1.77; P =.009). An extremely high level of HDL-C in men (8.1% of this population) was associated with a significant reduction in FMD. • Flow-mediated vasodilation (FMD) was smaller in the low high-density lipoprotein cholesterol (HDL-C) than in the high HDL-C group. • FMD was smaller in the extremely high HDL-C group than in the high HDL-C group. • There was no difference in FMD between the low and extremely high HDL-C groups. • Extremely high HDL-C was associated with a lower quartile of FMD. [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]

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]