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Vascular reactivity is a surrogate marker for atherosclerosis and is predictive of cardiovascular outcome. Non-cardiovascular surgery is associated with perioperative cardiovascular complications in high-risk patients. To evaluate the impact of non-cardiovascular surgery on reactive hyperaemia and arterial endothelial function and to investigate the relationships between endothelial dysfunction and invasive (laparotomy) or minimally invasive (laparoscopic) surgery, we prospectively evaluated 106 patients undergoing abdominal surgery under general anaesthesia (71 laparotomy, 35 laparoscopy). Measurements of blood pressure, heart rate and pain (on a visual analogue scale (VAS)) were undertaken. Brachial endothelium-dependent flow-mediated dilation (FMD), endothelium-independent dilation, nitroglycerin (NTG)-induced dilation and reactive hyperaemia were measured with high-resolution B-mode ultrasound on preoperative Day 1 (baseline), as well as 2 h and 1 and 7 days postoperatively. Blood pressure and heart rate were significantly higher 2 h postoperatively. Pain, as measured on the VAS, was higher (P < 0.01) and reactive hyperaemia and FMD were significantly lower (P < 0.001) at 2 h and 1 day postoperatively compared with values at baseline and on postoperative Day 7. By postoperative Day 7, FMD had recovered to baseline levels. Patients undergoing laparoscopic surgery had less FMD reduction on Days 1 and 7 (7.5 ± 1.5% and 7.9 ± 1.5%, respectively) compared with those undergoing laparotomy (6.4 ± 1.6% (P = 0.001) and 7.0 ± 1.6% (P = 0.006), respectively), consistent with potential cardiovascular benefit. Responses to NTG were stable throughout. Backward multivariate linear regression analysis indicated that FMD was independently related to age and VAS (model R = 0.486; F = 6.4; P < 0.001). Reactive hyperaemia and arterial endothelial function are significantly reduced in the early postoperative period, particularly after laparotomy compared with laparoscopy, which may be related to postoperative cardiovascular events., (© 2013 Wiley Publishing Asia Pty Ltd.) more...

Objective: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians., Design: Double-blind, placebo controlled, randomised crossover study., Setting: Community dwelling vegetarians., Participants: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited., Intervention: Vitamin B-12 (500 µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41)., Measurement: Flow-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound., Results: The mean age of the subjects was 45±9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150 pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09 mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09 mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028)., Conclusions: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention. more...

Ethnopharmacological Relevance: Salviae Miltiorrhizae Radix (Danshen) and Puerariae Lobatae Radix (Gegen) are principal herbs have long been used in combination for treating cardiovascular disease., Aims of Study: Danshen and Gegen in the ratio of 7:3 (DGW) have significantly reduced the carotid intimal-media thickening (IMT) in patients in our previous clinical study. In the present study, we have demonstrated the mechanisms on IMT reduction by investigating its key processes on both vascular smooth muscle cell (vSMC) and endothelial cells., Materials and Methods: The anti-proliferative effects of DGW on platelet-derived growth factor (PDGF) induced vSMC proliferation were studied by cell proliferation, cell cycle distribution, p-ERK and cyclin D expression level. The anti-migratory effect of DGW was investigated by using transwell apparatus. For human umbilical endothelial cells (HUVEC), the inhibitory effects of DGW on TNF-alpha induced cell adhesion, cell adhesion molecules expression, MCP-1 and IL-6 production were investigated., Results: DGW significantly inhibited A7r5 proliferation and exhibited G1/S cell cycle arrest by suppressing both p-ERK and cyclin D expression. Moreover, DGW showed anti-migratory effect against PDGF-induced A7r5 migration. In addition, DGW inhibited the cell adhesion as well as the expression of ICAM-1 and VCAM-1, the production of MCP-1 but not IL-6 in TNF-α stimulated HUVECs., Conclusions: Our study provided strong scientific evidence on IMT reduction in patients by modulating the key atherogenic events in both vSMC and endothelial cells., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.) more...

Background: Danshen and gegen (D&G) have long been used in treatment of angina and other cardiac symptoms in Chinese materia medica. Recent pharmacological studies suggest their therapeutic values. We aimed to evaluate the efficacy and safety of Salvia miltiorrhiza (danshen) and Pueraria lobata (gegen) in secondary prevention., Methods: One hundred (100) consecutive coronary patients (mean age 58 +/- 8 years) were randomized to adjunctive treatment with D&G combination (3 g) or placebo (6 capsules) for 24 weeks in double-blind parallel fashion, followed by optional open-label D&G (1.5 g/day) for 6 more months. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured using ultrasound., Results: Baseline characteristics were similar between the 2 groups. After 24 weeks and compared with baseline, there were no significant changes in blood pressures, blood hematological and biochemical profiles, or folate and homocysteine levels in both groups, but there was a mild decrease in low density lipoprotein (LDL) cholesterol in both groups (p < 0.05). Brachial FMD improved during D&G (p < 0.001) and less so during placebo treatment (p < 0.05), while improvement in carotid IMT was observed only in the D&G group (p < 0.05). After open-label D&G treatment for 6 more months (n = 45), further improvement in both brachial FMD (p < 0.0001) and carotid IMT (p < 0.0001) was observed. Eight (8) adverse events were reported-6 during placebo and 2 during D&G treatment-requiring treatment termination in 2 patients (on placebo)., Conclusions: D&G adjunctive treatment in coronary patients was well tolerated and effective in improving vascular function and structure. These two herbs may become a novel agent for secondary prevention. more...

Background: Both active and passive smoking are prevalent in China but cardiovascular diseases were less prevalent in the past. We studied the current relationship between surrogate atherosclerosis markers and smoking in Chinese., Methods: Endothelium-dependent flow-mediated dilation (FMD) of brachial artery and carotid intima-media thickness (IMT) were measured non-invasively by ultrasound in 616 apparently healthy Chinese (23% smokers), recruited from greater China and the USA., Results: The Chinese smokers had significantly impaired FMD (7.0+/-2.3 vs. 8.2+/-2.5%, p<0.001) and endothelium-independent vasodilation (GTN, 17.4+/-3.9 vs. 18.7+/-4.1%, p=0.001) and thicker IMT (0.61+/-0.13 vs. 0.58+/-0.12 mm, p=0.025). 91% of the smokers were male. Both endothelium-dependent (6.9+/-2.2 vs. 8.0+/-2.5%, p<0.001) and independent (17.3+/-3.5 vs. 18.2+/-3.7%, p=0.047) vasodilation were significantly lower in the male smokers than non-smokers, although their age and cholesterol levels were lower. FMD-to-GTN ratio in the smokers were lower (0.41+/-0.12 vs. 0.45+/-0.13, p=0.005). Multivariate analyses confirmed an independent adverse impact of smoking on vascular functions. There were no consistent interactions between subject location and impact of smoking on FMD and IMT., Conclusion: In these apparently healthy native and overseas Chinese subjects, smoking is adversely associated with endothelial dysfunction and arterial wall thickening, with serious implication in atherosclerosis prevention. more...

Objective: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children., Design: Case-control comparison., Subjects: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25+/-3) aged 9-12 y and 36 age- and gender-matched nonobese healthy children (BMI<21) from a school community., Measurements: The key parameters were: BMI, arterial endothelial function (ultrasound-derived endothelium-dependent dilation) and carotid artery IMT. The secondary parameters measured included body fat content, waist-hip ratio (WHR), blood pressures, blood lipids, insulin and glucose., Results: The two groups were well matched for blood pressures, cholesterol and glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese children. Overweight was associated with impaired arterial endothelial function (6.6+/-2.3 vs 9.7+/-3.0%, P<0.0001) and increased carotid IMT (0.49+/-0.04 mm vs 0.45+/-0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with BMI (P<0.003) on multivariate analysis., Conclusion: Obesity, even of mild-to-moderate degree, is independently associated with abnormal arterial function and structure in otherwise healthy young children. more...

Objective: Endothelial vasodilator dysfunction and carotid intima-media thickening are useful surrogate markers of cardiovascular disease, a major cause of morbidity and mortality in type 2 diabetic patients. However, because most studies reporting the relationships between endothelial function, intima-media thickness (IMT), and hyperglycemia have compared diabetic patients with healthy controls, we report their relationship with glycemia as a continuum., Methods and Results: Brachial artery endothelial function (flow-mediated dilatation [FMD]) and carotid IMT were measured noninvasively by high-resolution ultrasound B-mode imaging in 228 apparently healthy Chinese subjects recruited from Hong Kong and Macau. FMD and IMT were significantly associated with increasing levels of glycemia, particularly in the "high normal" glycemic range, with IMT increasing and endothelium-independent dilatation decreasing linearly across the glucose tertiles, and endothelium-dependent dilatation significantly lower in the upper glucose tertile compared with the other 2 groups (P<0.01). Using multiple linear regression, fasting glucose level was identified as an independent predictor of each of these markers of vascular function (P<0.004). Additionally, other conventional cardiovascular risk factors, including obesity, blood pressure, and an adverse lipid profile, were also related to levels of glycemia (P<0.05), further contributing to impaired vascular function., Conclusions: Increasing levels of glycemia and the coexistence of other cardiovascular risk factors in apparently healthy subjects are adversely associated with arterial endothelial dysfunction and intima-media thickening. more...

Purpose: Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function., Subjects and Methods: Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project. All subjects were given folic acid (10 mg/d) for 1 year. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound., Results: Folic acid supplementation for 1 year was associated with a significant increase in mean (+/-SD) plasma folate levels (24 +/- 5 nmol/L to 40 +/- 5 nmol/L; P < 0.001) and a significant decline in homocysteine levels (9.0 +/- 1.7 micromol/L to 7.9 +/- 2.0 micromol/L; P < 0.001). Flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses., Conclusions: These results demonstrate that long-term folic acid improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with hyperhomocysteinemia. more...

Objectives: The study evaluated whether heavy exposure to environmental tobacco smoke (passive smoking) might damage arterial function in modernized Chinese., Background: Heavy passive smoking is associated with arterial endothelial dysfunction in Caucasian, but not rural Chinese, subjects., Methods: We studied 20 young (mean age 36.6 +/- 7.0 years) nonsmoking asymptomatic casino workers (9 men) in Macau who were exposed to environmental tobacco smoke for over 8 h/day for at least two years and 20 normal subjects (control subjects). These two groups were carefully matched for age, gender, body mass index (BMI), blood pressure, vessel diameter, cholesterol and glucose levels. Brachial artery diameter was measured by high-resolution B-mode ultrasound at rest, after flow increase (causing flow-mediated endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator)., Results: Flow-mediated dilation (mean +/- SD% of diameter changes) was significantly lower in passive smokers (6.6 +/- 3.4%) compared with the controls (10.6 +/- 2.3%) (p < 0.0001). Nitroglycerin-induced dilation of the two groups were similar. Upon multivariate analysis, passive smoking exposure was the strongest independent predictor (beta = -0.59; p = 0.0001) for impaired flow-mediated endothelium-dependent dilation (model R2 = 0.75, F value = 6.1, p = 0.0001)., Conclusions: In modernized Chinese, as in Caucasians, exposure to heavy environmental tobacco smoke causes arterial endothelial dysfunction, a key early event in atherosclerosis. This may have serious implications for cardiovascular health in China, currently in a process of rapid modernization. more...

Objective: Arterial endothelial dysfunction is a key atherogenic event that may be related to oestrogen status. We therefore aimed to compare menopause-related changes in endothelial physiology in Chinese and Caucasian females., Methods: We studied 40 female subjects; 20 Chinese from a rural region of Southern China (ten premenopausal, aged 20-35 years, and ten postmenopausal, aged 55-66 years), and 20 age-matched Caucasian females from Sydney, Australia. All women had a clinical history, resting blood pressure and fasting lipids measured, and endothelial function assessed. Using high-resolution external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilatation) and after sublingual glyceryl trinitrate (GTW) (an endothelium-independent dilator)., Results: There was a significant decline in endothelium-dependent dilatation (EDD) comparing Caucasian females from the premenopausal versus postmenopausal groups (8.4+/-2.7% versus 2.7+/-2.9%; P<0.001). In contrast, there was no significant difference in EDD between pre- and postmenopausal Chinese (9.8+/-3.3% versus 8.3+/-1.7%; P=0.22). On multivariate analysis, postmenopausal status was associated with impaired EDD in Caucasian females (P<0.002) independent of serum cholesterol, blood pressure and vessel size. In contrast, EDD in the Chinese females was not significantly influenced by any of these factors. GTW-induced dilatation was also impaired in the older Caucasian females, a finding explained on multivariate analysis by the increased vessel size in this patient group (P=0.03)., Conclusion: Menopause is associated with impaired arterial endothelial function in Caucasian but not Chinese women. This suggests possible ethnic differences in menopause-related vascular changes. more...

Objectives: To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia., Background: Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known., Methods: Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 +/- 2.8 micromol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation., Results: Compared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 +/- 7.0 vs. 29.7 +/- 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 +/- 3.1 vs. 9.5 +/- 2.5 micromol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed., Conclusion: Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process. more...

Background: Hyperhomocyst(e)inemia is associated with premature peripheral vascular, cerebrovascular, and coronary artery disease. Because homocysteine has been found to be damaging to endothelial cells in animal and cell culture studies, we evaluated the association between hyperhomocysteinemia and arterial endothelial dysfunction (a marker of early atherosclerosis) in asymptomatic adult subjects., Methods and Results: Using high-resolution ultrasound, we measured endothelium-dependent flow-mediated dilation (EDD) and endothelium-independent nitroglycerin-induced dilation (GTN) of the brachial artery in 14 prospectively defined hyperhomocysteinemic (mean plasma homocysteine, 34.8+/-8.5 micromol/L), nonsmoking, healthy subjects aged 53+/-9 years and 14 control subjects with low plasma homocysteine levels (9.9+/-3.2 micromol/L). The two groups were well matched for age; sex; body mass index; blood pressure, blood cholesterol, folate, and vitamin B12 levels; and vessel diameter. EDD was significantly lower in hyperhomocysteinemic subjects (6.5+/-1.7%) than in subjects with low homocysteine levels (10.8+/-1.7%) (P<.001). GTN responses were similar in the two subject groups (P=.90). Multivariate analysis confirmed homocysteine level as the strongest predictor for impaired EDD, independent of age, sex, body mass index, or blood pressure, folate, vitamin B12, and cholesterol levels., Conclusions: Hyperhomocysteinemia is an independent risk factor for arterial endothelial dysfunction in healthy middle-aged adults. more...

The coronary flow reserve is abnormal in syndrome X, but the response to the cold pressor test, which in normals produces flow-mediated endothelium-dependent epicardial coronary dilation, has not been studied. In this study, in 12 patients with typical syndrome X and angiographically normal coronary arteries, the response to the cold pressor test was abnormal with a mean fall in diameter (10 +/- 8%) in 6 patients, no change in 1, and a minimal increase (4 +/- 2%) in 5 patients (normal increase 12 +/- 1%). The coronary blood flow fell slightly during the cold pressor test, and the coronary vascular resistance increased significantly (from 2.4 +/- 1.1 to 3.2 +/- 1.7 mm Hg/cm.s-1.mm2; p = 0.05), both abnormal responses. This study confirms that in syndrome X patients there is coronary endothelial dysfunction which is apparent in response to physiological stimuli induced by the cold pressor test. more...

Background: The prevalence of coronary artery disease in southern China is approximately one fifth that in "westernized" countries, even though approximately 70% of Chinese men smoke cigarettes and Chinese women have substantial passive exposure to cigarette smoke., Objectives: Endothelial dysfunction is an early event in atherosclerosis and occurs in young white active and passive smokers; we compared endothelial physiology in healthy young Chinese and white smokers and nonsmokers., Patients: 144 healthy adults who were 16 to 45 years of age: 72 Chinese persons in a village in southern China and 72 white persons in Australia and England who were matched for exposure to cigarette smoke. Each ethnic group comprised 36 controls (lifelong nonsmokers with no regular exposure to cigarette smoke; 16 men and 20 women) and 36 active or passive smokers (15 men and 21 women)., Measurements: Arterial endothelial function was tested with high-resolution external vascular ultrasonography, and brachial artery diameter was measured at rest, after flow increase (which causes endothelium-dependent dilatation), and after administration of sublingual nitroglycerin (an endothelium-independent dilator)., Results: Endothelium-dependent dilatation was similar in Chinese (7.9%) and white (8.4%) nonsmokers (P > 0.2). Among white persons, endothelium-dependent dilatation was lower in active or passive smokers (3.9%) than in nonsmokers (8.4%) (P < 0.001). Among Chinese persons, dilatation was not significantly lower in active or passive smokers (7.3%) than in nonsmokers (7.9%) (P > 0.2). Dilatation was higher in Chinese active or passive smokers (7.3%) than in white active or passive smokers (3.9%) (P < 0.001). Dilatation responses to nitroglycerin were similar in all groups (P = 0.17)., Conclusion: Young Chinese adults have less evidence of arterial endothelial dysfunction than young white adults with similar direct or indirect exposure to cigarette smoke. more...

Objectives: We sought to assess the effects of aging on the endothelial physiology of a group of Chinese adults., Background: Several studies have documented an association between aging and progressive arterial endothelial dysfunction in white subjects. We hypothesized that age-related endothelial dysfunction, an important event in atherosclerosis, might be less marked in southern Chinese subjects, in whom the prevalence of coronary heart disease is only approximately 20% of that in industrialized countries., Methods: We studied endothelial function in 76 healthy adults aged 16 to 70 years: 38 Chinese from a village of 3,000 people in southern China and 38 white subjects from Sydney, Australia. In each ethnic group, there were 19 younger persons (16 to 40 years) and 19 older adults (55 to 70 years). None had evidence of diabetes, hypertension or clinical vascular disease or had ever been regular cigarette smokers. With the use of high resolution external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator)., Results: Endothelium-dependent dilation was similar in young Chinese (mean +/- SD 8.3 +/- 2.5%), young whites (7.9 +/- 2.0%) and older Chinese (6.8 +/- 2.9%), but it was significantly impaired in older whites (1.8 +/- 2.5%, p < 0.001 by analysis of variance). On multivariate analysis, older age was associated with impaired endothelium-dependent dilation (p < 0.001) (independent of the effects of serum cholesterol, gender and vessel size) in the white but not in the Chinese subjects (p = 0.83). Nitroglycerin-induced dilation was not significantly different with aging in either ethnic group., Conclusions: Endothelium-dependent dilation is similar in the arteries of healthy young Chinese and white adults. With older age, however, Chinese subjects are less susceptible to impaired endothelial function. more...