Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
K S Woo
Publications and source records attributed to K S Woo.
Can streptokinase produce beneficial effects additional to coronary recanalization? Quantitative microvascular analysis of critically injured reperfused myocardium.
The aim of this study was to evaluate whether streptokinase (SK) may produce beneficial effects at the level of microvascular circulation in addition to coronary recanalization. Twenty mongrel dogs weighing 28.4 +/- 4.6 kg were randomized to receive SK (16,000-72,000 U/kg) or 20 ml saline (control) in an open-chest anterior descending artery occlusion (3 h) and reperfusion (2 h) model. Myocardial blood flow was measured by the radioactive microsphere technique and the state of microvascular circulation (red blood cell containing capillary counts and tissue red blood cell content) was evaluated in the infarcted subendocardial zone using computerized image analysis. The percentage (mean +/- SE) of cell-containing vessels normalized to nonischemic control areas was 166.5 +/- 7.5 in SK-treated infarcts while in untreated control infarcts it was more variable (130.0 +/- 15.6%) (2P > 0.1). The red blood cell content of infarcts treated with 2.0 megaunits SK was 3.9 +/- 0.6% compared with 6.7 +/- 0.9% in untreated control infarcts (2P = 0.029). Plasma viscosity was slightly reduced in SK-treated dogs (2P = 0.05), but no significant changes in blood fibrinogen, hemoglobin, blood flow, and high energy phosphate levels between control and SK-treated infarcts were observed. SK reduces congestion and results in more even reperfusion of the microvasculature in severely ischemic myocardium to which blood flow has been restored. This effect may be beneficial in the salvage and healing of clinical infarctions.
Animals↗
Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators.
OBJECTIVE: The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] 95-115 mm Hg). METHODS: A total of 1161 patients were randomized in a 2:2:1 ratio to 12 weeks of treatment with losartan 50 mg QD, possibly titrated to 100 mg QD (n = 461); candesartan 8 mg QD, possibly titrated to 16 mg QD (n = 468); or losartan 50 mg QD, possibly titrated to losartan 50 mg plus HCTZ 12.5 mg QD (n = 232). At 6 weeks, the regimens of patients not reaching a goal SiDBP <90 mm Hg were titrated as described, whereas patients achieving this goal continued with low-dose monotherapy. The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens, predefined as a maximum between-treatment difference in the mean change from baseline trough SiDBP of 2.5 mm Hg. RESULTS: At 12 weeks, changes in SiDBP/sitting systolic blood pressure (SiSBP) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg with candesartan 8 mg/16 mg demonstrated equivalence between the 2 monotherapy regimens (95% CI for difference in SiDBP, -1.6 to 0.2). At 12 weeks, the losartan 50 mg/50 mg plus HCTZ 12.5 mg regimen had reduced SiDBP/SiSBP significantly more (-14.3/-18.0 mm Hg) than either the candesartan 8 mg/16 mg (SiDBP, P = 0.045; SiSBP, P = 0.017) or losartan 50 mg/100 mg regimen (SiDBP and SiSBP, P = 0.001). During the last 6 weeks, patients whose regimen had been titrated to losartan 50 mg plus HCTZ 12.5 mg (n = 114) showed a greater reduction in SiDBP/SiSBP (-14.5/ -18.7 mm Hg) than did those whose regimen had been titrated to either losartan 100 mg (-10.5/-12.3 mm Hg; n = 211) or candesartan 16 mg (-11.5/-13.2 mm Hg; n = 206), representing a clinically meaningful > or = 2.5-mm Hg) difference. All 3 treatments were well tolerated, with few patients experiencing drug-related adverse events (6.9% losartan 50 mg/100 mg, 7.5% candesartan 8 mg/16 mg, 3.0% losartan 50 mg/ 50 mg plus HCTZ 12.5 mg). Candesartan 8 mg/16 mg increased serum uric acid levels (0.13 mg/dL; 95% CI, 0.04 to 0.23), whereas losartan 50 mg/100 mg decreased them (-0.14 mg/dL; 95% CI, -0.24 to -0.04), and losartan 50 mg/50 mg plus HCTZ 12.5 mg left them unchanged (0.06 mg/dL; 95% CI, -0.07 to 0.20). CONCLUSIONS: Losartan 50 mg/100 mg and candesartan 8 mg/16 mg were comparable treatments in terms of blood pressure reduction. After titration, losartan 50 mg plus HCTZ 12.5 mg was superior to either candesartan 16 mg or losartan 100 mg in reducing hypertension. Losartan, but not candesartan, lowered serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg.
Adult↗
The impact of heavy passive smoking on arterial endothelial function in modernized Chinese.
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.
Administration, Sublingual↗
Renin-angiotensin-aldosterone system gene polymorphisms and hypertension in Hong Kong Chinese.
In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease. The renin-angiotensin-aldosterone system (RAAS) helps maintain blood pressure and salt homeostasis and appears important in the pathogenesis of hypertension and some forms of vascular disease. We investigated three RAAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor A1166C polymorphisms in 232 hypertensive and 178 normotensive Chinese subjects. The hypertensives were generally more obese and dyslipidaemic. No significant differences in genotype or allele frequencies for any of the polymorphisms were identified between the groups, nor was there any interactive contribution to blood pressure by the ACE and AGT polymorphisms. However, there were large differences in genotype and allele frequencies between the healthy Chinese and published data for equivalent Caucasian populations. These findings suggest these polymorphisms are unlikely to be involved in the pathogenesis of hypertension in Chinese.
Adult↗
Beta-blockade in heart failure: a comparison of carvedilol with metoprolol.
OBJECTIVES: This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure. BACKGROUND: Beta-adrenergic blockade is of proven value in chronic heart failure. Metoprolol, a selective beta-blocker, is widely used, but recent trials suggest carvedilol, a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities, is also effective. It is uncertain, however, if these additional properties of carvedilol provide further clinical benefit compared with metoprolol. METHODS: In this randomized double-blind control trial, 51 patients with chronic heart failure and mean left ventricular (LV) ejection fraction of 26% +/- 1.8% were randomly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy after a four-week dose titration period for a total of 12 weeks. Response was assessed by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LV ejection fraction, two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability. RESULTS: Both carvedilol and metoprolol produced highly significant improvement in symptoms (p < 0.001), exercise capacity (p < 0.05) and LV ejection fraction (p < 0.001), and there were no significant differences between the two drugs. Carvedilol had a significantly greater effect on sitting and standing blood pressure, LV end-diastolic dimension and normalized the mitral E wave deceleration time. CONCLUSIONS: Both metoprolol and carvedilol were equally effective in improving symptoms, quality of life, exercise capacity and LV ejection fraction, although carvedilol lowers blood pressure more than metoprolol.
Adrenergic beta-Antagonists↗
Transcranial Doppler evaluation of microembolism immediately after direct-current cardioversion for atrial fibrillation in anticoagulated patients.
Transcranial Doppler monitoring showed no evidence of microemboli for 10 minutes after direct-current cardioversion for atrial fibrillation.
Adult↗
Comparison of frequencies of left ventricular systolic and diastolic heart failure in Chinese living in Hong Kong.
There is a wide variation (13% to 74%) in the reported prevalence of heart failure associated with normal left ventricular (LV) systolic function (diastolic heart failure). There is no published information on this condition in China. To ascertain the prevalence of diastolic heart failure in this community, 200 consecutive patients with the typical features of congestive heart failure were studied with standard 2-dimensional Doppler echocardiography. A LV ejection fraction (LVEF) >45% was considered normal. The results showed that 12.5% had significant valvular heart disease. Of the remaining 175 patients, 132 had a LVEF >45% (75%). Therefore, 66% of patients with a clinical diagnosis of heart failure had a normal LVEF. Heart failure with normal LV systolic function was more common than systolic heart failure in those >70 years old (65% vs 47%; p = 0.015). Most (57%) had an abnormal relaxation pattern in diastole and 14% had a restrictive filling pattern. In the systolic heart failure group, a restrictive filling pattern was more common (46%). There were no significant differences in the sex distribution, etiology, or prevalence of LV hypertrophy between these 2 heart failure groups. In conclusion, heart failure with a normal LVEF or diastolic heart failure is more common than systolic heart failure in Chinese patients with the symptoms of heart failure. This may be related to older age at presentation and the high prevalence of hypertension in this community.
Aged↗
Influence of gene polymorphisms of the renin-angiotensin system on clinical outcome in heart failure among the Chinese.
BACKGROUND: An association between the DD allele of the angiotensin-converting enzyme gene and a poorer outcome in patients with heart failure has been found in whites. The DD allele frequency is lower in Chinese, but the M235T variant of the angiotensinogen gene is more common in Chinese than whites; it is not known to what extent polymorphisms of the renin-angiotensin system affect clinical status or prognosis in Chinese patients with heart failure. METHODS: We assessed the relations among polymorphism of the angiotensin-converting enzyme gene, angiotensinogen M235T (AGT) gene, and angiotensin type I receptor A1166C gene with left ventricular systolic function, left and right ventricular diastolic function, serum angiotensin-converting enzyme, plasma aldosterone and atrial natriuretic peptide levels at presentation, and clinical outcome at 1 year (survival, hospital admissions) in a cohort of Chinese patients with typical systolic heart failure (n = 82). RESULTS: We confirmed the low prevalence of the angiotensin-converting DD and the angiotensin type I receptor CC genotypes, and high prevalence of the AGT TT genotype in Chinese subjects compared with whites. There was no relation between the various gene polymorphisms and survival at 1 year assessed by multiple regression or Cox regression survival analysis. The AC variant of the angiotensin type I receptor gene was associated with morbidity over a 1-year period (hospital admissions) and increased baseline aldosterone levels, but none of the other polymorphisms correlated with systolic or diastolic function, aldosterone or atrial natriuretic peptide levels. By multiple regression for effects on mortality rate, only atrial natriuretic peptide and age were significant. CONCLUSIONS: In Chinese patients with heart failure, polymorphisms of the renin-angiotensin system do not appear to be related to survival or severity, probably because of the different prevalence of these genotypes in the Chinese. Thus this study illustrates that large interethnic differences in the frequencies of genotype polymorphisms of the renin-angiotensin system exist and results from one ethnic group cannot be extrapolated to another.
Aldosterone↗
Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.
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.
Administration, Oral↗
Westernization of Chinese adults and increased subclinical atherosclerosis.
Cardiovascular event rates are much lower in China compared with developed countries. "Westernization" of diet and lifestyle in the Chinese, however, may lead to an increased prevalence of atherosclerosis-related diseases. Because carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis, we examined IMT and vascular risk profile in community-based groups of rural Chinese, Westernized urban Chinese, and urban whites. Mean IMT of the common carotid artery was measured in 348 healthy adults, aged 42+/-13 years (range 21 to 71 years); 116 subjects from rural China, 116 urban Chinese subjects living in Hong Kong or in Australia, and 116 urban Caucasians living in Australia. These 3 groups were matched for age, sex, and cigarette smoke exposure. Urban Chinese subjects had slightly better risk factor profile (higher HDL-cholesterol and lower blood pressure) compared with rural Chinese subjects. Despite this, however, the mean IMT was lowest in rural Chinese (0.50+/-0.10 mm), intermediate in urban Chinese (0.56+/-0.12 mm), and highest in urban whites (0.64+/-0.13 mm) (P<0.001 for comparisons between all groups). These differences in IMT were not altered after adjustment for the major traditional cardiovascular risk factors (serum lipids, smoking, and blood pressure or for body mass index). The influence of vascular risk factors on atherosclerosis between urban versus rural Chinese subjects was studied by multivariate regression models and by comparing the steepness of regression slopes between risk factors and IMT in the subject groups. The effects of smoking, HDL-cholesterol, and triglycerides on IMT were significantly greater in the urban compared with the rural Chinese (P<0.01). These data suggest that Westernization of Chinese subjects is associated with greater susceptibility to the pro-atherogenic effects of traditional vascular risk factors, such as lipids and smoking, and with evidence of increased IMT as a marker of subclinical atherosclerosis.
Adult↗
A sibling-pair analysis of fasting lipids and anthropometric measurements and their relationship to hypertension.
Fifty non-diabetic, young Chinese hypertensives were compared to their normotensive siblings with respect to body fat distribution and fasting lipid and glucose (FPG) profiles. Sitting BP in hypertensives met conventional hypertension criteria after a 4-week washout period on placebo. Hypertensives had greater body mass index (BMI), subscapular skin-fold thickness (SFT), waist circumference (W), waist-to-height (WHtR) and waist-to-hip ratio (WHR), p<0.0001 for all. Higher triglycerides (p=0.004) and lower HDL-cholesterol (p=0.015) concentrations were also observed. Weight, W, WHtR and BMI were higher in hypertensives in both male (n=9) and female gender-concordant sibling pairs (n=21). Higher WHR, hip circumference and subscapular SFT were only seen in the male hypertensives. Hypertension is associated with central adiposity and adverse lipid profiles in this group of young hypertensives, supporting the hypothesis that obesity, particularly central, is closely associated with hypertension in Chinese as in other ethnic groups.
Adult↗
Effect of beta-blockade on baroreceptor and autonomic function in heart failure.
Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart failure there is little information on their effects on autonomic and baroreceptor function which may have important prognostic implications. We sought to determine first whether beta-adrenoreceptor blockade will improve baroreceptor function and vagal tone in chronic heart failure, and second whether there were any differences between standard therapy with metoprolol and the second-generation vasodilating beta-blocker celiprolol. In this double-blind randomized placebo-controlled study 50 patients with stable chronic heart failure received either celiprolol 200 mg daily, metoprolol 50 mg twice daily or placebo for 12 weeks after a 4-week dose titration period. Thirty-five healthy normal subjects were also studied. Baroreceptor gain was assessed non-invasively by cross-spectral analysis of R-R and systolic blood pressure low- and high-frequency components (the alpha angle) during controlled respiration. High-frequency power was used as a measure of vagal modulation. Satisfactory recordings for analysis were obtained in 31 patients with heart failure. The results showed that at baseline baroreceptor gain (alphaHF) was significantly depressed in patients with heart failure compared with the normal control group (4.95+/-0. 55 versus 11.73+/-1.32 ms/mmHg, P<0.0001). After 12 weeks of treatment with metoprolol baroreceptor gain improved significantly whether measured while supine (P=0.03) or standing (P=0.009), and this was associated with a significant increase in R-R HF power (P=0. 008). There were no significant changes after treatment with celiprolol or placebo. We conclude that metoprolol but not celiprolol therapy restores baroreceptor gain towards normal and increases vagal tone in chronic heart failure. The ancillary properties of celiprolol do not appear to provide any advantages over metoprolol for the restoration of autonomic and baroreceptor function in heart failure.
Adrenergic beta-Antagonists↗
Body fatness and serum lipids of 11-year-old Chinese children.
It has been suggested that distribution of body fat has a stronger bearing on health risk than total body fat. Magnetic resonance imaging (MRI) was used to examine the distribution of fat and correlated with body fat assessed by the usual clinical methods-weight, weight-for-height, body mass index (BMI), triceps and subscapular skinfold thickness in 11-y-old Chinese children. Lipid profiles were used as indicators for coronary risk. Eighty-eight subjects had body fat distribution estimated by MRI, while 49 had serum lipids measured. Anthropometric parameters correlated significantly with total fat at the umbilical level measured by MRI (weight: r = 0.90 in boys, 0.75 in girls; BMI: r = 0.94 in boys, 0.87 in girls; percent median weight-for-height: r = 0.90 in boys, 0.79 in girls, triceps skinfold thickness: r = 0.89 in boys, 0.90 in girls; subscapular skinfold thickness: r = 0.93 in boys, 0.88 in girls). Obese subjects had proportionally less visceral fat than subcutaneous fat at umbilical level. Using stepwise multiple regression, predictive factors for high-density lipoprotein cholesterol were BMI in boys and breast-staging in girls. For triglycerides, it was genital staging in boys and for total cholesterol, it was breast-staging in girls. Visceral fat was not a significant determinant of serum lipids.
Adipose Tissue↗
Beta blockers in heart failure: a comparison of a vasodilating beta blocker with metoprolol.
OBJECTIVE: To determine whether a third generation vasodilating beta blocker (celiprolol) has long term clinical advantages over metoprolol in patients with chronic heart failure. DESIGN: A double blind placebo controlled randomised trial. SETTING: University teaching Hospital. PATIENTS: 50 patients with stable chronic heart failure (NYHA class II-IV) due to idiopathic dilated, ischaemic, or hypertensive cardiomyopathy, with left ventricular ejection fraction < 0.45. INTERVENTIONS: Celiprolol 200 mg daily (n = 21), metoprolol 50 mg twice daily (n = 19), or placebo (n = 10) for three months with a four week dose titration period. After the double blind period, patients entered an open label study (with placebo group receiving beta blockers) and were assessed after one year. MAIN OUTCOME MEASURES: Clinical response, efficacy, and tolerance were assessed by the Minnesota heart failure symptom questionnaire six minute walk test, Doppler echocardiography (systolic and diastolic function), radionuclide ventriculography, and atrial and brain natriuretic peptides measured at baseline and after three months. RESULTS: In the metoprolol group at 12 weeks v baseline there was a 47% reduction in symptom score (p < 0.001), improvement of NYHA class (mean (SEM), 2.6 (0.12) to 1.9 (0.13), p = 0.001), exercise distance (1246 (54) to 1402 (52) feet, p < 0.001), and left ventricular ejection fraction (26.9(3.1)% to 31(3.0)%, p = 0.016), and a fall in heart rate (resting, 79 (3) to 62 (3) beats/min, p < 0.001). In the celiprolol group there was a 38% reduction in symptom score (p = 0.02), less improvement in exercise distance (1191 (55) to 1256 (61) feet, p = 0.05), and no significant changes in NYHA class, left ventricular ejection fraction, or heart rate. Mortality at one year was 11% in metoprolol and 19% in the celiprolol group, and symptomatic improvement was maintained in the survivors. CONCLUSIONS: Both drugs were well tolerated but the vasodilator properties of celiprolol do not seem to provide any obvious additional benefit in the long term treatment of heart failure.
Adrenergic beta-Antagonists↗
New risk factors for coronary heart disease in Asia.
The increasing prevalence of traditional atherosclerotic risk factors have been documented in Asia but the real impact on prevalence of coronary heart disease (CHD) remains unclear. Smoking, hypertension, hypercholesterolaemia, diabetes mellitus and obesity are present in only 50% of CHD. In community studies of Chinese in Hong Kong and southern mainland-China, aging, smoking and hypercholesterolaemia were found to have a less impact on endothelial function in the Chinese compared with Caucasians in London and Sydney. As endothelial dysfunction is an early event in atherogenesis, there will be a strong need to search for newer risk factors for CHD in Asia, which may become more important in many Asian countries now in the process of modernization. Recently, heterozygous hyperhomocysteinaemia (with or without folate deficiency) was found to be an independent risk factor for arterial endothelial dysfunction, and hyperhomocysteinaemia in association with smoking was a significant risk factor for premature coronary heart disease in Hong Kong Chinese. Other newer factors which have emerged include folate deficiency, low HDL-cholesterol, insulin resistance, abdominal obesity, Methylene-tetrahydrofolate Reductase and Angiotensin Converting Enzyme gene polymorphism.
Adult↗
Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans.
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.
Adult↗
Differences in the effect of cigarette smoking on endothelial function in chinese and white adults.
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.
Adolescent↗