Effect of exercise training on endothelial function in men with coronary artery disease

The objective of this study was to investigate the effects of 12 weeks of standard cardiac rehabilitation on endothelial function, oxidative stress, and antioxidant defenses in patients with coronary artery disease. Twelve weeks of endurance exercise training led to an improvement in endothelial function as measured by brachial artery flow-mediated dilation (7.9% at baseline vs 11.1% at 12 weeks). Exercise training resulted in increased plasma nitrite and nitrate levels, increased plasma superoxide dismutase activity, and decreased oxidative stress.     

Relation of alcohol consumption to angiographically proved coronary artery disease in chinese men

Light-to-moderate alcohol consumption is believed to be protective against coronary artery disease (CAD) in many studies. However, the cardioprotective effects of alcohol intake lack epidemiologic evidence in a Chinese population. The present case-control study was designed to explore the relation between alcohol consumption and angiographically proved CAD in Chinese men. The study population consisted of 1,476 consecutive men 36 to 84 years of age who underwent coronary arteriography. Participants were categorized as nondrinkers, light drinkers, moderate drinkers, and heavy drinkers. Adjusted odds ratios for light, moderate, and heavy drinking were 1.16 (95% confidence interval 0.68 to 1.94), 1.78 (1.35 to 2.27), and 2.18 (1.46 to 3.25). Adjusted odds ratios were 1.36 (1.08 to 1.83) for drinking alcohol 2 to 3 days/week, 1.58 (1.17 to 2.26) for 4 to 5 days/week, and 2.03 (1.36 to 3.27) for 6 to 7 days/week. Compared to nondrinking, adjusted odds ratios were 1.03 (0.54 to 1.87) for drinking 0 to 15 years, 1.61 (1.28 to 2.14) for 16 to 30 years, and 1.98 (1.23 to 3.05) for > 30 years. In conclusion, moderate-to-heavy alcohol consumption increased the risk of CAD in Chinese men. CAD risk tended to increase with an increase in frequency and duration of drinking.     

Effects of rosiglitazone on endothelial function in men with coronary artery disease without diabetes mellitus

Recent data have shown that peroxisome proliferator-activated receptor-gamma agonists may exert protective effects on the vascular endothelium by amelioration of insulin resistance and through direct anti-inflammatory effects. In this study we assessed the effect of rosiglitazone on biochemical and biophysical indexes of endothelial function in male, nondiabetic patients with coronary artery disease. Consecutive male subjects (n = 71) with clinically stable, angiographically documented coronary artery disease and without diabetes mellitus were investigated. Patients were randomized in a double-blind manner to placebo or rosiglitazone for a total of 24 weeks. Flow-mediated dilation (FMD) of the brachial artery, C-reactive protein, von Willebrand factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels, and parameters of glucose and lipid metabolism were measured at baseline and after 12 and 24 weeks of treatment. Rosiglitazone treatment significantly reduced C-reactive protein (median 0.56 mg/L [interquartile range 0.33 to 1.02] to 0.33 mg/L [interquartile range 0.26 to 0.40], p <0.01), von Willebrand factor (139 +/- 47 to 132 +/- 44 IU/dl, p = 0.02), insulin resistance index (p = 0.05), and mean low-density lipoprotein (LDL) density (p <0.001) compared with placebo. However, no significant differences were seen between the rosiglitazone and placebo groups with regard to brachial artery FMD, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1 levels. Rosiglitazone treatment significantly increased LDL (2.62 +/- 0.72 to 2.95 +/- 0.84 mmol/L, p = 0.03) and triglyceride (1.23 +/- 0.63 to 1.56 +/- 0.98 mmol/L, p = 0.04) levels. Thus, rosiglitazone reduced markers of inflammation and endothelial activation, but this did not translate into an improvement in FMD. Increased LDL and triglyceride levels may have played a role.     

Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease

BACKGROUND: Several studies suggest that red wine is beneficial in coronary artery disease (CAD). Although the long-term effect of moderate red wine consumption on endothelial function is currently under investigation, there is little knowledge about its effect on postprandial endothelial function and haemostatic factors. The aim of the present study was to investigate the postprandial effects of alcohol content and the antioxidants of red wine on endothelial function and fibrinogen levels in CAD patients. METHODS: Fifteen males with angiographically documented CAD were recruited for the study. All volunteers ingested 250 ml of either red wine or de-alcoholized red wine on two different days. Blood samples (for analysis of fibrinogen and blood lipids) were collected and flow-mediated dilatation (FMD) was determined before and 30, 60 and 90 min following consumption of each beverage RESULTS: FMD was higher following the consumption of de-alcoholized red wine [type of wine effect, P=0.05 repeated measures analysis of variance (ANOVA)]. Furthermore, the pattern of the response was different between the two beverages, as FMD increased following the ingestion of de-alcoholized red wine, but it decreased after consumption of regular red wine (type of wine by time interaction effect, P=0.006 repeated measures ANOVA). Fibrinogen concentrations were unaltered CONCLUSIONS: Acute ingestion of red wine without alcohol led to higher FMD than ingestion of regular red wine in CAD patients. The acute effect of red wine on endothelial function may be different than its long-term effect and it could be attributed to its constituents other than alcohol.     

Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease

Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy. In experimental studies, activation of the inflammatory regulator, nuclear factor kappa B (NFlB), contributes to endothelial activation and reduced nitric oxide production. We treated patients with coronary artery disease with sulfasalazine, an inhibitor of NFκB, and placebo in a randomized, double-blind, crossover study design. Brachial artery flow-mediated dilation (FMD) and digital vascular function were measured at baseline and after each 6-week treatment period. Of the 53 patients enrolled in the crossover study, 32 (age 60 ± 10, 22% female) completed all the visits, with a high rate of study withdrawal due to gastrointestinal side effects. In a subset of 10 participants, we compared the effects of 4 days of sulfasalazine treatment (n = 5) to no treatment (n = 5) on NFκB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFlB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment. However, FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment. Short-term sulfasalazine inhibited NFlB activity; however, long-term treatment was poorly tolerated and did not improve endothelial function. Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease. Further studies are warranted to investigate the potential for NFlB inhibition to reduce cardiovascular risk.     

罗格列酮对冠心病合并2型糖尿病患者介入治疗后血管内皮功能的影响

目的观察罗格列酮对冠心病合并2型糖尿病患者介入术后血管内皮功能的影响。方法选择冠心病合并2型糖尿病行PCI患者102例,按照是否服用罗格列酮,随机分为治疗组(51例)和对照组(51例)。分别检测患者血液中NO、一氧化氮合酶(NOS)、内皮素1的含量变化,并观察患者的预后情况。结果与术前比较,2组患者在术后1、7 d时NO、NOS明显降低,内皮素1明显升高,差异有统计学意义(P0.05,P0.01);1个月时,对照组NO和NOS仍明显降低,差异有统计学意义(P0.05)。与对照组比较,治疗组患者的冠状动脉事件发生率明显降低,差异有统计学意义(P0.05)。结论罗格列酮可以通过改善血管内皮功能,并能减少冠心病合并2型糖尿病患者介入治疗后心血管事件的发生。     

Effect of chelation therapy on endothelial function in patients with coronary artery disease: PATCH substudy

OBJECTIVES: The purpose of this study was to evaluate the effect of chelation therapy with ethylenediamine tetraacetic acid (EDTA) on endothelium-dependent vasomotor responses in patients with documented coronary artery disease (CAD). BACKGROUND: Oxidative stress plays an important role in the dysfunction of endothelium and development of atherosclerosis. Modification of cardiac risk factors and employment of antioxidants have been shown to improve endothelial function. Ethylenediamine tetraacetic acid chelation therapy is considered to be a complementary therapy for patients with CAD and is proposed to have antioxidant properties. METHODS: A total of 47 patients enrolled in the Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health (PATCH) participated in this substudy and had complete data. High-resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated vasodilation (FMD) in patients with CAD in a randomized, double-blind, and placebo-controlled fashion. Patients were randomized to chelation therapy or placebo. The primary end point was the absolute difference in FMD after the first and 33rd treatments (6 months) of study groups compared with their baselines. RESULTS: At the baseline, the study population had mild impairment of FMD (7.2 +/- 3.4%). The first chelation treatment did not change FMD as compared with placebo (chelation 6.5 +/- 3.5% vs. placebo 7.4 +/- 2.9%; p value = 0.371). The brachial artery studies at six months did not demonstrate significant differences in FMD between study groups (placebo 7.3 +/- 3.4% vs. chelation 7.3 +/- 3.2%; p value = 0.961). CONCLUSIONS: Our results suggest that EDTA chelation therapy in combination with vitamins and minerals does not provide additional benefits on abnormal vasomotor responses in patients with CAD optimally treated with proven therapies for atherosclerotic risk factors.     

Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease

Aerobic exercise training improves endothelial vasomotor function in the coronary circulation of patients with coronary artery disease (CAD), an effect that has been attributed to local repetitive increases in shear stress on the endothelium. To study the effects of exercise on endothelial function in the peripheral circulation, we used vascular ultrasound to examine flow-mediated dilation and nitroglycerin-mediated dilation in the brachial and posterior tibial arteries of 58 subjects with CAD. Studies were performed at baseline and after 10 weeks in 40 subjects (aged 59 +/- 10 years) who participated in a supervised cardiac rehabilitation program that predominantly involved moderate intensity leg exercise (three 30-minute sessions/week), and 18 matched patients who did not exercise and maintained a sedentary lifestyle. Exercise was associated with a 29% increase in functional capacity (7.3 +/- 2.2 vs 9.4 +/- 2.7 METs, p <0.001), and significant improvement in endothelium-dependent, flow-mediated dilation in a conduit artery of the leg, but not the arm. Nitroglycerin-mediated dilation in the upper arm and lower extremity was unaffected. These findings suggest that exercise improves endothelial function in peripheral conduit arteries of patients with CAD and that the beneficial effect may be more marked in the vascular beds of the exercised limbs.     

Anti-cardiolipin antibodies and endothelial function in patients with coronary artery disease

Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti-beta2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 +/- 9.5% vs 8.0 +/- 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 +/- 13.4% vs 11.0 +/- 16.7%, p = 0.084). The mean levels of anti-beta2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL.     

Moderate alcohol consumption and coronary artery disease. A review

An inverse association between moderate alcohol consumption and coronary artery disease has been demonstrated in epidemiologic studies of diverse design. These include ecologic correlations, case-control, longitudinal and clinical studies. The consistency, strength and independence of the inverse relationship argues persuasively for a causal association. These data also suggest that both abstention and heavy alcohol use are associated with an increased risk for coronary artery disease. The effect of moderate alcohol consumption on lipoprotein and apolipoprotein levels is a biologically plausible and likely mechanism for this inverse association. Alcohol consumption elevates HDL cholesterol, although it is unclear whether the HDL subfractions HDL-2 and HDL-3 are beneficially altered. Recent evidence, however, suggests that the apolipoproteins may be more important indicators of coronary artery disease, and moderate alcohol consumption does beneficially alter these proteins. Alcohol may also affect coronary artery disease by other mechanisms, which may include fibrinolytic activity, coagulation, blood pressure, coronary vasoreactivity, and sociobehavioral factors.     

西拉普利对冠心病患者颈动脉斑块及血管内皮功能的影响

目的:探讨西拉普利对冠心病患者颈动脉斑块及血管内皮功能的影响.方法:64例并发颈动脉斑块的冠心病患者被随机分为西拉普利组(n=33)和对照组(n=31),以高分辨率超声技术分别检测患者治疗前、治疗6个月及1年后的血流介导的肱动脉舒张反应(FMD)、最大颈动脉内中膜厚度(IMT)的变化. 结果:治疗6个月及1年后,西拉普利组FMD较治疗前均有明显增加;治疗1年后,对照组FMD较治疗前也有明显增加,但西拉普利组的改善更为明显(P均＜0.05);治疗1年后,西拉普利组IMT较治疗前明显减小(P＜0.05),对照组无明显变化(P＞0.05). 结论:在常规治疗的基础上加用西拉普利可以进一步改善冠心病患者内皮功能,延缓动脉粥样硬化的进展.     

Effect of acute testosterone on myocardial ischemia in men with coronary artery disease

The effect of acute testosterone administration on exercise-induced myocardial ischemia was assessed in 14 men with coronary artery disease and low plasma testosterone concentrations in a study of randomized, double-blind, crossover design. Testosterone increased time to 1-mm ST-segment depression compared with placebo by 66 (15 to 117) seconds (p = 0.016), suggesting a beneficial effect of testosterone on myocardial ischemia in these patients.     

西拉普利对冠心病患者颈动脉斑块及血管内皮功能的影响

目的：探讨西拉普利对冠心病患者颈动脉斑块及血管内皮功能的影响。方法：64例并发颈动脉斑块的冠心病患者被随机分为西拉普利组(n=33)和对照组(n= 31),以高分辨率超声技术分别检测患者治疗前、治疗6个月及1年后的血流介导的肱动脉舒张反应(FMD)、最大颈动脉内中膜厚度(IMT)的变化。结果：治疗6个月及1年后,西拉普利组FMD较治疗前均有明显增加；治疗1年后,对照组FMD较治疗前也有明显增加,但西拉普利组的改善更为明显(P均＜0．05)；治疗1年后,西拉普利组IMT较治疗前明显减小(P＜0．05),对照组无明显变化(P＞0．05)。结论：在常规治疗的基础上加用西拉普利可以进一步改善冠心病患者内皮功能,延缓动脉粥样硬化的进展。     

Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease

Background Studies on the effect of estrogen on atherosclerotic coronary artery disease (CAD) risk in women have produced conflicting results. Similar confusion, but fewer data, exists on the effect of testosterone on CAD risk in men. Methods We used ^99mTc sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men (mean age, 69.1 ± 6.4 years) with provocable myocardial ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of testosterone designed to increase testosterone 2 or 6 times baseline. Results Serum testosterone increased 137 ± 58% and 488 ± 113%, and estradiol levels increased 27 ± 46% and 76 ± 57%, (P < .001 for all) during the 2 testosterone infusions. There were no differences among the placebo or testosterone groups in peak heart rate, systolic blood pressure, maximal rate pressure product, perfusion imaging scores, or the onset of ST-segment depression. Conclusions Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD. (Am Heart J 2002;143:249-56.)     

Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease

Endothelial progenitor cells (EPC) predict morbidity and mortality in patients at cardiovascular risk.Patients with low EPC counts and impaired endothelial colony forming activity have a higher incidence for cardiovascular events compared to patients with high EPC counts and favorable colony forming activity. The pathophysiological basis for this finding may be an insufficient endothelial cell repair by EPC.We postulate that EPC influence coronary endothelial function which itself is relevant for the outcome of patients at cardiovascular risk. To test this hypothesis in humans, endothelial function was invasively assessed in 90 patients with coronary heart disease by quantitative coronary angiography during intracoronary acetylcholine infusion. Flow cytometry of mononuclear cells isolated from peripheral blood was performed to assess CD133(+) or CD34(+)/KDR(+) EPC. EPC function was assessed ex vivo by determination of endothelial colony forming units. Low EPC number as well as impaired endothelial colony forming activity correlated with severely impaired coronary endothelial function in univariate analysis. Multivariate analysis revealed that only the number of EPC predicts severe endothelial dysfunction independent of classical cardiovascular risk factors. Endothelial function closely correlates with the number of circulating EPC providing new mechanistic insights and options for risk assessment in patients with coronary heart disease.