Intensity of lipid lowering with statins and brachial artery vascular endothelium reactivity after acute coronary syndromes (from the BRAVER trial)

The time course and differential effects of statin regimens on endothelial function after acute coronary syndromes (ACSs) are unknown and could contribute to the superiority of a more intense strategy. A subset of subjects who were enrolled in the PROVE IT-TIMI 22 trial (n = 50) underwent evaluation of vascular reactivity by high-resolution brachial ultrasound. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent sublingual nitroglycerin-mediated dilation (NMD) were measured at baseline and at 48 hours, 1 month, and 4 months after the initiation of 40 mg of pravastatin (n = 26) or 80 mg of atorvastatin (n = 24). After 4 months, low-density lipoprotein cholesterol was decreased by 32% in the atorvastatin group but was not different from baseline after ACS in the pravastatin group. C-reactive protein decreased similarly in the 2 groups. Brachial artery diameters at rest were similar in the 2 groups and at each time point of the trial. FMD and NMD increased significantly after 4 months by 27% and 24%, respectively (p <0.05), with no difference between groups. There was no correlation between the change in FMD and the change in lipids or C-reactive protein. In subjects who had received previous statin therapy (n = 15), there was no significant variation in FMD (p = 0.140) and NMD (p = 0.129). In conclusion, initiation of statin therapy soon after ACS is associated with improvements in endothelium-dependent and independent vascular reactivities after 4 months.     

Pravastatin Prevents Myocardium from Ischemia-Induced Fibrosis by Protecting Vascular Endothelial Cells Exposed to Oxidative Stress

Hypothesis Statins potently prevents cardiac myocytes from acute ischemia besides chronic inhibition of cholesterol synthesis. We investigated how pravastatin preserves the cardiac function after myocardial infarction (MI). Methods Echocardiographically comparing rats with myocardial ischemia (MI group) with those treated with pravastatin (MI/statin group), we found that cardiac contractility was statistically preserved in the MI/statin whereas it was deteriorated in MI group. Results Histochemical analysis suggested that ischemia-induced cardiac fibrosis was prevented by pravastatin. Because there was no significant myocyte apoptosis reflecting myocytes loss between two groups, ischemia-induced interstitial fibrosis might affect the contractility. Conclusion We hypothesized that statin may directly affect vascular endothelial cells regulating blood supply to the myocardium rather than affecting myocytes. Pravastatin perturbed H₂O₂-induced endothelial NOS reduction and inhibited H₂O₂-increased caspase-3 activation in cultured vascular endothelial cells. These data suggested that pravastatin prevent cardiac dysfunction by acting on vascular endothelial cells. Furthermore, early administration of pravastatin to the patients during acute onset of myocardial infarction may be beneficial to prevent myocardial damage caused by fibrosis associated with ischemia.     

Effect of mild endurance exercise training and pravastatin on peripheral vasodilatation of forearm resistance vessels in patients with coronary artery disease.

BACKGROUND: Improved endothelial function may contribute to the beneficial effects of cholesterol lowering therapy in patients with coronary artery disease (CAD), but results of the effect of statin therapy on endothelial function are disparate in these patients. Exercise training has been reported to improve endothelial function of patients at risk of or with established CAD. The goal of the study was to compare the effect of mild exercise training or statin therapy on forearm endothelial function in CAD patients with average cholesterol levels. DESIGN AND METHODS: Twenty-eight sedentary male patients with angiographically documented CAD and average pretreatment total plasma cholesterol levels (5.1+/-0.9 mmol/l) aged 42-75 years were included. They were randomly assigned in a 2 : 1 order to either statin therapy (pravastatin, 40 mg daily) or exercise training therapy (mild endurance exercise three or more times a week). The effects of 10 weeks of either treatment on endothelium-dependent and independent vasodilation of forearm resistance vessels was assessed by plethysmography. Cardiopulmonary exercise testing was performed at baseline and after 10 weeks. RESULTS: Ten weeks of pravastatin therapy significantly reduced low-density lipoprotein cholesterol (from 3.8+/-0.6 to 3.1+/-0.6 mmol/l at study end, P=0.04) and the ratio of total to high-density lipoprotein cholesterol (from 4.9+/-0.8 to 3.7+/-0.7 mmol/l, P=0.002). Exercise training did not significantly modify the lipid profile. Peak oxygen consumption, maximal achieved workload and exercise duration tended to improve in the exercise training group but remained unchanged in the pravastatin-treated group. Neither 10 weeks of pravastatin nor mild endurance exercise training improved endothelium-dependent or independent vasomotor function in forearm resistance vessels. CONCLUSIONS: In patients with CAD and average cholesterol levels, 10 weeks of treatment with mild endurance exercise training or with pravastatin failed to improve endothelium-dependent or independent vasomotor function in forearm resistance vessels.     

Short- and long-term changes of flow-mediated vasodilation in patients under statin therapy

BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been shown to improve in response to lipid-lowering therapy and other therapeutic interventions, usually within 1 to 2 months. Whether FMD remains improved under therapy in the longer term is unknown. HYPOTHESIS: The aim of this study was to examine the short- and long-term changes of FMD under statin therapy. METHODS: Flow-mediated vasodilation and nitroglycerin-mediated vasodilation (NMD) of the BA were measured with high-resolution ultrasound (13 MHz) at baseline and at 4 and 10 months in 18 consecutively recruited patients with coronary artery disease (CAD), in whom statin therapy was newly established. RESULTS: The decrease of total plasma cholesterol levels after 4 and 10 months of statin therapy (243 +/- 31 vs. 186 +/- 30 vs. 191 +/- 40 mg/dl; p < 0.001) was accompanied by an increase in FMD from 4.4 +/- 3.8% at baseline to 9.6 +/- 2.7% at 4 months and to 9.5 +/- 2.6% at 10 months (p < 0.001). Nitroglycerin-mediated vasodilation showed a trend toward improvement after 4 months (14.6 +/- 7.5 vs. 19.1 +/- 3.6 vs. 19.4 +/- 5.6%; NS). The FMD/NMD ratio also rose significantly after 4 months and remained improved after 10 months of statin therapy (0.31 +/- 0.25 vs. 0.52 +/- 0.16 vs. 0.50 +/- 0.14; p < 0.01). CONCLUSION: Statin therapy is associated with sustained improvement of endothelial function up to 10 months. These data support the utility of FMD for the assessment of vascular function in response to lipid-lowering therapy or other therapeutic interventions in long-term studies.     

Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty

AIM: To determine whether statin therapy initiated early in acute myocardial infarction together with thrombolytic therapy in patients with acute myocardial infarction results in clinical benefit through early plaque stabilization. METHODS AND RESULTS: The study population consisted of 77 patients who underwent coronary balloon angioplasty of the infarct-related artery during the first month of acute myocardial infarction. These patients belonged to the cohort of the Pravastatin Turkish Trial (PTT). Forty of them were assigned randomly to have immediate pravastatin (40 mg/day) therapy adjunctive to thrombolytic therapy regardless of serum lipid levels and received statin treatment throughout the study. Lipid levels were determined immediately after admission and before angioplasty and at the end of 6 months. Patients were re-evaluated clinically and angiographically for cardiovascular adverse events and restenosis after a 6-month follow-up period.The baseline angiographic and clinical characteristics of the two groups were similar.The incidence of angina was significantly lower in the pravastatin group (30.0%, 12 patients) compared to the control group (59.5%, 22 patients) (p = 0.018).The cumulative major adverse cardiac events in the pravastatin group were significantly lower when compared to the control group (32.5% vs. 75.6%, p = 0.0001). CONCLUSIONS: Early initiation of pravastatin therapy immediately after an acute myocardial infarction significantly decreased the frequency of major cardiac adverse events. Such early potential clinical benefits further strengthen the rationale for starting statin treatment as soon as possible after acute coronary events particularly in patients in whom invasive intervention is planned.     

The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease

OBJECTIVES: The goal of this study was to determine the relative prognostic importance of noninvasive measures of endothelial function and atheroma burden in patients with coronary artery disease (CAD). BACKGROUND: Direct measurement of atherosclerosis by carotid ultrasound and endothelial function assessment by brachial artery flow-mediated dilation (FMD) have both been shown to predict vascular events. The combined prognostic utility of carotid ultrasound and FMD relative to traditional risk markers and cardiovascular fitness has not been evaluated. METHODS: A total of 152 patients with CAD underwent metabolic testing, exercise stress tests, carotid ultrasound, and endothelial function measurements. RESULTS: Patients were followed for 34 +/- 10 months during which 22 vascular events occurred. Peak FMD (p = 0.012) and FMD/nitroglycerin-mediated dilation (NMD) ratio (p = 0.008) were lower in subjects with events. Univariate analysis with Cox proportional hazards modeling identified plaque area (p = 0.0047), total area (p = 0.0085), peak FMD (p = 0.01), FMD/NMD ratio (p = 0.008), stress test workload (p = 0.027), long-acting nitroglycerin (NTG) (p = 0.0071), and calcium blockers (p = 0.0057) as predictors of adverse events. Multivariate analysis showed that FMD/NMD ratio (p < 0.0001), carotid plaque area (p = 0.06), and NTG (p = 0.005) were independent predictors. Based on median values, subjects were divided into high and low "plaque burden" groups and into high and low FMD/NMD subgroups. Patients with high FMD/NMD had low event rates irrespective of the degree of carotid atheroma. Patients with low FMD/NMD and high "plaque burden" had the highest event rate (p < 0.05). CONCLUSIONS: The structural and functional status of the vasculature are independent predictors of coronary events as shown by noninvasive measurement of endothelial function and carotid atheroma burden in patients with CAD. Preserved endothelial function attenuates the risk of future events associated with a high plaque burden.     

辛伐他汀对急性冠脉综合征病人血管内皮功能保护作用的时效及量效关系探讨

目的 探讨中小剂量他汀类药物的血管内皮功能保护作用。方法 选择因有典型临床症状而收住院的急性冠脉综合征（ACS）病人85例，采用随机、单盲、对照、自身配对设计的研究方法分为4组，对照组仅给予常规治疗及低脂饮食；辛伐他汀低、中、高剂量组分别在常规治疗基础上给予辛伐他汀片20mg／d，40mg／d，80mg／d,每晚睡前服用，治疗8周。服药0周、4周、8周及停药2周时分别检测内皮素-1（ET-1）、一氧化氮（NO）、肱动脉血管内皮依赖性舒张功能（FMD）和非血管内皮依赖性舒张功能（NMD）指标。结果 辛伐他汀各治疗组与治疗前及对照组相比具有明显降低ET～1及升高NOFMD的作用（P〈0．05），作用最佳者为80mg组，40mg组次之，20mg组再次之，停药2周，各指标均有所恢复，但与治疗前比较，80mg组尚存轻度降低ET-1的作用。结论 不同剂量辛伐他汀具有血管内虐保护作用． 短期内存在时间一剂量依赖关系，但随着用药时间的延长这种依赖关系削弱。     

普伐他汀治疗非缺血性心力衰竭的初步观察

目的 观察小剂量普伐他汀对非缺血性心力衰竭（心衰）患者心脏功能的影响及应用的安全性。方法 连续人选2005年1月至2006年7月医院就诊的非缺血性病因的心衰患者61例,随机分为普伐他汀（20mg／d）组（n=30）与对照组（n=31）,治疗期6个月。观察治疗前后患者心脏功能、肱动脉血管内皮功能、炎症因子与生化指标的变化。结果 标准心衰治疗的基础上加用普伐他汀20mg／d,与对照组相比,3个月时患者加压反应性充血前后血管内径变化百分率增加;6个月时NYHA分级改善,血浆脑利钠肽水平下降,左心室内径缩小,左室射血分数增加,血浆肿瘤坏死因子-俚有所下降（均为P〈0．01）;对照组患者NYHA分级改善（P〈0．05）,左室射血分数有改善的趋势（P=0．052）。普伐他汀组患者的总胆固醇降低（P〈0．05）,高密度脂蛋白胆固醇无明显变化,无肝、肾功能异常,肌酸激酶无明显增高,1例患者因为过敏反应（皮疹）终止治疗。结论 非缺血性心衰患者在标准心衰治疗的基础上加用普伐他汀20mg／d治疗6个月安全、有效,可以显著改善左室重构与心功能状态,并改善内皮功能,降低炎症因子水平。     

Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation

OBJECTIVES: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients. BACKGROUND: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown. METHODS: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10). RESULTS: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy). CONCLUSIONS: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.     

Impact of hypertriglyceridemia on endothelial dysfunction during statin ± ezetimibe therapy in patients with coronary heart disease

Despite the use of statin therapy and achieving the target for low-density lipoprotein cholesterol, a substantial number of coronary events are not prevented, and residual risk factors remain unsettled. Recently, ezetimibe has been shown to reduce not only low-density lipoprotein cholesterol but also triglyceride (TG) levels. The aim of this study was to investigate the associations of residual risk factors, mainly hypertriglyceridemia, with endothelial function during statin therapy in patients with coronary heart disease and examine the effect of ezetimibe add-on therapy. A total of 109 consecutive patients with coronary heart disease during statin therapy were enrolled. Lipid profile was measured and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in a fasting state. Next, 32 patients with high TG levels (≥150 mg/dl) were prospectively assigned to the ezetimibe add-on group or the no-ezetimibe group, and endothelial function was assessed after 3 months. Multivariate linear regression analysis demonstrated that serum TG and high-density lipoprotein cholesterol levels were independent determinants of percentage FMD (β = -0.210 and 0.208, respectively, p <0.05). In patients with high TG levels, ezetimibe add-on therapy significantly improved percentage FMD (from 3.3 ± 1.1% to 4.0 ± 1.1%, p <0.005), whereas no significant change was observed in the no-ezetimibe group. Moreover, the improvement in percentage FMD was significantly associated with reduction in serum TG levels (β = -0.387, p <0.05) independent of the change in serum low-density lipoprotein cholesterol levels. In conclusion, hypertriglyceridemia is independently associated with endothelial dysfunction in patients with coronary heart disease during statin therapy. Ezetimibe add-on therapy improves endothelial function in these high-risk populations.     

叶酸对冠心病患者支架术后血管内皮功能的影响

目的 探讨叶酸能否改善冠心病患者支架术后的血管内皮功能.方法 共184例冠心病患者,在行冠状动脉支架术后,随机分为叶酸治疗（20 mg/d）92例和对照组92例.随访6个月,观察两组同型半胱氨酸水平.以超声测定肱动脉血流介导的舒张功能（FMD）变化来评价血管内皮功能,并观察两组间的差别.结果 叶酸治疗组血浆同型半胱氨酸水平低于对照组[（8.83±3.33）μmol/L比（13.18±5.08）μmol/L,P＜0.01].叶酸治疗后,FMD由（4.72±1.73）%增加至（8.54±1.45）%,P＜0.01.结论 叶酸治疗可能通过降低同型半胱氨酸以外的途径改善血管内皮功能,对介入治疗后的冠心病患者发挥潜在益处.     

The effect of statin therapy on ventricular late potentials in acute myocardial infarction

AIMS: To determine whether early statin therapy in acute myocardial infarction has any effect on ventricular late potentials which are considered as a noninvasive tool for evaluation of arrhythmogenic substrate. METHODS AND RESULTS: Study population consisted of prospectively enrolled 72 patients presenting with acute myocardial infarction (<6 h). Thirty-four of the patients were randomized to pravastatin (40 mg/day) on admission irrespective of lipid levels. All patients received thrombolytic therapy. Signal-averaged ECG recordings were obtained serially prior to thrombolytic therapy, 48 h after and 10 days later. Late potentials were defined as positive if signal-averaged ECG met at least two of Gomes criteria: filtered total QRS duration >114 ms, root mean square voltage of the last 40 ms of the QRS <20 mV, or the duration of the terminal low (<40 mV) amplitude signals >38 ms. Changes observed in signal-averaged ECG recordings after thrombolysis were evaluated statistically with regard to statin usage. There were no significant differences between the clinical characteristics of the two randomized groups. There was a significant decrease in the rates of late potentials between the first and third signal-averaged ECG recordings after thrombolytic therapy in pravastatin group. Pravastatin group also had lower incidence of ventricular arrhythmias compared with control group (26 vs. 63%, P=0.021). The in-hospital cardiovascular event rates were also lower in statin group. CONCLUSION: Early use of pravastatin reduces the incidence of late potentials following thrombolytic therapy in acute myocardial infarction. Statin therapy also seems to be reducing the incidence of in-hospital ventricular arrhythmias. These beneficial effects of statins might be explained through prevention of new myocardial ischemic episodes due to early plaque stabilization or regulation of endothelial and platelet functions.     

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.     

Vascular endothelial growth factor release following coronary artery bypass surgery: extracorporeal circulation versus 'beating heart' surgery.

AIMS: The aim of this study was to examine the circulating levels of vascular endothelial growth factor, following coronary artery bypass graft surgery performed using both standard cardiopulmonary bypass or the 'octopus technique' on the beating heart. BACKGROUND: Vascular endothelial growth factor has a number of effects that are beneficial in the setting of coronary artery bypass graft surgery including cardioprotection, potent angiogenic activity and amelioration of intimal hyperplasia. Hypoxia is a powerful stimulator of vascular endothelial growth factor expression yet the ability of ischaemia, occurring during coronary artery bypass graft surgery, to induce vascular endothelial growth factor production is unknown. METHODS AND RESULTS: Serum vascular endothelial growth factor levels were determined in patients undergoing coronary artery bypass graft surgery with standard cardiopulmonary bypass (CPB-CABG group; n=20), with off-pump coronary artery bypass; (OP-CABG; n=12) and in patients undergoing non-cardiac major surgery (n=6). The effect of hypoxia on vascular endothelial growth factor release by neonatal rat cardiac myocytes in vitro was studied.In the CPB-CABG group vascular endothelial growth factor levels were significantly increased to 78.5+/-39.3 and 110.5+/-16.3 pg. microl(-1)8 and 24 h post-operatively, declining to 14.9+/-9.9 pg. microl(-1)by 48 h to pre-operative values (14.4+/-8.6 pg. microl(-1)). Significantly higher vascular endothelial growth factor levels were also present in the OP-CABG group 3, 6 and 24 h post-operatively (levels 136. 6+/-29.3, 143+/-26.12 pg. microl(-1)and 93.5+/-20.1 pg. microl(-1), respectively). However, non-cardiac major surgery did not result in elevated vascular endothelial growth factor levels post-operatively (46.36+/-9.76 vs pre-surgery levels of 26.84+/-6.1 pg. microl(-1)). Either 15 min or 3 h of hypoxia stimulated vascular endothelial growth factor release from neonatal rat cardiac myocytes in vitro. Twenty-four and 48 h post hypoxia, levels of vascular endothelial growth factor were significantly elevated by approximately 17.5- and 48.5-fold respectively. CONCLUSIONS: These data demonstrate myocardial ischaemia secondary to CPB-CABG and OP-CABG to be a potent stimulator of vascular endothelial growth factor production, which may have implications for graft endothelialization and cardiovascular haemodynamics post-operatively.     

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease

OBJECTIVES: The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. BACKGROUND: Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. METHODS: We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. RESULTS: Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 +/- 2.8%) compared with those without an event (7.0 +/- 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40). CONCLUSIONS: Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.     

缬沙坦对心脏X综合征患者内皮功能的影响及其临床意义

目的探讨缬沙坦对心脏X综合征患者血清一氧化氮(NO)、内皮素-1(ET-1)及内皮依赖性血管舒张功能的影响。方法 36例心脏X综合征患者给予缬沙坦80mg,1次/d,随访治疗12周,另入选同期健康体检者26例。复查心脏X综合征患者治疗前后NO、ET-1及血流介导的肱动脉内皮依赖性血管舒张功能(FMD)及运动平板试验的变化。结果用药12周后,与治疗前比较,心脏X综合征患者的NO上升和FMD提高(P<0.05);ET-1降低和最大ST段压低幅度明显降低(P<0.05);运动总时间、ST段压低1mm时间明显延长。结论缬沙坦可改善血管内皮功能,并提高患者的运动耐量。     

Vascular endothelial dysfunction is associated with reversible myocardial perfusion defects in the absence of obstructive coronary artery disease.

BACKGROUND: The purpose of this study was to investigate whether endothelial dysfunction contributes to abnormal myocardial perfusion imaging (MPI) observed in patients without obstructive coronary artery disease (CAD). It is unclear whether reversible MPI defects detected in the absence of obstructive CAD represent underlying vascular pathology or are false-positive MPI results. Recent evidence suggests that coronary endothelial dysfunction might play a role in the pathogenesis of these defects. METHODS AND RESULTS: We prospectively recruited 36 patients with chest discomfort, reversible abnormalities on MPI, and nonobstructive or absent CAD (stenosis <50% on coronary angiography). The control group (n = 55) consisted of patients with chest discomfort and similar cardiac risk factors but with normal MPI findings. Vascular endothelial function was assessed in the brachial artery by ultrasound as the response to hyperemia and reported as percent flow-mediated dilation (FMD). Response to sublingual nitroglycerin was used as an indicator of endothelium-independent vasodilation. The patients with abnormal MPI findings and nonobstructive CAD had a significantly lower FMD (9.0% +/- 7.2%), indicating endothelial dysfunction, compared with those with similar risk factors and normal MPI findings (12% +/- 5.2%) (P = .03). Baseline brachial artery size and endothelium-independent dilation were similar between groups. On multivariate analysis, only endothelial dysfunction was predictive of reversible MPI defects. CONCLUSIONS: Patients with chest pain and reversible MPI defects but without obstructive CAD have lower FMD indicative of endothelial dysfunction, as compared with similar patients with normal MPI findings. The possibility of a causal link between reversible MPI defects and endothelial dysfunction needs further exploration.     

Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease

OBJECTIVES: The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). BACKGROUND: Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. METHODS: In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment. RESULTS: Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group. CONCLUSIONS: Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events.     

Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial.

OBJECTIVES: Our objective was to determine the timing of benefit with intensive statin therapy after an acute coronary syndrome (ACS) in two time windows: an early window soon after an ACS and a late window in more stable patients. BACKGROUND: The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial showed that the use of intensive statin therapy improved clinical outcomes over two years in ACS patients versus standard therapy. The relative contributions of early or late effects to the overall clinical efficacy of intensive therapy are presently unclear. METHODS: A total of 4,162 patients with ACS were recruited in the PROVE IT-TIMI 22 trial. Patients were randomized to intensive statin therapy (atorvastatin, 80 mg) or standard therapy (pravastatin, 40 mg). The composite triple end point of death, MI, or rehospitalization for recurrent ACS was determined in each group at 30 days. The composite triple and primary end points were assessed in stable patients from six months to the end of study, after censoring for clinical events before six months. RESULTS: The composite end point at 30 days occurred in 3.0% of patients receiving atorvastatin 80 mg versus 4.2% of patients receiving pravastatin 40 mg (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.52 to 0.99; p = 0.046). In stable patients, atorvastatin 80 mg was associated with a composite event rate of 9.6% versus 13.1% in the pravastatin 40 mg group (HR = 0.72; 95% CI, 0.58 to 0.89; p = 0.003). CONCLUSIONS: Intensive statin therapy early after ACS leads to a reduction in clinical events at 30 days, consistent with greater early pleiotropic effects. In stable patients, intensive statin therapy provides long-term reduction in clinical events when compared with standard therapy. Thus, ACS patients should be started in-hospital and continued long-term on intensive statin therapy.     

Investigation of flow-mediated dilation response in normal coronary angiographic patients

Normal findings from coronary angiography do not always show normal endothelial functions. An impaired flow-mediated dilation (FMD) can be a useful marker of the presence of endothelial dysfunction. Hypertension, left ventricular hypertrophy, hypercholesterolemia, and vasospastic angina pectoris can negatively affect FMD response. FMD responses of normal subjects and patients with coronary artery pathology were compared in a prospective cross-sectional study. Patients were divided into 3 groups. Group I patients had a positive exercise stress test and angiographically normal coronary arteries. Group II patients had angiographically significant coronary artery stenosis and stable angina pectoris. Group III had normal results from an exercise stress test and no chest pain. It was concluded that flow-mediated dilation response cannot predict coronary angiographic results. Patients with normal findings from coronary angiography may have impaired endothelial functions.