Endothelial dysfunction in young patients with acute ST-elevation myocardial infarction

Endothelial dysfunction may be particularly important in the pathogenesis of young patients with acute myocardial infarction (AMI), because they have different clinical characteristics compared with older patients. We investigated endothelial function in relation to AMI in this young age group. From January 2005 to March 2008, 29 of 31 consecutive patients with acute ST-elevation myocardial infarction (STEMI) who were <40 years old and received direct percutaneous coronary intervention (PCI) were enrolled in the study. We compared the coronary risk factors and flow-mediated vasodilation (FMD) in the brachial artery between the acute STEMI patients and 29 age- and gender-matched controls that did not have AMI. Baseline brachial artery diameter and responses to glyceryl trinitrate were similar between the two groups. In contrast, FMD was significantly lower in the young acute STEMI group than in the control (3.47 ± 4.08 vs. 7.45 ± 4.67%, p = 0.001) and correlated with the Thrombolysis in Myocardial Infarction (TIMI) risk score. The impaired FMD in the acute STEMI group was independent of smoking, hyperlipidemia, hypertension, nitrate use, or body mass index. In multiple logistic regression analysis, only FMD and age, not traditional cardiovascular risk factors, were found to be significantly associated with acute STEMI (odds ratio = 0.75, 95% CI 0.63-0.90, p < 0.01). In conclusion, independent of conventional risk factors, severe endothelial dysfunction occurs in young acute STEMI patients and correlates with TIMI score. In addition to age, impaired FMD is the only significant factor associated with acute STEMI in this young population.     

Evaluation of left ventricular diastolic function using an ambulatory radionuclide monitor: relationship to left ventricular systolic performance

Abnormalities of left ventricular (LV) filling may occur prior to systolic dysfunction in patients with both coronary and noncoronary heart disease. To determine the incidence of diastolic dysfunction and to assess the relationship of such dysfunction to systolic performance, we measured systolic and diastolic function at rest in a series of healthy volunteers (n = 10) and in patients with cardiovascular disease (n = 42). Twenty patients had coronary artery disease (CAD) with prior myocardial infarction, six patients had CAD without myocardial infarction, and the remaining 16 patients had a variety of noncoronary heart diseases, including valvular heart disease, dilated cardiomyopathy, and hypertensive disease. The 42 patients manifested a wide variation in LV systolic function (ejection fractions ranged from 6% to 65%). Patients with reduced LV ejection fraction (EF) manifested a reduction in cardiac output and peak ejection rate proportionate to the reduction in EF. Diastolic function showed a fall in LV peak (PFR) and average (AFR) filling rates; these were reduced in proportion to the fall in EF. Heart rate was an insensitive index of the magnitude of impairment of LV systolic function. These data suggest that measurements of diastolic function do not provide additional information in patients with impaired systolic function.     

Peripheral vascular endothelial function correlates with exercise capacity in women

BACKGROUND: Vascular endothelial function has been observed to correlate with exercise capacity in predominantly male populations. Gender-based differences exist in the clinical course of coronary artery disease, and previous studies indicate that estrogen may influence endothelial function. These observations raise the possibility that the relationship between endothelial function and exercise capacity in women may differ from that in men. HYPOTHESIS: This study aimed to determine whether peripheral vascular endothelial function correlates with exercise capacity in women. METHODS: Women who were referred for clinically indicated exercise testing with technetium-99 myocardial perfusion imaging were consecutively recruited. To ensure a population free of exercise limitation due to ischemic heart disease, women without myocardial perfusion defects were included for analysis in this study (n = 105). Endothelial function was assessed by brachial artery ultrasound flow-mediated vasodilation (FMD). Exercise capacity was defined as the duration of exercise on a symptom-limited Bruce protocol. RESULTS: Mean FMD was 11.8 +/- 0.6%, and median FMD was 12%. Subjects with an FMD less than the median of 12% had a significantly shorter exercise time than those with FMD > or = 12% (411 +/- 17 vs. 482 +/- 24 s, p = 0.014). There was a significant correlation between FMD and exercise time (r = 0.34, p < 0.001). Age and body mass index were additional predictors of exercise time; however, the relationship between FMD and exercise time was independent of these variables. CONCLUSION: Brachial artery FMD correlates with exercise capacity in women, even in the absence of ischemic heart disease.     

Interdependence of Cardiac and Endothelial Function in Patients with Symptomatic Chronic Heart Failure of Nonischemic Etiology

Objective: Endothelial dysfunction has emerged as a therapeutic target in patients with chronic congestive heart failure (CHF). Endothelial dysfunction may impair left ventricular (LV) systolic function by increasing systemic vascular resistance. Conversely, LV impairment may negatively impact endothelial function by reducing shear stress and vascular nitric oxide (NO) bioavailability. This study was undertaken to determine the association between LV and endothelial function in patients with CHF. Methods: Echocardiographic and vascular ultrasound studies were performed to measure left ventricular ejection fraction (LVEF) and brachial artery flow-mediated vasodilatation (FMD) in 30 subjects with stable New York Heart Association class II–III CHF. All patients received optimal medical therapy. Results: LVEF averaged 25 ± 9% and brachial artery FMD 1.3 ± 2.4%. LVEF strongly correlated with FMD among all patients (r = 0.64, P< 0.001) and among those patients with nonischemic (n = 19, r = 0.66, P = 0.002), but not in patients with ischemic etiology (n = 11, r = 0.27, P = 0.42). Conclusions: LVEF and endothelium-dependent NO vasodilatation are strongly correlated in stable ambulatory patients with systolic CHF of nonischemic etiology. Our study underscores the mutual interaction between central cardiac and peripheral vascular function, thus strengthening a mechanistic rationale for the systemic beneficial effects of interventions targeting either the heart or the vascular endothelium in CHF.     

Clinical Covariates of Abnormal Heart Rate Turbulence in Coronary Patients

Background: The aim of this study is to evaluate the association between heart rate turbulence (HRT) parameters and clinical characteristics of coronary artery disease (CAD) patients. Methods and Results: In 122 patients (mean age 62 ± 9 years) with angiographically documented CAD, 24‐hour Holter monitoring with HRT analysis was performed to evaluate turbulence onset (TO) and turbulence slope (TS). There was a significant correlation between TO and TS (P =?0.31; P < 0.001) . According to quartile values, TO ≥?0.37% and TS ≤ 4.25 ms/RR were considered as abnormal in this patient population. Average values of TO were higher and TS lower in patients over 60 years, in patients with a past history of myocardial infarction and in those with EF < 40%. Considering pharmacotheraphy, higher (better) values of TS were observed in patients on statins, nitrates, and beta‐blockers while lower TS values were noted in patients on calcium blockers. Patients with abnormal parameters of HRT compared to group with normal HRT values were characterized by features of more advanced CAD: age over 60 years (75% vs 49%), past history of MI (75% vs 64%), and EF < 40% (25% vs 3%). Multivariate analysis revealed age > 60 years (OR 1.27; P = 0.002) and EF < 40% (OR 1.39; P = 0.001) as independent clinical factors associated with abnormal HRT parameters. Conclusions: HRT parameters are influenced by clinical characteristics and pharmacotherapy of studied patients with TS more than abnormal TO depending on clinical characteristics of patients. Advanced age, prior myocardial infarction and left ventricular dysfunction are key factors influencing values of HRT parameters.     

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events and restenosis in patients undergoing coronary stent implantation: a prospective study

BACKGROUND: Endothelial dysfunction plays a key role in atherosclerosis and predicts future cardiovascular events in individuals with or without coronary artery disease and improves with risk reduction therapy. We sought to determine the predictive value of endothelial dysfunction for long-term cardiovascular events and in-stent restenosis in patients undergoing percutaneous coronary intervention (PCI). METHODS: Using high-resolution ultrasound, we assessed endothelial function by using the brachial artery flow-mediated dilation (FMD) method in 135 patients with coronary artery disease before elective coronary stenting. Patients were prospectively followed up for an average of 12 months after PCI. RESULTS: Thirty patients had an event during follow-up including cardiac death (four patients), myocardial infarction (nine patients), unstable angina/non-ST elevation myocardial infarction (15 patients), and stroke (two patients) and in-stent restenosis was determined in 16 of these patients. Endothelium-dependent FMD was significantly lower in patients who had an event compared with those without an event (4.7+/-1.9 vs. 6.0+/-2.0%, P=0.007), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. FMD was the only predictor of cardiovascular events (P=0.03). Impaired endothelial function was associated with a significantly higher incidence of cardiovascular events and in-stent restenosis by Kaplan-Meier analysis. When a cutoff point of 7.5% was used, flow-mediated dilation had a sensitivity of 93%, specificity of 37%, and negative predictive value of 95% for cardiovascular events. CONCLUSION: Impaired brachial artery FMD is associated with long-term cardiovascular events and in-stent restenosis in patients undergoing PCI. Noninvasive assessment of endothelial function may serve as a surrogate marker for the estimation of future cardiovascular event risk and long-term follow-up in these patients.     

Assessment of Endothelial Function in Alzheimer's Disease: Is Alzheimer's Disease a Vascular Disease?

OBJECTIVES: To compare endothelial function of people with Alzheimer's disease (AD) with that of people without. DESIGN: Case-control study. SETTING: Geriatric medicine outpatient clinic of a university hospital. PARTICIPANTS: Twenty-five patients with AD who were free of vascular risk factors and 24 healthy elderly controls were enrolled. Exclusion criteria were diabetes mellitus, hypertension, dyslipidemia, evident stroke, smoking, documented coronary artery disease, history of myocardial infarction, heart failure, acute or chronic infection, malignancy, peripheral artery disease, renal disease, rheumatologic diseases, alcohol abuse, and certain drugs that may affect endothelial function. Both groups underwent comprehensive geriatric assessment and neuropsychiatric assessment. MEASUREMENTS: Endothelial function was evaluated according to flow-mediated dilation (FMD) from the brachial artery. RESULTS: Mean age +/- standard deviation was 78 +/- 5.9 in the group with AD (11 female and 14 male) and 72.1 +/- 5.8 in the control group (9 female and 11 male). Multiple linear regression analysis revealed that FMD was significantly lower in patients with AD (median 3.45, range 0-7) than controls (median 8.41, range 1-14) (P < .001), independent of age. It was also found that FMD values were inversely correlated with the stage of the disease as determined according to the Clinical Dementia Rating scale (r=-0.603, P < .001). CONCLUSION: Endothelial function is impaired in patients with AD. Endothelial function was worse in patients with severe AD. These findings provide evidence that vascular factors have a role in the pathogenesis of AD.     

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension

BACKGROUND: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening. METHODS: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance. RESULTS: On univariate analysis, there were significant negative correlations between FMD and SSPG (r = -0.695, P <.0001) or IMT (r = -0.449, P <.004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG (P <.03) and systolic BP (P <.02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG (P <.002). CONCLUSIONS: One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.     

Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Summary Endothelial dysfunction is considered to be the first step in atherogenesis as well as a predictor of adverse cardiovascular events in patients with coronary artery disease (CAD), while endothelial function improvement is associated with improved clinical outcome. Nebivolol is a beta₁-adrenoreceptor antagonist with an independent beneficial action on endothelial function, increasing nitric oxide bioavailability. The aim of the present study was to examine the effects of nebivolol on endothelial function in the brachial artery in patients with CAD compared with another selective beta₁ adrenergic receptor antagonist, atenolol. Thirty-five patients with stable CAD were randomized to receive either 5 mg nebivolol (n = 17) or 50 mg atenolol (n = 18) daily for 4 weeks. Each patient underwent measurement of endothelial function by means of flow-mediated dilatation (FMD) of the brachial artery before and after 4 weeks of treatment. All vasoactive drugs and cardiovascular risk factors were comparable in the two groups. No significant differences were observed between the two groups at baseline in FMD. In the atenolol group FMD remained unchanged at the end of the 4-week treatment, but in patients treated with nebivolol FMD showed a significant increase by the end of the treatment period (3.9 ± 2.7% vs. 5.6 ± 2.9%, p = 0.047) leading to a significantly higher value compared to patients treated with atenolol (5.6 ± 2.9% vs. 3.4 ± 3.2%, p = 0.041). Beta₁ blockade by nebivolol but not atenolol improves endothelial dysfunction in patients with CAD, an effect that might further reduce the risk for cardiovascular events in patients with CAD.     

Cardiovascular risk factor profiles and endothelial function in coronary artery disease patients treated with statins.

Although endothelial dysfunction is associated with cardiovascular risk factors and is improved by cholesterol-lowering therapy, the relationship between endothelial function and cardiovascular risk factor profiles has not been fully investigated in coronary artery disease patients who have been treated with statins. We investigated endothelial function in male hypercholesterolemic patients (n=53) who underwent statin therapy over 6 months in a cross-sectional study. Patients were classified into three groups based on the results of coronary angiography: a normal coronary artery group (n=15), an angina pectoris group (n=20) and a myocardial infarction group (n=18). Endothelial function was assessed by measuring flow-mediated dilatation after reactive hyperemia in the brachial artery, and serum lipid, lipoprotein (a), glucose and insulin levels were measured. Significant associations were observed between the status of coronary disease and systolic blood pressure, lipoprotein (a), glucose and insulin levels (p <0.05, respectively), and the levels of these risk factors in the myocardial infarction group were higher than those in the other groups. Flow-mediated dilatation was also associated with the status of coronary disease (p <0.05), and the myocardial infarction group showed the lowest levels of flow-mediated dilatation (p <0.05). Flow-mediated dilatation was negatively correlated with systolic and diastolic blood pressures, serum levels of lipoprotein (a), glucose and insulin, and the status of coronary disease. Stepwise multiple regression analysis also revealed that lipoprotein (a), diastolic blood pressure and the status of myocardial infarction were significantly correlated with impaired vasodilatation. Serum lipids, age and smoking habit were independent of flow-mediated dilatation. In conclusion, even after cholesterol-lowering treatment, male patients with myocardial infarction still had endothelial dysfunction, and higher levels of lipoprotein (a) may be associated with endothelial dysfunction in such patients.     

Relations of left ventricular mass and systolic function to endothelial function and coronary flow reserve in healthy, new discovered hypertensive subjects

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47+/-10 years old, 26.6+/-2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (beta=-0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (beta=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.     

Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus

To determine whether endothelial dysfunction precedes the clinical diagnosis of diabetes mellitus, we investigated the relation of endothelial flow-mediated dilation (FMD) with fasting plasma glucose among a multiethnic population-based cohort of 579 nondiabetic subjects without previous myocardial infarction or stroke enrolled in the Northern Manhattan Study (age 66 +/- 9 years; 41% men, 16% white, 15% black, and 68% Hispanic). Impaired fasting glucose or prediabetic status, defined as a fasting glucose level of 100 to 125 mg/dl, was present in 95 subjects (16%). Endothelial function was determined using FMD during reactive hyperemia. Multiple linear regression analyses were used to assess the relation between plasma glucose and endothelial function after adjustment for potential confounders. FMD was significantly lower (4.9 +/- 3.8% vs 6.1 +/- 3.7%, p = 0.003) in those with impaired fasting glucose than in subjects with normal fasting glucose. Prediabetic status was significantly associated with impaired FMD (odds ratio 1.9, 95% confidence interval 1.1 to 3.1, p = 0.02). After adjustment for age, gender, body mass index, and hypertensive status, a higher fasting glucose was significantly associated with a lower FMD (beta = -0.024 +/- 0.012, p = 0.04) in a continuous linear relation. Thus, for each 10-mg/dl increase in plasma glucose, a 0.24% decrease occurred in FMD. Impaired FMD was present among prediabetics. An elevated fasting plasma glucose level is associated with impaired endothelial function among nondiabetics. These results further support the role of hyperglycemia in the pathogenesis of vascular dysfunction at different stages of diabetes development and the role of impaired fasting glucose as a risk factor for macrovascular disease.     

急性心肌梗死直接PCI后心电图ST段回落幅度与血管内皮功能的关系

目的:探讨急性心肌梗死(AMI)直接经皮冠状动脉介入术(PCI)后心电图ST段回落幅度与血管内皮功能的关系。方法:AMI直接PCI后梗死相关血管(IRA)血流达TIMI3级患者51例,按ST段回落幅度分为A组32例(ST段迅速回落组)和B组19例(ST段持续抬高组)。所有患者于发病(7±2)d和3个月测量肱动脉流量介导舒张(FMD)和硝酸甘油介导舒张(NMD)。正常对照组25例。结果:AMI发病1周时A组和B组FMD(5·42%±2·27%与1·99%±1·63%,P<0·05)和NMD(15·08%±8·79%与6·84%±3·92%,P<0·05)均明显低于正常对照组(FMD9·60%±3·41%,NMD22·17%±8·49%);AMI发病后3个月A、B2组的FMD(9·06%±1·98%与5·44%±1·91%,P<0·01)和NMD(20·90%±5·78%与12·93%±4·71%,P<0·01)均较基础状态增加,A组内皮功能基本恢复正常,B组虽然有恢复但未达到正常状况。结论:AMI血管内皮功能明显受损,成功再灌注后ST段持续抬高的患者受损更明显。随着时间的延长内皮功能有所恢复,ST段持续抬高的患者恢复差于ST段迅速回落者。     

无症状心肌缺血与高敏C反应蛋白和内皮功能失调

目的 探讨无症状心肌缺血（SMI）的发生是否与炎症因子和内皮功能失调有密切的关系。方法 对148例稳定性冠心病患者采用24h动态心电图监测,分为SMI组和非SMI组。并行血脂、血糖、高敏C反应蛋白（hsCRP）等测定,高分辨率超声评估肱动脉内皮功能。结果 60例患者（40．5％）动态心电图记录SMI,非SMI组与SMI组相比,hsCRP浓度明显降低（0．91±0．36：1．86±0．52,P〈0．05）,血流介导性舒张（FMD）功能有明显改善（3．02±1．46：6．36±3．79,P〈0．05）。多因素分析发现SMI仅与FMD（β=-0．452,P=0．046,OR=1．572）和hsCRP（β=1．233,P=0．036,OR=1．632）有独立相关性。结论 无症状冠心病患者仍有较高的SMI发生率;FMD、hsCRP与SMI之间有较强的相关性,提示炎症和内皮功能失调可能是SMI发生的机制之一,hsCRP和FMD有可能作为筛选SMI的替代指标。     

Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: a dose-response effect dependent on endothelial nitric oxide synthase

BACKGROUND: Patients with coronary artery disease (CAD) have impaired endothelial function. Simvastatin therapy has been demonstrated to significantly improve endothelial function in these patients. Although withdrawal of statins is a frequent problem in clinical practice, the effects after discontinuation of statins treatment on endothelial function in patients with CAD are largely unknown. OBJECTIVE: This study investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients with CAD and the underlying mechanisms. METHODS: We recruited 30 patients with established CAD. They were treated with 20 mg simvastatin for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed in the brachial artery using high-resolution ultrasound at baseline, 4 weeks during simvastatin treatment, and 1 week after termination of therapy. 20 healthy subjects were also studied as a control group. Furthermore, we investigated underlying mechanisms on human umbilical vein endothelial cells (HUVECs) confluent monolayers at passages 2-3. HUVECs were exposed to simvastatin. After 24 h cells were repeatedly washed to remove the drugs, and the conditioned mediums were collected at the indicated time points. The nitric oxide (NO) production and levels of eNOS mRNA after 24 h of withdrawal of statins were examined. RESULTS: (1) Abrupt discontinuation of simvastatin treatment leads to a rebound of serum total cholesterol (21.3%) and LDL cholesterol (18.2%) in patients within 1 week, but they were still lower than the baseline values (P<0.05 for each parameter). (2) A significant decreased of FMD (-59.3%) was observed in patients after discontinuation of simvastatin in 1 week, and furthermore, the FMD was even lower than the baseline levels (4.6% vs. 5.6%, P<0.05). The reduction of FMD was not correlated with the change of LDL cholesterol (r=-0.343, P=0.081). In contrast to the unchanged LDL cholesterol level, abrupt discontinuation of therapy caused a rapid and significant decrease in FMD from 10.6% to 5.2% in healthy subjects at day 1, but it returned to baseline levels within 1 week. (3) In HUVECs, a maximum decrease of nitrite levels (-80%) was observed at 6 h after stopping simvastatin treatment, which was below the control levels. 24 h after stopping 10(-5) mmol/L and 10(-6) mmol/L simvastatin treatment, eNOS mRNA expression decreased to -71% and -42% (P<0.05), respectively. CONCLUSIONS: Abrupt withdrawal of simvastatin treatment not only acutely and completely abrogates its beneficial effects on endothelial function in patients with CAD, but also induced further vascular injury compared with pretreatment status, independent of cholesterol levels. The underlying mechanism of these negative effects may be related to the suppression of endothelial NO production, which are dose-dependent.     

The Relation between the Color M‐Mode Propagation Velocity of the Descending Aorta and Coronary and Carotid Atherosclerosis and Flow‐Mediated Dilatation

Background: To improve clinical outcomes, noninvasive imaging modalities have been proposed to measure and monitor atherosclerosis. Common carotid intima‐media thickness (CIMT) and brachial artery flow‐mediated dilatation (FMD) have correlated with coronary atherosclerosis. Recently, the color M‐mode‐derived propagation velocity of descending thoracic aorta (AVP) was shown to be associated with coronary artery disease (CAD). Methods: CIMT, FMD, and AVP were measured in 92 patients with CAD and 70 patients having normal coronary arteries (NCA) detected by coronary angiography. Patients with acute myocardial infarction, renal failure or hepatic failure, aneurysm of aorta, severe valvular heart disease, left ventricular ejection fraction <40%, atrial fibrillation, frequent premature beats, left bundle branch block, and inadequate echocardiographic image quality were excluded. Results: Compared to patients with normal coronary arteries, patients having CAD had significantly lower AVP (29.9 ± 8.1 vs. 47.5 ± 16.8 cm/sec, P < 0.001) and FMD (5.3 ± 1.9 vs. 11.4 ± 5.8%, P < 0.001) and higher CIMT (0.94 ± 0.05 vs. 0.83 ± 0.14 mm, P < 0.001) measurements. There were significant correlations between AVP and CIMT (r =−0.691, P < 0.001), AVP and FMD (r = 0.514, P < 0.001) and FMD and CIMT (r =−0.530, P < 0.001). Conclusions: The transthoracic echocardiographic determination of the color M‐mode propagation velocity of the descending aorta is a simple practical method and correlates well with the presence of carotid and coronary atherosclerosis and brachial endothelial function. (Echocardiography 2010;27:300‐305)     

Combined use of endothelial function assessed by brachial ultrasound and high-sensitive C-reactive protein in predicting cardiovascular events

BACKGROUND: Endothelial function plays a key role in determining the clinical manifestations of atherosclerotic lesions. Elevated high-sensitive C-reactive protein (hsCRP) relates to long-term prognosis of cardiovascular disease. HYPOTHESIS: We test the hypothesis that combined use of endothelial function and hsCRP could increase predictive value of future cardiovascular events. METHODS AND RESULTS: 205 patients were followed up for a median period of 24 months. Endothelial function was assessed using brachial ultrasound to measure endothelium-dependent flow-mediated vasodilation (FMD). Cox regression analyses were conducted for the 205 subjects, with cardiovascular events being defined as myocardial infarction, hospitalization due to congestive heart failure, percutaneous coronary intervention, coronary artery bypass grafting, and ischemic stroke. Twenty nine (14%) developed cardiovascular events. Both FMD and hsCRP were significantly predictive of cardiovascular events (relative risk for patients with FMD<3% as compared to those with FMD>6%, 4.65, 95% confidence interval (CI): 1.30-16.66, p=0.018; relative risk for the highest as compared with the lowest tertile of hsCRP level, 3.59, 95% CI: 1.32-9.74, p=0.012, respectively). Further risk analysis was performed among four groups classified by FMD (FMD >or= 6% or<6%) and half percentile of hsCRP (hsCRP >or= 1 or<1 mg/dL). Relative risks for the FMD<6%/hsCRP >or= 1 mg/dL group compared to FMD >or= 6%/hsCRP<1 mg/dL group increased markedly to 12.598 (95% CI: 1.69 to 94.14, p=0.014) for cardiovascular events. CONCLUSIONS: Patients with suspected coronary artery disease may benefit from risk stratification based on both endothelium-dependent FMD and hsCRP, since combined these two factors contribute significantly toward the incidence of cardiovascular events.     

Impaired endothelial function in patients with myocardial bridge

OBJECTIVE: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. In this study, we aimed to evaluate the existing atherosclerosis and noninvasive endothelial function of brachial artery in patients with MB. METHODS: The present study included 50 patients (group I) who had MB in left anterior descending (LAD) on coronary angiography. All of the coronary artery segments were evaluated by intravascular ultrasound (IVUS). Endothelial function was assessed with measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. The study also included 30 healthy control subjects (group II). Patients in the group I were further subdivided into two subgroups based on the findings on IVUS: group IA included 20 patients without atherosclerotic lesions and group IB included 30 patients with atherosclerotic coronary artery disease in addition to MB. RESULTS: FMD values were found to be significantly lower in the patients with MB (group I) than in the control (6.4 +/- 3% vs 11 +/- 4%, P <0.001). In regard to FMD values in subgroups, FMD was 7 +/- 2% in the group IA and 5.8 +/- 1% in the group IB (P = 0.023). On IVUS, atherosclerotic plaque was found proximal to the bridge in the same coronary artery segment in addition to MB in 75% of the patients in group I (group IB). No atherosclerotic plaque was found in within or distal segments of MB. CONCLUSION: Endothelial function is impaired in patients with MB and there is an increased tendency for atherosclerosis proximal to the bridge in the patients with MB. Endothelial dysfunction is more severe in the patients with atherosclerosis proximal to the bridge.     

Vascular endothelial function in patients with slow coronary flow

BACKGROUND: Slow coronary flow (SCF) in a normal coronary angiogram is a well-recognized clinical entity, but its etiopathogenesis remains unclear. DESIGN: The aim of the study was to determine endothelial function in patients with SCF using a flow-mediated dilatation (FMD) technique in the brachial artery. METHODS: Coronary flow was quantified using the corrected thrombosis in myocardial infarction (TIMI) frame count (CTFC) method. Endothelial function was studied in 27 patients with SCF (23 men, four women, mean age 47.6+/-8.7 years) and in 30 people with normal coronary flow (NCF) (22 men and eight women, mean age 47.5+/-7.4 years). RESULTS: The flow-mediated diameter increase in the SCF group was significantly smaller than that in the NCF group (3.48+/-0.10% compared with 9.11+/-0.10%, P < 0.001). The percentage of nitroglycerine (NTG)-induced dilatation was not significantly different between patients with SCF and people with NCF (16.8+/-1.1% compared with 17.1+/-1.1%, P = 0.87). Simple regression analysis showed that mean CTFC (CTFC(m)) was strongly and inversely related to the percentage of FMD (r = -0.29, P < 0.01) in all participants. When the patients with SCF were excluded, CTFC(m) was still inversely related to the percentage of FMD (r = -0.36, P < 0.05). CTFC(m) was also inversely related to NTG-induced dilatation in the 57 participants (r = -0.23, P < 0.05). Multiple regression analysis showed that CTFC(m) was inversely related to the percentage of FMD only (r = -0.37, P < 0.05). CONCLUSIONS: These findings suggest that endothelial function is impaired in people with SCF and that CTFC correlates well with endothelial dysfunction.     

Exaggerated exercise blood pressure is related to impaired endothelial vasodilator function

BACKGROUND: Persons with high normal blood pressure (BP) or mild hypertension who also have an exaggerated BP response to exercise are at risk for worsening hypertension. The mechanisms that explain this relationship are unknown. We examined the relationships of endothelial vasodilator function and of aortic stiffness with exercise BP. METHODS: Subjects were 38 men and 44 women, aged 55 to 75 years, with untreated high normal BP or mild hypertension but otherwise healthy. Exercise was performed on a treadmill. Endothelial vasodilator function was assessed as brachial artery flow-mediated vasodilation (FMD) during reactive hyperemia. Aortic stiffness was measured as pulse wave velocity (PWV). RESULTS: Among men, resting systolic BP explained 34% of the variance (P < .01) in maximal exercise systolic BP and FMD explained an additional 11% (P < .01); resting systolic BP explained 23% of the variance in maximal pulse pressure (PP) (P < .01), and FMD explained an additional 10% (P < .01). Among women, resting systolic BP was the only independent correlate of maximal systolic BP (R2 = 0.12, P < .03) and FMD correlated negatively with maximal PP (R2 = 0.12, P < .03). Among men, FMD was the only independent correlate of the difference between resting and maximal systolic BP (R2 = 0.20, P < .02). The FMD was the only independent correlate of the difference between resting and maximal PP among men (R2 = 0.17, P < .03) and among women (R2 = 0.12, P < .03). The PWV did not correlate with exercise BP responses. CONCLUSIONS: These results suggest that impaired endothelial vasodilator function may be a mechanism contributing to exercise hypertension and may also be one link between exaggerated exercise BP and worsening hypertension.