Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.

OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (deltaAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 +/- 0.46 and 6.97 +/- 0.88 vs. 3.67 +/- 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 +/- 4.0 vs. 24.2 +/- 3.3 and 26.8 +/- 3.2 mol/liter, p < 0.05). After insulin administration, the deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the deltaAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.     

Cardiological syndrome X. Non-invasive assessment of endothelial function and arterial compliance

BACKGROUND: Mechanisms responsible for cardiological syndrome X are complex and not well understood. It has been postulated that impaired endothelial function and abnormal reactivity of coronary vessels may play a role in the pathogenesis of this condition. AIM: To assess mechanical properties of peripheral arterial vessels and both endothelium-dependent and endothelium-independent vessel reactivity in patients with or without atherosclerotic lesions in coronary arteries. METHODS: The study group consisted of 100 patients with typical angina and positive exercise test who underwent coronary angiography. Based on angiographic results, the patients were divided into two groups: 50 patients with normal coronary angiograms and 50 age- and gender-matched patients with at least one significant coronary artery lesion (coronary artery disease (CAD) group). The control group consisted of 40 healthy volunteers without risk factors of atherosclerosis. The compliance of arterial vessels was assessed by automatic measurement of pulse wave velocity (PWV). Endothelial function was examined by ultrasonographic measurement of the diameter of brachial artery following passive hyperaemia (endothelium-dependent vessel distension) and following nitroglycerine (endothelium-independent mechanism). RESULTS: Among all three studied groups, the PWV values were the highest in patients with CAD. Patients with syndrome X had significantly higher PWV than in controls. A cut-off PWV value of 10.5 m/s distinguished patients with syndrome X from those with CAD. Endothelium-dependent arterial distensibility was significantly lower in patients with syndrome X than in controls; the lowest values were observed in patients with CAD. Among patients with syndrome X, the endothelium-dependent arterial vessel distensibility was the only parameter significantly influencing PWV results. CONCLUSIONS: PWV was significantly increased in patients with syndrome X which suggests a decreased arterial vessel compliance. These results and the impairment of endothelium-dependent relaxation suggest a similar pathomechanism of altered arterial reactivity in patients with syndrome X and in patients with CAD.     

Role of endothelin-1 in genesis of coronary artery disease

BACKGROUND: The endothelial cells produce the most potent vasoconstrictor known as endothelin-1. Elevated plasma levels of endothelin have been associated with coronary artery disease, essential hypertension and heart failure. The aims of the present study were, to compare the plasma endothelin-1 levels in coronary artery disease patients and healthy controls, to confirm endothelin-1 as surrogate marker for coronary artery disease and to compare the presence of endothelin-1 like immunoreactivity in aortic and internal mammary artery specimens obtained during coronary artery bypass graft surgery. METHODS AND RESULTS: The circulating levels of endothelin-1 were determined by enzyme-linked immunoassay in patients of coronary artery disease (n=145) and compared with healthy controls (n=70). Tissue endothelin-1 immunoreactivity was examined by immunohistochemical method in aortic and internal mammary artery tissue specimens obtained from 20 patients of coronary artery disease during coronary artery bypass grafting to understand the role of endothelin in atherosclerosis. Significantly higher levels (p < 0.001) of endothelin-1 were observed in all patients of coronary artery disease as compared to healthy controls. The immunoreactivity of endothelin-1 was localized to endothelial cell layer in internal mammary artery whereas in aortic specimens, in addition to endothelial cell layer, immunoreactivity was seen in the cytoplasm of smooth muscle cells of intima and media. CONCLUSIONS: The significant increase in plasma endothelin-1 in coronary artery disease cases as compared to healthy subjects and presence of tissue endothelin-1 immunoreactivity in smooth muscle cells of intimal as well as medial layers of aorta confirms the role of endothelin-1 as a surrogate marker of atherosclerosis.     

Serum paraoxonase 1 activity and oxidative markers of LDL in patients with cardiac syndrome X

OBJECTIVE: Myocardial ischaemia in cardiac syndrome X (CSX) is believed to be due to microvascular dysfunction. Increased oxidative stress is one of the suspected mechanisms of microvascular dysfunction. The aim of this study was to evaluate the oxidative status in patients with CSX, by determining serum paraoxonase-1 (PON 1) activity in addition to LDL-oxidation markers. METHODS AND RESULTS: This cross-sectional study consisted of patients with CSX (group I, n = 30), patients with coronary artery disease (group II, n = 31), and healthy controls (group III, n = 32). Lipid parameters, PON-1 activity, and LDL oxidation markers (conjugated-diene and thiobarbituric acid-reactive substance-TBARS) were measured. Endothelium-dependent vasodilatation was determined by brachial artery ultrasonography. There were no significant differences in serum LDL, apolipoprotein-B, baseline LDL-diene, and LDL-TBARS levels between groups. There were no differences in both apolipoprotein-A1 and HDL levels between group I and group III. Apolipoprotein-A1 and HDL levels were significantly lower in group II than group I patients (P < 0.001). PON-1 activity was lowest in group II patients. Average PON-1 activity in group I was in between of group II and group Ill. The percent change of LDL-diene levels after stimulation was significantly higher in group II than in groups I and III (P = 0.005 and P = 0.02, respectively). The percent change of LDL-TBARS levels was lowest in group I (P = 0.03). There was a moderate correlation between endothelium-dependent vasodilatation and PON-1 activity in group I (r = 0.43, P = 0.04). CONCLUSIONS: Enhanced oxidative stress might be one of the causes of impaired endothelial functions resulting in myocardial ischaemia and chest pain in patients with CSX. The relatively preserved HDL and apolipoprotein-A1 levels in patients with CSX might be a protective mechanism against progression of coronary microvascular dysfunction to atherosclerotic coronary artery disease.     

Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X)

BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.     

Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations

Our objective was to compare brachial artery endothelium dependent and independent vasodilation in lupus patients and healthy females, by means of high-resolution noninvasive brachial artery ultrasound. Endothelially mediated vasodilation was estimated noninvasively by examination of brachial artery responses to postischemic reactive hyperemia and endothelial independent vasodilation from response to sublingual glycerlynitrate (GTN) using high-resolution external vascular ultrasound. Five patients with known coronary artery disease (CAD), five with subclinical CAD, five with no CAD and five control subjects were assessed. Endothelium dependent vasodilation was significantly blunted in lupus patients with CAD as compared with healthy female controls (0.11 versus 11.1%, P = 0.018). Corresponding values for lupus patients with subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject, endothelium dependent vasodilation (EDV) was related to endothelium independent vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN in individual subjects. This ratio was markedly depressed in lupus patients with CAD as compared with control subjects (0.12 versus 1.15). The corresponding EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69 and 0.65, respectively. The conclusion was that flow mediated vasodilation in lupus patients with coronary artery disease is markedly depressed as compared to healthy subjects.     

The relation between Helicobacter pylori infection and cardiac syndrome X: a preliminary study

Cardiac syndrome X is defined by an angina pectoris with normal or near normal coronary angiogram.We evaluated the association of Helicobacter pylori (HP) infection with cardiac syndrome X (CSX). We studied 30 patients with CSX, 30 cases with stable angina and also 30 healthy controls. All three groups underwent urea breath test (UBT). Fifty percent (15 out of 30) of CSX patients had positive UBT result (> or =200 dpm), while two other groups did not have the positive results. Regarding high prevalence of HP infection in patients with CSX in our study and probable causative effect of chronic infection in coronary artery diseases, possible role of HP infection in the pathogenesis of CSX is suggested. However well designed clinical trial studies are needed to confirm this preliminary result.     

The peripheral vascular response to exercise is impaired in patients with risk factors for coronary artery disease

BACKGROUND: Abnormal coronary and brachial artery responses have been described in individuals with risk factors for coronary artery disease (CAD). Peripheral arterial tonometry (PAT), a newly developed digital plethysmographic technique was used to assess peripheral vascular response to exercise in healthy controls and individuals with risk factors. METHODS AND RESULTS: Continuous finger PAT during Bruce protocol exercise test was performed in 30 subjects with risk factors for CAD and 30 healthy individuals. Compared with baseline, the PAT wave amplitude at peak exercise decreased in the subjects but increased in the controls: 83 +/- 28% vs. 114 +/- 40% respectively, p < 0.01. CONCLUSIONS: A different pattern of systemic vascular response to exercise was found in individuals with risk factors for atherosclerosis. Since the vascular behavior in these patients is probably related to endothelial dysfunction, it may be that peripheral arterial tonometry can be used as a simple, readily available technique to assess endothelial function.     

Differential mononuclear cell activity and endothelial inflammation in coronary artery disease and cardiac syndrome X

BACKGROUND: Circulating mononuclear cells could be activated with endothelial inflammation in patients with coronary artery disease (CAD). In some patients with normal coronary angiograms, myocardial ischemia could also present with coronary microvascular dysfunction (cardiac syndrome X). This study was undertaken to investigate whether mononuclear cell activation and endothelial inflammation can present in syndrome X patients. METHODS: We evaluated the biochemical parameters, circulating soluble adhesion molecules, circulating superoxide free radicals, and mononuclear cell activity in 32 patients with syndrome X, 34 with angiographically documented CAD, and 17 age- and gender-matched healthy control subjects. RESULTS: Compared to that in control subjects, plasma high-density lipoprotein was reduced (P<0.001) and insulin to glucose ratio increased (P=0.02) in CAD patients. Circulating level of soluble intracellular adhesion molecule-1 was significantly higher in both syndrome X and CAD patients than in control subjects (P<0.01), whereas the levels of soluble vascular cell adhesion molecule (P=0.02) and von Willebrand factor (P=0.01) were increased in CAD patients only. The peak (P<0.001) and total counts of superoxide free radicals in whole blood (P<0.001) was significantly higher in syndrome X patients than in the other two groups. However, phorbol-12-myristate-13-acetate-induced superoxide free radical generation of mononuclear cells was increased in CAD (10.5+/-4.6%, P=0.01) but not in syndrome X patients (8.7+/-2.0%) as compared with control subjects (7.7+/-0.5%). CONCLUSIONS: The results indicated that the activity of mononuclear cells was increased with significant endothelial inflammation and injury in CAD patients. In syndrome X patients, though circulating superoxide free radicals were increased, there was minimal endothelial inflammation without mononuclear cell activation. The relatively preserved lipid and metabolic profiles might contribute to less vascular inflammation in syndrome X patients.     

The endothelial leukocyte adhesion molecule. Role in coronary artery disease

OBJECTIVES: It is hypothesized that adhesion molecules could be an early predictor of coronary artery disease. The endothelial leucocyte adhesion molecule (ELAM) is expressed on activated endothelial cells only and it has been found to exist in a soluble form. This soluble form (sELAM) may be an important marker for endothelial cell damage. The aim of the present study was to compare the sELAM levels in coronary artery disease (CAD) subjects and healthy controls and to evaluate their clinical usefulness. METHODS AND RESULTS: sELAM were measured using enzyme immunoassay methods in 145 subjects having angiographically determined CAD and compared with 70 healthy, normotensive controls having a normal stress test/angiogram. Significantly higher values (p < 0.0001 ) were observed in CAD subjects as compared to controls. Also, subjects who underwent angioplasty and were later on readmitted with restenosis within 1 year had significantly higher levels of sELAM as compared to those who did not get restenosis within a year. CONCLUSIONS: These findings show that sELAM concentration is elevated in the presence of CAD and is useful for determining the presence of coronary atherosclerosis. An increased level of sELAM in patients susceptible to restenosis supports a role for white blood cell/endothelial interaction in restenosis after angioplasty.     

Increased P wave dispersion: a new finding in patients with syndrome X

The present clinical study was undertaken in patients with syndrome X, namely angina with normal coronary arteries, to investigate the presence of increased P wave dispersion by comparing patients with coronary artery disease (CAD) and healthy control subjects. Three groups were studied - group A, 21 patients (48 6 years) with syndrome X; group B, 16 patients (56 9 years) with CAD; and group C, 16 healthy subjects (49 8 years). Patients with CAD were older than those in groups A and C (P=0.005 and P=0.035, respectively). All groups demonstrated similar PQ, QRS and RR intervals. Group B had a lower minimum P wave duration than group C (P=0.05). P wave dispersion in group A was found to be higher than that in groups B and C (P=0.018 and P=0.0001, respectively). Patients with syndrome X demonstrated increased P wave dispersion compared to patients with CAD and healthy subjects. High sympathetic tone or autonomic imbalance observed in patients with syndrome X may affect intra-atrial and interatrial conduction times, and leave them prone to develop atrial arrhythmias.     

Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X.

AIMS: Endothelial dysfunction and subangiographic atheroma have been reported in patients with cardiac syndrome X (CSX) but little is known regarding chronic inflammation and reduced arterial distensibility as pathogenic mechanisms. We assessed whether markers of inflammation and arterial distensibility differ in CSX patients compared to control subjects. METHODS AND RESULTS: We studied 30 consecutive CSX patients (mean age 57+/-6 years, 25 women) and 30 healthy controls (mean age 54+/-8 years, 25 women). High sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with CSX compared to controls (2.6 [1.7-4.5] vs 1.5[0.7-2.7] mg/l, P=0.02). Hs-CRP levels correlated with carotid intima-media thickness (IMT) (Spearman's rho=0.51; P=0.013). CSX patients also had significantly increased mean IMT values than controls (P<0.0001). Arterial stiffness and elastic modulus were also significantly increased in CSX patients compared to control subjects (P=0.04 and P=0.04, respectively). Distensibility tended to be lower in CSX patients than controls although this difference did not reach statistical significance. CONCLUSIONS: This study showed for the first time that compared to control subjects, patients with CSX have higher hs-CRP serum levels, increased mean common carotid artery IMT and increased arterial stiffness. The role of these abnormalities in the pathogenesis of CSX deserves investigation.     

Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X.

OBJECTIVES: The purpose of this study was to investigate whether a direct relation can be demonstrated between myocardial perfusion defects detected during dobutamine stress test (DST) by cardiovascular magnetic resonance (CMR) and impairment of coronary microvascular dilatory function in patients with cardiac syndrome X (CSX). BACKGROUND: Despite the fact that coronary microvascular dysfunction has been shown in most patients with CSX, the ischemic origin of CSX remains debated. No previous study assessed whether a strict relation exists between abnormalities in myocardial perfusion and coronary microvascular dysfunction in CSX patients. METHODS: Eighteen CSX patients (mean age 58 +/- 7 years, 7 men) and 10 healthy control subjects (mean age 54 +/- 8 years, 4 men) underwent myocardial perfusion study by gadolinium-enhanced CMR at rest and at peak DST (maximal dose 40 microg/kg/min). Coronary flow response (CFR) to adenosine (140 microg/kg/min in 90 s) in the left anterior descending (LAD) coronary artery was assessed by high-resolution transthoracic echo-Doppler and expressed as the ratio between coronary flow velocity at peak adenosine and at rest. RESULTS: At peak DST, reversible perfusion defects on CMR were found in 10 CSX patients (56%) but in none of the control subjects (p = 0.004). The CFR to adenosine in the LAD coronary artery was lower in CSX patients than in control subjects (2.03 +/- 0.63 vs. 3.29 +/- 1.0, p = 0.0004). The CSX patients with DST-induced myocardial perfusion defects in the LAD territory on CMR had a lower CFR to adenosine compared with those without perfusion defects in the LAD territory (1.69 +/- 0.5 vs. 2.31 +/- 0.6, p = 0.01). A significant correlation was found in CSX patients between CFR to adenosine and a DST perfusion defect score on CMR in the LAD territory (r = -0.45, p = 0.019). CONCLUSIONS: Our data concurrently show DST-induced myocardial perfusion defects on CMR and reduced CFR in the LAD coronary artery territory in CSX patients, thus giving strong evidence that a dysfunction of coronary microcirculation resulting in myocardial perfusion abnormalities is present in these patients.     

Peripheral Vascular Endothelial Dysfunction in Patients With Angina Pectoris and Normal Coronary Arteriograms

Objectives. We sought to determine endothelium-dependent vasodilator function in the brachial artery of patients with microvascular angina pectoris.Background. Previous studies suggest the presence of endothelial dysfunction of the coronary microcirculation in patients with microvascular angina pectoris. It is not known whether endothelial dysfunction in these patients is a generalized process or whether it is confined to the coronary microcirculation only.Methods. In 11 women (mean [±SD] age 60.1 ± 7.8 years) with microvascular angina (anginal pain, normal epicardial coronary arteries, positive exercise stress test), endothelium-dependent vasodilation was assessed in the brachial artery by measuring the change in brachial artery diameter in response to hyperemic flow. Results were compared with 11 age- and gender-matched patients with known three-vessel coronary artery disease and 11 age- and gender-matched healthy control subjects. In all subjects, the intima–media thickness (IMT) of the common carotid artery was also measured.Results. Flow-mediated dilation (FMD) was comparable in patients with microvascular angina and coronary artery disease (1.9 ± 2.5% vs. 3.3 ± 3.3%, p = NS) but was significantly lower in patients with microvascular angina than in healthy control subjects (1.9 ± 2.5% vs. 7.9 ± 3%, p < 0.05). IMT was significantly lower in patients with microvascular angina than in those with coronary artery disease (0.64 ± 0.08 vs. 1.0 ± 0.28 mm, p < 0.05) and was comparable between patients with microvascular angina pectoris and healthy control subjects (0.64 ± 0.08 vs. 0.56 ± 0.14 mm, p = NS). IMT ≥0.8 mm was observed in 1 of 11 patients with microvascular angina, 1 of 11 control subjects and 10 of 11 patients with coronary artery disease.Conclusions. These findings suggest that endothelial dysfunction in microvascular angina is a generalized process that also involves the peripheral conduit arteries and is similar to that observed in atherosclerotic disease. IMT could be helpful in discriminating patients with microvascular angina and atherosclerotic coronary artery disease.     

Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.     

AT1-receptor blockade with irbesartan improves peripheral but not coronary endothelial dysfunction in patients with stable coronary artery disease

Activation of the renin-angiotensin-aldosterone system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis. Studies evaluating the effect of AT1-receptor blockers on endothelial dysfunction in patients with coronary artery disease (CAD) revealed mixed results. Studies addressing the effects of AT1-receptor blockers on the coronary and peripheral function in the same study population, are still lacking. We therefore aimed to test the effects of long-term therapy with the AT1-receptor blocker irbesartan (IRB) on both, the coronary and peripheral endothelial function in patients with CAD. Seventy-two patients with CAD were randomly assigned to double-blinded treatment for 6 months with IRB 300 mg per day or placebo, respectively. Coronary and peripheral endothelial function were measured by intracoronary infusion of acetylcholine (final intracoronary concentration 10(-7.3) to 10(-5.6)M) and by determining flow-dependent dilation (FMD) of the brachial artery, respectively. IRB significantly improved FMD, while no change of coronary endothelial function was observed. Interestingly, plasma levels of N(G),N(G)-dimethyl-arginine, and the isoprostane excretion rate were not modified. IRB treatment improves peripheral but not coronary endothelial dysfunction in patients with CAD. Since reduced FMD of the brachial artery has been shown to be associated with a high-cardiovascular event rate, improvement of FMD by IRB may lead to better prognosis of patients with CAD.     

Soluble VCAM-1 and E-selectin, but not ICAM-1 discriminate endothelial injury in patients with documented coronary artery disease

It has been shown that endothelial cell adhesion molecules play an important role in the development of coronary atherosclerosis and inflammatory disease. We sought to test whether soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin are increased in patients with documented coronary artery disease (CAD). Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured in 40 patients with documented CAD, 20 subjects with angiographically documented normal coronary arteries, and 14 healthy volunteers. Patients with documented CAD exhibited significant elevation of VCAM-1 (535 +/- 227.1 ng/ml, p = 0.0001), E-selectin (69.4 +/- 29.4 ng/ml, p = 0.006), but not ICAM-1 (320.5 +/- 65.1 ng/ml, p = 0.9) concentrations as compared to subjects with normal coronary arteries (252.3 +/- 79.8, 49.7 +/- 22.0 and 311.4 +/- 40.2 ng/ml), and healthy controls (110.0 +/- 17.7, 29.0 +/- 2.0 and 237.5 +/- 46.5 ng/ml), respectively. Soluble markers of endothelial injury are not uniformly increased in patients with documented CAD as compared to those with normal coronary arteries and healthy controls. However, VCAM-1 and E-selectin, but not ICAM-1 could identify endothelial injury in such patients.     

Late systolic wave on brachial artery blood flow velocity pattern in patients with coronary artery disease and its relation to vascular stiffness

Duplex-Doppler study typically exhibits triphasic brachial artery blood flow velocity pattern in subjects classified as normal without clinically evident atherosclerotic complications, heart disease, hypertension, or diabetes mellitus. In this study, the authors described the late systolic wave on the brachial artery blood flow velocity pattern in patients with coronary artery disease and investigated the relation between late systolic wave and vascular stiffness. Blood flow profile and velocity of the brachial artery were determined noninvasively by ultrasound pulsed-Doppler technique under the guidance of a B-mode ultrasound image in 96 patients with coronary artery disease (CAD). The control group consisted of 23 healthy subjects with no or maximally 2 risk factors (only among age, cigarette smoking, obesity, and gender) for vascular disease. None of the patients and controls had clinical evidence of arterial disorders at upper extremities. In 32 patients (33%) with CAD, a late systolic wave was observed in the brachial artery Doppler study. On the other hand, no late systolic wave was observed in the healthy subjects. In addition, multivessel disease, hypertension, advanced age, diabetes, and smoking were significantly more frequent in patients with the late systolic wave. In conclusion, peripheral arterial abnormalities induced by vascular stiffness may produce alterations in regional wave reflections, and the normal triphasic pattern of the brachial artery blood flow may change by the appearance of the late systolic wave.     

老年冠心病患者冠状动脉病变程度与血管内皮功能的关系

目的探讨老年冠心病患者冠状动脉病变程度与血管内皮功能的关系。方法应用高分辨率彩色多普勒超声诊断仪对176例健康老年人(健康对照组)及161例老年冠心病患者(冠心病组)进行肱动脉血管内皮功能的超声检测,并对老年冠心病组患者冠状动脉病变支数与肱动脉血管内皮功能进行分析。结果反应性充血(reactive hyperemia,RH)后血管内径的变化率(flow-mediated diameter,FMD)及RH在老年冠心病组分别为6.05%及56.29%,而在健康对照组则分别为16.12%及127.23%,差异有显著性意义(P<0.001)。FMD在1支冠状动脉病变时为6.37%,在2支冠状动脉病变时下降为5.69%,而在3支冠状动脉病变时仅为3.94%;RH在1支冠状动脉病变时为62.19%,在2支冠状动脉病变时下降为53.45%,而在3支冠状动脉病变时仅为40.13%,差异有显著性意义(P<0.01)。结论老年冠心病组血管内皮功能较健康对照组明显减退。随着冠心病患者冠状动脉血管病变程度的增加,血管内皮功能进一步减退。血管内皮功能的减退在一定程度上可能反映了冠状动脉血管病变的严重程度。     

Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS).Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function.