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.     

Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C

Endothelial dysfunction in the coronary artery contributes to the pathogenesis of variant angina, and endothelial dysfunction in variant angina may be associated with increased oxidant stress in the systemic arteries. We investigated whether endothelial dysfunction exists in the peripheral artery in patients with variant angina, and also examined the effect of vitamin C, an antioxidant, on endothelium-dependent vasodilation. Using high-resolution ultrasound, both the flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual nitroglycerin-induced vasodilation (NTG-D, endothelium-independent vasodilation) in the brachial artery were measured in 28 patients with variant angina and 24 control subjects who had normal coronary arteries. FMD was significantly impaired in patients with variant angina compared with control subjects (1.8 +/- 2.2% vs 6.4 +/- 4.9%, p <0.001). FMD and NTG-D before and after intravenous administration of either vitamin C or placebo were measured in 17 patients with variant angina. FMD significantly improved after the administration of vitamin C (from 2.2 +/- 2.4% to 4.5 +/- 1.6%, p <0.01), but not after administration of the placebo (from 2.0 +/- 2.6% to 1.7 +/- 1.9%). The improved FMD due to vitamin C in patients with variant angina, however, was not significantly different from that in the control subjects. NTG-D was not significantly different between patients with variant angina and control subjects (14.0 +/- 7.8% vs 13.6 +/- 5.0%) and it was also not affected by vitamin C. In conclusion: (1) FMD in the brachial artery is impaired in patients with variant angina, and (2) the acute administration of the antioxidant, vitamin C, was observed to reverse this endothelial dysfunction. These findings support the theory that the systemic inactivation of nitric oxide due to oxidative stress might exist in patients with variant angina.     

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.     

The value of ECG and echocardiography during stress testing for identifying systemic endothelial dysfunction and epicardial artery stenosis.

BACKGROUND: In the stress imaging era, ECG positivity is regarded as a frequent source of false-positive responses. However, it is known that normal coronary arteries frequently coexist with abnormal endothelial function in patients with chest pain. AIM: To evaluate the anatomical coronary epicardial, and functional systemic endothelial determinants of wall motion and electrocardiographic responses during stress testing. METHOD: Sixty-eight in-hospital patients with chest pain syndrome, no previous myocardial infarction, and off nitrate therapy at the time of testing underwent, on different days, in random order and within 1 month: (1) stress ECG echo testing (with dipyridamole in 43, dobutamine in 3, and exercise in 22 patients); (2) coronary angiography; (3) endothelium-dependent, flow-mediated dilation of the brachial artery during reactive hyperaemia using high-resolution ultrasound. Criteria of positivity were: ST segment depression >0.1mm in the stress ECG; regional dysfunction >2 segments demonstrated by stress-echo; diameter reduction >50% on coronary angiography; and <5% flow-mediated dilation as revealed by endothelial function. RESULTS: Significant coronary artery disease was present in 39 patients, and was predicted on multivariate analysis by stress-induced wall motion abnormalities (OR=108.8; 95% CI=8.5-1,389.4, P=0.0003), but not by either ST segment depression (P=0.13; OR=0.47; 95% CI=0.7-1.3) or reduced flow-mediated dilation (P=0.81; OR=0.87; 95% CI=0.27-2.8). Abnormal flow-mediated dilation was present in 53 patients (78%), and was predicted by stress-induced ST segment depression (P=0.023; OR=6.2; 95% CI=1.3-30.5), but not by either stress echo positivity (P=0.66; OR=0.77; 95% CI=0.23 to 2.5) or angiographically assessed coronary artery disease. There was no correlation between flow-mediated dilation and extent of coronary artery disease as assessed by the angiographic Duke score (from 0=normal to 100=most severe disease): r=-0.13, P=0.91. CONCLUSION: Epicardial coronary artery anatomy affects wall motion abnormalities, and systemic endothelial dysfunction affects ST segment depression during stress. However, echocardiographic positivity is unrelated to endothelial dysfunction, and electrocardiographic positivity is an inaccurate predictor of coronary stenosis. An integration of ECG and functional markers is warranted in the stress testing lab.     

Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events

The aim of this pilot study was to test the prognostic value of serial measurements of peripheral endothelial function, assessed by brachial artery flow-mediated dilation (FMD), in patients with angiographically proven coronary artery disease. In 68 patients, FMD was measured on the day after coronary angiography and again after a mean of 14 +/- 12 months. Patients were divided into two groups: absolute improvement in FMD > or = 3% (FMD-improver = FMD-i) and < 3% (FMD-non-improver = FMD-ni). After a mean follow-up of 44 +/- 12 months, cardiovascular events were recorded. Baseline characteristics were similar between groups, except the number of risk factors which was smaller in FMD-i (1.6 +/- 0.7 vs 2.1 +/- 0.9, p < 0.02). Cardiovascular events were more frequent in FMD-ni (9 vs 1 event; p < 0.05). In Kaplan-Meier analysis, a trend towards a better outcome in patients with improved FMD was found using the log-rank test (p = 0.08). The single baseline FMD showed no relationship with late cardiovascular events. Thus, 'delta-FMD' may be more closely related to prognosis than a single FMD measurement.     

External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris

OBJECTIVES: The goal of this study was to investigate the influence of short-term external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in patients with coronary artery disease (CAD). BACKGROUND: In patients with CAD, the vascular endothelium is usually impaired and modification or reversal of endothelial dysfunction may significantly enhance treatment. Although ECP therapy reduces angina and improves exercise tolerance in patients with CAD, its short-term effects on FMD in patients with refractory angina pectoris have not yet been described. METHODS: We prospectively assessed endothelial function in 20 consecutive CAD patients (15 males), mean age 68 +/- 11 years, with refractory angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV), unsuitable for coronary revascularization, before and after ECP, and compared them with 20 age- and gender-matched controls. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation were assessed before and after ECP therapy, using high-resolution ultrasound. RESULTS: External counterpulsation therapy resulted in significant improvement in post-intervention FMD (8.2 +/- 2.1%, p = 0.01), compared with controls (3.1 +/- 2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced vasodilation between ECP and controls (10.7 +/- 2.8% vs. 10.2 +/- 2.4%, p = 0.85). External counterpulsation significantly improved anginal symptoms assessed by reduction in mean sublingual daily nitrate consumption, compared with controls (4.2 +/- 2.7 nitrate tablets vs. 0.4 +/- 0.5 nitrate tablets, p <0.001 and 4.5 +/- 2.3 nitrate tablets vs. 4.4 +/- 2.6 nitrate tablets, p = 0.87, respectively) and in mean CCS angina class compared with controls (3.5 +/- 0.5 vs. 1.9 +/- 0.3, p <0.0001 and 3.3 +/- 0.6 vs. 3.5 +/- 0.5, p = 0.89, respectively). CONCLUSIONS: External counterpulsation significantly improved vascular endothelial function in CAD patients with refractory angina pectoris, thereby suggesting that improved anginal symptoms may be the result of such a mechanism.     

Clinical correlates of coronary cineangiography in young males with myocardial infarction.

Thirty-eight men who suffered acute transmural myocardial infarction before age 40, and after recovery were New York Heart Association functional Class I or II, were studied by noninvasive means and by coronary angiography in order to determine whether these nonivasive studies could predict the presence of significant coronary artery disease remote from that felt to be responsible for the previous myocardial infarction. Patients were divided into two groups on the basis of the absence (Group I) or presence (Group II) of obstructive disease in a major coronary artery supplying myocardium remote from the prior myocardial infarction. There were 21 patients in Group I and 17 patients in Group II. They did not differ with respect to age, abnormalities of lipid or glucose metabolism, family history, history of hypertension or cigarette use, presence of obesity, or infarct localization. Ten of 17 patients in Group II had angina pectoris; only 3/21 patients in Group I had angina pectoris (p less than 0.01). All 12 patients tested in Group II had a positive maximal exercise tolerance test; only 1/17 patients tested in Group I was similarly positive (p less than 0.001). The absence of angina pectoris and the presence of a negative maximal exercise tolerance test is strong evidence against the pressure of significant CAD remote from that responsible for the prior myocardial infarction.     

Acute and mid-term combined hormone replacement therapy improves endothelial function in post-menopausal women with angina and angiographically normal coronary arteries.

AIMS AND BACKGROUND: Coronary endothelial dysfunction improves after acute oestradiol treatment in women with angina and normal coronary angiograms. We sought to analyse whether this effect is also seen in the peripheral circulation and whether it is sustained after a mid-term period of treatment. METHODS: We studied 20 women with angina, signs suggestive of myocardial ischaemia and normal coronary angiograms. In five of them, coronary and peripheral endothelial functions were studied at baseline. Brachial artery flow-mediated dilation was reanalysed after 24 h of transdermal oestradiol treatment. In the other 15 women, brachial artery vasoreactivity was studied at baseline and after a 6-week period of treatment with transdermal oestradiol and medroxyprogesterone (HRT) or placebo in a double-blinded crossover fashion. RESULTS: An abnormal coronary artery response to acetylcholine was observed in all women as well as impaired brachial flow-mediated dilation. Brachial flow-mediated dilation significantly increased after 24 h of oestradiol treatment (4.8+/-0.8% vs 0.06+/-0.6%, P<0.001). Peripheral flow-mediated dilation also increased after a 6-week period of HRT compared with baseline (4.1+/-3% vs 0.4+/-1%, P<0.01) and placebo treatment (4.1+/-3% vs 0.6+/-1.7%, P<0.01). CONCLUSION: Impaired endothelium-dependent vasodilation exists both at the coronary and peripheral circulation in post-menopausal women with angina and normal coronary angiograms. Flow-mediated dilation improves in these women after short and mid-term therapy with transdermal oestradiol irrespective of concomitant progesterone use.     

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.     

Diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease in patients with variable threshold angina pectoris

Patients with chronic stable angina pectoris may present with either fixed or variable threshold symptoms. To evaluate the diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease (CAD) in patients with variable threshold angina, 216 consecutive candidates for coronary angiography were investigated prospectively. For comparison, a group of 55 consecutive patients with fixed threshold angina was studied under the same conditions. Patients with prior myocardial infarction or angiographically documented CAD were excluded. Within 4 months of Holter monitoring, the advised coronary angiography was performed in 77% of the patients with variable threshold angina and in 89% of the patients with fixed threshold angina (p less than 0.05). The prevalence of CAD was markedly lower in patients with variable threshold angina compared to patients with fixed threshold angina (54 vs 90%, p less than 0.001). CAD patients of both subgroups, however, did not differ significantly with respect to the number of obstructed vessels, the Gensini coronary score, the number with impaired left ventricular function (ejection fraction less than 50%) or the duration of ischemic episodes during Holter monitoring. Diagnostic accuracy of Holter monitoring did not differ between variable and fixed threshold angina groups (67 vs 78%). In 91% of the patients results obtained by Holter monitoring could be compared to the results of a bicycle stress test. In patients with fixed threshold angina the diagnostic accuracy was similar for both tests (80 vs 80%). In patients with variable threshold angina, the diagnostic accuracy of Holter monitoring exceeded that of the exercise stress test (68 vs 55%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of epicardial and systemic flow-mediated vasodilation in patients with atypical angina but no evidence of atherosclerotic disease

BACKGROUND: Atypical angina represents a diagnostic challenge and can be observed in the absence of significant coronary atherosclerosis. Endothelial dysfunction is a relevant marker of prognosis, considering cardiovascular events. The aim of the present study was to compare flow-mediated vasodilation (FMD) in systemic peripheral and epicardial coronary arteries. If noninvasive measurements of FMD in systemic arteries correlated with invasive measurements of coronary FMD, this may facilitate diagnostic approaches and determination of prognosis in patients with atypical angina in the future. Patients with atherosclerosis were excluded, because structural changes of coronary vessels may impair adequate comparison. METHODS: Endothelial function (ENF) of epicardial and systemic arteries was examined in 61 consecutive patients with atypical angina in whom significant atherosclerosis was excluded by coronary angiography. ENF of the epicardial arteries was examined during heart catheterization, measuring diameter changes of the proximal left anterior descending coronary artery (LAD) in response to reactive hyperemia, induced by locally administered adenosine via infusion catheter to the mid-segment of the LAD (coronary FMD [FMDc]). ENF of the radial artery was examined with high-resolution ultrasound, measuring peripheral FMD (FMDp) in response to reactive hyperemia induced by distal cuff occlusion. Endothelium-independent vasoreactivity to glycerol trinitrate was assessed. RESULTS: In patients with atypical angina in the absence of atherosclerosis, there was a significant correlation in ENF between coronary and systemic arteries (r=0.437; P=0.001). The underlying disease was myocardial inflammation (Inf) in 48 patients, in whom the mean (+/- SD) ENF of epicardial (FMDc-Inf 3.40+/-5.55%) and systemic (FMDp-Inf 3.69+/-2.93%) arteries was significantly impaired (P<0.001), compared with 13 control (Co) patients who had normal myocardial biopsies (FMDc-Co 14.51+/-8.62%; FMDp-Co 7.69+/-3.42%). FMD of coronary (r=-0.353; P=0.005) and systemic (r=-0.542; P<0.001) arteries correlated significantly with myocardial inflammation and endothelial activation. CONCLUSIONS: There was a significant correlation in FMD between coronary and systemic arteries in patients with atypical angina but without significant atherosclerosis. Inflammatory processes are associated with endothelial dysfunction of both vascular regions.     

Brachial artery flow-mediated vasodilation in patients with cardiac syndrome X

Cardiac syndrome X (CSX) differs from coronary artery disease (CAD) and is characterized by angina, positive stress test, and patent coronary arteries. The probable mechanism is a microvascular disorder associated with endothelial dysfunction. In this study, brachial artery flow-mediated vasodilation was used as well as the endothelin-1 assay to assess endothelial function in patients with cardiac syndrome X (CSX), coronary artery disease (CAD), and healthy controls. All subjects underwent a 2-step brachial artery flow-related vasodilatation test. Serum endothelin-1, one of the most potent constricting factors, was measured for all participants. Patients with CSX had a lower brachial artery dilation ratio than controls but higher than that of CAD patients. Control subjects and CSX patients had higher endothelin-1 levels than CAD patients. CSX patients were found to have worse endothelial function than healthy volunteers, but patients with CAD had even worse endothelium function than CSX patients.     

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.     

Relationship between endothelial function in the coronary and brachial arteries

BACKGROUND: Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries. HYPOTHESIS: We investigated the relationship between coronary and peripheral endothelial function. METHODS: In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 microg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values. RESULTS: Flow-mediated dilation (FMD) of the brachial artery was 5.0 +/- 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 microg/min, r = 0.31, p < 0.05) but also with the change in CBF (ACh at 3 microg/min, r = 0.39, p < 0.05; ACh at 30 microg/min, r = 0.46, p < 0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF. CONCLUSIONS: These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.     

Benefits of statin treatment in cardiac syndrome-X1.

AIMS: The pathophysiological mechanism in cardiac syndrome-X (anginal chest pain, positive exercise test, and angiographically normal coronary arteries) has been suggested as an impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. The aim of this study was to determine whether statins with proven beneficial effects on endothelium, have any effect on endothelial functions and exercise induced ischaemia in cardiac syndrome-X. METHODS AND RESULTS: Study population consisted of prospectively enrolled 40 patients with cardiac syndrome-X. Patients with left ventricular hypertrophy, hypertension, diabetes mellitus, and LDL levels >/=160 mg/dl were excluded. Half of the patients received pravastatin (40 mg/day) for 3 months irrespective of their lipid values, according to a single-blind, randomized, placebo-controlled design. Endothelial functions were assessed with high-resolution vascular ultrasound, which measured the brachial artery flow mediated dilatation (FMD). Lipid measurements, symptom limited exercise tests and vascular ultrasound images were obtained before and at the end of 3 months. After the treatment, FMD improved significantly in pravastatin group. Exercise duration, and time to 1mm-ST depression were significantly prolonged after statin therapy. Ischaemic symptoms and ECG findings during exercise test disappeared completely in 5 (26%) patients in the statin group. However, there were no significant changes in FMD and exercise parameters in placebo group. CONCLUSIONS: Statin therapy resulted in beneficial effects on both exercise induced ischaemia and FMD in cardiac syndrome-X. The mechanism of this beneficial effect is probably the result of improvement in endothelial functions.     

Unstable angina, myocardial infarction and sudden death after an exercise stress test

We performed coronary angiography within 95 minutes of the onset of symptoms in seven patients with an acute coronary event after an exercise stress test. The test was normal in six patients. Previous angiography in four patients revealed no evident or moderate obstructive coronary arterial disease. After the test, unstable angina developed in two patients, acute myocardial infarction in four and ventricular fibrillation in one, who was successfully resuscitated. At acute angiography the coronary artery involved was occluded in four and sub-totally obstructed in three. In three cases, coronary occlusion was due to thrombosis, vasospasm, or both. In six vessels there was an eccentric lesion, which is consistent with a ruptured plaque. These findings show that physical exercise can unexpectedly provoke an acute coronary event with sub-total or total occlusion of a previous angiographically normal or moderately obstructed coronary artery. The mechanism is probably related to exercise-induced plaque rupture which can produce coronary (sub)occlusion by coronary thrombosis, spasm, or both.     

Relation of angina pectoris to coronary artery disease in aortic valve stenosis

One hundred three patients with isolated, severe aortic stenosis (AS) were retrospectively analyzed to determine the relation of angina pectoris to angiographically significant coronary artery disease (CAD). All patients underwent coronary angiography regardless of the presence or absence of angina. Angina was significantly associated with CAD (p less than 0.002), with a sensitivity of 78% and a specificity of 53%. However, 25% of the patients without angina had angiographically significant CAD, and in these patients there was a 70% prevalence of 1-vessel disease. Patients with isolated, severe AS should undergo coronary angiography to identify coexistent CAD accurately. The absence of angina does not reliably exclude angiographically significant CAD.     

Usefulness of Holter monitoring to improve the sensitivity of exercise testing in determining the degree of myocardial revascularization after coronary artery bypass grafting for stable angina pectoris

To assess whether Holter monitoring improves the sensitivity of exercise testing in identifying incomplete myocardial revascularization, both tests were performed in 45 patients from 3 to 5 months after elective coronary artery bypass grafting (CABG) for stable angina pectoris. Coronary angiography revealed incomplete revascularization in 26 patients. Six of these 26 had 52 episodes of ST-segment depression during Holter monitoring and myocardial ischemia during exercise testing. Their exercise capacity was significantly lower than that of 10 other patients in whom the results of exercise testing only were positive (heart rate at 0.1 mV ST-segment depression 112 +/- 9 vs 123 +/- 15 beats/min, p less than 0.001). In the other 10 patients with incomplete myocardial revascularization the results of both investigations were negative. The graft patency rate was lower in patients with a positive response to exercise testing than in those with a negative response (52% vs 71%, p less than 0.005). Myocardial revascularization was angiographically complete in 19 patients. In 18 of these 19 patients the findings of both investigations were negative; in 1 patient Holter monitoring revealed episodes of ST-segment elevation suggestive of variant angina. Thus, after CABG for stable angina pectoris the results of Holter monitoring do not improve the sensitivity of exercise testing in identifying patients with angiographically incomplete myocardial revascularization because findings are positive only in patients with low exercise capacity. Both tests fail to show evidence of myocardial ischemia in most patients with angiographically complete myocardial revascularization.     

Endothelial vasomotor dysfunction in the brachial artery is associated with late in-stent coronary restenosis

OBJECTIVES: This study examined whether endothelial dysfunction in the brachial artery might be associated with late in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). BACKGROUND: Simple and noninvasive identification of late ISR might help to select patients who require further angiographic evaluation. METHODS: Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was measured before (initial FMD) and at six months (follow-up FMD) after PCI in 141 consecutive patients who had elective and successful PCI with bare metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease. Follow-up angiography was performed at six months after PCI in all patients. RESULTS: With multivariate logistic regression analysis, the impairment (< or = 4.8% dilation from baseline diameter) of FMD at follow-up showed the strongest association with late ISR (defined as > 50% diameter stenosis, n = 46) independently of other clinical and angiographic variables known to be associated with ISR (odds ratio 7.4, 95% confidence interval 2.8 to 19.2, p < 0.001), whereas the initial FMD did not have the association. The sensitivity of impaired FMD at follow-up (69%) in detecting ISR was higher than chest pain during the follow-up period (45%), with comparable specificity. The impaired FMD in combination with the chest pain increased the sensitivity to 90%. CONCLUSIONS: The impairment of FMD in the brachial artery at the time of follow-up was independently and closely associated with late ISR in native coronary arteries. The noninvasive assessment of FMD at the time of follow-up might be useful for identification of late ISR.     

Value of stress and long-term ECG in the diagnosis of silent myocardial ischemia in patients with coronary heart disease

Symptomatic and asymptomatic myocardial ischemia during exercise testing and during daily activities (ST-segment analysis on 24-h Holter ECG) was studied in 109 patients with stable angina pectoris and proven coronary artery disease (coronary stenoses greater than 70%) (group I) and in 20 patients with angiographically normal coronary arteries or minimal changes (group II). During exercise testing, 94/109 (86.2%) group I patients and 6/20 (30%) group II patients showed ST-segment depression greater than or equal to 0.1 mV. During Holter ECG, transient ST-segment depression (greater than or equal to 0.1 mV; greater than or equal to 1 min) was observed in 76/109 (69.7%) group I patients and in 5/20 (25%) group II patients; all patients with positive Holter ECG also had a positive exercise tests result. Heart rate and exercise duration at the onset of ischemia during stress testing were useful parameters to estimate the incidence of ischemic episodes during Holter ECG. Patients with asymptomatic positive exercise tests showed a significantly higher percentage of asymptomatic ischemic episodes during Holter ECG than patients with a symptomatic positive exercise test (89% vs. 68% asymptomatic ischemic episodes; p less than 0.001). Therefore, in patients with coronary artery disease and stable angina pectoris, the exercise test provides information also about the activity of ischemic heart disease during daily activities.