Increased plasma fibrinopeptide A levels during attacks induced by hyperventilation in patients with coronary vasospastic angina

Plasma fibrinopeptide A levels, beta-thromboglobulin levels and platelet factor 4 levels were estimated by enzyme-linked immunosorbent assay before and after hyperventilation in 12 patients with coronary vasospastic angina and in 12 control subjects matched for age and gender. In all 12 study patients, anginal attacks accompanied by electrocardiographic (ECG) changes (ST elevation in 11 patients and ST depression in 1 patient) were induced by hyperventilation. Coronary angiography was performed on 11 of the 12 patients, and coronary artery spasm with the same ECG changes was induced by intracoronary injection of acetylcholine in all 11. The plasma fibrinopeptide A levels increased significantly from 2.0 +/- 0.4 to 10.0 +/- 2.4 ng/ml during the attack (p less than 0.001) in the study patients, but remained unchanged before and after hyperventilation in the control subjects. The plasma levels of beta-thromboglobulin and platelet factor 4 remained unchanged after hyperventilation in both groups. Our data indicate that coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery.     

Circadian variation of plasma fibrinopeptide A level in patients with variant angina

Plasma levels of fibrinopeptide A (FPA), beta-thromboglobulin (BTG), and platelet factor 4 (PF4) were examined on venous plasma samples taken every 4 hours for 24 hours in 20 patients with variant angina and 20 patients with stable exertional angina together with 24-hour Holter recordings. The mean plasma FPA levels (ng/ml) at 2:00 PM, 6:00 PM, 10:00 PM, 2:00 AM, 6:00 AM, and 10:00 AM were 4.6 +/- 1.0, 3.1 +/- 0.5, 6.1 +/- 1.6, 9.9 +/- 2.4, 8.7 +/- 1.4, and 4.2 +/- 0.8 in patients with variant angina (p less than 0.01) and 1.8 +/- 0.2, 2.3 +/- 0.3, 1.9 +/- 0.3, and 2.3 +/- 0.2 in those with stable exertional angina. In seven patients with variant angina, we also examined the effects of heparin (3,000 units), given subcutaneously at 6:00 PM, 10:00 PM, and 2:00 AM, on the plasma FPA levels and the anginal attacks. Although heparin suppressed the elevation and circadian variation of plasma FPA levels, it did not suppress the attacks and their circadian variation in these patients. Plasma FPA levels increased significantly from 3.7 +/- 0.5 to 12.5 +/- 2.7 ng/ml during or immediately after an attack in the seven patients with no heparin. On the other hand, the plasma levels of BTG and PF4 were increased in patients with variant angina as compared with those with stable exertional angina but did not show a significant circadian variation in both groups. We conclude that 1) plasma levels of FPA, BTG, and PF4 were increased in patients with variant angina as compared with those with stable exertional angina; 2) there was a significant circadian variation in the plasma levels of FPA in parallel with that of the frequency of the attacks with the peak level occurring from midnight to early morning in patients with variant angina; and 3) elevated levels of plasma FPA are the result and not the cause of coronary spasm.     

Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina

To examine whether or not magnesium suppresses coronary spasm, the effect of magnesium infusion on anginal attacks induced by hyperventilation was studied in 20 patients with variant angina. In all patients, anginal attacks associated with ischemic ST segment changes on the electrocardiogram were repeatedly induced by hyperventilation. The study was performed in the early morning successively for 3 days. On days 1 and 3 (control studies), 50 minutes before the hyperventilation test, a 5% glucose solution was infused as a placebo. On day 2 (magnesium study), 50 minutes before the hyperventilation test, magnesium sulfate (0.27 mM/kg body wt) was infused during a 20-minute period. During the control studies, anginal attack was induced by hyperventilation in all 20 patients, whereas during the magnesium study, anginal attack was induced by hyperventilation in only six (30%) of the 20 patients (p less than 0.001 vs. control studies). The changes in arterial blood pH and PCO2 caused by hyperventilation were not significant between the control study and the magnesium study. Mean serum magnesium concentration increased from 2.2 +/- 0.2 to 6.0 +/- 0.5 mg/dl immediately after infusing magnesium and was 4.5 +/- 0.6 mg/dl before the hyperventilation test during the magnesium study. We conclude that magnesium suppresses anginal attacks induced by hyperventilation in patients with variant angina.     

U wave inversion during attacks of variant angina.

Sequential 12 lead electrocardiograms were recorded during angina pectoris induced by ergonovine maleate in 38 patients with variant angina. Transient U wave inversion was observed in 17 patients with ST segment elevation in anterior chest leads, but in only three of 21 patients with ST segment elevation in the inferior leads associated with right coronary artery spasm. In the 17, all of whom had spasm of the left anterior descending coronary artery, the sensitivity of ST segment elevation in V5 was only 41%, and that of U wave inversion 71%. U wave inversion without ST segment elevation occurred during attacks in 35% of patients. During the recovery phase, the sensitivity of U wave inversion was 82% in V4 and 65% in V5, though ST segment elevation was absent in both V4 and V5. Thus, inverted U waves without ST segment elevation often appear in marginal ischaemic zones or during the time of recovery from temporary ischaemia. Detection of inverted U waves should aid in the diagnosis of variant angina when only lead V5 is used as a monitor and when electrocardiograms are recorded only during the recovery phase.     

Biphasic changes (initial increase and late decrease) in coronary sinus venous oxygen saturation during anginal attacks induced by intracoronary acetylcholine in patients with variant angina.

In order to evaluate the effects of intracoronary acetylcholine on coronary resistance vessels, oxygen saturation in coronary sinus blood was continuously measured to compare its dynamic changes during intracoronary injection of acetylcholine in both patients with variant angina and control subjects. Group 1 consisted of 6 patients without coronary artery disease. Group 2 consisted of 10 patients with variant angina and spasm in the left anterior descending coronary artery. A fiberoptic reflection oximetry system was used for the continuous measurement of coronary sinus venous oxygen saturation. Acetylcholine (20 micrograms) was injected directly into the left coronary artery over 30 s. In the group 1 patients, coronary sinus venous oxygen saturation was increased from 39 +/- 2% (mean +/- SEM) to 54 +/- 3% at 30 s, continuously climbed to 70 +/- 3% at 60 s and then gradually decreased to 53 +/- 5% at 120 s after the initiation of intracoronary injection of acetylcholine. In contrast, in the group 2 patients, coronary sinus venous oxygen saturation was transiently increased from 39 +/- 2% to 56 +/- 4% at 30 s, reversed, decreased to 52 +/- 4% at 60 s and then rapidly decreased to 36 +/- 3% at 120 s with the onset of chest pain associated with electrocardiographic ischemic changes. Coronary arteriography during attacks demonstrated a total or subtotal occlusion of the left anterior descending coronary artery due to severe spasm in all of the 10 patients. The extent of increases in coronary sinus venous oxygen saturation at 30 s after acetylcholine injection was not significantly different between the two groups (group 1: 15 +/- 4%, group 2: 17 +/- 3%). Heart rate, blood pressure and rate-pressure product were essentially unchanged at 30 s after intracoronary injection of acetylcholine in both groups. These data suggest that in control adult humans, coronary blood flow was increased through dilatation of resistance vessels by acetylcholine, while in patients with variant angina, coronary blood flow was transiently increased by dilatation of resistance vessels, after which it was suddenly decreased by spasm of an epicardial artery induced by this agent. Relaxant responses to acetylcholine of coronary resistance vessels appear to be preserved well in patients with variant angina.     

Two electrocardiographic patterns with or without transient T-wave inversion during recovery periods of variant anginal attacks

Continuous electrocardiographic recordings during anginal attacks in patients with variant angina were reviewed. Twenty-seven attacks in 15 patients were associated with transient T-wave inversion during recovery periods of angina (type A), while in another 69 attacks in 28 patients there was no T-wave inversion (type B). In none of the patients was there an ischemic T-wave inversion during angina-free periods. Both the maximum elevation (0.79 +/- 0.57 mV) and duration (5.3 +/- 1.2 min) of ST-segment deviation of type A attacks were significantly higher and longer than those of type B (0.44 +/- 0.27 mV, 2.8 +/- 1.4 min). Ten patients who had both type A and type B attacks one time or the other were selected for further evaluation. In these 10, the duration of ST-segment elevation was significantly longer during type A attacks (5.2 +/- 1.2 min, n = 18) than during type B attacks (2.7 +/- 1.2 min, n = 20) but there was no significant difference in the maximum ST-segment elevation. Giant U-wave inversion appeared in 15% of the type A attacks, but never in type B. Therefore, the T-wave abnormality related to ischemic episodes in patients with variant angina seems to be associated with more severe ischemia of longer duration than milder episodes of transient ischemia.     

Prognostic significance of electrocardiographic change during anginal attack in patients with unstable angina

OBJECTIVE AND METHODS: We examined the prognostic significance of electrocardiographic change during anginal attack, C-reactive protein and fibrinogen in 169 patients with unstable angina. RESULTS: During the 90-day follow-up period, 26 patients (15%) exhibited new cardiac events (death, myocardial infarction or urgent revascularization). Using multivariate analysis, ST depression (relative risk 7.507 [95 % confidence intervals 1.842-30.592], p<0.01) during anginal attack was found to be an independent risk factor to predict cardiac events as well as diabetes mellitus, an increased total cholesterol level and the use of a thrombolytic agent. C-reactive protein and fibrinogen did not have prognostic significance. CONCLUSION: ST depression during anginal attack is an independent risk predictor for new cardiac events in patients with unstable angina.     

不稳定型心绞痛患者同型半胱氨酸内皮素及纤维蛋白肽A的变化及意义

目的 :探讨不稳定型心绞痛 (UAP)患者血中同型半胱氨酸 (Hcy)、内皮素 (ET)及纤维蛋白肽A(FPA)的变化及意义。方法 :分别测定UAP患者 (37例 )、正常人 (31例 )血中Hcy、ET及FPA值。结果 :UAP患者Hcy、ET及FPA值均明显高于正常人 [(12 .4 9± 5 .4 7)∶(4 .38± 1.14 ) μmol/L]、[(12 9.37± 2 6 .6 2 )∶(6 5 .0 6±13.76 )ng/L]及 [(8.87± 2 .11)∶(3.4 5± 0 .6 0 ) μg/L],均 P <0 .0 5 ,Hcy与ET呈正相关 (r =0 .4 5 ,P <0 .0 5 )。结论 :Hcy、ET及FPA的改变可能参与了UAP的病理生理过程     

Increased QT dispersion in patients with Prinzmetal's variant angina and cardiac arrest

OBJECTIVES: We sought to compare QT dispersion in patients presenting with Prinzmetal's variant angina complicated by cardiac arrest or syncope and patients with uncomplicated variant angina. BACKGROUND: Despite the usually benign course of treated Prinzmetal's variant angina, a proportion of vasospastic angina patients develop ventricular arrhythmias and sudden death in association with coronary spasm. Increased QT dispersion has been suggested to increase susceptibility to ventricular arrhythmias in patients with coronary artery spasm. METHODS: We studied 25 consecutive patients (mean age 58 years; 14 men) with classical Prinzmetal's variant angina and documented coronary artery spasm. None of the patients had coronary artery stenoses < or =40%. Five patients had suffered a documented cardiac arrest, two had recurrent syncope and 18 had no arrhythmic events or syncopal episodes. In all patients QT dispersion (QT maximum-QT minimum in every ECG lead) was measured on the baseline 12-lead electrocardiogram at study entry using a digitising board. RESULTS: Mean (+/-S.D.) QT dispersion of study patients was 62.3+/-19.5 ms. QT dispersion in patients with cardiac arrest and syncope (79.4+/-17.3 ms) was significantly higher compared to patients with no such events (56.3+/-16.9 ms), (95% CI 7.5-38.8, P=0.005). No significant clinical, biochemical or angiographic differences were found between patients with and those without cardiac arrest or syncope. CONCLUSION: QT dispersion is increased in patients with Prinzmetal's variant angina complicated by cardiac arrest and syncope compared to patients without such events. Increased QT dispersion may be both a substrate for sudden cardiac death and a marker of risk in patients with Prinzmetal's variant angina.     

The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks

Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased peripheral circulating inflammatory cells and plasma inflammatory markers in patients with variant angina

BACKGROUND: Emerging data suggest that inflammation may play an important role in the pathogenesis of coronary artery disease. However, the relation of inflammatory status to coronary vasospasm has been less investigated in patients with variant angina (VA). PURPOSE: The aim of this study, therefore, was to determine peripheral circulating white blood cells as well as monocyte cells and plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels in patients with VA, and to compare patients with VA, stable coronary artery disease, and controls with angiographically normal coronary arteries. METHOD: Thirty-three consecutive patients with documented VA, 26 with stable coronary artery disease, and 22 normal controls (with angiographically normal coronary arteries) were involved in this study. The peripheral blood was taken, and white blood cells and monocyte cells were counted. The plasma concentrations of CRP and IL-6 were also evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The data showed that white blood cell counts and monocyte cell counts were significantly higher in patients of the VA group than in the other two groups (white blood cell counts: 7340+/-1893/mm vs. 6187+/-1748/mm vs. 5244+/-1532/mm, P<0.05, respectively; monocyte cell counts: 510+/-213/mm vs. 425+/-209/mm vs. 383+/-192/mm, P<0.05, respectively). Similarly, levels of plasma CRP and IL-6 were also significantly higher in patients of the VA group than in patients with stable coronary artery disease (CRP: 0.42+/-0.21 mg/l vs. 0.27+/-0.14 mg/l; IL-6: 10.4+/-1.0 pg/dl vs. 6.2+/-0.7 pg/dl, P<0.01, respectively), and patients with normal controls (CRP: 0.42+/-0.21 mg/l vs. 0.17+/-0.10 mg/l; IL-6: 10.4+/-1.0 pd/dl vs. 3.0+/-0.7 pg/dl, P<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with VA. CONCLUSION: Taken together, these findings suggested that more chronic, severe inflammation might be involved in the pathogenesis of VA, manifested by increased counts of circulating inflammatory cells and elevated plasma levels of CRP and IL-6.     

Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina.

OBJECTIVES: We sought to examine whether estradiol (E2) supplementation suppresses anginal attacks in women with variant angina. BACKGROUND: Estrogen is known to improve endothelial function. Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general, and endothelial dysfunction seems to be involved in the pathogenesis of coronary spasm. METHODS: Fifteen postmenopausal women with variant angina (mean age 54.2 years) were given a hyperventilation (HV) test, a provocation test for coronary spasm, in the early morning of day 1 (baseline), day 3 (after 2-day transdermal E2 supplementation, 4 mg) and day 5 (after 2-day placebo administration). We measured the flow-mediated (endothelium-dependent) dilation (FMD) of the brachial artery with the ultrasound technique before each HV test. RESULTS: The anginal attacks with ST segment elevation were induced by HV in all patients on days 1 and 5. However, no attacks were induced on day 3. Supplementation with E2 augmented FMD (3.5 +/- 0.6*, 8.9 +/- 0.7 and 4.0 +/- 0.5* on days 1, 3 and 5, respectively; *p < 0.01 vs. day 3). The serum E2 levels on days 1, 3 and 5 were 22.7 +/- 2.8*, 96.2 +/- 9.2 and 30.7 +/- 7.1* pg/ml, respectively (*p < 0.01 vs. day 3). CONCLUSIONS: The present results demonstrated for the first time, to our knowledge, that E2 supplementation suppresses the HV-induced attacks in women with variant angina, in part because of the improvement of endothelial function.     

Inhibition of Rho-kinase by fasudil preventing anginal attacks associated with spastic angina: a case report

An 86-year-old woman was admitted with unstable angina pectoris. Plain old balloon angioplasty (POBA) was performed for 90% stenosis at segment 7 of the left coronary artery with concomitant treatment with nitrate, calcium antagonists, and nicorandil. Five days after POBA, she again suffered chest pain at rest with ST depression by electrocardiography, despite increased doses of calcium-antagonist and nicorandil. Coronary arteriography showed no evidence of restenosis (50%) at the POBA site. The involvement of coronary artery spasm was considered and intravenous treatment with a Rho-kinase inhibitor, fasudil, was started, which resulted in disappearance of the anginal attacks. She refused to continue the fasudil treatment on day 5, which resulted in reappearance of anginal attacks. Third coronary angiography showed a 90% restenosis at POBA site and percutaneous coronary intervention was again performed. This case suggests that a Rho-kinase inhibitor is potentially effective to prevent anginal attacks in spastic angina.     

A clinical study of postinfarction angina (PIA): the significance of electrocardiographic ST segment changes during anginal attacks]

We studied the clinical significance of electrocardiographic ST segment changes during PIA attacks. Of 478 AMI patients admitted to the CCU of our hospital within 48 hours after onset, we evaluated 73 (15.3%) with PIA. According to electrocardiographic ST segment changes during PIA attacks, the patients were divided into three groups, namely ST elevation at the same infarction site (same site elevation group), ST depression at the same site (same site depression group), and ST depression at other sites (other site depression group), and their pathological condition was studied. There were 33 patients (45.2%) in the same site elevation group, 19 (26.0%) in the same site depression group, and 21 (28.8%) in the other site depression group. The predominant infarction areas were anteroseptal and inferior wall in the same site elevation group, NTMI in the same site depression group, and inferior wall in the other site depression group. PIA usually occurred within 4 days after the onset of infarction in the same site elevation group, and within 5-7 days in the other site depression group, but no uniform trend was observed in the same site depression group. With respect to the number of vessels showing disease, cases of single-vessel disease tended to predominate in the same site elevation group, while cases of three-vessel disease tended to predominate in the same site depression group and the other site depression group. Stenosis rates in the vessels responsible for infarction were high in the same site elevation group in the acute period. Prognoses were poorest in the same site depression group.(ABSTRACT TRUNCATED AT 250 WORDS)