Sulfido-peptide leukotrienes in coronary heart disease - relationship with disease instability and myocardial ischaemia.

BACKGROUND: Urinary excretion of leukotriene (LT) E(4) is an index of LTC(4) biosynthesis and platelet-neutrophil interactions, which may occur in coronary heart disease and contribute to myocardial ischaemia. Enhanced LTC(4) biosynthesis may be a consequence of myocardial ischaemia or be linked to its pathogenetic substrate. METHODS AND RESULTS: Overnight urine collections were obtained from 17 patients with chronic stable angina, three patients with Prinzmetal's angina, 16 patients with non ST-elevation acute coronary syndromes (NSTE-ACS) and six patients with acute ST-elevation myocardial infarction (STEMI). LTE(4) excretion was measured by enzyme immunoassay after HPLC separation. Compared with healthy controls (51.1 +/- 21.3 pg mg(-1) creatinine, mean +/- SD, n = 11) and with non-coronary cardiac controls (36.6 +/- 9.8 pg mg(-1) creatinine, n = 9), LTE(4) excretion was unchanged in stable angina (40.5 +/- 25.8 pg mg(-1) creatinine), but significantly (P < 0.01) increased in NSTE-ACS (122.7 +/- 137.2 pg mg(-1) creatinine) and STEMI (213.4 +/- 172.4 pg mg(-1) creatinine). In these patients, LTE(4) excretion rapidly dropped after day 1, consistent with effective coronary reperfusion. In patients with NSTE-ACS, the increase in LTE(4) excretion was entirely restricted to patients with recent (< 48 h) spontaneous anginal episodes. Myocardial ischaemia elicited by a positive exercise stress test was not accompanied by any detectable increase in LTE(4) excretion, while a significant (P < 0.01) increase was detected after a single-vessel percutaneous coronary interventions (PCI) procedure (n = 10), as compared with diagnostic angiography (n = 9). CONCLUSIONS: In coronary heart disease, increased LTC(4) biosynthesis is restricted to ACS and not linked to myocardial ischaemia per se, but likely to the occurrence of plaque disruption.

Significance of urinary liver-fatty acid-binding protein in cardiac catheterization in patients with coronary artery disease.

OBJECTIVES: We investigated the significance of urinary liver fatty acid-binding protein (U-L-FABP) monitoring during cardiac catheterization in patients with cardiovascular disease (CVD). Methods The subjects included 27 consecutive patients with stable angina (SAP group) or acute coronary syndrome (ACS group) who had undergone successful percutaneous coronary intervention (PCI), and 12 patients were also enrolled as controls (C group). Urinary and serum parameters were measured immediately before and after and 1 day after PCI. RESULTS: The ratio of U-L-FABP to U-creatinine (U-Cr) (U-L-FABP/U-Cr) in the ACS group was significantly higher than those in both the SAP and C groups before PCI. In addition, none of the patients in the SAP group showed contrast-induced nephropathy (CIN) based on the levels of serum (S)-Cr and U-L-FABP/U-Cr after PCI. Although none of the patients in the ACS group showed CIN according to S-Cr, the level of U-L-FABP/U-Cr was continuously high throughout the study period. Moreover, since there were significant differences in U-L-FABP/U-Cr, U-N-acetyl-beta-D-glucosaminidase, S-uric acid and % medication with calcium channel blockers before PCI between the ACS and SAP groups, a multiple regression analysis was performed using these parameters. It showed that U-L-FABP/U-Cr was most closely associated with the classification of SAP and ACS (p<0.0001). The cut-off level for the greatest sensitivity and specificity for U-L-FABP for the diagnosis of ACS was 13.4 microg/g. Cr in all subjects (sensitivity 0.800, specificity 0.963). CONCLUSIONS: To the best of our knowledge, this is the first report indicating that the measurement of U-L-FABP can be beneficial for in the diagnosis of ACS.

Increased isoprostane content in coronary plaques obtained from vulnerable patients.

8-Iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), a representative isoprostane, is a reliable biomarker for enhanced oxidant stress in vivo. Its urinary excretion has been proposed as a risk marker in patients with coronary heart disease. Isoprostane content has not yet been well elucidated so far in human coronary plaques. The aim of this study was to evaluate content of immunoreactive 8-iso-PGF(2)(alpha) in directional coronary atherectomy (DCA) specimens from patients with coronary heart diseases. Twenty-seven patients with stable angina pectoris (SAP) and 8 vulnerable patients (5 patients with unstable angina pectoris and 3 with recent myocardial infarction) were subjected to DCA. The specimens from SAP consisted of 14 de novo and 13 restenotic lesions, whereas those from the vulnerable patients were all de novo lesions. Total 8-iso-PGF(2)(alpha) content in the DCA specimens from the vulnerable patients was significantly greater than that from patients with SAP (5.48 (2.70-10.43) versus 2.38 (1.19-4.32)ng/g tissue, median (interquartile range), P<0.05). There was no significant difference in total 8-iso-PGF(2)(alpha) content between de novo and restenotic lesions from patients with SAP (3.25 (1.48-5.05) versus 1.57 (0.62-2.47)ng/g tissue, respectively, P=0.895). Total 8-iso-PGF(2)(alpha) content in apparently normal peripheral artery specimens was only 0.34 (0.26-0.46)ng/g tissue. In conclusion, 8-iso-PGF(2)(alpha) was enriched in the DCA specimens from vulnerable patients, suggesting a crucial role of free radicals in formation of vulnerable plaques and a putative benefit of anti-oxidant therapy on these patients.

Comparison of urinary biopyrrin levels in acute myocardial infarction (after reperfusion therapy) versus stable angina pectoris and their usefulness in predicting subsequent cardiac events.

We examined the relation between oxidative stress and cardiac events in patients with acute myocardial infarction (AMI). There is now increasing evidence that reactive oxygen species cause reperfusion injury to the previously ischemic myocardium after reperfusion. We measured urinary biopyrrin/creatinine levels, an oxidative stress marker, in 41 patients with AMI, 34 patients with stable angina pectoris (SAP), and 29 control subjects. In the patients with AMI, urine samples were taken before, at 4 and 24 hours, and at 1 and 2 weeks after reperfusion therapy. Of these 41 patients with AMI, 38 received reperfusion therapy, and the urinary biopyrrin/creatinine levels (micromol/g.creatinine) before reperfusion were significantly higher than those of the other 2 groups (AMI 4.24 +/- 0.49, SAP 2.45 +/- 0.15, control subjects 2.31 +/- 0.16; p = 0.0003 vs AMI). The onset of reperfusion significantly increased the levels of urinary biopyrrins/creatinine, and this time course was mapped out, peaking at 4 hours (8.21 +/- 0.96 vs 4.24 +/- 0.49 before, p = 0.0001), and decreasing to control levels between 24 hours and 7 days. The peak levels of urinary biopyrrins/creatinine were higher in the positive cardiac event group than in the negative cardiac event group (11.89 +/- 1.77 vs 7.57 +/- 1.00 micromol/g.creatinine, p = 0.029). These findings add further evidence that oxidative stress contributes to the complications of reperfusion injury, and suggest that urinary assessment of biopyrrins may be useful in predicting subsequent cardiac events after reperfusion in AMI.

Prognostic implications of autonomic function assessed by analyses of catecholamines and heart rate variability in stable angina pectoris.

OBJECTIVE: To assess the prognostic impact of autonomic activity, as reflected by catecholamines and heart rate variability (HRV), in patients with stable angina pectoris. DESIGN: Double blind, randomised treatment with metoprolol or verapamil. 24 hour ambulatory ECG, used for frequency domain analyses of HRV, and symptom limited exercise tests at baseline and after one month of treatment. Catecholamine concentrations were measured in plasma (rest and exercise) and urine. SETTING: Single centre at a university hospital. PATIENTS: 641 patients (449 men) with stable angina pectoris. MAIN OUTCOME MEASURES: Cardiovascular (CV) death, non-fatal myocardial infarction (MI). RESULTS: During follow up (median 40 months) there were 27 CV deaths and 26 MIs. Patients who died of CV causes had lower total power and high (HF), low (LF), and very low (VLF) frequency components of HRV. HRV was not altered in patients who suffered non-fatal MI. Catecholamines did not differ between patients with and those without events. Metoprolol increased HRV. Verapamil decreased noradrenaline (norepinephrine) excretion. Multivariate Cox analyses showed that total power, HF, LF, and VLF independently predicted CV death (also non-sudden death) but not MI. LF:HF ratios and catecholamines were not related to prognosis. Treatment effects on HRV did not influence prognosis. CONCLUSIONS: Low HRV predicted CV death but not non-fatal MI. Neither the LF:HF ratio nor catecholamines carried any prognostic information. Metoprolol and verapamil influenced LF, HF, and catecholamines differently but treatment effects were not related to prognosis.

Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases after spasm provocation tests in patients with coronary spastic angina.

BACKGROUND: Bilirubin apparently functions as an antioxidant in vivo by reacting with reactive oxygen species, and, as a result, becomes oxidized. The urinary excretion of oxidative metabolites of bilirubin, biopyrrins, could be a biological marker for in vivo production of reactive oxygen species. The purpose of this study was to examine the extent of oxidative stress in patients with possible ischemic heart diseases (n=44) by measuring urinary biopyrrins by enzyme-linked immunosorbent assay before and after the spasm provocation test (SPT). METHODS: Spot urine samples were collected five times; 1 day before, in the morning just before, immediately after, 6 h after, and 1 day after the SPT. Nineteen patients were positive to SPT judged from the specific changes in electrocardiogram for myocardial ischemia following intracoronary injections of ergonovine. RESULTS: The baseline data such as age, sex, number of risk factors and concentrations of serum bilirubin, and the measured hemodynamic parameters of heart rate, blood pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction were not different between the positive and negative groups. The baseline concentrations of biopyrrins during the control period were not significantly different between the two groups. However, they increased significantly after the SPT, thereby the magnitude of increases immediately after and 6 h after the SPT were significantly (P<0.001 and P<0.01, respectively) greater in the positive group than in the negative. CONCLUSION: The present findings strongly suggest that coronary arterial occlusion augments production of biopyrrins, which indicates exposure to oxidative stress in patients with ischemic heart diseases.

Particular fractions of microproteinuria in patients with stabile angina pectoris and without a clinical nephropathy.

The determination of microalbuminuria is a valuable method in the diagnosis of renal and vascular diabetes or hypertension complications. Recently, microalbuminuria appeared to be the predictor of coronary heart diseases (CHD). The presented study comprised 26 patients with stable angina pectoris (AP) and 27 healthy volunteers. We simultaneously evaluated microproteinuria during the first morning and afternoon miction and the 24-h blood pressure. Amongst patients with AP all urine protein concentrations were increased (results in g/mol creatinine): alpha-1-microglobulin (1.04 + 0.13 vs. 0.47 + 0.05, p < 0.001) albumin (0.95 + 0.15 vs. 0.61 + 0.05, p < 0.05) and IgG (1.00 + 0.17 vs. 0.55 + 0.05, p < 0.01) were higher, in comparison to control group values. Indices for diurnal blood pressure rhythm were significantly lower in the AP group for both systolic (1.07 + 0.01 vs. 1.14 + 0.01 p < 0.001) and diastolic (1.09 + 0.02; vs. 1.21 + 0.03 p < 0.01) pressures. A physiological increase of albumin from the afternoon sample was only observed in the control group. Thus, our AP patients demonstrated signs of subclinical nephropathy in both the proximal tubuli and glomeruli.

Enhanced excretion of urinary leukotriene E4 in coronary artery disease and after coronary artery bypass surgery.

BACKGROUND: Excretion of leukotriene (LT) E4, the major urinary metabolite of cysteinyl leukotrienes in humans, is increased in patients with unstable angina and myocardial infarction, suggesting that cysteinyl leukotrienes are released into the circulation during episodes of myocardial ischaemia. Furthermore, leukotrienes are known to induce potent vasoconstrictive effects in human atherosclerotic coronary arteries and the saphenous vein. Accordingly, we measured urinary excretion of LTE4 in patients with stable coronary artery disease both before and after coronary artery bypass surgery, and in age-matched healthy controls, to study the relation between the systemic synthesis of cysteinyl leukotrienes and stable coronary artery disease, as well as the possible changes after bypass surgery. METHODS: LTE4 was isolated from urine samples by solid-phase extraction, purified by reverse-phase high-performance liquid chromatography, and subsequently quantified by radioimmunoassay. RESULTS: In patients with coronary artery disease, preoperative urinary LTE4 levels were normally distributed on a log10 scale, with a genometric mean of 115 pmol/mmol creatinine (95% confidence interval 67-196) compared with 63.0 pmol/mmol creatinine (95% confidence interval 47.9-82.7) in healthy subjects (P < 0.05). Urinary LTE4 levels increased further in patients after coronary artery bypass surgery with levels peaking on the second day after surgery (266.2 pmol/mmol creatinine, 95% confidence interval 167.2-423.9) at significantly higher than preoperative levels (P < 0.02), and then decreasing by day 3. CONCLUSIONS: Levels of cysteinyl leukotrienes are raised in coronary artery disease patients both before and after coronary artery bypass surgery. As these mediators are capable of inducing potent vasoconstrictive effects on atherosclerotic coronary arteries and the saphenous vein, our results could have important clinical and possibly therapeutic implications.

[The effect of anaprilin on the reaction of the sympathetic-adrenal system to graded physical loading in healthy subjects and patients with ischemic heart disease]. / Vliianie anaprilina na reaktsiiu simpatiko-adrenalovoi sistemy pri dozirovannoi fizicheskoi nagruzke u zdorovoykh liudei i bol'nykh ishemicheskoi bolezn'iu serdtsa.

The specific features of responses of the sympathoadrenal system during its activation by graded exercise (E), including that along with anaprilin induced blockade of beta-adrenoceptors, were determined from the urinary excretion of norepinephrine, epinephrine, dopamine, and dioxyphenylalanine in 54 healthy males and 22 patients with postinfarction cardiosclerosis concurrent with Functional Class I-II angina pectoris on effort. E caused hyperreactivity of the sympathoadrenal system, as appeared as significantly greater increases in the levels of catecholamines and their precursors in the patients than in the healthy persons. A single anaprilin dose of 40 mg abolished the responsiveness to exercise and improved its tolerance. The revealed features of sympathoadrenal responsiveness to exercise with and without anaprilin suggest that the patients with coronary heart disease have sympathoadrenal dysfunction, which shows one of the possible mechanisms responsible for the cardioprotective effect of beta-adrenoblockers in this disease.

[Hypertension, heart failure and angina pectoris. Diurnal rhythm of urinary excretion of catecholamines]. / Nadcisnienie tetnicze, niewydolnosc krazenia, angina pectoris. Dobowy rytm wydalania katecholamin.

Adrenaline, noradrenaline and dopamine excretion was investigated in essential hypertension (n = 20), atherosclerotic heart failure (n = 20, NYHA class II and III), chronic angina (n = 10) and in healthy controls, in four time intervals: between 600-1200, 1200-1800, 1800-2400, 2400-600. Fluorimetric method of Anton and Sayre was employed. In patients with essential hypertension the circadian rhythm of adrenaline, noradrenaline and dopamine excretion was maintained but in all time intervals excretion of dopamine was decreased. In individuals with congestive heart failure due to atherosclerosis and in patients with ischemic heart disease, physiological circadian rhythm of adrenaline and noradrenaline excretion was found to be abolished. This was not the case with dopamine excretion which was undisturbed.

Fibrinopeptide A excretion in urine: a marker of the cumulative thrombin activity in stable versus unstable angina patients.

Plasma levels and 24-hour urine excretion of fibrinopeptide A were measured in a consecutive series of 179 patients with angina pectoris. Sixty-four patients had stable angina and 115 patients had unstable angina. Urine was collected over 24 hours the day before coronary arteriography, and blood samples were taken at the end of urine collection. When the values of fibrinopeptide A in plasma and in the 24-hour urine specimens were compared, no significant correlation was found in patients with either stable (rs = 0.16, difference not significant) and unstable (rs = 0.07, difference not significant) angina. The concentrations of fibrinopeptide A in the plasma did not differ significantly when patients with stable angina (range 0.1 to 82.6, median 7.4 ng/mL) were compared with patients with unstable angina (range 0.2 to 61.7, median 14 ng/mL, p = 0.055), whereas fibrinopeptide A 24-hour urinary excretion was significantly higher in patients with unstable angina (range 0.3 to 38.1, median 11.8 micrograms/24 hr) than in patients with stable angina (range 0.4 to 38.1, median 3.8 micrograms/24 hr, p less than 0.001). Twenty-four-hour urine excretion of fibrinopeptide A in patients with unstable angina and angiographically documented intracoronary thrombi were higher than the corresponding values in patients with unstable angina without such angiographic characteristic (p less than 0.001). The largest increase in plasma and urine concentration of fibrinopeptide A was observed in patients whose first episode of angina at rest occurred within the previous 48 hours. We conclude that the cumulative thrombin activity, assessed by 24-hour urinary excretion of fibrinopeptide A, is a more useful index, compared with single fibrinopeptide A measurement in plasma, for discriminating between patients with stable and with unstable angina pectoris.

A prospective study of the diagnostic value of urinary thromboxane in patients presenting with acute chest pain.

In chance single-case observations thromboxane excretion has been reported to increase several days prior to myocardial infarction. To test its frequency and potential diagnostic value we prospectively measured thromboxane excretion in 166 consecutive patients who had presented to the emergency unit with acute chest pain indicative of ischaemia. Thromboxane excretion at presentation was increased, sometimes dramatically, in 17 of 33 (52%) patients with unstable angina, in 42 of 73 (57%) patients with definite myocardial infarction, but in only two of 14 (14%) patients with stable angina. Nineteen of 29 patients undergoing early angiography had detectable intracoronary thrombi, and these patients excreted significantly more thromboxane than patients without thrombi. Ongoing platelet activation may be detected by increased thromboxane excretion in more than 50% of the patients presenting with unstable angina and myocardial infarction, particularly in those with intracoronary thrombi, but it is not a general phenomenon that can be used in diagnosis.

Urinary fibrinopeptide A levels in ischemic heart disease.

Because acute coronary thrombosis can cause unstable coronary artery disease, fibrinopeptide A, a reliable marker of coagulation activity, may play a role in the evaluation of unstable ischemic syndromes. A new method of fibrinopeptide A sampling, spot urine normalized to urinary creatinine, was evaluated in patients with stable and unstable angina pectoris and acute myocardial infarction. Serial samples were obtained to characterize the changes in urinary fibrinopeptide A levels over time in patients with ischemic heart disease. Admission values (mean +/- SD) were similar in the control group (3.3 +/- 1.4 ng/mg creatinine) and the stable angina group (3.2 +/- 1.1 ng/mg creatinine) (p = NS). Values in the unstable angina group (5.7 +/- 2.6 ng/mg creatinine) were higher than those in the control (p = 0.008) and stable angina (p less than 0.001) groups. Myocardial infarction admission values (8.4 +/- 10.0 ng/mg creatinine) were higher than those in the control (p = 0.005) and stable angina (p less than 0.001) groups, but not higher than those in the unstable angina group. Peak values (the highest of multiple samples) were higher in the unstable angina group (7.6 +/- 5.9 ng/mg creatinine) than in the stable angina group (4.0 +/- 1.0 ng/mg creatinine) (p = 0.04), but not in the control group (4.5 +/- 1.9 ng/mg creatinine) (p = 0.056). The two patients with unstable angina with the highest peak values subsequently exhibited infarction. Peak values in patients with infarction (44.5 +/- 60.0 ng/mg creatinine) were significantly higher than those in patients with unstable (p = 0.03) or stable (p = 0.002) angina and control patients (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Circadian rhythms of mineral-excreting kidney function in healthy persons and their changes in ischemic heart disease]. / Okolosutochnye ritmy mineralvydelitel'noi funktsii pochek u zdorovykh lits i ikh izmeneniia pri ishemicheskoi bolezni serdtsa.

Seventy normal persons and 100 patients with coronary disease were examined for circadian rhythms of urine and minerals excretion. The data obtained demonstrate that normal persons were characterized by circadian rhythms of urine and minerals excretion with a definite confidence interval of mesor and amplitude fluctuations. Angina pectoris of effort was marked by infradian rhythms of mineral excreting renal function. Monotherapy with beta-blockers or calcium antagonists given in courses entailed the recovery of the circadian rhythms of mineral-excreting renal function. Parameters of the rhythms of urine and minerals excretion in patients with angina pectoris of effort and rest noticeably differed from those in patients with angina pectoris of effort. In 30.7 percent of the persons, the use of the mathematic methods did not reveal any significant rhythms. The circadian range was found to predominate among the significant rhythms. Antianginal treatment did not produce any appreciable changes.

Creatine determinations as an early marker for the diagnosis of acute myocardial infarction.

In the acute phase of acute myocardial infarction (3-8 h after onset of symptoms) an early transient increase in the creatine concentration of serum, saliva, and especially of urine can be observed. Due to the renal threshold, urine values give a much better discrimination between infarction patients and controls than do serum determination. In some patients secondary peaks of serum and urine creatine concentrations can be seen about 24-36 h after hospital admission. Intramuscular injections of 5.0 mL of a saline solution and muscular trauma interfere with the test, but with angina pectoris interference is absent or limited. Creatine leakage from myocardium is insufficient to explain the observed creatinuria in infarctions, and intact extra-cardiac tissues are believed to be involved in creatine release.

Biochemical evidence of platelet activation in patients with persistent unstable angina.

Thromboxane released from activated platelets and prostacyclin of the vessel wall may act as potent antagonistic modulators of platelet aggregability and coronary vascular tone. Therefore, urinary excretion of their major metabolites, 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1 alpha, was studied in 16 patients presenting with prolonged angina at rest. The 10 patients whose condition did not improve under vigorous antianginal treatment within 48 hours exhibited higher thromboxane metabolite excretion than did the 6 patients who responded to therapy (2,208 +/- 1,542 versus 609 +/- 312 ng/g creatinine; p less than 0.001). Elevated values were also found in four of eight patients with sustained postinfarction angina. Enhanced thromboxane metabolite excretion was frequently associated with angiographic evidence of thrombus formation. When nine patients were restudied in a stable phase after 11 +/- 5 months, thromboxane metabolite excretion was consistently normal or high normal. Excretion of prostacyclin metabolites was not depressed in any patient but correlated weakly with thromboxane (r = 0.41). Thus, enhanced thromboxane production as an index of platelet activation may identify patients with active thrombus formation who could benefit most from platelet inhibitory treatment.

Coronary artery thrombosis and elevated urine immunoreactive thromboxane B2.

Immunoreactive thromboxane B2 (i-TXB2) was measured by radio-immunoassay (RIA) in urines collected over eight hours on the day of admission in 25 patients who were admitted with the diagnosis of myocardial infarction. In 16 of the patients myocardial infarction was confirmed by ECG and plasma enzymes. Another patient presented with pulmonary embolism and the remaining eight patients had angina pectoris. A further eight hour urine collection was obtained 24 hours later from eleven of the sixteen patients with myocardial infarction. In these eleven patients myocardial infarction was associated with five fold higher urine i-TXB2 (2.72 +/- 0.48 ng/ml) at the day of admission when compared to patients admitted under the same diagnosis but found to have angina only (0.51 +/- 0.08 ng/ml, p less than 0.001). In patients with myocardial infarction the urine i-TXB2 values were reduced 24 hours later (1.58 +/- 0.27 ng/ml, p less than 0.01). One patient was followed with urine i-TXB2 from three days prior to diagnosis of myocardial infarction and to one day prior to a second infarction. In this patient i-TXB2 was highest three days prior to infarction. We conclude that this early elevation of urine i-TXB2 three days prior to diagnosis of infarction and the increased i-TXB2 in patients with myocardial infarction when compared to patients with angina suggest thromboxane is probably released from activated platelets prior to infarction. We suggest that urine i-TXB2 may be of value in the differential diagnosis between myocardial infarction and angina.

Abrupt withdrawal of atenolol in patients with severe angina. Comparison with the effects of treatment.

The effects of abrupt withdrawal of atenolol, a long acting cardioselective beta blocker, were studied in 20 patients with severe stable angina pectoris admitted to hospital for coronary arteriography. During the 144 hour postwithdrawal period no serious coronary events occurred. Mean and maximal daily heart rates rose steadily for at least 120 hours. No important arrhythmias were noted on ambulatory electrocardiographic monitoring. Treadmill exercise testing at 120 hours showed little reduction in the times to angina, ST depression, and maximal exercise when compared with those recorded at 24 hours. This deterioration was small when contrasted with the improvements in these indices produced by atenolol treatment in a similar group of patients not admitted to hospital. No change in catecholamine concentrations or acceleration of the heart rate response to exercise occurred after atenolol withdrawal, suggesting that rebound adrenergic stimulation or hypersensitivity was absent or insignificant. Catastrophic coronary events after beta blockade withdrawal (the beta blockade withdrawal syndrome) have occurred almost exclusively in patients taking propranolol, many of whom had unstable angina at the time of withdrawal. This study showed that in patients with stable angina, even when severe, the abrupt withdrawal of atenolol can be expected to result in only minor clinical consequences. The risk to any patient of so called rebound events after withdrawal of beta blockade seems to be related to both the clinical setting and the agent being used.