Alexei P. Yurenev, Vincent DeQuattro, Peter B. Dubov, Eugene N. Ostroumov, Igor A. Elena B. Konyaeva, Elena V. Balyakina, Shavkat E. Atachanov, Alexander I. Kosenko, Eugeni G. Popov, Zufar A. Gabbasov, and Vladimir P. Gulyaev
The aim of this study was to determine the signifi cance of the "coronary factor" in patients with es sential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organiza tion criteria). Silent, ie, painless ST-segment de pression, was found in 34 patients on whom echo cardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included T1 stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catechol amines and /?-endorphins were obtained in blood samples during silent ischemia. T1 scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The 201
Nikulin,
patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 / a n o l / L adeno sine diphosphate; one patient in this group had cor onary atherosclerosis. LVH and the platelet aggre gation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and /?-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different path ogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia. Am J Hypertens 1992;5:169S-174S
201
T
he percentage of cardiac complications in hy pertensive patients remains high despite suc cesses achieved in the treatment of essential hypertension (EH). These complications may be associated with asymptomatic coronary insufficiency in some patients with EH owing to ischemia or athero1
KEY WORDS: Left ventricular hypertrophy, coronary insufficiency, silent ischemia.
sclerotic lesions in the coronary arteries, or to silent, undiagnosed myocardial infarction, the frequency of which is three to four times higher among hypertensives than among patients with normal blood pressure. The latter may reflect clinical evidence of a relationship be tween arterial hypertension and hypalgesia in patients with EH. One could assume, therefore, that the wellknown phenomenon of silent ischemia in patients with coronary artery disease (CAD) may also be a factor among hypertensive patients. Determination of the nature and characteristics of this phenomenon in patients with EH and left ventricular hypertrophy (LVH) is problematic because of nonspe cific ST-segment changes on the electrocardiogram (ECG) in general and in this category of patients in par ticular. In our study, we proceeded from the assumption that chronic ischemia of the hypertrophied myocardium 2
3
From the Institutes of Clinical Cardiology and Experimental Cardiol ogy, USSR Cardiology Research Center, Russian Academy of Medical Sciences of the USSR, Moscow, Russia (APY, PBD, ΕΝΟ, IAN, HBK, HVB, SEA, AIK, EGP, ZAG, VPG) and the Department of Medicine, University of Southern California School of Medicine, Los Angeles, California (VDQ). Address correspondence and reprint requests to Alexei P. Yurenev, Professor of Medicine, Institute of Clinical Cardiology, Cardiology Research Center, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia.
Downloaded from https://academic.oup.com/ajh/article-abstract/5/6_Pt_2/169S/130202 by University of Zurich user on 03 January 2020
Silent Myocardial Ischemia in Patients With Essential Hypertension
4,5
MATERIALS AND METHODS Sixty-one men with EH stage II (according to the World Health Organization classification) aged 35 to 61 years (mean 50.5 ± 1.2 years) were studied. Patients with documented CAD, a history of myocardial infarction, congestive heart failure, left bundle branch block, constant atrial fibrillation, diabetes mellitus, and valvular abnormalities were excluded. A 7-day "wash-out" period for each patient preceded the beginning of the study. Holter Monitoring The 61 patients were examined with a Medilog 4000-111 system (Oxford Medical Limited, Abingdon, Oxfordshire, England), and V I and V5 ECG leads were recorded under ambulatory conditions. Each patient also was able to record all episodes of chest pain by pressing an "event" button which recorded the signal on tape. In order to exclude positional ECG changes, initial ECG recordings were made with the patient in different positions (lying down, sitting, while hyperventilating, and during the Valsalva maneuver). The Medilog-4500 replay system, used in conjunction with a visual display terminal, allowed us to evaluate trends in heart rate and ST-segment changes. An STsegment depression of 1 min or more at the J-point + 80 msec, with an amplitude of more than 0.1 mV, from the initial ST level was considered an ischemic episode. The duration of each episode was defined, as well as maximal ST-segment depression and heart rate. Abnormalities in the ST-segment without any chest pain were considered to be silent ischemia. Intraesophageal Atrial Pacing A bipolar electrode catheter was inserted through the esophagus and positioned against the left atrium of each patient. A Servocard ST-1000 stimulator (Lubliana, Yugoslavia) with a 4-msec duration of generated impulses was used. Atrial stimulation started at 100 beats/min and was increased 15 beats each min until an ST-segment displacement of 0.1 mV at the J-point + 60 msec was achieved in the first two poststimulation cycles, or until angina pectoris appeared or a rate of 160 beats/min was obtained.
Treadmill Test This test was conducted on a Cambridge XT-1000 treadmill machine with an MC-400 ECG recorder according to the Bruce protocol. The test was interpreted as positive if chest pain was noted or if an ST-segment depression of 0.1 mV appeared at the J-point + 60 msec. 6
Myocardial Scintigraphy Gamma camera Sigma-420 (Technicer, Milwaukee, Wl) with computer analysis was used with 2 mL intravenous infusion of T1 (74 mBq) at rest and at peak pacing. Information was gathered in three standard projections (anterior, left anterior oblique at 45° and at 90°) 5 to 10 min after administration of the radionuclide and after 4 h. A decrease in T1 accumulation in any segment or an increase in the perfusion defect, as compared to the image at rest, was considered a reversible defect. Clearance abnormalities were defined as a delay in T1 withdrawal in any segment after 4 h. 201
201
201
Echocardiographic Study A Toshiba (Tochigi-ken Japan) Sonolayer SSH-40A with electronic (2.4 or 3.5 mHz) probe was used. Left ventricular myocardial mass (LVMM) was estimated according to Teichholz' formula. Coronary angiography was performed according to Judkin's technique in three standard projections for the left coronary artery and in two projections for the right coronary artery. Obstructive atherosclerosis was diagnosed when the artery lumen was reduced more than 50%. Platelet aggregation was determined by a laser analyzer. This new method of studying platelets and the process of cell excretion was developed at the Institute of Experimental Cardiology, USSR Cardiology Research Center, and has been described previously. Radii of aggregates (in relative units) generated under 5 X 1 0 ~ mol/L adenosine diphosphate (ADP) concentration were measured. Using high-performance liquid chromatography, plasma concentrations of epinephrine, norepinephrine, and /^-endorphins were estimated in 12 patients. Blood samples were drawn after 30 min of walking (50 steps per min) and at the moment of silent ST-segment depression by setting the alarm on the QMed monitor. Results were processed by paired Student's t test and expressed as the mean ± standard error. 7
8
9
7
10
RESULTS The duration of EH in the study group (n = 34) was 14.4 ± 1 . 4 years. Arterial blood pressure was 163.6 ± 3.0/102.0 ± 1.8 mm Hg. Baseline ST-segment depression and T-wave inversion were obtained in 25 patients. Mean LVMM was 204.6 ± 7.1 g (range 151 g to 317 g). Fifteen patients had hyperlipidemia. The frequency of silent ischemia in the patients was
Downloaded from https://academic.oup.com/ajh/article-abstract/5/6_Pt_2/169S/130202 by University of Zurich user on 03 January 2020
is the main mechanism causing ST-segment deviations among hypertensives. Although ST-segment abnormalities, detected by ECG Holter monitoring, and loading tests are known to be associated with transient myocardial ischemia, LVH development and lesions of the small coronary vessels in EH, even in the absence of atherosclerosis of the large epicardial arteries, may also provoke myocardial ischemia, reducing the coronary reserve of the hypertrophied myocardium. In association with other conditions, myocardial ischemia can cause ST-segment changes. Our objectives in the present study were to evaluate the phenomenon of silent myocardial ischemia in EH and to determine the pathogenetic mechanisms leading to its development.
201
18 r
16 co 14 ω •§
12-
ω
"8- ιο-
0-2
2-4
4-6
6-8
8-10 10-12 12-14 14-16 16-18 18-20 20-22 22-24
Time of day (24 hr clock)
FIGURE 1. Twenty-four-h distribution of silent ST-segment depression in patients with hypertensive heart disease.
25 ρ
20 C/) CD
-o ο
CL CD
1
3
Ο
ω Ε =3 ~z.
10 -
5 -
60
70
80
90
100
110
120
130
140
150
160
Heart rate (beats per minute)
FIGURE 2. Distribution of heart rate at the time of episodes of silent ST-segment depression in hypertensive patients.
scending artery), and three cases in which no lesions were detected. Platelet aggregation was tested in six patients in group I and was found to be significantly increased (74.05 ± 82.46 in response to 0.5 //mol/L ADP). Plasma concentration of norepinephrine and ^-en dorphins increased in all group I patients during a silent ischemic episode (Table 1). Among the group II patients (ie, those with reversible perfusion defects and clearance abnormalities), five cases had ST-segment depression in the ECG leads dur ing pacing, and three had negative intraesophageal pac ing. LVMM was more than 200 g in three patients. Coro nary angiography demonstrated four cases with obstructive atherosclerosis of the coronary arteries, one case with a nonstenotic lesion (less than 5 0 % narrow ing) in the anterior descending artery, one case with a reduction in the distal part of the anterior descending artery, one case with a muscle bridge in the mid-third part of the anterior descending artery, and one case with no changes in the coronary arteries. In seven patients, platelet aggregation was 14.56 ± 23.21 in response to 0.5 //mol/L ADP. In five patients, the plasma concen tration of norepinephrine increased significantly during silent ischemia (Table 1). Based on linear discriminant analysis, patients could be classified as being in group I or group II by the follow ing equation: r = 2.121 X l g PA + 0.016 X LVMM 6.015, where l g PA = platelet aggregation. When r is more than 0, the patient can be assigned to group II (Figure 3). In other words, patients with EH and in creased LVMM and high platelet aggregation may have coronary insufficiency in the absence of atherosclerotic lesions of the coronary arteries. A correlation was found between LVMM and the degree of norepinephrine in crease during silent ischemia (Figure 4).
Downloaded from https://academic.oup.com/ajh/article-abstract/5/6_Pt_2/169S/130202 by University of Zurich user on 03 January 2020
from one to nine episodes during a 24-h period and was prolonged, lasting from 1 to 42 min; ST-segment de pression ranged from 1 to 3 mm. Most episodes of silent ischemia occurred during a patient's usual daily activi ties (morning wake-up, on the way to work or profes sional activity) (Figure 1). Depression of the ST-segment usually paralleled an increase in heart rate (Figure 2). Two patients had an increased heart rate up to 90 to 100 beats/min 1 to 2 min prior to ST-segment depression, but maximal ST-segment deviation was observed at a heart rate of 60 to 90 beats/min. In two patients, silent events were recorded without an increase in heart rate, while Holter monitoring showed that, in 89.7% of the patients, ST-segment depression occurred with a- heart rate 10 to 20 beats/min lower than during the stress test. Twenty-four patients had a positive intraesophageal pacing test; 10 patients had a negative result. The tread mill test was positive in 22 patients and negative in 10. In two cases, the test was stopped owing to an insuffi cient increase in blood pressure before the patient had achieved the target heart rate. The results from the in traesophageal pacing and treadmill test were similar in all cases. T1 stress scintigraphy showed reversible perfusion defects in 15 patients. In seven cases (group I), no clear ance abnormalities were associated with these defects; in eight cases (group II), clearance abnormalities were found. Among the patients in group I, reversible perfu sion defects in different segments were accompanied by ECG-detected coronary insufficiency (ST-segment de pression) in the same location. LVMM was more than 200 g. Coronary angiography performed in the group I pa tients showed one case of obstructive (more than 5 0 % narrowing) atherosclerosis in the circumflex artery, three cases of coronary artery luminal irregularity (two in the right coronary artery and one in the anterior de-
TABLE 1. CONCENTRATION OF PLASMA CATECHOLAMINES INITIALLY AND DURING EPISODES OF SILENT ISCHEMIA IN HYPERTENSIVE PATIENTS Epinephrine Norepinephrine ^-Endorphins (ng/mL) (ng/mL) (pmol/L) Groups 0.146 ± 0 . 0 4 1 -0.022 ±0.065
0.474 ±0.1151 + 0.312* ± 0 . 2 3
0.099 ± 0.033 + 0.015 ± 0 . 0 8
0.515 ± 0 . 1 3 2 + 0.15* ± 0 . 1 1 6
11.56 ± 3 . 2 7 + 6.029* ± 5 . 8 8 1 43.98 ± 12.99 + 8.44 + 10.34
* Statistical significance of change from initial level: * = Ρ < .05.
DISCUSSION Episodes of silent ischemia during ECG Holter monitor ing were detected in 5 7 % of the present series of hyper tensive patients. According to different authors, the fre quency of this phenomenon in patients with EH varies from 16 to 7 5 % . Such a wide range in the prevalence of silent ischemia can be explained by the lack of homoge neity among the patients observed and the small num ber of studies. Some investigators ' have reported silent ischemia in 1 6 % of hypertensives with asympto matic EH. Others have reported that 7 5 % of their pa tients with EH had unchanged coronary arteries; these patients, however, were older and had more pro nounced hypertension. The features of the episodes (duration, time of appear ance, total number during a 24-h period, and association with heart rate) do not differ much from those described for patients with C A D . ' Detection of a lower heart rate on Holter monitoring during transient episodes of silent ischemia, as compared with ECG changes in re sponse to stress tests, can be explained not only by the temporarily increased myocardial demand for oxygen 11 12
13
14
but also by transient deviations in coronary flow. This point of view is in accord with Maseri's conception of a transient decrease in coronary flow superimposed on a reduced coronary reserve resulting from coronary ather osclerosis or other reasons. Also confirming this point of view is that our patients sometimes did not show STsegment depression although there was a significant, spontaneous increase in heart rate and some episodes of silent ischemia were recorded without heart rate changes. 15
0.2 r ^
Ε σ)
S. LU
The aim of this study was to determine the signifi cance of the "coronary factor" in patients with es sential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organiza tion criteria). Silent, ie, painless ST-segment de pression, was found in 34 patients on whom echo cardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included T1 stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catechol amines and /?-endorphins were obtained in blood samples during silent ischemia. T1 scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The 201
Nikulin,
patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 / a n o l / L adeno sine diphosphate; one patient in this group had cor onary atherosclerosis. LVH and the platelet aggre gation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and /?-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different path ogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia. Am J Hypertens 1992;5:169S-174S
201
T
he percentage of cardiac complications in hy pertensive patients remains high despite suc cesses achieved in the treatment of essential hypertension (EH). These complications may be associated with asymptomatic coronary insufficiency in some patients with EH owing to ischemia or athero1
KEY WORDS: Left ventricular hypertrophy, coronary insufficiency, silent ischemia.
sclerotic lesions in the coronary arteries, or to silent, undiagnosed myocardial infarction, the frequency of which is three to four times higher among hypertensives than among patients with normal blood pressure. The latter may reflect clinical evidence of a relationship be tween arterial hypertension and hypalgesia in patients with EH. One could assume, therefore, that the wellknown phenomenon of silent ischemia in patients with coronary artery disease (CAD) may also be a factor among hypertensive patients. Determination of the nature and characteristics of this phenomenon in patients with EH and left ventricular hypertrophy (LVH) is problematic because of nonspe cific ST-segment changes on the electrocardiogram (ECG) in general and in this category of patients in par ticular. In our study, we proceeded from the assumption that chronic ischemia of the hypertrophied myocardium 2
3
From the Institutes of Clinical Cardiology and Experimental Cardiol ogy, USSR Cardiology Research Center, Russian Academy of Medical Sciences of the USSR, Moscow, Russia (APY, PBD, ΕΝΟ, IAN, HBK, HVB, SEA, AIK, EGP, ZAG, VPG) and the Department of Medicine, University of Southern California School of Medicine, Los Angeles, California (VDQ). Address correspondence and reprint requests to Alexei P. Yurenev, Professor of Medicine, Institute of Clinical Cardiology, Cardiology Research Center, 3rd Cherepkovskaya Street 15a, Moscow 121552, Russia.
Downloaded from https://academic.oup.com/ajh/article-abstract/5/6_Pt_2/169S/130202 by University of Zurich user on 03 January 2020
Silent Myocardial Ischemia in Patients With Essential Hypertension
4,5
MATERIALS AND METHODS Sixty-one men with EH stage II (according to the World Health Organization classification) aged 35 to 61 years (mean 50.5 ± 1.2 years) were studied. Patients with documented CAD, a history of myocardial infarction, congestive heart failure, left bundle branch block, constant atrial fibrillation, diabetes mellitus, and valvular abnormalities were excluded. A 7-day "wash-out" period for each patient preceded the beginning of the study. Holter Monitoring The 61 patients were examined with a Medilog 4000-111 system (Oxford Medical Limited, Abingdon, Oxfordshire, England), and V I and V5 ECG leads were recorded under ambulatory conditions. Each patient also was able to record all episodes of chest pain by pressing an "event" button which recorded the signal on tape. In order to exclude positional ECG changes, initial ECG recordings were made with the patient in different positions (lying down, sitting, while hyperventilating, and during the Valsalva maneuver). The Medilog-4500 replay system, used in conjunction with a visual display terminal, allowed us to evaluate trends in heart rate and ST-segment changes. An STsegment depression of 1 min or more at the J-point + 80 msec, with an amplitude of more than 0.1 mV, from the initial ST level was considered an ischemic episode. The duration of each episode was defined, as well as maximal ST-segment depression and heart rate. Abnormalities in the ST-segment without any chest pain were considered to be silent ischemia. Intraesophageal Atrial Pacing A bipolar electrode catheter was inserted through the esophagus and positioned against the left atrium of each patient. A Servocard ST-1000 stimulator (Lubliana, Yugoslavia) with a 4-msec duration of generated impulses was used. Atrial stimulation started at 100 beats/min and was increased 15 beats each min until an ST-segment displacement of 0.1 mV at the J-point + 60 msec was achieved in the first two poststimulation cycles, or until angina pectoris appeared or a rate of 160 beats/min was obtained.
Treadmill Test This test was conducted on a Cambridge XT-1000 treadmill machine with an MC-400 ECG recorder according to the Bruce protocol. The test was interpreted as positive if chest pain was noted or if an ST-segment depression of 0.1 mV appeared at the J-point + 60 msec. 6
Myocardial Scintigraphy Gamma camera Sigma-420 (Technicer, Milwaukee, Wl) with computer analysis was used with 2 mL intravenous infusion of T1 (74 mBq) at rest and at peak pacing. Information was gathered in three standard projections (anterior, left anterior oblique at 45° and at 90°) 5 to 10 min after administration of the radionuclide and after 4 h. A decrease in T1 accumulation in any segment or an increase in the perfusion defect, as compared to the image at rest, was considered a reversible defect. Clearance abnormalities were defined as a delay in T1 withdrawal in any segment after 4 h. 201
201
201
Echocardiographic Study A Toshiba (Tochigi-ken Japan) Sonolayer SSH-40A with electronic (2.4 or 3.5 mHz) probe was used. Left ventricular myocardial mass (LVMM) was estimated according to Teichholz' formula. Coronary angiography was performed according to Judkin's technique in three standard projections for the left coronary artery and in two projections for the right coronary artery. Obstructive atherosclerosis was diagnosed when the artery lumen was reduced more than 50%. Platelet aggregation was determined by a laser analyzer. This new method of studying platelets and the process of cell excretion was developed at the Institute of Experimental Cardiology, USSR Cardiology Research Center, and has been described previously. Radii of aggregates (in relative units) generated under 5 X 1 0 ~ mol/L adenosine diphosphate (ADP) concentration were measured. Using high-performance liquid chromatography, plasma concentrations of epinephrine, norepinephrine, and /^-endorphins were estimated in 12 patients. Blood samples were drawn after 30 min of walking (50 steps per min) and at the moment of silent ST-segment depression by setting the alarm on the QMed monitor. Results were processed by paired Student's t test and expressed as the mean ± standard error. 7
8
9
7
10
RESULTS The duration of EH in the study group (n = 34) was 14.4 ± 1 . 4 years. Arterial blood pressure was 163.6 ± 3.0/102.0 ± 1.8 mm Hg. Baseline ST-segment depression and T-wave inversion were obtained in 25 patients. Mean LVMM was 204.6 ± 7.1 g (range 151 g to 317 g). Fifteen patients had hyperlipidemia. The frequency of silent ischemia in the patients was
Downloaded from https://academic.oup.com/ajh/article-abstract/5/6_Pt_2/169S/130202 by University of Zurich user on 03 January 2020
is the main mechanism causing ST-segment deviations among hypertensives. Although ST-segment abnormalities, detected by ECG Holter monitoring, and loading tests are known to be associated with transient myocardial ischemia, LVH development and lesions of the small coronary vessels in EH, even in the absence of atherosclerosis of the large epicardial arteries, may also provoke myocardial ischemia, reducing the coronary reserve of the hypertrophied myocardium. In association with other conditions, myocardial ischemia can cause ST-segment changes. Our objectives in the present study were to evaluate the phenomenon of silent myocardial ischemia in EH and to determine the pathogenetic mechanisms leading to its development.
201
18 r
16 co 14 ω •§
12-
ω
"8- ιο-
0-2
2-4
4-6
6-8
8-10 10-12 12-14 14-16 16-18 18-20 20-22 22-24
Time of day (24 hr clock)
FIGURE 1. Twenty-four-h distribution of silent ST-segment depression in patients with hypertensive heart disease.
25 ρ
20 C/) CD
-o ο
CL CD
1
3
Ο
ω Ε =3 ~z.
10 -
5 -
60
70
80
90
100
110
120
130
140
150
160
Heart rate (beats per minute)
FIGURE 2. Distribution of heart rate at the time of episodes of silent ST-segment depression in hypertensive patients.
scending artery), and three cases in which no lesions were detected. Platelet aggregation was tested in six patients in group I and was found to be significantly increased (74.05 ± 82.46 in response to 0.5 //mol/L ADP). Plasma concentration of norepinephrine and ^-en dorphins increased in all group I patients during a silent ischemic episode (Table 1). Among the group II patients (ie, those with reversible perfusion defects and clearance abnormalities), five cases had ST-segment depression in the ECG leads dur ing pacing, and three had negative intraesophageal pac ing. LVMM was more than 200 g in three patients. Coro nary angiography demonstrated four cases with obstructive atherosclerosis of the coronary arteries, one case with a nonstenotic lesion (less than 5 0 % narrow ing) in the anterior descending artery, one case with a reduction in the distal part of the anterior descending artery, one case with a muscle bridge in the mid-third part of the anterior descending artery, and one case with no changes in the coronary arteries. In seven patients, platelet aggregation was 14.56 ± 23.21 in response to 0.5 //mol/L ADP. In five patients, the plasma concen tration of norepinephrine increased significantly during silent ischemia (Table 1). Based on linear discriminant analysis, patients could be classified as being in group I or group II by the follow ing equation: r = 2.121 X l g PA + 0.016 X LVMM 6.015, where l g PA = platelet aggregation. When r is more than 0, the patient can be assigned to group II (Figure 3). In other words, patients with EH and in creased LVMM and high platelet aggregation may have coronary insufficiency in the absence of atherosclerotic lesions of the coronary arteries. A correlation was found between LVMM and the degree of norepinephrine in crease during silent ischemia (Figure 4).
Downloaded from https://academic.oup.com/ajh/article-abstract/5/6_Pt_2/169S/130202 by University of Zurich user on 03 January 2020
from one to nine episodes during a 24-h period and was prolonged, lasting from 1 to 42 min; ST-segment de pression ranged from 1 to 3 mm. Most episodes of silent ischemia occurred during a patient's usual daily activi ties (morning wake-up, on the way to work or profes sional activity) (Figure 1). Depression of the ST-segment usually paralleled an increase in heart rate (Figure 2). Two patients had an increased heart rate up to 90 to 100 beats/min 1 to 2 min prior to ST-segment depression, but maximal ST-segment deviation was observed at a heart rate of 60 to 90 beats/min. In two patients, silent events were recorded without an increase in heart rate, while Holter monitoring showed that, in 89.7% of the patients, ST-segment depression occurred with a- heart rate 10 to 20 beats/min lower than during the stress test. Twenty-four patients had a positive intraesophageal pacing test; 10 patients had a negative result. The tread mill test was positive in 22 patients and negative in 10. In two cases, the test was stopped owing to an insuffi cient increase in blood pressure before the patient had achieved the target heart rate. The results from the in traesophageal pacing and treadmill test were similar in all cases. T1 stress scintigraphy showed reversible perfusion defects in 15 patients. In seven cases (group I), no clear ance abnormalities were associated with these defects; in eight cases (group II), clearance abnormalities were found. Among the patients in group I, reversible perfu sion defects in different segments were accompanied by ECG-detected coronary insufficiency (ST-segment de pression) in the same location. LVMM was more than 200 g. Coronary angiography performed in the group I pa tients showed one case of obstructive (more than 5 0 % narrowing) atherosclerosis in the circumflex artery, three cases of coronary artery luminal irregularity (two in the right coronary artery and one in the anterior de-
TABLE 1. CONCENTRATION OF PLASMA CATECHOLAMINES INITIALLY AND DURING EPISODES OF SILENT ISCHEMIA IN HYPERTENSIVE PATIENTS Epinephrine Norepinephrine ^-Endorphins (ng/mL) (ng/mL) (pmol/L) Groups 0.146 ± 0 . 0 4 1 -0.022 ±0.065
0.474 ±0.1151 + 0.312* ± 0 . 2 3
0.099 ± 0.033 + 0.015 ± 0 . 0 8
0.515 ± 0 . 1 3 2 + 0.15* ± 0 . 1 1 6
11.56 ± 3 . 2 7 + 6.029* ± 5 . 8 8 1 43.98 ± 12.99 + 8.44 + 10.34
* Statistical significance of change from initial level: * = Ρ < .05.
DISCUSSION Episodes of silent ischemia during ECG Holter monitor ing were detected in 5 7 % of the present series of hyper tensive patients. According to different authors, the fre quency of this phenomenon in patients with EH varies from 16 to 7 5 % . Such a wide range in the prevalence of silent ischemia can be explained by the lack of homoge neity among the patients observed and the small num ber of studies. Some investigators ' have reported silent ischemia in 1 6 % of hypertensives with asympto matic EH. Others have reported that 7 5 % of their pa tients with EH had unchanged coronary arteries; these patients, however, were older and had more pro nounced hypertension. The features of the episodes (duration, time of appear ance, total number during a 24-h period, and association with heart rate) do not differ much from those described for patients with C A D . ' Detection of a lower heart rate on Holter monitoring during transient episodes of silent ischemia, as compared with ECG changes in re sponse to stress tests, can be explained not only by the temporarily increased myocardial demand for oxygen 11 12
13
14
but also by transient deviations in coronary flow. This point of view is in accord with Maseri's conception of a transient decrease in coronary flow superimposed on a reduced coronary reserve resulting from coronary ather osclerosis or other reasons. Also confirming this point of view is that our patients sometimes did not show STsegment depression although there was a significant, spontaneous increase in heart rate and some episodes of silent ischemia were recorded without heart rate changes. 15
0.2 r ^
Ε σ)
S. LU
