|
Galal El-Din Nagib El-Kilany, MD, FESC,
FISCU.
Cardiology Departments, Tanta University & Cairo University,
Egypt.
Introduction |
An increased
incidence of false positive stress test results among
hypertensive patients with left ventricular hypertrophy
(LVH) has been reported. Thus our study designed to evaluate
the incidence of coronary artery disease (CAD) by stress
thallium-201 scintigraphy (MPI) single photon emission
computed tomography (SPECT) in large series of high risk
hypertensive population complaining of chest pain (hypertension
with one or more other risk factors for CAD). |
| Patients and
methods |
Among 214 patients
referred to our nuclear cardiology laboratory, eighty
seven hypertensive patients (high risk) complaining of
chest pain underwent MPI (Myocardial Perfusion Imaging)
and coronary angiography. Complete laboratory investigation
has been done for all patients enrolled in this study
(blood suger profile, lipid profile, renal function tests
and complete blood picture). Body mass index, waist and
hip circumference was measured for all patients. |
Results |
The patient’s
mean age was 52 ± 7 years. The EKG evidence of CAD was
present in 51% of patients.Significant coronary artery
disease (more than 50% luminal narrowing of one or more
epicardial coronary artery) was documented in 46% of hypertensive
patients enrolled in this study by coronary angiography
and thallium scintigraphy. The over all sensitivity,
specificity and diagnostic accuracy of treadmill stress
test for the diagnosis of CAD were 77%, 38% and 56% respectively
as compared to TI 201 scintigraphy and coronary angiography.
There was strong evidence of high false positive results
of treadmill test in hypertensive patients with LVH (specificity
35%). Interestingly, 47% of patients with LVH showed evidence
of myocardial ischemia by MPI, which was not statistically
significant from hypertensive group without LVH (45%).
Hypertension among Egyptian population was commonly associated
with the following risk factors for CAD: Diabetes Mellitus
(26%), Dyslipidemia (38%), Obesity (37%), Smoking (38%)
and Family history of CAD in (46%). |
Conclusion |
(1) Hypertension
is a common disease in Egyptian population. (2)The incidence
of CAD in Egyptian hypertensive patients is high irrespective
to the presence or absence of LVH. (3) Hypertension is
a syndrome and not a single disease entity, it is associated
with other diseases and biochemical abnormalities in 92%
of cases. (4) Stress myocardial perfusion imaging is considered
a non-invasive technique of choice in the evaluation of
myocardial ischemia in high risk hypertensive patients
with chest pain. (5) Exercise stress test lacks: specificity,
accuracy, positive predictive value and negative predictive
value in diagnosing myocardial ischemia in patients with
hypertension and LVH. (6) MPI is of crucial importance
in hypertensive patients with chest pain due to high incidence
of CAD in such patients population and high sensitivity
and specificity of this test for the diagnosis of myocardial
ischemia. |
| Keywords |
hypertension
angina cardiovascular diseases imaging |
Introduction
Among hypertensive patients with left ventricular hypertrophy
the incidence of false positive exercise stress test has been
reported to be high. (1) Thus, our study was designed
to evaluate the diagnostic accuracy, sensitivity and specificity
of treadmill test as compared to stress thallium-201 scintigraphy
in large series of hypertensive patients with or without left
ventricular hypertrophy (LVH), documented by echocardiography.
Also, chest pain in hypertensive patients (with and without
LVH) has been evaluated by stress myocardial perfusion Imaging,
in order to verify which category of patients prone to acute
ischemic insult (positive stress thallium-201 single photon
emission computed tomography. Coronary angiography has been
performed for all patients who showed an abnormal scan.
The nature of chest pain in hypertensive patients is still
a matter of debate, in this trial we try to answer this major
problem…
The major causes of chest pain in hypertensive patients are:
- True coronary artery disease (myocardial
ischemia).
- Relative ischemia (subendocardial ischemia)
in LVH.
- Microvascular angina.
- Non-cardiac chest pain.
- Aortic dissection.
Patients and Methods
214 consecutive patients referred to our nuclear
cardiology laboratory for thallium 201-stress SPECT between
August and December 1999 were included in this study.
The inclusion criteria were: (1) Evidence of
hypertension ³ 140/90 mmHg measured at least three times over
an interval of 6 weeks duration; (2) presence of LVH confirmed
by 2-dimensional echocardiographic study; (3) stress thallium
201 SPECT performed within 3 months of the echocardiographic
study. (4) Coronary angiography for patients who showed positive
MPI study. Patients with hypertrophic cardiomyopathy and asymmetric
septal hypertrophy were excluded.
Standard 2-dimensional echocardiography was
performed and measurements were obtained in the parasternal
long-axis view by experienced echocardiographers. A septal and
LV posterior wall thickness >11mm was considered diagnostic
of LV hypertrophy. Standard criteria were used in the electrocardiographic
diagnosis of LV hypertrophy.(2)
Exercise perfusion SPECT was performed in 214
patients using the standard Bruce protocol. Blood pressure,
heart rate and a 12-lead electrocardiogram were recorded at
l minute intervals throughout the test. Pharmacologic stress
SPECT was done in those patients with LBBB and in those with
neuromuscular disorders. The stress agent was dipyridamole,
which was administered intravenously at a dose of 142 mg/Kg/min
over 4 minutes. Thallium-201 (3.0 mcui) was injected either
at peak exercise or 4 minutes after dipyridamole administration
(peak effect). Imaging 5 to 10 minutes after thallium injection
and redistribution images2 were taken by a standard gamma cameras
3-4 hours later, reconstruction and reorientation were done
as previously reported.(3) Tomographic images2 were
interpreted by experienced nuclear cardiologists who were blind
to the clinical findings. The vascular territories were assigned
in a standard manner: antero septal, anterior, and antero lateral
wall were assigned to the left anterior descending artery, and
the postero lateral wall to the left circumflex artery and the
inferior and posterior walls to the right coronary artery.(4)
A definite focal decrease in the tracer distribution that measured
³ 3% of the LV mass on the stress polar maps was considered
abnormal, the reconstructed stress and 3-to-4 hour redistribution
images2 were analyzed semi quantitatively in the basal, mid
and apical short axis view so the left ventricle was divided
into 13 segments through short axis, vertical long axis and
horizontal long axis views and the uptake in each myocardial
segment for each of the stress and redistribution images2 was
graded on a 5-point scale as follows:
2:normal; 1.5:mildly reduced; 1:moderately
reduced; 0.5:severely reduced, and 0:absent.
For the purpose of analysis, a segment was considered
to have a reversible defect (ischemic), if thallium uptake in
the stress images2 was reduced but was increased by at least
one grade in the redistribution images2,(5) Figure
(2) and (3).
Figure 1: Relation between hypertension and other risk
factors
| Risk
factors |
Non-Hypertensive
n = 126
|
Hypertensive
N = 87 |
X2 |
p-value |
| No. |
% |
No. |
% |
| Age
< 45 years
> 45 years |
51
76 |
40.2
59.8 |
19
68 |
21.8
78.2 |
7.87 |
0.005* |
| Diabetes mellitus |
22 |
17.5 |
25 |
26.4 |
2.49 |
> 0.05 |
| Dyslipidemia |
44 |
34.6 |
33 |
37.9 |
0.24 |
> 0.05 |
| + ve family
history of CAD |
48 |
37.5 |
40 |
46.0 |
1.43 |
> 0.05 |
| Myocardial
infarction |
13 |
10.2 |
7 |
8.0 |
0.29 |
> 0.05 |
| Obesity |
30 |
23.6 |
32 |
36.8 |
4.34 |
0.037* |
| Smoking |
75 |
59.1 |
33 |
37.9 |
9.22 |
0.002 |
| Uric acid |
5 |
3.9 |
4 |
4.6 |
0.06 |
> 0.05 |
| Sex
Male
Female |
105
22 |
82.7
17.3 |
61
26 |
70.1
29.9 |
4.68 |
0.03* |
| PTCA |
10 |
7.9 |
3 |
3.4 |
1.77 |
> 0.05 |
*Results are reported as mean
± SD, p value, ANOVA test and Multiple Logistic Regression
| Figure 2: Exercise stress
test showing significant ST segment depression of 3mm
in leads: II, III, aVF, V4, V5 (B) in patients with
hypertension and LVH with strain pattern (A). |
| Figure 3: SPECT thallium scintigraphy
showing stress induced perfusion defects at the septum,
apex and anterior wall which showed complete reversibility
at the redistribution images2 of a patient with hypertension
and chest pain. |
Results are reported as
mean ± SD, p value, ANOVA test, and Multiple Logistic Regression,
univariant analysis (c2).
Results
Among 214 patients retrospectively
selected, eighty seven patient have hypertension (40.7 %).
The patients mean age was 52±7.6
years, 70.1% males and 29.9% females. The most currently associated
risk factors with hypertension were: diabetes mellitus (26%),
dyslipidemia (37.9%), family history for coronary artery disease
(46%), myocardial infraction (8%), obesity (36.8%), smoking
(37.9%) and hyperuricemia (4.6%), figures (1) and (4).
All patients who have shown positive
scan by MPI have evidence of CAD by coronary angiography.
Electrocardiographic evidence
of LV hypertrophy was present in 44 hypertensive patients
(50%). In all of our patients, the hypertrophy was concentric,
with a mean septal wall thickness of 13.2+1.1.4mm,
where as the mean posterior wall thickness was 12.6±1.0 mm.
Evidence of coronary artery disease was documented in 40 of
the 87 hypertensive patients with chest pain (46%) by stress
thallium scintigraphy.
The overall sensitivity, specificity,
positive predictive value, negative predictive value, and
accuracy of treadmill test (stress test) for the diagnosis
of coronary artery disease in the total group were: 77.5%,
38.3%, 51.7%, 66.7 and 56.3%, respectively.
The sensitivity, specificity,
accuracy, positive predictive value, and negative predictive
value of stress test for the diagnosis of myocardial ischemia
in those patients with LV hypertrophy (by echocardiography)
were 86%, 35.3%, 59.4% 54.2% and 75%, respectively.
Which means that, 51.7% (31 out
of 60 cases) have true positive test by treadmill test when
compared to myocardial perfusion imaging. Also there was high
incidence of false positive results by exercise stress test
(specificity 38.3% in the total group and 35.3% in those with
LVH).
One of the interesting observation
in our study revealed by the univariant analysis:
- Obesity, smoking, male sex, old age,
LVH (from electrocardiographic criteria) are associated
with hypertension.(p<0.05).
- Moreover, the predictors of CAD (those
with positive TI-201 scan ) by multiple logestic regression
have been shown to be related to the : Increased age,
male sex, smoking, history of myocardial infarction and
coronary angioplasty (p<0.05), figure (6).
Surprisingly, fifteen hypertensive
patients (15) out of thirty two (32) who have LVH, had evidence
of CAD by stress thallium scintigraphy (46.9%), which is not
statistically significant from the remainder group (those
without LVH) who showed evidence of reversible myocardial
ischemia by perfusion imaging in 45.5% of cases (25 patient
out of 55 patients).
A statistically unique data in
this study showed that hypertension is not a single disease
entity, but is associated with other diseases and risk factors
in 92% of the study cases, figure (5).
The commonly associated diseases
with hypertension in this study was: dyslipidemia (37.9%),
obesity (36.8%), diabetes mellitus (26%) and hyperuricemin
in (4.6%) of cases only, so it is better to choose the name
“Hypertension syndrome” than systemic hypertension, according
to the last observation.
In this study, positive family
history for CAD was present in 46% of cases, 37.9% of patients
were dyslipidemic and 37.9% smokers.
Figure 4: Figure shows
the percentage of the most currently associated risk factors
with hypertension
Figure 5: Figure shows
the percentage of associated risk factors with hypertension
(92%), versus hypertension alone (as a single disease entity).
Figure 6: CAD in relation
to risk factors among Egyptian population
Discussion
This study is one of the largest
trials thus far reported in Egyptian publications assessing
the value of stress thallium SPECT in patients with and without
LV hypertrophy (proven by echocardiography) and reported the
value of stress myocardial perfusion imaging in hypertensive
patients with chest pain. The main finding in this study is:
a high incidence of hypertension in the studied group in Egypt
(40.7%), also, the incidence of CAD in hypertensive patients
was high (46%) by stress thallium scintigraphy. Irrespective
to the presence or absence of LV hypertrophy by echocardiography.
The gold standard in the present
study was stress thallium scintigraphy in detection of myocardial
ischemia (reversible perfusion defects), which is known to
have equally high sensitivity and specificity despite the
presence of LV hypertrophy by Al shami(6) and Ambrosi
et al.(7)
It has been suggested that myocardial
perfusion defects may occur during stress scintigraphy in
hypertensive patients without obstructive coronary artery
disease(8). Some of these perfusion defects may
be related to microvascular disease(9).
De puey et al studied 100 renal
hypertensive patients and reported a decrease in thallium–201
lateral/septal count in 35 patients, mimicking an old lateral
wall scar.
However, only 12 of their patients
had echocardiography and coronary angiography was not performed
at all. A recent study by Periyanan et al(11) concluded
that: Both exercise and pharmacologic thallium-201 SPECT have
good sensitivity and specificity for diagnosing the presence
and location of coronary artery disease in large series of
patients with LV hypertrophy.
There is considerable disagreement
regarding the diagnostic accuracy of exercise testing specially
in females and in those subjects with abnormal resting electrocardiogram
(as in hypertensive patients with LV hypertrophy and strain
pattern), added to the previous limitation of treadmill testing
is it’s low sensitivity of around 68% in the meta analysis
which was published before by Gianrossi et al(12).
In the present study, the positive
predictive value of stress ECG test was 51.7% in detection
of CAD among hypertensive patients in the total group, which
is concordant to the previous studies. (12) In
spite of high sensitivity of treadmill test in this study
(86%) in their ability for detection of CAD in hypertensive
patients with LVH, the specificity is very low (35.3%), which
means a high false positive results in patients with LV hypertrophy.
In which myocardial perfusion imaging is the technique of
choice in detection of reversible perfusion defects (ischemic
segments) in such patients population.
Limitations
The high incidence of CAD in
our patient may be related to the nature of the studied patients
in which 92% of hypertensive patients enrolled in this study
associated with other risk factors for CAD making them at
high risk for developing CAD.
Is this high risk group is the
answer of why our hypertensive patients have increased incidence
of CAD, or the incidence of myocardial ischemia is so high
in hypertensive patients complaining of chest pain? This needs
further documentation by a large scale study.
Recommendation
Myocardial perfusion imaging
is of crucial importance in most of our hypertensive patients
with chest pain to uncover the nature of their chest pain,
whether it is due to true myocardial ischemia or microvascular
angina or it is a result of a relative ischemia (LVH) or a
non cardiac chest pain. Moreover , treatment of associated
diseases and modification of risk factors that are currently
associated with hypertensive patients is mandatory in order
to improve the prognosis and reduce the risk of CAD. Certain
drugs that did not interfere with lipid metabolism are preferred
as calcium antagonists and angiotensin converting enzyme inhibitors.
Also a disease modifying agents (to stop the progression and
induce regression of CAD) as oral hypocholesterolemic drugs
as early use of statins in high risk patients and patients
with dyslipidemia. Proper control of blood suger in diabetics
and prediabetics by drugs (insulin and oral hypoglycemics)
and diet control should be strict to reduce the incidence
of CAD in hypertensive diabetic patients. The fact that 36.8%
of our hypertensive patients were associated with obesity,
so weight reduction by diet control and regular exercise should
be encouraged. Lastly, smoking should be prohibited (incidence
is 37.9% in this study) in all hypertensive patients as well
as in all general population to reduce the risk and incidence
of cardiovascular diseases.
Conclusion
- Hypertension is a common disease in
Egyptian population.
- The incidence of CAD in Egyptian hypertensive
patients is high irrespective to the presence or absence
of LVH.
- Hypertension is a syndrome and not a
single disease entity, it is associated with other diseases
and biochemical abnormalities in 92% of cases.
- Stress thallium-201 SPECT is considered
a non-invasive technique of choice in the evaluation of
myocardial ischemia in hypertensive patients with chest
pain.
- Exercise stress test lacks: specificity,
accuracy, positive predictive value and negative predictive
value in diagnosing myocardial ischemia in hypertensive
patients.
- Myocardial perfusion imaging is of crucial
importance in hypertensive patients with chest pain due
to high incidence of CAD in such patients population.
- Acknowledgement
To my dear Prof. Mokhtar Gomaa,
As. Prof. Adel Allam, Al-Azhar University, Cairo–Egypt, for
their great help, encouragement and guidance of this work
which enrich the field of nuclear cardiology.
References
- Wasserman AG, Katz RJ, Varghese PJ,
Leiboff RH, Bren GG, Schlesselman S, Vama VM. Reba RC,
Ros. AM, Exercise radionuclide ventriculographic responses
in hypertensive patients with chest pain. N Engl J Med
1984; 311:1276-1280.
- Levy D, Labib SB. Anderson KM, Christiansen
JC, Kannel WB, Castelli WP. Determinants of sensitivity
and specificity of electrocardiographic criteria for left
ventricular hypertrophy. Circulation 1990: 815-820.
- Mahmarian JJ, Boyce TM, Goldberg PK,
Cocanogher MK, Roberts R, Verani MS. Quantitative exercise
thallium-201 single photone emission computed tomography
for the enhanced diagnosis of ischemic heart disease.
J Am Coll Cardiol 1990: 15: 318-329.
- Nishimura S, Mahmarian JJ, Boyce TM,
Verani MS. Quantitative thallium-201 single-photon emission
computed tomography during maximal pharmacologic coronary
vasodilation with adenosine for assessing coronary artery
disease. J Am Col Cardiol 1991; 18: 736-745.
- Francids J. Klocke et al: perfusion
imaging: Interpretation of regional differences during
flow augmentation and detection of hibernating myocardium.
- Alshami AA, Jolly SR, Smith FL, Reeves
WC, Movahed A. Exercise testing in patients with electrocardiogaraphic
evidence of left ventricular hypertrophy. Clin Nucl Med
1994:19:904-909.
- Ambrosi P, Habib G, Kreitman B, Metras
D, Riberi A, Fagere G, Bernaard P, Luccioni R. Thallium
perfusion and myocardial hypertrophy in transplanted heart
recipients with normal or near-normal coronary arteriograms.
Eur Heart J. 1994; 15: 1119-1123.
- Houghton JL, Frank MJ, Carr AA, Von
Dohlen TW, Prisant LM. Relations among impaired coronary
flow reserve, left ventricular hypertrophy and thallium
perfusion defects in hypertensive patients without obstructive
coronary artery disease. J Am Coll Cardiol 1990; 15:43-51.
- klepzig M, Eisenlohr H, Steindl J, Schmiebusch
H. Strauer BE. Media hypertrophy in hypertensive coronary
resistance vessels. J Cardiovasc Pharmacol 1987; 10(suppl
6); S97-S102.
- Depuey EG, Guertler-Krawczynska E, Perkins
JV, Robbins WL, Whelchel JD, Clements SD, Alterations
in myocardial thallium- 201 distribution in patients with
chronic systemic hypertension undergoing single-photon
emission computed tomography. Am. J Cardiol 1988; 62:
234-238.
- Periyanan vaduganathan, Zuo-xiang He,
Mahmarian et al: Diagnostic accuracy of stress thallium-201
tomography in patients with left ventricular hypertrophy.
Excerpta Medica, Inc, 1998 , 1205-1207.
- Gianrossi, R, Detrono, R, Mulvihill,
D, et al. Exercise - Induced ST depression In the diagnosis
of coronary artery disease: A meta analysis. Circulation
80: 87, 1989.
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