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MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
21
Effect of high doses of atorvastatin on the endothelium function
of the coronary arteries
Audrius Šimaitis, Aleksandras Laucevičius1
Klaipėda Seamen’s Hospital, 1 Department of Cardiology, Vilnius University, Lithuania
Key words: atherosclerosis, coronary heart disease, endothelium dysfunction, acetylcholine test, atorvastatin.
Summary. Objective. The aim of this study is to investigate the role of high doses of
atorvastatin (80 mg per day) in the treatment of endothelium dysfunction of the coronary
arteries.
Material and methods. Intracoronary acethylcholine test was performed for 28 (16 in
treatment group and 12 in control group) patients who had normal coronary angiogram or
minimal lesions (stenosis <50%) and symptomatic coronary heart disease. Acetylcholine
was given into left coronary artery in three stages (2 min each) at estimated intracoronary
concentrations 10-6 mol/l, 3.3×10-6 mol/l,and 10-5 mol/l. Treatment group patients were given
atorvastatin 80 mg per day. Intracoronary acetylcholine test was repeated after six months.
The target segment was the segment that exhibited the maximal constrictive response at
baseline in a given patient.
Results. Total cholesterol was reduced by 40.6±11.2% (p<0.001), low density lipoproteins cholesterol by 55.4±14% (p<0.001), triglycerides by 29.6% (p<0.05) and high density lipoproteins cholesterol was increased by 24.7% (p<0.05) in atorvastatin group after 6
months of therapy. No significant lipid changes were observed in the control group. Sixteen
target segments in the treatment group and 12 segments in the control group were selected
for primary efficacy parameter. The vasoconstrictor reaction to acetylcholine was similar
at baseline in both groups: –16.8%±11.6% of diameter in atorvastatin group and –
–6
14.2%±13.7% in control group (p=0.58) at dose 10 mol/l, –43.5%±21.2% in atorvastatin
–6
group and –41.2%±22.4% in control group (p=0.79) at dose 3.3×10 mol/l, –64.5%±12.4%
in atorvastatin group and –57.4%±15.6% in control group (p=0.35) at dose
–5
10 mol/l. Treatment with high doses of atorvastatin markedly decreased acetylcholine –
induced vasoconstriction: –6.5%±14.5% of diameter in atorvastatin group versus –
–6
18.3%±14.0% in control group (p=0.04) at dose 10 mol/l, –19.7%±22.8% in atorvastatin
–6
group versus –40.0%±25.0% in control group (p=0.034) at dose 3.3×10 mol/l, –
29.9%±21.3% in atorvastatin group (6 segments) versus –48.7%±19.0% in control group
–5
(3 segments, p=0.24) at dose 10 mol/l.
Conclusion. Treatment with high doses of atorvastatin significantly improves endothelium-mediated response to acetylcholine in the coronary arteries of the patients with minimal lesions.
Introduction
Endothelium dysfunction (ED) of the coronary
arteries is the earliest expression of the coronary
heart disease (CHD) process in the coronary
arteries (1). It stays and progresses through all
stages in CHD. How to make prompt diagnosis of
the endothelium dysfunction and to administer
effective treatment yet to be established. Recently,
it has been established that most of the acute
coronary syndromes occur in nonsignificant (<50%)
lesions (2). Furthermore, in 1 case out of 100
myocardial infarction (MI) occurs in the coronary
arteries where any lesions could not be detected by
coronaroangiography (3). The early detection of the
Correspondence to A. Šimaitis, Klaipėda Seamen’s Hospital, Liepojos pl. 45, 5809 Klaipėda, Lithuania
E-mail: [email protected]
22
Audrius Šimaitis, Aleksandras Laucevičius
endothelium dysfunction and coronary heart disease
could prevent the progression of the CHD, it would
be possible to avoid threatening expressions of CHD
(myocardial infarction, unstable angina pectoris,
coronary car diomyopathy). Noninvasive and
invasive methods for the detections of the ED were
introduced recently. They are in the process of
development.
There are no studies concerning the effect of
the atorvastatin to the ED. Furthermore, most of
the previous studies with atorvastatin enrolled
patients with far advanced atherosclerotic disease
(stenosis >50% at least in one of the coronary
arteries) (4,5). Based on these facts we decided to
perform study for the patients who have CHD,
minimal lesions (stenosis <50%) in the coronary
arteries and endothelium dysfunction. Such patients
were treated with high doses of atorvastatin (80 mg
per day). The aim of this trial is to study the role of
high doses of atorvastatin (80 mg per day) in the
treatment of ED in patients with minimal lesions in
the coronary arteries. The study was conducted in
Klaipeda’s Seamen Hospital in 2001 year ;
Lithuanian Bioethics Committee approved the
protocol of the study.
Methods and patients
Patients who had satisfied the inclusion criteria
(symptomatic CHD, minimal lesions (<50%) in the
coronary arteries, low density lipids (LDL) cholesterol
level is ³3 mmol/l, endothelium dysfunction during
intracoronary acetylcholine test and left ventricular
ejection fraction >40%) were included into the study.
It was prospective, open label, parallel group trial.
Patients were divided into two groups: treatment group
(21 patient) and control group (19 patient). The
acetylcholine test was repeated after 6 months for 28
patients: 16 in the treatment group and 12 in the control
group (Table 1). To avoid human factor in allocating
patients to the groups the first 21 patients were
assigned to the treatment group, the next 19 ones were
assigned to the control group. The first group (16
patients) was treated with atorvastatin 80 mg per day;
the control group (12 patients) was treated with
conventional treatment except cholesterol lowering
therapy; other medications used by them did not differ.
Patients were treated for 6 months. Laboratory tests
were repeated after 3 and 6 months.
Acetylcholine was given into left coronary artery
in thr ee stages (2 min each) at estimated
intracoronary concentrations 10-6 mmol/l, 3.3x10-6
mmol/l, 10-5 mmol/l (5). The dose of acetylcholine
was not increased further if the infusion of
acetylcholine caused severe (>50%) narrowing of
the diameter of the epicardial artery. The vasospasm
of the cor onar y ar tery was abolished by the
intracoronary nitroglycerin (300 mg); in case this
dose was insufficient it was repeated 1-2 times.
We chose three segments of the left anterior descending coronary artery and three segments in left
circumflex artery from the control angiogram (proximal, middle and distal) in each patient for the analysis. For each patient 6 segments were analysed; the
target segment for statistics was segment that ex-
Table 1. Baseline characteristics of the patients
Characteristic
Number of patients
Number of females
Age average (years)
Smoking (n)
Hypertension (n)
Exercise-induced angina
Angina at rest
Previous acute coronary syndrome
Total cholesterol (mmol/l)
LDL-cholesterol (mmol/l)
HDL-cholesterol (mmol/l)
Triglycerides (mmol/l)
Ejection fraction
Atorvastatin
group
Control
group
16
8 (50%)
58.3±11.4
4 (25%)
11 (69%)
11 (69 %)
14 (88%)
7 (44%)
6.1±1
4.6±1
1±0.2
1.3±0.6
66±6.2%
12
3 (25%)
52±11.4
4 (33%)
9 (75%)
10 (83%)
10 (83%)
4 (33%)
6.1±1.5
4.1±1.5
1.4±0.4
1.6±0.7
64±7.2%
p
0.1
0.08
0.32
0.37
0.2
0.36
0.28
0.74
0.46
<0.05
0.47
0.22
MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
Effect of high doses of atorvastatin on the endothelium function of the coronary arteries
hibited the maximal constrictive response at baseline
in a given patient. The target segment was analysed
after 6 months. Its vasomotor reaction before treatment and after was compared in the treatment and
control groups. All the other segments were analysed
by the same method. If the coronary artery did not
respond with the spasm >50% during all acetylcholine stages endothelium dysfunction was diagnosed
if the narrowing of the diameter was >5%. Diameter
of the coronary artery was calculated directly from
the X-ray film.
Statistical analysis. The programs “Statistica”,
“SPSS”, and “MS Excel” were usd for the data
analysis. All the variables were filed in the “MS
Excel” sheets. General linear model, Spearman and
correlation analyses were used to assess the impact
of different factors to the endothelium dysfunction.
The primary efficacy parameter was the net change
in the acetylcholine pr ovoked per cent
vasoconstriction of the target segment between
baseline and follow-up angiographic protocols. The
mean of the net percent change in 6 months was
compar ed between ator vastatin and contr ol
treatment groups. All analyses were two-tailed, and
a value of p<0.05 was considered significant.
Results are presented as mean±SE. Secondary
analyses based on all segments and analyses based
on mean diameter responses were done by usage
of one or more of the statistical methods, as
described for the primary end point.
Results
No significant lipid changes were observed in
the control group (Table 3) after 6 months. Total
cholesterol, LDL cholesterol, triglycerides concentrations were markedly reduced in the treatment
group; high density lipids (HDL) cholesterol increased. There was statistically significant difference of the total cholesterol, LDL cholesterol and
HDL cholesterol concentrations between the groups
after 6 months (Table 2). HDL cholesterol was significantly higher in the control group before the
treatment. This difference was not established after 6 months (Figure 1).
16 tar get segments (maximal constr ictive
response at baseline in a given patient) in the
treatment group and 12 segments in the control
group were selected for primary efficacy parameter.
The vasomotor reaction to acetylcholine was similar
at baseline (Table 4) in both groups: –16.8%±11.6%
in the atorvastatin group and –14.2%±13.7% in the
contr ol gr oup (p=0.58) at dose 10 -6 mmol/l,
–43.5%±21.2% in atorvastatin the group and
–41.2%±22.4% in the control group (p=0.79) at dose
3.3x10-6 mmol/l, –64.5%±12.4% (10 segments) in
atorvastatin the group and –57.4%±15.6% (5
Table 2. Lipid changes in the atorvastatin group after 3 and 6 months
Lipids
Total cholesterol (mmol/l)
LDL-cholesterol (mmol/l)
HDL-cholesterol (mmol/l)
Triglycerides (mmol/l)
Before
After
3 months
After
6 months
Change after
6 months (%)
6.1±1
4.6±1
1±0.2
1.3±0.6
3.7±1.1**
1.9±1.1**
1.3±0.4**
1.2±0.7
3.6±0.7**
2±0.5**
1.2±0.3*
0.9±0.6*
–40.6
–55.4
+24.7
–29.6
* p<0.05, ** p<0.01.
Table 3. Lipid changes in the control group after 3 and 6 months
Lipidai
Before
After
3 months
After
6 months
Change after
6 months (%)
Total cholesterol (mmol/l)
LDL-cholesterol (mmol/l)
HDL-cholesterol (mmol/l)
Triglycerides (mmol/l)
6,1±1,5
4,1±1,5
1,4±0,4
1,6±0,7
6,4±1,6
4,6±1,4*
1,2±0,3
1,2±0,6*
6,3±1,4
4,4±1,4
1,2±0,2
1,6±0,8
+2,3
+7,1
–8,2
–4,3
* p<0.05.
MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
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Audrius Šimaitis, Aleksandras Laucevičius
Atorvastatin group
Concentration mmol/l
7
* p<0.01
** p<0.05
6.3
6
5
*
4
3.6
3
4.4
*
2
2
1.2 1.2
1
0
Control group
Total Chol.
LDL-chol.
HDL- chol.
**
1.6
0.9
Triglycerids
Fig. 1. Blood lipid changes of both groups after 6 months
segments) in control the group (p=0.35) at dose
10 -5 mmol/l. The number of segments in third
acetylcholine stage was due to the fact that for the
part of the patients acetylcholine infusion was
stopped at the second stage because of the coronary
spasm > 50%. The endothelium independent
reaction did not differ in both groups (Table 4).
Treatment with high doses of atorvastatin
markedly decreased acetylcholine (Table 5, figure
2) induced vasoconstriction: –6.5%14.5% in the
atorvastatin group versus –18.3%±14.0% in the
contr ol gr oup (p=0.04) at dose 10 -6 mmol/l,
–19.7%±22.8% in the atorvastatin group versus
–40.0%±25.0% in the control group (p=0.034) at
dose 3.3x10 -6 mmol/l. There was no statistical
difference due to the small number of segments in
the third stage: –29.9%±21.3% in the atorvastatin
group (6 segments) versus –48.7%±19.0% in the
control group (3 segments, p=0.24). However the
comparison of the target segments of the the
atorvastatin group before treatment and after the
treatment reveals less pronounced endothelium
dependent reaction after six months: –64.5±12.4%
(10 segments) before treatment and –29.9±21.3%
(6 segments) after treatment (p=0.001).
All dysfunctional segments of both groups were
compared also. 86 segments with vasoconstrictive
response at the baseline of the atorvastatin group
Table 4. Comparison of the target segments of the treatment and control groups before
treatment
Stage
Atorvastatin group (%)
Control group (%)
p
I stage
II stage
III stage
Nitro
–16.8±11.6
–43.5±21.2
–64.5±12.4 (10 segm.)
–7.2±16.1
–14.2±13.7
–41.2±22.4
–57.4±15.6 (5 segm.)
0.3±18.2
0.58
0.79
0.35
0.29
Table 5. The comparison of the target segments of the treatment and control groups after
treatment.
Stage
I stage
II stage
III stage
Nitro
Atorvastatin group (%)
Control group (%)
p
–6.5±14.5
–19.7±22.8
–29.9±21.3 (6 segm.)
–16.2±16.4
–18.3±14.0
–40.0±25.0
–48.7±19.0 (3 segm.)
7.7±14.3
0.04
0.034
0.24
0.16
MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
Effect of high doses of atorvastatin on the endothelium function of the coronary arteries
25
0
Diameter change %
-10
-20
-30
p=0.04
-40
-50
-60
p=0.034
-70
-80
I stage
Atorva-I visit
II stage
Control-I visit
III stage
Atorva-III visit
Control-III visit
Fig. 2. Vasomotor function of target segments at baseline and follow-up
and 71 of the control group were analyzed further.
Both groups (Table 6) showed statistically similar
vasoconstrictive reaction to acetylcholine at the
baseline: –10.0%±12.3% in the atorvastatin group
and –10.8%±10.7% in the control group (p=0.69)
at dose 10 -6 mmol/l, –27.4%±19.7% in the the
atorvastatin group and –27.0%±17.4% in the control
gr oup (p=0.9) at dose 3.3x10 -6 mmol/l,
–40.8%±20.1% in the atorvastatin group (55
segments) and –41.3%±16.9% in the control group
(30 segments, p=0.35) at dose 10 -5 mmol/l.
Endothelium independent reaction was mor e
expressed in the control group (Table 6). This
difference could be due to the fact that the dose of
the nitroglycerin was not standardized. Initial dose
was 300 mg; the dose could be repeated 1 – 3 times
until the spasm would be abolished.
The treatment with high doses of atorvastatin
markedly decreased acetylcholine (Table 7, figure
3) induced vasoconstriction: –5,4%±12,1% in the
atorvastatin group versus –12.8%±12.7% in the
control gr oup (p<0.001) at dose10 -6 mmol/l,
–14.1%±18.5% in the atorvastatin group versus
–29.8%±20.1% in the control group (p<0.001) at
dose 3.3x10 -6 mmol/l, – 24.8%±17.8% in the
ator vastatin gr oup (35 segments) ver sus
–39.0%±17.7% in the control group (18 segments,
p=0.008) at dose 10-5 mmol/l. The endothelium in-
Table 6. Comparison of all dysfunctional segments of the treatment and control groups before
treatment
Stage
Atorvastatin group (%)
Control group (%)
p
I stage
II stage
III stage
Nitro
–10.0±12.3
–27.4±19.7
–40.8±20.1 (55 segm.)
–8.9±16.1
–10.8±10.7
–27.0±17.4
–41.3±16.9 (30 segm.)
2.4±18.2
0.69
0.9
0.35
0.02
Table 7. The comparison of all dysfunctional segments of the treatment and control groups after
treatment.
Stage
Atorvastatin group (%)
Control group (%)
I stage
II stage
III stage
Nitro
–5.4±12.1
–14.1±18.5
–24.8±17.8 (35 segm.)
–11.7±15.1
–12.8±12.7
–29.8±20.1
–39.0±17.7 (18 segm.)
6.6±15.1
MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
p
<0.001
<0.001
0.008
0.03
26
Audrius Šimaitis, Aleksandras Laucevičius
Diameter change %
0
-10
-20
-30
p<0.001
-40
-50
p<0.001
p=0.008
-60
I stage
Atorva-I visit
II stage
Control-I visit
Atorva-III visit
III stage
Control-III visit
Fig. 3. Vasomotor function of all segments at baseline and follow-up
dependent reaction to nitroglycerin was unchanged
in both groups at the baseline and at the follow-up.
Logistical analysis (impr ovement of the
endothelium function after the treatment >5% – 1,
the absence of such an effect – 0; variables (those
with p<0.10) were analyzed according to regression
analysis) revealed that informative features in both
groups were cholesterol and triglycerid blood
concentrations. According to the “Backward
stepwise” method non-improvement situations could
be predicted by 60% and improvement situations
could be predicted by 91% in the atorvastatin group.
Over all accur ate pr ognosis is 81.3 %. Nonimprovement situations could be predicted by 85.7%
and improvement situations could be predicted by
20% in the control group. Overall accurate prognosis
is 58.3 %.
Adverse events. Liver enzymes increased more
than 3 times upper limit for two patients. Both were
withdrawn from the study, in one month enzymes
became normal. For one patient (female, S.T., 64
years) the dose of atorvastatin was reduced to 40
mg because of safety (CPK increased 2.5 times,
patient had no symptoms). One patient complained
of weakness and bad appetite.
Discussion
According to the invasive studies statins and ACE
inhibitors improve endothelium dysfunction. Among
the statins lovastatin and pravastatin have the positive effect (4,7,8). Atorvastatin according to our findings markedly improved endothelium function in the
patients with symptomatic CHD and minimal lesions
in the coronary arteries. Anderson investigated the
effect of lovastatin to the acetylcholine induced
vasoconstriction of the coronary arteries (7). Ace-8
tylcholine was given in the three stages: 10 mol/l,
-7
-6
10 mol/l, 10 mol/l. Lovastatin reduced the endothelium dysfunction of the coronary arteries by 11%
-6
at the acetylcholine concentration of 10 mol/l while
we observed improvement of 10.3% at the same
dose; all the dysfunctional segments improved by
13.3%. LDL-cholesterol was reduced by 38% in
Anderson’s study while LDL-cholesterol was reduced by 55.4% in our study. However, it should be
noted that Anderson assessed the average vasoconstriction of the two dysfunctional segments in
one coronary artery. Therefore we cannot make
direct comparison between Anderson’s and our
studies. Furthermore, the duration of the treatment
was different: patients were on lovastatin for 1 year,
patients on atorvastatin were for 6 months.
Egashira (4) conducted the study on the effect
of pravastatin to the endothelium dysfunction of the
coronary arteries. Nine patients were enrolled; they
were given 10-20 mg of pravastatin. Coronary artery segment at the distance of 3 mm from the tip
of the intracoronary Doppler catheter was selected
as the target segment. Total cholesterol was reduced
by 31.3%; in our study this figure was 40.6%.
Pravastatin reduced acetylcholine provoked vasoconstriction by 9%. This figure is lower in compare
with the atorvastatin effect. However, there are
few differences between two studies. Firstly, the
MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
Effect of high doses of atorvastatin on the endothelium function of the coronary arteries
dose of pravastatin was low (10-20 mg). Secondary, the method of the selection of the coronary artery segment was different. Our target segment was
the segment which exhibited the maximal vasoconstriction while the Egashira’s chosen segment was
not necessary the segment with the most pronounced
vasoconstriction.
CARATS study (9) was not able to demonstrate
the efficacy of the simvastatin to improve the endothelium function of the coronary arteries. However, simvastatin had positive effect on the endothelium function in the brachial artery studies (10).
The results of the ENCORE I and ENCORE II
studies should be published soon (5). Both studies
are trying to look into the effect of cerivastatin,
nifedipine, their combination and high doses of
cerivastatin to the endothelium function. The findings of ENCORE II trial are of special attention
because this study will assess the impact of the
statins to the size of the atherosclerotic plaque.
The positive role of the statins in the set of the
endothelium dysfunction could be explained not only
by their ability to reduce LDL-cholesterol but also
by their direct and various actions to the arterial
wall. Mevalonat and other intermediate cholesterol
synthesis products are necessary for the cell proliferation and for other important cellular functions.
Ability to influence arterial wall explains antisclerotic
qualities of the statins. One of these effects is the
inhibition of the proliferation and migration of the
smooth muscle cells, which play the key role in the
formation of the atherosclerotic plaque (11). According to the experimental studies (11) such an
effect is possessed by fluvastatin, simvastatin,
atorvastatin, cerivastatin. Furthermore, statins have
other equally (11) important pleiotropic properties:
increasing of the LDL resistance to oxidation
(lovastatin, pravastatin, simvastatin), lowering of
plasma viscosity (lovastatin, pravastatin), reducing
platelet aggregation (pravastatin, simvastatin). Despite all these positve pleiotropic effects the positive clinical impact of them is yet to be proven.
According to the invasive studies quinalapril had
a positive role to counteract the acetylcholine induced vasocontriction of the coronary arteries in
the TREND trial (12).. In the TREND study the
target segment was the one with the maximal
vasocontriction (54 in the placebo group and 51 in
the treatment group); the investigators also assessed
all the other measured segments (202 segments in
the placebo arm and 178 in the quinalapril arm).
MEDICINA (2003) Vol. 39, No. 1 - http://medicina.kmu.lt
27
-6
Acetylcholine was given in two stages: 10 mol/l,
-4
10 mol/l. Quinalapril reduced the endothelium dysfunction of the target segments by 4.5% at the ace-6
tylcholine concentration of 10 mol/l while we observed improvement of 10.3% at the same dose.
This figure was 0.6% for all segments in the
TREND trial, while it was 4.6% in our study. This
considerable difference suggests that statins because of their pleiotropic effects may have more
pronounced positive effect to the endothelium dysfunction of the coronary arteries.
The positive role of the ACE inhibitors is explained by their ability to protect the artery wall from
the harmful effect of the angiotensin II by lowering
the plasma concentration of the latter. ACE inhibitors studies showed the decrease of the coronary
events for the patients with depressed LV function.
It is thought that ACE inhibitors decrease the angiotensin II concentration while increasing bradykinin concentration. It was the main factor contributing to positive results in depressed LV function trials as well as in TREND trial. Perindoprilat also
exhibited positive effect to the endothelium dysfunction of the coronary arteries (13). Noninvasive brachial artery studies were able to demonstrate the
positive effect of the ramipril. Data regarding the
enalapril are conflicting. However, most of them
were not able to reveal any positive effect of the
enalapril in the set of the endothelium dysfunction
(14).
Finally, statins (ator vastatin, pravastatin,
lovastatin) and ACE inhibitors with tissue affinity
(quinalapril, perindoprilat) are able to reduce the
endothelium dysfunction of the coronary arteries
according to the invasive studies. The treatment of
the endothelium dysfunction is still in the early stages
of the development. However, the fact that we have
the medication that is able to have impact to the
endothelium dysfunction gives hope that cardiologist will be able to treat the early endothelium dysfunction in the future.
Conclusions
1. Atorvastatin reduced total cholesterol concentration by 41%, LDL cholesterol by 55%, triglycerides concentration by 30% and increased HDL concentration by 25%.
2. Treatment with high doses of atorvastatin
markedly improved the endothelium function for the
patients with coronary heart disease and minimal
lesions in the coronary arteries.
28
Audrius Šimaitis, Aleksandras Laucevičius
Didelių atorvastatino dozių poveikis vainikinių arterijų
endotelio funkcijai
Audrius Šimaitis, Aleksandras Laucevičius1
Klaipėdos jūrininkų ligoninė, 1Vilniaus universiteto Kardiologijos klinika
Raktažodžiai: aterosklerozė, koronarinė širdies liga, endotelio disfunkcija, acetilcholino mėginys,
atorvastatinas.
Santrauka. Tikslas. Šio darbo tikslas – ištirti, kokį poveikį turi didelės atorvastatino dozės (80 mg per parą)
vainikinių arterijų disfunkcijai.
Tyrimo medžiaga ir metodai. Tirti pacientai, kurie skundėsi koronarinei širdies ligai būdingais simptomais ir
kuriems koronarografijos metu rasta nereikšmingų pakitimų (vainikinių arterijų stenozė mažesnė kaip 50 proc.).
Vainikinių arterijų disfunkcija diagnozuota intrakoronarino acetilcholino mėginio metu. Acetilcholino buvo lašinama
trimis pakopomis (po dvi minutes): numanoma acetilcholino koncentracija vainikinėse arterijose 10–6 mol/l,
3,3×10–6 mol/l ir 10–5 mol/l. 16-kai gydymo grupės pacientų buvo skiriama atorvastatino 80 mg per parą, 12-ka
pacientų sudarė kontrolinę grupę. Po šešių mėnesių pakartotas acetilcholino mėginys.
Rezultatai. Po šešių mėnesių bendrasis cholesterolis atorvastatino grupėje sumažėjo 40,6 proc. (p<0,01),
mažo tankio lipoproteinų cholesterolis sumažėjo 55,4 proc. (p<0,01), didelio tankio lipoproteinų cholesterolis
padidėjo 24,7 proc. (p=0,015), trigliceridų sumažėjo 29,6 proc. (p=0,026). Po šešių mėnesių kontrolinėje grupėje
lipidų kiekis nepakito. Prieš gydymą šių segmentų diametro pokytis į acetilcholiną buvo vienodas: –16,8±11,6
proc. atorvastatino grupėje ir –14,2±13,7 proc. kontrolinėje grupėje pirmos pakopos metu (p=0,58); –43,5±21,2
proc. atorvastatino grupėje ir –41,2±22,4 proc. kontrolinėje grupėje antros pakopos metu (p=0,79); –64,5±12,4
proc. (10 segmentų) atorvastatino grupėje ir –57,4±15,6 proc. (5 segmentai) kontrolinėje grupėje trečios pakopos
metu (p=0,35). Po gydymo labiausiai sureagavusių į acetilcholiną segmentų atorvastatino grupėje buvo gerokai
mažesnis negu kontrolinės grupės tiriamųjų: –6,5±14,5 proc. atorvastatino grupėje ir –18,3±14,0 proc. kontrolinėje
grupėje pirmos pakopos metu (p=0,04); –19,7±22,8 proc. atorvastatino grupėje ir –40,0±25,0 proc. kontrolinėje
grupėje antros pakopos metu (p=0,034); –29,9±21,3 proc. (6 segmentai) atorvastatino grupėje ir –48,7±19,0
proc. (3 segmentai) kontrolinėje grupėje trečios pakopos metu (p=0,24).
Išvada. Gydymas didelėmis atorvastatino dozėmis žymiai sumažino vainikinių arterijų endotelio disfunkciją
ligoniams, sergantiems koronarine širdies liga ir turintiems vainikinėse arterijose minimalių pakitimų, kurių rasta
koronarografijos metu.
Adresas susirašinėjimui: A. Šimaitis, Klaipėdos jūrininkų ligoninė, Liepojos pl. 45, 5809 Klaipėda.
El. paštas: [email protected]
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Received 6 September 2002, accepted 22 October 2002
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