J Cardiol 2001 Dec; 38（6）: 311 – 317

Effect of Chlamydia pneumoniae
Infection on Coronary Flow Reserveand Intimal Hyperplasia After Stent
Implantation in Patients With
Angina Pectoris
Takahiro
Masashirou

TANAKA, MD
MATSUSHITA, MD

Yukiko

OKA, MD

Toshikatsu

SADA, MD

Yuji

KIRA, MD

Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Objectives. Chlamydia pneumoniae（C. pneumoniae）has been detected in tissue from coronary atherosclerotic vascular lesions and may be involved in the pathogenesis of atherosclerosis. However, the effectof prior C. pneumoniae infection on coronary intimal hyperplasia after stent implantation and on coronary
microvascular function is unknown.
Methods. Seventy-three patients with stable angina pectoris and a single de novo coronary lesion werestudied prospectively. All patients underwent successful coronary angioplasty and stent implantation forthe stenotic lesion. Blood samples were tested for prior C. pneumoniae infection before the procedure, andpatients were divided into two groups : Seropositive and seronegative. Coronary ﬂow reserve was measured in the non-stenotic coronary vessel before angioplasty, and quantitative coronary arteriography was
performed at the stent implantation site before angioplasty and 6 months later in all patients.
Results. Coronary ﬂow reserve in the non-stenotic vessel was signiﬁcantly lower in the seropositive
group than in the seronegative group（2.51 ± 0.35 vs 2.76 ± 0.43, p ＜ 0.05）. The minimum luminal diameter was smaller and late loss was greater in the seropositive group than in the seronegative group（minimum luminal diameter : 1.52 ± 0.59 vs 1.91 ± 0.79 mm, p ＜ 0.05, late loss : 1.17 ± 0.55 vs 0.76 ± 0.67,
p ＜ 0.05）. However, there was no signiﬁcant difference in the restenosis rate or target lesion revascularization rate between the two groups.
Conclusions. Prior C. pneumoniae infection may accelerate intimal hyperplasia after stent implantationand impair coronary microvascular function in the non-stenotic coronary vessels.
─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2001 Dec ; 38（6）
: 311−317

Key Words
Atherosclerosis
Intravascular Doppler
Microcirculation coronary ﬂow reserve

INTRODUCTION
Percutaneous transluminal coronary angioplasty（PTCA）is an important method for the treatment ofcoronary artery disease. However, stent implantation restenosis develops in approximately 30% ofRestenosis
Stent
Infectious disease Chlamydia pneumoniae

patients within 6 months of PTCA, mainly becauseof coronary intimal hyperplasia1−3）. Several complex interactions between cellular and extracellularfactors that could contribute to restenosis have been
identiﬁed.
Previous studies have demonstrated the potential──────────────────────────────────────────────
公立昭和病院 循環器科 : 〒 187−8510 東京都小平市天神町 2−450
Department of Cardiology, Showa General Hospital, Tokyo
Address for correspondence : TANAKA T, MD, Department of Cardiology, Showa General Hospital, Tenjin-cho 2−450, Kodaira,Tokyo 187−8510
Manuscript received May 29, 2001 ; revised July 25, 2001 ; accepted July 26, 2001

311

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Tanaka, Matsushita, Oka et al

involvement of infectious agents in the pathogenesis of atherosclerosis and coronary artery disease.
Chlamydia pneumoniae（C. pneumoniae）, a human
respiratory pathogen, has been detected in tissue
specimens obtained from coronary atherosclerotic
vascular lesions and may be a contributing pathogenic factor4,5）. Recently, preliminary studies haveexamined the possible relationship between C.
pneumoniae infection and restenosis after PTCA,
although the results are controversial6,7）.
In addition to the large coronary conduit vessels,
the coronary microvasculature is very important in
the regulation of coronary artery blood ﬂow.
Coronary ﬂow reserve, which reﬂects coronary
microvascular function, is determined by measuring coronary ﬂow velocity before and after theadministration of coronary vasodilators. Coronary
ﬂow reserve provides important diagnostic information in a variety of cardiac diseases8,9）. Recent
clinical reports have demonstrated that coronary
ﬂow reserve is reduced in several diseases, includhypertension 11） anding
diabetes 10） ,12）
hyperlipidemia , which are also risk factors forcoronary atherosclerosis. However, there are noreports on the effects of prior C. pneumoniae infection on coronary microvascular function.
The present study investigated the effects of C.
pneumoniae infection on coronary microvascularfunction and examined whether prior C. pneumoniae infection affects intimal hyperplasia after stentimplantation in patients with angina pectoris.
SUBJECTS AND METHODS
Study population
Seventy-three patients（60 men and 13 women,mean age 65 ± 10 years）with stable angina pectoris and a single de novo coronary lesion werestudied prospectively. All patients had single vessel
disease with a stenotic lesion ＞− 75% and no othersigniﬁcant stenoses. Patients with chronic total
occlusion, acute myocardial infarction, old myocardial infarction, dilated or hypertrophic cardiomyopathy, or marked valvular disease were excluded.
All patients undergoing PTCA and stent implantation were scheduled for follow-up angiography 6months after the procedures. All patients gave written informed consent to a protocol approved by the
Ethics Committee of the Showa General Hospital.
Coronary angioplasty and angiography
Coronary angioplasty and stent implantation

were performed using a standard method. A balloon catheter of appropriate size was advanced overa guide wire through a 6F or 7F guiding catheterand positioned at the site of stenosis. After sufﬁcient predilation, coronary stent implantation was
performed in all patients. After stent implantation,
100 mg of aspirin and 200 mg of ticlopidine a day
were given to all patients as antiplatelet therapy
until follow-up angiography. Quantitative coronary
angiography（ QCA）data were analyzed using acomputerized QCA system（QCA-CMS, Medical
Imaging System Co., Ltd.）before and immediately
after PTCA and stent implantation, and after amean follow-up of 6 months. The minimum luminal diameter, reference diameter, and lesion length
were measured, and the late loss was calculated as
the minimum luminal diameter at follow-up minus
the minimum luminal diameter immediately after
stent implantation. The rate of restenosis（＞ 50%
stenosis）at the target lesion and the target lesion
revascularization rate were also analyzed.
Coronary ﬂow reserve measurement
Left and right coronary angiography were performed using a standard method after intracoronary
injection of 150 to 200μg of nitroglycerin. Before
coronary angioplasty, a 0.014-inch Doppler ﬂow
wire（FloWire, Cardiometrics, Mountain View）was
advanced into the coronary artery without the
stenotic lesion through a guiding catheter. The ﬂow
velocity pattern was monitored on a video display.
The coronary ﬂow velocities were determined fromsingle-frame images（ Flomap, Cardiometrics,
Mountain View）. Doppler velocities were recorded
under steady state conditions and coronary ﬂow
velocity measurements were obtained at baseline
and at peak hyperemia after bolus intracoronary
injection of adenosine 25 to 50μg13）. The coronary
ﬂow reserve was calculated as the ratio of hyperemic to baseline averaged peak velocity. The bloodpressure, heart rate, and surface electrocardiography were continuously monitored.
Blood samples and laboratory analysis
Blood was taken under standardized conditions,and all laboratory determinations were performed
in a blinded fashion. Speciﬁc antibodies against C.
pneumoniae were identiﬁed by a microimmunoﬂuorescence method. Blood samples were used todetermine the C. pneumoniae IgG titer. Patientswere divided into two groups, seropositive and
J Cardiol 2001 Dec; 38（6）: 311 – 317

Chlamydia and Coronary Microcirculation

313

Table 1 Patient characteristics
Seropositive group（n＝47）

Seronegative group（n＝26）

p value

Age（yr）

63±10

67±10

NS

Gender（male/female）

39/8

21/5

NS

Hemodynamics
Heart rate（beats/min）

77±12

72±10

NS

Systolic blood pressure（mmHg）

136±25140±23NS

Diastolic blood pressure（mmHg）

79±15

82±19

NS

Mean blood pressure（mmHg）

99±18

104±18NSHyperlipidemia

18
（38）

11
（42）

NS

Hypertension

21
（44）

11
（42）

NS

Diabetes mellitus

17
（36）

10
（38）

NS

Smoking

15
（32）

9（35）

NS

Nitrates

44
（94）

23
（88）

NS

ACE-inhibitor

18
（38）

8（30）

NS

Calcium antagonist

21
（44）

9（35）

NS

Lipid lowering agent

17
（36）

9（35）

NS

Coronary risk factors

Drug treatment

Continuous values are mean±SD.（ ）: %.
Seropositive＝positive Chlamydia pneumoniae titer ; Seronegative＝negative Chlamydia pneumoniae titer ; ACE＝angiotensin converting enzyme.

seronegative patients, based on the titer. Patientswere considered seropositive when the IgG titerwas ＞− 0.9.
Statistical analysis
Values in the two groups were compared by the
unpaired t-test or the χ2 test for categorical variables. All measurements are expressed as themean ± SD, and a p value ＜ 0.05 was considered
statistically signiﬁcant.
RESULTS
C. pneumoniae serostatus and patient characteristics
C. pneumoniae IgG serum antibody titer was
positive in 47 patients（64%）and negative in 26
patients（36%）. In the study population, seropositive and seronegative individuals showed similarbasic characteristics, hemodynamic parameters,
risk factors for coronary artery disease, and drug
treatment（Table 1）.
PTCA and QCA data
The angiographic ﬁndings, the calculated parameters at baseline, immediately after PTCA, and at
J Cardiol 2001 Dec; 38（6）: 311– 317

the 6-month follow-up, the target vessel, lesion
type, and stents used are listed in Table 2. There
were no differences between the two groups withrespect to the reference diameter, minimal luminal
diameter, percentage diameter stenosis, and lesion
length before angioplasty. There were no differences in the minimum luminal diameter and percentage diameter stenosis just after the stent implantation between the two groups. No differences
between the two groups were found with respect tothe target vessel, lesion type, or type of stent used.
Although the left anterior descending artery wastreated more frequently than the other two vessels
and multi-link stents were used in most patients,
there were no signiﬁcant differences between thetwo groups.
Based on the follow-up QCA data, the minimum
luminal diameter was smaller in the seropositive
group than in the seronegative group（1.52 ± 0.59
vs 1.91 ± 0.79 mm, p ＜ 0.05）, and the late loss
was greater in the seropositive group than inseronegative group（ 1.17 ± 0.55 vs 0.76 ± 0.67mm, p ＜ 0.05）. However, there were no signiﬁcantdifferences between the two groups with respect tothe restenosis rate or the target lesion revasculariza-

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Tanaka, Matsushita, Oka et al

Table 2 PTCA and QCA ﬁndings
Seropositive group（n＝47）

Seronegative group（n＝26）

p value

Reference diameter（mm）

2.84±0.31

2.88±0.28

NS

MLD
（mm）

0.72±0.22

0.70±0.29

NS

Diameter stenosis（%）

74.1±12.775.0±13.3

NS

Lesion length（mm）

6.9±4.4

8.0±5.1

NS

MLD
（mm）

2.79±0.25

2.81±0.40

NS

Diameter stenosis（%）

4.1±0.23

3.3±0.39

NS

MLD
（mm）

1.52±0.59

1.91±0.79＜0.05

Diameter stenosis（%）

41.5±18.0

34.0±20.6

NS

Late loss（mm）

1.17±0.55

0.76±0.67＜0.05

Restenosis rate（%）

12
（26%）

7（27%）

NS

TLR
（%）

9（19%）

6（23%）NS

Before angioplasty

Post stent implantation

Follow-up

Target vessel

NS

LAD

29

18

Cx

9

5

RCA

9

3

Type A

15

9Type B27

14Type C

5

3

GFX

1

2

Multi-link

39

22

NIR

7

2

Lesion type（ACC/AHA）

NS

Stent usedNS

PTCA＝percutaneous transluminal coronary angioplasty ; QCA＝quantitative coronary angiography ; MLD＝minimum luminal diameter ; TLR＝target lesion revascularization ; LAD＝left anterior descending artery ; Cx＝left circumflex artery ; RCA＝right coronary artery ; ACC/AHA＝American College of Cardiology/American
Heart Association. Other abbreviations as in Table 1.

tion rate. No correlation was recognized between
the C. pneumoniae IgG serum antibody titer andminimum luminal diameter or late loss.
Coronary ﬂow data
The basal averaged peak velocity did not differ
between the two groups, but coronary ﬂow reserve
was lower in the seropositive group than in theseronegative group（ 2.51 ± 0.35 vs 2.76 ± 0.43,
p ＜ 0.05 ; Table 3）.
DISCUSSION
The results of the present study indicate that C.
pneumoniae infection might accelerate intimal
hyperplasia after coronary stent implantation. We

also found that C. pneumoniae infection might alter
coronary microvascular function, as reﬂected by
impaired coronary ﬂow reserve.
Restenosis after coronary stent implantation is aserious complication due to its effect on secondary
coronary morbidity. Despite considerable efforts,
the results of various pharmacologic and interventional approaches to prevent restenosis after stentimplantation have been unsatisfactory1,2）. In thepresent study, C. pneumoniae infection was found
not to be a risk factor for restenosis or indicator fortarget lesion revascularization, although the incidence of intimal hyperplasia represented by lateloss was signiﬁcantly greater in seropositive than inseronegative patients. The most likely reason for
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Chlamydia and Coronary Microcirculation

315

Table 3 Coronary flow data
Seropositive group（n＝47）

Seronegative group（n＝26）

Baseline APV（cm/sec）

16.8±18.7

14.9±16.6

NS

Coronary flow reserve2.51±0.35

2.76±0.43＜0.05

p value

Values are mean±SD.
APV＝averaged peak velocity. Other abbreviations as in Table 1.

this discrepancy is that the angiographic differencesin the minimum luminal diameter and late loss
between the two groups were so small. As a result,
the restenosis rate and target lesion revascularization rate were not reﬂected by the minor luminalchanges.
Preliminary studies have examined the relationship between C. pneumoniae infection and restenosis after coronary intervention, but the results arecontroversial6,7）. C. pneumoniae was been detected
in tissue specimens obtained from coronary atherosclerotic vascular lesions by coronary atherectomy
and was implicated as a contributing pathogenic
factor4）. C. pneumoniae was detected in a larger
number of specimens obtained from restenotic tissue than from primary lesions14）. However, the difference did not reach statistical signiﬁcance. Recent
in vitro studies have indicated that C. pneumoniae
can infect and reproduce in human endothelial
cells, smooth muscle cells, and macrophages15）.
Based on these studies, C. pneumoniae infection
may affect the intimal hyperplasia that occurs after
stent implantation.
The present study indicated that C. pneumoniae
infection might impair coronary microvascularfunction. Coronary ﬂow reserve was signiﬁcantly
lower in seropositive patients than in seronegative
patients. The baseline coronary ﬂow velocity was
equivalent in the two groups, so the mechanism
responsible for the impairment of coronary ﬂow
reserve in C. pneumoniae seropositive patientsmight involve restricted diastolic function at thecoronary microvascular level. Serologic evidence
for C. pneumoniae infection precedes both thedevelopment of early and advanced atherosclerotic
lesions16）, suggesting that C. pneumoniae infection
might have an atherogenic effect on both the coronary conduit vessels and on the microvascular vessels. Based on these factors, C. pneumoniae
seropositive patients might have a lower ischemic
threshold than seronegative patients with coronary
artery disease. Ongoing trials of pharmacologic
J Cardiol 2001 Dec; 38（6）: 311– 317

therapy will determine whether anti-chlamydial
antibiotics such as azithromycin can prevent theacceleration of atherosclerosis associated with C.
pneumoniae infection17）. In the near future, these
antibiotics may reduce intimal hyperplasia after
stent implantation and coronary microvascular dysfunction.
There are a few limitations to the present study.
First, the study population was so small that therestenosis rate and target lesion revascularization
rate could not be shown to be statistically different.
Second, this study did not include a control group,
so our results only permit comparisons between
patients with or without demonstrated C. pneumoniae infection and with coronary artery disease. We
could not determine the exact time when patientswere infected with C. pneumoniae, so it is impossible to demonstrate that C. pneumoniae infection
induced coronary atherosclerosis. To solve these
problems, we must include patients with C. pneumoniae seropositive or seronegative but withoutcoronary artery disease. Third, only C. pneumoniae
IgG titers were measured in the present study, but
we must examine other parameters, including C.
pneumoniae IgA, IgM, and C. pneumoniae DNA in
the future18−20）. Fourth, intravascular ultrasonography is a more speciﬁc diagnostic method to evaluate intimal hyperplasia than coronary angiography.
However, intravascular ultrasonography was not
used in the follow-up examination of coronary vessels, so a further study is necessary to acquire moreaccurate data on the intimal hyperplasia after stentimplantation.
CONCLUSIONS
Our data indicate that C. pneumoniae infection
affects coronary artery intimal hyperplasia andimpairs coronary microvascular function. These
results may support the beneﬁcial effect of antimicrobial therapy for the treatment of coronary arterydisease.

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Tanaka, Matsushita, Oka et al

要約

狭心症患者における冠動脈ステント留置後の冠血流予備能と内膜増殖に及ぼす Chlamydia pneumoniae 感染の影響
田中

茂博
定

目

松下匡史郎
利 勝

吉良

岡

由紀子

有二

的 : 冠動脈の動脈硬化病変組織に Chlamydia pneumoniae（C. pneumoniae）が病理学的に証明されて以来，C. pneumoniae 感染が冠動脈硬化の一因との説がある．しかしながら，C. pneumoniae 先行感染が冠動脈ステント留置後の内膜増殖反応，再狭窄率，さらに冠末梢動脈における微小循環に与える影響についての報告はない．そこで，C. pneumoniae 感染の冠動脈ステント留置後の内膜増殖および冠血流予備能からみた冠末梢循環に与える影響について検討した．
方

法: 待期的に経皮的冠動脈形成術を施行し，ステントを留置した 1 枝病変の労作性狭心症 73例を対象とし，採血上 C. pneumoniae 抗体陽性症例および抗体陰性の 2 群に分類した．両群において Doppler ﬂow wire を用い，非狭窄冠動脈枝の冠血流予備能を，また 6 ヵ月後のステント留置部位の冠動脈造影所見をそれぞれ比較検討した．
結果 : 非狭窄冠動脈枝の冠血流予備能は抗体陰性群に比べて，抗体陽性群で有意に低値であった（2.51 ± 0.35 vs 2.76 ± 0.43，p ＜ 0.05）．抗体陰性群に比べて，抗体陽性群では治療 6 ヵ月後のス
テント留置部の最小血管径は有意に小さく（1.52 ± 0.59 vs 1.91 ± 0.79 mm, p ＜ 0.05），晩期損失径は有意に大きかった（1.17 ± 0.55 vs 0.76 ± 0.67 mm，p ＜ 0.05）．しかしながら，両群間で再狭窄率，
再血行再建術施行率に差は認められなかった．
結語 : C. pneumoniae の先行感染は冠末梢動脈の拡張機能障害作用を惹起し，ステント留置後の内膜増殖反応を促進させる．

J Cardiol 2001 Dec; 38（6）: 311−317

References
1）Serruys PW, de Jaegere P, Kimeneij F, Macaya C, Rutsch
W, Heyndrickx G, Emanuelsson H, Marco J, Lagrand V,
Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ : A
comparison of balloon-expandable-stent implantation withballoon angioplasty in patients with coronary artery disease. N Engl J Med 1994 ; 331 : 489−495
2）Fishman DL, Leon MB, Baim DS, Schatz RA, Savage MP,
Penn IM, Detre K, Veltri L, Ricci D, Nobuyoshi M,
Cleman M, Heuser R, Almond D, Teistein PS, Fish RD,
Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld J,
Bailey S, Ellis S, Rake R, Goldberg S : A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med
1994 ; 331 : 496−501
3）Epstein SE, Speir E, Unger EF, Guzman RJ, Finkel T : The
basis of molecular strategies for treating coronary restenosis after angioplasty. J Am Coll Cardiol 1994 ; 23: 1278−
12884）Muhlestein JB, Hammond EH, Carlquist JF, Radicke E,
Thomson MJ, Karagounis LA, Woods ML, Anderson JL :Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic
versus other forms of cardiovascular disease. J Am Coll
Cardiol 1996 ; 27: 1555−1561
5）Maass M, Bartels C, Engel PM, Mamat U, Sievers HH :Endovascular presence of viable Chlamydia pneumoniae is
a common phenomenon in coronary artery disease. J Am
Coll Cardiol 1998 ; 31: 827−832
6）Carlsson J, Miketic S, Mueller KH, Brom J, Ross R, vonEssen R, Tebbe U : Previous cytomegalovirus or
Chlamydia pneumoniae infection and risk of restenosis
after percutaneous transluminal coronary angioplasty.
Lancet 1997 ; 350: 12257）Zhou YF, Csako G, Grayston JT, Wang SP, Yu ZX, Shou
M, Leon M, Epstein SE : Lack of association of restenosis
following coronary angioplasty with elevated C-reactive
protein levels or seropositivity to Chlamydia pneumoniae.
Am J Cardiol 1999 ; 84: 595−5988）Kirkeeide RL, Gould KL, Parsel L : Assessment of coronary stenoses by myocardial perfusion imaging during
pharmacologic coronary vasodilation : Ⅶ. Varidation ofcoronary ﬂow reserve as a single integrated functional measure of stenosis severity reﬂecting all its geometric dimensions. J Am Coll Cardiol 1986 ; 7: 103−1139）Klocke FJ : Measurements of coronary ﬂow reserve :Deﬁning pathophysiology versus making decisions about
patient care. Circulation 1987 ; 76: 1183−118910）Nahser PJ Jr, Brown RE, Oskarsson H, Winniford MD,
Rossen JD : Maximal coronary ﬂow reserve and metabolic
coronary vasodilation in patients with diabetes mellitus.
Circulation 1995 ; 91: 635−640
11）Palombo C, Kozakova M, Magagna A, Bigalli G, Morizzo

J Cardiol 2001 Dec; 38（6）: 311 – 317

Chlamydia and Coronary Microcirculation

C, Ghiadoni L, Virdis A, Emdin M, Taddei S, L Abbate A,
Salvetti A : Early impairment of coronary ﬂow reserve andincrease in minimum coronary resistance in borderline
hypertensive patients. J Hypertens 2000 ; 18: 453−459
12）Egashira K, Hirooka Y, Kai H, Sugimachi M, Suzuki S,
Inou T, Takeshita A : Reduction in serum cholesterol withpravastatin improves endothelium-dependent coronary
vasomotion in patients with hypercholesterolemia.
Circulation 1994 ; 89: 2519−252413）Jeremias A, Filardo SD, Whitbourn RJ, Kernoff RS, Yeung
AC, Fitzerald PJ, Yock PG : Effects of intravenous andintracoronary adenosine 5 ′-triphosphate as compared withadenosine on coronary ﬂow and pressure dynamics.
Circulation 2000 ; 101: 318−323
14）Campbell LA, O Brien ER, Cappuccio AL, Kuo CC, Wang
SP, Stewart D, Patton DL, Cummings PK, Grayston JT :Detection of Chlamydia pneumoniae TWAR in humancoronary atherectomy tissues. J Infect Dis 1995 ; 172 :585−58815）Gaydos CA, Summersgill JT, Shaney NN, Ramirez JA,
Quinn TC : Replication of Chlamydia pneumoniae in vitro
in human macrophages, endothelial cells, and aortic arterysmooth muscle cells. Infect Immun 1996 ; 64: 1614−162016）Davidson M, Kuo CC, Middaugh JP, Campbell LA, Wang
SP, Newman WP Ⅲ, Finley JC, Grayston JT : Conﬁrmed
previous infection with Chlamydia pneumoniae（TWAR）
and its presence in early coronary atherosclerosis.

J Cardiol 2001 Dec; 38（6）: 311– 317

317

Circulation 1998 ; 98: 628−63317）Anderson JL, Muhlestein JB, Carlquist J, Allen A, Trehan
S, Nielson C, Hall S, Brady J, Egger M, Horne B, Lim T :Randomized secondary prevention trial of azithromycin inpatients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection : Theazithromycin in Coronary Artery Disease : Elimination of
Myocardial Infection with Chlamydia（ACADEMIC）study.
Circulation 1999 ; 99: 1540−154718）Choussat R, Montalescot G, Collet JP, Jardel C, Ankri A,
Fillet AM, Thomas D, Raymond J, Bastard JP, Drobinski
G, Orﬁlia J, Agut H, Thomas D : Effect of prior exposure
to Chlamydia pneumoniae, Helicobactor pylori, or
cytomegalovirus on the degree of inﬂammation and oneyear prognosis of patients with unstable angina pectoris or
non-Q-wave acute myocardial infarction. Am J Cardiol
2000 ; 86: 379−384
19）Wong YK, Dawkins KD, Ward ME : Circulating
Chlamydia pneumoniae DNA as a predictor of coronary
artery disease. J Am Coll Cardiol 1999 ; 34: 1435−143920）Thomas M, Wong Y, Thomas D, Ajaz M, Tsang V,
Gallagher PJ, Ward ME : Relation between direct detectionof Chlamydia pneumoniae DNA in human coronary arteries at postmortem examination and histological severity（stary grading）of associated atherosclerotic plaque.
Circulation 1999 ; 99: 2733−2736