Abstract

Aims

Inflammation, endothelial cell function and the coagulation system have been demonstrated to be involved in the onset and course of unstable angina. Whether a proinflammatory state independently determines outcome is unknown and has not been determined yet in a clinically well defined study population of consecutive patients admitted with unstable angina.

Methods and Results

Markers of inflammation, coagulation activation and endothelial cell function were determined on admission in blood of 211 consecutive patients with severe unstable angina and were related to the in-hospital course. Refractory unstable angina occurred in 76 patients (36%) during their hospital stay. In a univariate analysis, C-reactive protein (P=0·03), fibrinogen (P<0·001) and erythrocyte sedimentation rate (P=0·001) levels were significantly higher in patients with refractory unstable angina, when compared with patients who had an uneventful clinical course. The odds ratios (95% CI) adjusted for age, sex, body mass index, smoking behaviour and cholesterol levels of the occurrence of refractory unstable angina for patients in the highest quartile compared with patients in the lowest quartile of inflammatory markers were 2·19 (0·94–5·11) for C-reactive protein, 2·83 (1·13–7·10) for fibrinogen and 4·72 (1·70–13·09) for the erythrocyte sedimentation rate. The findings were not affected by the presence or absence of myocardial necrosis or the interval between onset of angina and blood collection. No association was found between markers of coagulation activation or markers of endothelial cell function, and in-hospital outcome.

Conclusion

We found that in a clinically well-defined study population of patients with severe unstable angina, a proinflammatory state is an important and independent determinant of short-term outcome. The data strengthen the importance of inflammation in this syndrome.

f1
Correspondence: P. W. H. M. Verheggen, MD, Dept. of Cardiology, Eemland Hospital, P.O. Box 1502, 3800 BM Amersfoort, The Netherlands.

References

1
Fuster
V
, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes: Part 1 and 2.
N Engl J Med
 .
1992
;
326
:
242
–50,
2
Chesebro
JH
, Fuster V. Thrombosis in unstable angina.
N Engl J Med
 .
1992
;
327
:
192
–194
3
Maseri
A
. Ischemic heart disease. New York: Churchill Livingstone; 1995.
4
Muhlestein
JB
, Hammond EH, Carlquist JF. 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
Saikku
P
. Chlamydia pneumoniae.
Eur Heart J
 .
1993
;
14
:
62
–65
6
Linnanmaki
E
, Leinonen M, Matilla K, Nieminen MS, Viltonen V, Saikku P. Chlamydia pneumoniae.
Circulation
 .
1993
;
87
:
1130
–1134
7
van der Wal
AC
, Becker AE, van de Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterised by an inflammatory process irrespective of the dominant plaque morphology.
Circulation
 .
1994
;
89
:
36
–44
8
Sato
T
, Takebayashi S, Kohchi K. Increased subendothelial infiltration of the coronary arteries with monocytes/macrophages in patients with unstable angina: Histological data on 14 autopsied patients.
Atherosclerosis
 .
1987
;
68
:
191
–197
9
Kohchi
K
, Takebayashi S, Hiroki T, Nobuyoshi M. Significance of adventitial inflammation of the coronary artery in patients with unstable angina: results at autopsy.
Circulation
 .
1985
;
71
:
709
–716
10
Neri Serneri
GG
, Abbate R, Gori AM. A transient intermittent lymphocyte activation is responsible for the unstability of angina.
Circulation
 .
1992
;
86
:
790
–797
11
Mazzone
A
, de Servi B, Ricevuti G. Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease.
Circulation
 .
1993
;
88
:
358
–363
12
Moreno
PR
, Falk E, Palacios IF, Nervell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes: implication for plaque rupture.
Circulation
 .
1994
;
90
:
775
–778
13
Moreno
PR
, Bernardi VH, Lopez-Cuellar J. Macrophages, smooth muscle cells, and tissue factor in unstable angina.
Circulation
 .
1996
;
94
:
3090
–3097
14
Neri Serneri
GG
, Prisco D, Martini F. Acute T-cell activation is detectable in unstable angina.
Circulation
 .
1997
;
95
:
1806
–1812
15
Merlini
PA
, Bauer KA, Oltrona L. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction.
Circulation
 .
1994
;
90
:
61
–68
16
Ardissino
D
, Merlini PA, Gamba G. Thrombin activity and early outcome in unstable angina pectoris.
Circulation
 .
1996
;
93
:
1634
–1639
17
Ardissino
D
, Gamba MG, Merlini PA. Fibrinopeptide A excretion in urine: a marker of the cumulative thrombin activity in stable versus unstable angina patients.
Am J Cardiol
 .
1991
;
68
:
58B
–63B
18
Jude
B
, Agraou B, McFadden EP. Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.
Circulation
 .
1994
;
90
:
1662
–1668
19
Meade
TW
. Fibrinogen in ischemic heart disease.
Eur Heart J
 .
1995
;
16
:
31
–35
20
Berk
BC
, Weintraub WS, Alexander RW. Elevation of C-reactive Protein in ‘active’ coronary artery disease.
Am J Cardiol
 .
1990
;
65
:
168
–172
21
Liuzzo
G
, Biasucci LM, Gallimore JR. The prognostic value of C-Reactive Protein and Serum Amyloid A Protein in severe unstable angina.
N Engl J Med
 .
1994
;
331
:
417
–424
22
Biasucci
LM
, Vitelli A, Liuzzo G. Elevated levels of interleukin-6 in unstable angina.
Circulation
 .
1996
;
94
:
874
–877
23
Becker
RC
, Cannon CP, Bovill EG. Prognostic value of plasma fibrinogen concentration in patients with unstable angina and non-Q-wave myocardial infarction.
Am J Cardiol
 .
1996
;
78
:
142
–147
24
Toss
H
, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease.
Circulation
 .
1997
;
96
:
4204
–4210
25
Bottiger
L
, Carlson LA. Risk factors for ischemic vascular death for men in the Stockholm Prospective study.
Atherosclerosis
 .
1980
;
36
:
389
–408
26
Gillum
RF
, Mussolino ME, Makuc DM. Erythrocyte sedimentation rate and coronary heart disease: the NHANES I epidemiologic follow-up study.
J Clin Epidemiol
 .
1995
;
48
:
353
–361
27
Thompson
SG
, Kienast J, Pyke SDM, Haverkate F, van de Loo J. Hemostatics factors and the risk of myocardial infarction or sudden death in patients with angina pectoris.
N Engl J Med
 .
1995
;
332
:
635
–641
28
Kuller
LH
, Tracey RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study.
Am J Epidemiol
 .
1996
;
144
:
537
–547
29
Haverkate
F
, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina.
Lancet
 .
1997
;
349
:
462
–466
30
Ridker
PM
, Cushman M, Stampfer MJ, Tracey RP, Hennekens CH. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men.
N Engl J Med
 .
1997
;
336
:
973
–979
31
Oltrona
L
, Ardissino D, Merlini P, Spinola A, Chiodo F, Pezzano A. C-reactive protein elevation and early outcome in patients with unstable angina pectoris.
Am J Cardiol
 .
1997
;
80
:
1002
–1006
32
Von Clauss
A
. Rapid physiological coagulation method in determination of fibrinogen.
Acta Haematol
 .
1957
;
17
:
237
–246
33
Astrup
T
, Brakman P, Nissen U. The estimation of fibrinogen. A revision.
Scan J Clin Invest
 .
1965
;
17
:
57
–65
34
Verheijen
JH
, Chang GTG, Kluft C. Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma.
Thromb Haemost
 .
1984
;
51
:
392
–395
35
Donelly
R
, Hillis WS. Cardiac troponin T.
Lancet
 .
1993
;
341
:
410
–411
36
Ikeda
U
, Ohkawa F, Seino Y. Serum interleukin-6 levels become elevated in acute myocardial infarction.
J Mol Cell Cardiol
 .
1992
;
24
:
579
–584
37
Miyao
Y
, Yasue H, Ogawa H. Elevated plasma interleukin-6 levels in patients with acute myocardial infarction.
Am Heart J
 .
1993
;
126
:
1299
–1304
38
Panniteri
G
, Marino B, Campa PP, Martucci R, Testa U, Peschle C. Interleukin 6 and 8 as mediators of acute phase response in acute myocardial infarction.
Am J Cardiol
 .
1997
;
80
:
622
–625
39
Neumann
F-J
, Ott I, Gawaz M. Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.
Circulation
 .
1995
;
92
:
748
–755
40
Ross
R
. The pathogenesis of atherosclerosis: a perspective for the 1990s.
Nature
 .
1993
;
362
:
801
–809
41
Cermak
J
, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to induce tissue factor.
Blood
 .
1993
;
82
:
513
–520
42
Pepys
MB
, Rowe IF, Baltz ML. C-reactive protein: binding to lipids and lipoproteins.
Int Rev Exp Pathol
 .
1985
;
27
:
83
–111
43
Volanakis
JE
. Complement activation by C-reactive protein complexes.
Ann N Y Acad Sci
 .
1982
;
389
:
235
–250

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