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Enhanced Inflammatory Response to Coronary Angioplasty in Patients With Severe Unstable Angina
From the Istituto di Cardiologia, Universitá Cattolica, Roma, Italy (G.L., A.B., L.M.B., G.C., A.G.R., F.C., A.M.); Immunological Medicine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK (J.R.G., M.B.P.); and Istituto di Ricerche di Biologia Molecolare, P. Angeletti, Pomezia, Italy (A.V., S.A., G.C.).
Correspondence to Giovanna Liuzzo, MD, Istituto di Cardiologia, Universitá Cattolica del Sacro Cuore Largo A. Gemelli, 8-00168 Rome, Italy.
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background—Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B).
Methods and Results—Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001).
Conclusions—Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.
Key Words: angina • angioplasty • plaque • interleukins
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In patients with severe unstable angina, elevated plasma levels of C-reactive protein (CRP) and serum amyloid A protein (SAA) are associated with an unfavorable short-term prognosis.1 The acute-phase response observed in unstable angina patients may be a primary component of instability because it is not due to myocardial cell necrosis, because it is unrelated to elevation of troponin T1 ; to ischemia, because it is normal in patients with severe variant angina2 ; or to activation of the hemostatic system, because it does not increase after its activation.3 The levels may remain elevated for months after waning of symptoms.4
A long-term predictive value of elevated CRP levels was found in patients with documented coronary artery disease and angina5 6 and in individuals with multiple risk factors.7 Moreover, in the Physicians' Health Study, among low-risk individuals, CRP levels within the normal range were linearly related to the incidence of myocardial infarction over a follow-up period of 8 years.8
The mechanisms that relate the level of acute-phase proteins to short- and long-term prognoses in acute coronary syndromes are unclear. The aim of this study was to investigate whether "active" coronary plaque disruption could explain the systemically detectable inflammatory response in unstable angina. Therefore, we measured plasma concentration of CRP and SAA and serum concentration of interleukin-6 (IL-6) in patients with stable and unstable angina undergoing single-vessel PTCA. As control, we also studied patients with stable and unstable angina undergoing diagnostic coronary angiography.
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Methods |
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The study was designed as a prospective study; thus, all study conditions and inclusion and exclusion criteria were established before patient recruitment began.
Patients
In protocol A, 2 groups of patients were prospectively
studied.
Group 1 consisted of 30 of 68 consecutive patients with stable angina lasting >6 months who underwent elective single-vessel PTCA in our institute between July 1993 and July 1995.
Group 2 consisted of 56 of 116 consecutive patients admitted to our Critical Care Unit between July 1993 and July 1995 with severe unstable angina (Braunwald IIIB) who underwent single-vessel coronary angioplasty. Twenty-five patients underwent urgent PTCA because of refractory unstable angina (ie, angina refractory to full medical therapy, including intravenous heparin); the remaining 31 patients underwent elective PTCA >48 hours after waning of symptoms (range, 3 to 10 days).
Exclusion criteria for both groups were prior PTCA or bypass surgery (10 patients in group 1 and 9 in group 2), left ventricular ejection fraction <30% (6 patients in group 1 and 2 in group 2), left bundle-branch block (4 patients in group 1 and 4 in group 2), and inflammatory conditions likely to be associated with an acute-phase response (12 patients in group 1 and 7 in group 2). Furthermore, in group 2, 6 patients were excluded because they had suffered an acute myocardial infarction within the previous 4 weeks, 15 were excluded because they had elevated serum levels of creatine kinase and/or troponin T (>0.1 µg/L) on admission, and 8 patients initially included in the study were excluded because they had acute complications after PTCA. Finally, 6 patients in group 1 and 9 in group 2 initially included in the study were excluded because they had abnormal levels (>0.1 µg/L) of troponin T after PTCA.
In protocol B, to better assess the role of plaque disruption in inducing a systemically detectable inflammatory response, we studied patients with stable and unstable angina undergoing diagnostic coronary angiography because the stimuli elicited by coronary angiography are the closest to PTCA, except for plaque rupture and the brief episodes of ischemia induced by balloon inflation. Therefore, the time course of CRP, SAA, and IL-6 was assessed in 12 patients with stable angina (group 3) and in 15 patients with unstable angina (group 4) undergoing a diagnostic coronary angiography in the same period. Patients in groups 3 and 4 fulfilled the inclusion criteria of groups 1 and 2, respectively.
The protocols were approved by the Ethics Committee of the Catholic University of Rome; all patients gave informed consent.
Study Design
Blood Sampling
Venous blood samples were taken immediately before PTCA
and 6, 24, 48, and 72 hours after the end of the procedure (protocol A)
and before and 6, 24, and 48 hours after diagnostic
coronary angiography (protocol B). Coded plasma and serum
samples were stored at -70°C and analyzed for CRP, SAA, and
IL-6 in a single batch at the end of the study; all categorization and
management of patients were independent of these results. In addition,
troponin T, a specific marker of myocardial necrosis, was measured in
venous blood samples taken immediately before PTCA and coronary
angiography and 6 and 24 hours after the end of the procedures to rule
out the possible role of myocardial cell damage in inducing the
inflammatory response.
Diagnostic Coronary Angiography
Coronary angiography was performed with the standard
technique in all patients. After medication with diazepam and local
anesthesia, a femoral artery sheath was placed by a
single-wall entry technique.
Percutaneous Transluminal Coronary
Angioplasty
Routine PTCA was performed with monorail balloon catheters in
all patients. Procedural variables, symptoms, and ECG changes
during PTCA were carefully recorded (Table 1
).
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Laboratory Assays
CRP and SAA were assayed as previously
described1 ; 90% of normal CRP values are <0.3
mg/dL and 99% are <1.0 mg/dL. CRP levels begin to rise 6 hours after
an acute stimulus and peak after 24 to 48 hours. Eighty-two percent of
normal SAA values are <0.5 mg/dL and 96% are <1.0 mg/dL. Circulating
concentrations of SAA can reach peak value within 24 to 48 hours of an
acute stimulus.
IL-6 was measured with a commercial assay kit (Quantikine human IL-6 R&D system). The range of values detected by the assay is 3 to 300 pg/mL. IL-6 levels begin to rise 45 to 60 minutes after endotoxin injection in healthy volunteers and peak after 2 to 4 hours.9 IL-6 levels were undetectable (ie, <3 pg/mL) in healthy volunteers in our laboratory.
Troponin T was measured with a commercial enzyme immunoassay kit (Boehringer Mannheim).
Statistical Analysis
Because CRP, SAA, and IL-6 values do not follow a normal
distribution, comparisons between groups were carried out with the
Mann-Whitney or Kruskal-Wallis test as appropriate. Comparisons within
groups were carried out with the Friedman test; for a value of
P<0.05, pairwise comparisons were carried out with the
Wilcoxon test with Bonferroni's correction. Correlations were
determined with the Spearman rank correlation test. The remaining
continuous variables were compared by use of t tests for
paired and unpaired variables as appropriate. Proportions were
compared by a 
2 test. CRP, SAA, and IL-6
values are expressed as medians and ranges; the remaining variables
are expressed as mean±SD. Values of P<0.05 (2 tailed) were
considered statistically significant.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Thirty patients with stable angina (group 1) and 56 with unstable angina (group 2) completed protocol A. The 56 unstable angina patients were divided according to acute-phase protein and IL-6 levels before PTCA into group 2A, which comprised patients with acute-phase protein and IL-6 levels within the normal ranges, and group 2B, which included patients with raised levels.
Twelve patients with stable angina (group 3) and 15 patients with unstable angina (group 4) completed protocol B.
Demographic and clinical data, angiographic findings, and procedural
variables were similar among the 3 groups of patients studied in
protocol A (Table 1
). Clinical characteristics and angiographic
findings of patients who underwent diagnostic uncomplicated
coronary angiography (protocol B) are summarized in Table 2.
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Inflammatory Response to PTCA (Protocol A)
Stable Angina
Before PTCA, plasma concentrations of CRP and/or SAA were
elevated (>0.3 and >0.5 mg/dL, respectively) in 4 of 30 patients
(13%). After PTCA, the median levels of CRP and SAA did not change
(P=0.09 and P=0.88, respectively) (Table 3 and Figure 1). Baseline IL-6 levels were detectable
only in 3 of 30 patients (10%); all 3 had elevated levels of CRP and 2
had elevated levels of SAA. In response to PTCA, IL-6 median levels in
group 1 did not change (P=0.58) (Table 3).
|
|
) (group 1), unstable angina
patients with normal levels of acute-phase proteins before PTCA (
)
(group 2A), and unstable angina patients with high levels of
acute-phase proteins before PTCA (
) (group 2B) are indicated. Median
values of CRP and SAA significantly increased in group 2B, reaching
peak values at 24 and 48 hours, respectively, but not in groups 1 and
2A.
Unstable Angina
Before PTCA, CRP and SAA plasma concentrations were within normal
limits in 16 of 56 patients (29%, group 2A). CRP was elevated in 40
patients (71%; group 2B); in 35 of these patients, SAA was also
elevated. Baseline IL-6 levels were detectable in only 1 of the 16
group 2A patients and in 30 of the 40 group 2B patients.
After PTCA, the median levels of CRP, SAA, and IL-6 did not
change in group 2A (Table 3 and Figure 1). Conversely, in the 40
patients with raised levels before PTCA (group 2B), the serum
concentration level of IL-6 increased significantly 6 hours after the
end of the procedure from the baseline value of 2.8 to 6.5 pg/mL
(P=0.002) and reached the peak value at 24 hours (9 pg/mL,
P<0.001 versus baseline) (Table 3 and Figure 2). CRP and SAA also increased, with a
peak value at 24 hours for CRP (from 0.90 to 2.26 mg/dL,
P<0.001) and at 48 hours for SAA (from 1.20 to
4.20 mg/dL, P<0.001) (Table 3 and Figures 1 and 2). There
was a significant correlation between the peak values of IL-6 and those
of CRP and SAA (r=0.70, P<0.001 for CRP and
r=0.64, P=0.006 for SAA).
|
), SAA
(
), and serum levels of IL-6 (
Inflammatory Response to Coronary Angiography
(Protocol B)
Stable Angina
Before coronary angiography, CRP and SAA plasma
concentrations were normal in all 12 patients, and IL-6 was elevated in
4 and normal in 8 of the 12 patients. CRP and SAA did not change after
the procedure, and IL-6 showed only a slight but not significant
increase (Table 4 and Figure 3).
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Unstable Angina
Before coronary angiography, CRP plasma concentrations
were elevated in 13 of 15 patients; in 12 of these, SAA and IL-6 were
also elevated. After coronary angiography, CRP, SAA, and IL-6
increased from 0.46 to 1.86 mg/dL, from 0.40 to 1.53 mg/dL, and from
4.5 to 8.4 pg/mL at 24 hours, respectively (all P<0.05)
(Table 4 and Figure 3).
Correlation Between Baseline and Peak Levels of CRP and SAA After
PTCA and Coronary Angiography
In the overall population of 86 patients, there was a significant,
close correlation between the baseline levels of CRP and SAA and the
respective increases after PTCA (r=0.86 and
r=0.63, respectively; all P<0.001) (Figure 4). The baseline and peak levels of CRP
and SAA also were linearly correlated in the overall group of 27
patients who underwent uncomplicated coronary angiography
(protocol B) (r=0.78 and r=0.76, respectively;
all P<0.001) (Figure 5).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Our findings show that the trauma of PTCA is followed by an increase in IL-6 levels only in those unstable angina patients with detectable levels of this cytokine before the procedures and that the increase in IL-6 is followed by a marked increase in CRP and SAA. This acute-phase reaction cannot be attributed simply to the disruption of particularly "active" coronary plaques because it was also observed in the absence of PTCA after the trauma of cardiac catheterization and coronary angiography, which, although small and by itself insufficient to stimulate an acute-phase response in patients with stable angina, is sufficient to do so in patients with unstable angina with elevated baseline levels of CRP. These findings, together with the linear correlation between baseline and postprocedural peak CRP and SAA levels, suggest that the magnitude of the acute-phase response is determined to a greater extent by the individual responsiveness than by the type of provocative stimuli.
IL-6 and Acute-Phase Response in Unstable Angina
CRP and SAA (half-lives of 
19 hours) represent more
practical clinical markers of inflammation than IL-6, the major
determinant of their production,10 11 12
because of its much shorter half-life (4
hours).13 IL-6 is a multifunctional
cytokine regulating humoral and cellular immune responses, thus
playing a central role in inflammation, host defense mechanisms against
infection, and tissue injury.10 11 12 IL-6
synthesis is increased in response to a variety of stimuli, including
viruses and bacterial endotoxin,9 through the
production of IL-1,14
interferon-
,15 and tumor necrosis
factor,14 15 which may also act on several cell
types in human atherosclerotic lesions in which the IL-6 gene was found
to be transcribed.16 IL-6 stimulates smooth
muscle cell proliferation17 and has procoagulant
properties.13 18 19 Raised blood levels of IL-6
are common in patients with unstable angina and are positively
correlated with in-hospital prognosis.20
Our findings of a significant positive correlation between the peak value of IL-6 and those of CRP and SAA after PTCA support the hypothesis that in vivo IL-6 also is the major inducer of acute-phase protein production as previously shown in human hepatoma cell cultures,11 although they do not rigorously prove it.
Mechanisms of Acute-Phase Response After PTCA and Coronary
Angiography
Patients exhibiting a large increase in IL-6, CRP, and SAA
after PTCA may have more "active" lesions. For example, their
lesions may contain more oxidized LDL (which can trigger acute-phase
protein production directly),21 more
virus-infected cells (expected to activate mononuclear cells
and enhance cytokine production), and/or more
inflammatory infiltrates containing activated lymphocytes and
monocyte/macrophages,22 23 which could be
also responsible for their elevated baseline levels. However, this
hypothesis cannot explain the acute-phase response after
diagnostic coronary angiography.
The CRP, SAA, and IL-6 "responders" after both PTCA and coronary angiography may be more sensitive than the other patients to even small inflammatory stimuli, and their hyperresponsiveness may be indicated by their elevated baseline levels. A genetically determined variability of response was reported for cytokine production by human monocytes after endotoxin stimulation in vitro24 and for inflammatory responses to oxidized lipoproteins in inbred mouse strains.21 Finally, monocytes and granulocytes of patients with elevated levels of CRP and IL-6 may produce more cytokines and reactive oxygen species in response to subliminal stimuli.25 26 27 The hypothesis of an enhanced individual acute-phase responsiveness is suggested by 2 observations. First, the significant increase in acute-phase proteins observed after uncomplicated coronary angiography cannot be attributed to plaque disruption. Second, there is a positive correlation between baseline and peak values of acute-phase reactants after PTCA and uncomplicated angiography.
This interpretation is consistent with our recent observation that monocytes of unstable patients are hyperresponsive to lipopolysaccharide (LPS) challenge in vitro.28
On the basis of this study, we cannot postulate the nature of the inflammatory stimuli acting during diagnostic coronary angiography. We also cannot exclude that groin puncture, although performed under strict sterile conditions, might introduce traces of LPS in the circulation and that LPS might be responsible for "in vivo hyperreaction" during angiography. However, delivery of LPS cannot occur only in unstable patients with high levels of CRP but if present must be a common phenomenon; thus, this observation is in line with our hypothesis that unstable angina patients with high levels of CRP might be hyperresponsive to proinflammatory stimuli.
If this hypothesis is confirmed, the acute-phase hyperresponsiveness may help to explain the marked elevation of acute-phase proteins observed in patients with persistent severe unstable angina associated with unfavorable in-hospital outcome.1 It might also explain the long-term prognostic value of elevated CRP levels in patients with known ischemic heart disease5 6 and in apparently healthy subjects.7 8 Thus, individuals with high acute-phase responses to low-grade stimulation by chronic infection, oxidized LDL, or other reactions may be at increased risk of acute thrombotic complications.29
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Acknowledgments |
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This study was supported by the National Research Council, targeted project Prevention and Control Disease Factors, Rome, Italy (research grant 94.00518.PF41); by the European Community (Biomed 2 research grant PL951505); and by the Associazione Ricerche Coronariche, Rome, Italy.
Received May 29, 1998; revision received August 4, 1998; accepted August 13, 1998.
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K. Toutouzas, A. Colombo, and C. Stefanadis Inflammation and restenosis after percutaneous coronary interventions Eur. Heart J., October 1, 2004; 25(19): 1679 - 1687. [Abstract] [Full Text] [PDF]
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J.P. Ottervanger, P. Armstrong, E.S. Barnathan, E. Boersma, J.S. Cooper, E.M. Ohman, S. James, L. Wallentin, M.L. Simoons, and For the GUSTO IV-ACS Investigators Association of revascularisation with low mortality in non-ST elevation acute coronary syndrome, a report from GUSTO IV-ACS Eur. Heart J., September 1, 2004; 25(17): 1494 - 1501. [Abstract] [Full Text] [PDF]
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J.-J. Li, C.-H. Fang, H. Jiang, C.-X. Hunag, Q.-Z. Tang, X.-H. Wang, and G.-S. Li Increased C-Reactive Protein Level After Renal Stent Implantation in Patients with Atherosclerotic Renal Stenosis Angiology, September 1, 2004; 55(5): 479 - 484. [Abstract] [PDF]
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S. Z.H. Rittersma, R. J. de Winter, K. T. Koch, C. E. Schotborgh, M. Bax, G. S. Heyde, J. P. van Straalen, K. J. Mulder, J. G.P. Tijssen, G. T. Sanders, et al. Preprocedural C-Reactive Protein Is Not Associated with Angiographic Restenosis or Target Lesion Revascularization after Coronary Artery Stent Placement Clin. Chem., September 1, 2004; 50(9): 1589 - 1596. [Abstract] [Full Text] [PDF]
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C. Kluft Identifying patients at risk of coronary vascular disease: the potential role of inflammatory markers Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C21 - C27. [Abstract] [Full Text] [PDF]
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M. Schillinger, M. Exner, E. Minar, W. Mlekusch, M. Mullner, C. Mannhalter, F. H. Bach, and O. Wagner Heme oxygenase-1 genotype and restenosis after balloon angioplasty: a novel vascular protective factor J. Am. Coll. Cardiol., March 17, 2004; 43(6): 950 - 957. [Abstract] [Full Text] [PDF]
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M. Schillinger, W. Mlekusch, R. M. Wolfram, A. C. Budinsky, M. Exner, H. Rumpold, O. Wagner, B. Pokrajac, R. Potter, and E. Minar Endovascular Brachytherapy: Effect on Acute Inflammatory Response after Percutaneous Femoropopliteal Arterial Interventions Radiology, February 1, 2004; 230(2): 556 - 560. [Abstract] [Full Text] [PDF]
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C. B. Granger, K. W. Mahaffey, W. D. Weaver, P. Theroux, J. S. Hochman, T. G. Filloon, S. Rollins, T. G. Todaro, J. C. Nicolau, W. Ruzyllo, et al. Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) Trial Circulation, September 9, 2003; 108(10): 1184 - 1190. [Abstract] [Full Text] [PDF]
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S. Kobayashi, N. Inoue, Y. Ohashi, M. Terashima, K. Matsui, T. Mori, H. Fujita, K. Awano, K. Kobayashi, H. Azumi, et al. Interaction of Oxidative Stress and Inflammatory Response in Coronary Plaque Instability: Important Role of C-Reactive Protein Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1398 - 1404. [Abstract] [Full Text] [PDF]
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J. S. Hochman Cardiogenic Shock Complicating Acute Myocardial Infarction: Expanding the Paradigm Circulation, June 24, 2003; 107(24): 2998 - 3002. [Full Text] [PDF]
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G. J. Blake and P. M. Ridker C-reactive protein and other inflammatory risk markers in acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 37S - 42S. [Abstract] [Full Text] [PDF]
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T Lenderink, E Boersma, C Heeschen, A Vahanian, M.-J de Boer, V Umans, M.J.B.M van den Brand, C.W Hamm, M.L Simoons, and for the CAPTURE investigators Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA Eur. Heart J., January 1, 2003; 24(1): 77 - 85. [Abstract] [Full Text] [PDF]
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T. P. Smith Atherosclerosis and Restenosis: An Inflammatory Issue Radiology, October 1, 2002; 225(1): 10 - 12. [Full Text] [PDF]
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M. Schillinger, M. Exner, W. Mlekusch, H. Rumpold, R. Ahmadi, S. Sabeti, M. Haumer, O. Wagner, and E. Minar Vascular Inflammation and Percutaneous Transluminal Angioplasty of the Femoropopliteal Artery: Association with Restenosis Radiology, October 1, 2002; 225(1): 21 - 26. [Abstract] [Full Text] [PDF]
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M. E. Korkmaz, E. Tayfun, H. Muderrisoglu, A. Yildirir, B. Ozin, M. Ulucam, and M. Turan Carbon Coating of Stents Has No Effect on Inflammatory Response to Primary Stent Deployment Angiology, September 1, 2002; 53(5): 563 - 568. [Abstract] [PDF]
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M. R. Cusack, M. S. Marber, P. D. Lambiase, C. A. Bucknall, and S. R. Redwood Systemic inflammation in unstable angina is the result of myocardial necrosis J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1917 - 1923. [Abstract] [Full Text] [PDF]
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E. Ronner, E. Boersma, G.-J. Laarman, G. A. Somsen, R. A. Harrington, J. W. Deckers, E. J. Topol, R. M. Califf, and M. L. Simoons Early angioplasty in acute coronary syndromes without persistent st-segment elevation improves outcome but increases the need for six-month repeat revascularization: An analysis of the pursuit trial J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1924 - 1929. [Abstract] [Full Text] [PDF]
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G.J. Blake and P.M. Ridker C-reactive protein and prognosis after percutaneous coronary intervention Eur. Heart J., June 2, 2002; 23(12): 923 - 925. [Full Text] [PDF]
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C. Kluft Is C-reactive protein an additional, surrogate end-point for statin treatment? Eur. Heart J., May 2, 2002; 23(10): 761 - 764. [Full Text] [PDF]
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A. Maseri and D. Cianflone Inflammation in acute coronary syndromes Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B8 - B13. [Abstract] [PDF]
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D. H. Walter, S. Fichtlscherer, M. B. Britten, P. Rosin, W. Auch-Schwelk, V. Schachinger, and A. M. Zeiher Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation J. Am. Coll. Cardiol., December 1, 2001; 38(7): 2006 - 2012. [Abstract] [Full Text] [PDF]
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T. Tokunou, T. Ichiki, K. Takeda, Y. Funakoshi, N. Iino, H. Shimokawa, K. Egashira, and A. Takeshita Thrombin Induces Interleukin-6 Expression Through the cAMP Response Element in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., November 1, 2001; 21(11): 1759 - 1763. [Abstract] [Full Text] [PDF]
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C. Monaco, F. Crea, G. Niccoli, F. Summaria, D. Cianflone, R. Bordone, G. Bellomo, and A. Maseri Autoantibodies against oxidized low density lipoproteins in patients with stable angina, unstable angina or peripheral vascular disease; pathophysiological implications Eur. Heart J., September 1, 2001; 22(17): 1572 - 1577. [Abstract] [PDF]
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D. P. Chew, D. L. Bhatt, M. A. Robbins, M. S. Penn, J. P. Schneider, M. S. Lauer, E. J. Topol, and S. G. Ellis Incremental Prognostic Value of Elevated Baseline C-Reactive Protein Among Established Markers of Risk in Percutaneous Coronary Intervention Circulation, August 28, 2001; 104(9): 992 - 997. [Abstract] [Full Text] [PDF]
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A. M. Lincoff, D. J. Kereiakes, M. A. Mascelli, L. I. Deckelbaum, E. S. Barnathan, K. K. Patel, B. Frederick, M. T. Nakada, and E. J. Topol Abciximab Suppresses the Rise in Levels of Circulating Inflammatory Markers After Percutaneous Coronary Revascularization Circulation, July 10, 2001; 104(2): 163 - 167. [Abstract] [Full Text] [PDF]
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G. Liuzzo, D. J. Angiolillo, A. Buffon, V. Rizzello, C. Colizzi, F. Ginnetti, L. M. Biasucci, and A. Maseri Enhanced Response of Blood Monocytes to In Vitro Lipopolysaccharide-Challenge in Patients With Recurrent Unstable Angina Circulation, May 8, 2001; 103(18): 2236 - 2241. [Abstract] [Full Text] [PDF]
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D. H. Walter, S. Fichtlscherer, M. Sellwig, W. Auch-Schwelk, V. Schachinger, and A. M. Zeiher Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation J. Am. Coll. Cardiol., March 1, 2001; 37(3): 839 - 846. [Abstract] [Full Text] [PDF]
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J. Figueras, Y. Monasterio, R. M. Lidon, E. Nieto, and J. Soler-Soler Thrombin formation and fibrinolytic activity in patients with acute myocardial infarction or unstable angina: in-hospital course and relationship with recurrent angina at rest J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2036 - 2043. [Abstract] [Full Text] [PDF]
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G. Y. H. Lip and A. D. Blann Thrombogenesis and fibrinolysis in acute coronary syndromes: Important facets of a prothrombotic or hypercoagulable state? J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2044 - 2046. [Full Text] [PDF]
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L.M. Biasucci C-reactive protein and dangerous liaisons Eur. Heart J., October 1, 2000; 21(19): 1560 - 1562. [PDF]
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G. Caligiuri, G. Paulsson, A. Nicoletti, A. Maseri, and G. K. Hansson Evidence for Antigen-Driven T-Cell Response in Unstable Angina Circulation, September 5, 2000; 102(10): 1114 - 1119. [Abstract] [Full Text] [PDF]
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W. Wijns and F. Ribichini CRP: does it stand for C oronary R estenosis P rediction? Eur. Heart J., July 2, 2000; 21(14): 1121 - 1123. [PDF]
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M. Gottsauner-Wolf, G. Zasmeta, S. Hornykewycz, M. Nikfardjam, E. Stepan, P. Wexberg, G. Zorn, D. Glogar, P. Probst, G. Maurer, et al. Plasma levels of C-reactive protein after coronary stent implantation Eur. Heart J., July 2, 2000; 21(14): 1152 - 1158. [Abstract] [PDF]
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Y Hojo, U Ikeda, T Katsuki, O Mizuno, H Fukazawa, K Kurosaki, H Fujikawa, and K Shimada Interleukin 6 expression in coronary circulation after coronary angioplasty as a risk factor for restenosis Heart, July 1, 2000; 84(1): 83 - 87. [Abstract] [Full Text] [PDF]
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T. SUZUKI, S. ISHIWATA, K. HASEGAWA, K. YAMAMOTO, and T. YAMAZAKI Raised interleukin 6 concentrations as a predictor of postangioplasty restenosis Heart, May 1, 2000; 83(5): 578 - 578. [Full Text]
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P. M. Ridker, N. Rifai, M. J. Stampfer, and C. H. Hennekens Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men Circulation, April 18, 2000; 101(15): 1767 - 1772. [Abstract] [Full Text] [PDF]
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G. Liuzzo, L. M. Biasucci, J. R. Gallimore, G. Caligiuri, A. Buffon, A. G. Rebuzzi, M. B. Pepys, and A. Maseri Enhanced inflammatory response in patients with preinfarction unstable angina J. Am. Coll. Cardiol., November 15, 1999; 34(6): 1696 - 1703. [Abstract] [Full Text] [PDF]
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K. Simon, E. Ory, and T. Bohm Enhanced Inflammatory Response to Coronary Angioplasty in Patients With Severe Unstable Angina Circulation, November 9, 1999; 100 (19): e95 - e95. [Full Text] [PDF]
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U. Ikeda, Y. Hojo, T. Katsuki, and K. Shimada Enhanced Inflammatory Response to Coronary Angioplasty in Patients With Severe Unstable Angina Circulation, November 9, 1999; 100 (19): e96 - e96. [Full Text] [PDF]
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A. Blum Inflammatory Response in Unstable Angina Circulation, November 9, 1999; 100 (19): e97 - e97. [Full Text] [PDF]
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H. Rus and F. Niculescu Inflammatory Response in Unstable Angina Circulation, November 9, 1999; 100 (19): e98 - e98. [Full Text] [PDF]
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N. Rifai, R. Joubran, H. Yu, M. Asmi, and M. Jouma Inflammatory Markers in Men with Angiographically Documented Coronary Heart Disease Clin. Chem., November 1, 1999; 45(11): 1967 - 1973. [Abstract] [Full Text] [PDF]
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