(Circulation. 1999;100:1958-1963.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Independent Prognostic Value of Elevated C-Reactive Protein in Unstable Angina
From Servicio de Cardiología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Correspondence to Oscar Bazzino, MD, FACC, Servicio de Cardiología, Hospital Italiano, Gascón 450, Buenos Aires (1181), Argentina. E-mail obazzino{at}hitalba.edu.ar
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—There is growing evidence of the prognostic importance of C-reactive protein (CRP) in unstable angina. However, the independent value of CRP relative to other conventional markers at different stages of treatment has not been established. Therefore, we assessed the in-hospital and 90-day prognostic values of serum CRP in unstable angina. We also compared the relation of CRP at admission and discharge with 90-day outcome.
Methods and Results—One hundred ninety-four consecutive patients were included in a derivation (n=105) and a validation set (n=89). Serum CRP was measured at admission, at 48 hours, and at hospital discharge. A cutoff point of 1.5 mg/dL for CRP provided optimum sensitivity and specificity for adverse outcome, based on the receiver operator curves. No association was found between CRP on admission and in-hospital outcome. CRP at admission, adjusted for age, ECG findings on admission, silent ischemia, left ventricular wall motion score, and high-risk clinical presentation, was related to the combined end point of refractory angina, myocardial infarction, or death at 90 days (hazard ratio [HR] 1.9, 95% CI 1.2 to 8.3, P=0.002). CRP at hospital discharge was the strongest independent marker of an adverse outcome (HR 3.16, 95% CI 2.0 to 5.2, P=0.0001). These results were confirmed in the validation set (CRP at discharge: HR 3.3, 95% CI 2.0 to 7.69, P=0.0001).
Conclusions—In unstable angina, CRP is a strong independent marker of increased 90-day risk. Compared with CRP at admission, CRP at discharge is better related to later outcome and could be of great utility for risk stratification.
Key Words: angina • prognosis • proteins
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The appearance of a thrombus superimposed on the erosion or fissure of an atherosclerotic plaque is the mechanism involved in the sudden development of acute ischemic syndromes.1 2 3 4 According to a newly developed concept, the presence of inflammation at the site of the atherosclerotic lesion might play an important role in the natural history of endothelial injury. This possibility is supported by histological and hematologic evidence.5 6 7 8 9 There is also increased concentration of acute-phase serum reactants such as C-reactive protein (CRP) in patients with unstable angina.10
Selection of a therapeutic strategy for patients with unstable angina may be difficult because of the heterogeneous prognosis of this clinical syndrome.11 12 13 According to recently published data, many patients admitted with unstable angina and elevated CRP levels have an adverse outcome in the hospital and during the subsequent months.14 15 16 However, there is no information regarding the independent value of this finding or about the meaning of CRP determinations carried out at different times during the in-hospital evolution.
The aim of this study was to analyze the relation between CRP values measured at admission and discharge and the in-hospital and 90-day outcomes and to compare it with other conventional risk markers such as clinical variables, left ventricular function, or the presence of silent ischemia after admission.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
We included 194 consecutive patients admitted to the coronary care unit for ischemic chest pain at rest during the 24 hours before admission. Candidates for thrombolysis and those showing abnormal elevation of total serum creatine kinase-MB (CK-MB) on admission or during the first 24 hours were excluded. We also excluded patients with left bundle-branch block or Braunwald type A angina, (angina pectoris subsequent to a precipitating extracardiac cause) or patients with concomitant inflammatory diseases, cancer, or other significant heart diseases. The study was approved by the ethics committee of the Hospital Italiano de Buenos Aires, and all patients gave written informed consent to participate.
Study Design
In this prospective study, 105 patients were included in a
derivation set. All results were subsequently validated prospectively
in a different group of patients (validation set, n=89). Complete
clinical data and blood samples for laboratory measurements were
collected at admission. Serum CK-MB level and a baseline ECG were
obtained at entry and repeated at 6, 12, and 24 hours and every 24
hours thereafter. A 24-hour Holter monitoring was carried out
immediately on admission. A 2D echocardiogram was performed within the
initial 24 hours. Serum CRP levels were measured on admission, at 48
hours, and at hospital discharge. CRP measurements, Holter tracings,
and 2D echocardiogram tape recordings were analyzed by
staff members who were not involved in patient care. Test results were
not available to the attending physicians.
All patients were followed up for 90 days after admission or until the occurrence of a major event.
Definitions and End Points
The primary end point was the combination of death of any cause,
acute myocardial infarction, and/or refractory angina during the 90
days after hospital admission. The definition of refractory angina
during initial or subsequent hospitalizations was based on the
appearance of ischemic chest pain at rest associated with
ST-segment alterations in patients treated with
nitroglycerin, aspirin, ß-blockers, and
intravenous heparin.
Acute myocardial infarction was diagnosed in the presence of chest pain lasting >20 minutes, characteristic ECG alterations, and plasma CK-MB elevation greater than twice the normal or previous elevated value. All end points were validated by a designated committee that was unaware of the CRP results.
Determination of CRP
Blood samples were stored in evacuated tubes at -20°C to be
processed within 24 hours by automated microparticle immunoassay
(ELISA). The CRP detection range corresponds to values of 0.1 to 12.0
mg/dL, with an interassay variation coefficient of <5% (normal values
<0.3 mg/dL). Measurements were calibrated according to the 85/506
World Health Organization international reference standard.
Holter Recordings
Modulated frequency recorders (range 0.05 to 40 Hz)
were used for this test, according to American Heart Association
standards. The recordings were read by 2 independent
experienced investigators who were unaware of the clinical data. An
ischemic episode was defined as a horizontal or downsloping
ST-segment depression, 
1 mm from baseline and at 0.08 seconds
from the J point, lasting 1 minute. A 2-minute interval or greater
was required for the diagnosis of a new ischemic episode.
Tracings were recorded at a speed of 25 mm/s, and for each
patient the following parameters were assessed with the
Delmar Avionics Dynamic Electrocardioscanner Trendsetter Unit: presence
or absence of silent ischemia, total number of episodes, and
total duration of ischemia (in minutes).
2D Echocardiograms
A 2D echocardiogram was performed on admission to the
coronary care unit (median time elapsed since the beginning of
pain 12 hours, range 0 to 24 hours). For the analysis of left
ventricular function and wall motion abnormalities, we used
the segmentation model accepted by the American Society of
Echocardiography,17 which divides the
left ventricle into 16 segments and establishes a regional wall motion
score for each segment according to the following grading system: 1,
normal; 2, hypokinesis; 3, akinesis; and 4, dyskinesis. An acute wall
motion alteration was defined by the presence of a score >1 in at
least 1 segment. Left ventricular wall motion index (LVWMI)
was calculated according to the formula LVWMI=
wall motion scores of
the 16 segments/total number of visualized segments.
Studies were recorded in all conventional ultrasonic windows and independently reviewed by 2 experienced investigators who examined the records without knowledge of the patient’s clinical information. Echocardiograms were performed with Toshiba 870 equipment and a 2.5-MHz transducer, and the images were digitized with TomTec Imaging Systems version 5.14 equipment and software.
Statistical Analysis
The degree of univariate association between each
clinical or laboratory datum and the main end point was examined by use
of the 
2 test (2-tailed) with Yates’
correction and Fisher’s exact test when appropriate. The Kaplan-Meier
technique (log-rank test) was applied to survival analysis. To
establish a cutoff point between low and high levels, deciles of CRP
values of the derivation set and the corresponding rates of the primary
combined end point at 90 days were related via a receiver operator
characteristic (ROC) curve. This procedure was repeated with the use of
the values obtained at admission, 48 hours, and discharge. The CRP
value showing the maximum likelihood ratio in the curve with the larger
area was established as the cutoff point between normal and elevated
CRP. This cutoff point was prospectively tested in the validation
set.
Cox proportional hazard analysis was used to evaluate the independent contribution of CRP levels to the risk of new events. Univariate predictors of potential significance and CRP values were included for a forward stepwise selection. Selected variables were age (cutoff point 65 years), the presence of ST-segment depression on admission ECG, the presence of silent ischemia in the 24-hour Holter recording, LVWM score (cutoff point 1.5), and the finding of high-risk characteristics at admission (according to National Heart, Lung, and Blood Institute [NHLBI] classification). Two models (considering the CRP values on admission and at discharge separately) were tested. In the latter model, patients who had an in-hospital end point or who were submitted to a revascularization procedure before discharge were excluded.
Spearman’s correlation coefficients were calculated to explore the
relation between the variables selected for the model. Candidate
markers were tested with the likelihood ratio
2 test. A prognostic score was calculated for
each patient as the sum of the weights assigned to the variables in
the multivariate analysis. The overall
predictive ability of the final model was assessed with the area under
the ROC curve in both sets, and its sensitivity and specificity to
predict 90 day-outcome were calculated. To define the incremental value
of elevated CRP when added in a stepwise fashion to a statistical model
that contained the clinical variables without the CRP values, we
created a prognostic model by using all clinical, ECG, Holter, and 2D
echocardiographic variables and determined the area
under the ROC curve. Subsequently, we added the CRP data to this model
and redetermined the ROC curve to determine whether this improved the
ROC area of the previous model. The procedure was also performed in
reverse order and repeated in the validation set. The statistical
significance of the difference between both ROC curves (derivation and
validation) was determined.
Statistical analysis was performed with the SPSS system 7.5 (Statistical Package for the Social Sciences) and the ROC analyzer program version 6.0.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Derivation Set
Baseline Characteristics
The CRP values (median and 25% to 75% interquartile ranges) on admission, at 48 hours, and at hospital discharge were 0.50 (0.20 to 1.9), 0.70 (0.28 to 3.75), and 0.90 (0.30 to 4.1) mg/dL, respectively (normal range <0.3 mg/dL).
The levels of CRP changed significantly between admission and
discharge. Among 30 patients with CRP levels >0.3 mg/dL on admission,
values remained elevated until discharge in 12 and dropped to normal in
18 patients. In the group of 75 patients with normal CRP on admission,
CRP levels persisted below 0.3 mg/dL in 45 but were abnormally elevated
at discharge in the remaining 30 patients (Figure 1
).
|
The area of the ROC curves relating CRP levels to 90-day outcome, at
baseline, 48 hours, and discharge were 0.70±0.069, 0.82±0.058, and
0.84±0.054, respectively. The highest likelihood ratio corresponded to
a value of 1.5 mg/dL in the discharge CRP ROC curve (likelihood ratio
5.6, 95% CI 2.3 to 12.1). Baseline characteristics of patients
according to CRP levels at admission (above or below 1.5 mg/dL) are
compared in Table 1. In patients
with elevated CRP, a greater prevalence of prior hypertension (90%
versus 67.7%, P=0.015) and a lower prevalence of smoking
(26.7 versus 57.3% P=0.005) were noted.
|
There were no differences regarding in-hospital treatment, for example,
use of intravenous nitroglycerin, oral
aspirin, or intravenous heparin, or in the use of
coronary angiography and revascularization
procedures up to 90 days between patients with CRP levels at admission
above or below 1.5 mg/dL (Table 1
).
Correlation With In-Hospital and 90-Day Events
Univariate Analysis
Univariate markers of worse in-hospital evolution were
the presence of ST-segment depression on admission ECG, detection of
silent ischemia, and high-risk presentation (NHLBI
class) (Table 2). There was no
significant association between CRP level on admission or the LVWM
score and the rate of in-hospital events. Median values and 25% to
75% interquartile ranges of CRP were 0.75 (0.3 to 0.6) and 0.4 (0.2 to
0.9), respectively (P=NS, Wilcoxon rank sum test).
The occurrence of refractory angina, myocardial infarction, or death at
90-day follow-up was related to CRP level at admission (34.7 versus
73.3%, OR 5.18, 95% CI 2.02 to 13.2, P<0.001) and
discharge (15.1% versus 78.8%, OR 20.89, 95% CI 6.8 to 64.2,
P<0.001) (Table 3).
Kaplan-Meier survival curves of patients with CRP at discharge above
and below 1.5 mg/dL are shown in Figure 2. The 90-day prognosis was also related
to the high-risk category of the NHLBI classification and the presence
of silent ischemia in the Holter recording (Table 2).
|
|
|
Multivariate Analysis
Independent markers of in-hospital events were the finding of
silent ischemia (hazard ratio [HR] 1.69, 95% CI 1.01 to
2.89, P=0.041) and the presence of ST-segment depression on
baseline ECG (HR 1.62, 95% CI 0,96 to 2.74, P=0.07).
CRP level at hospital discharge showed the strongest independent
association with the combined end point of refractory angina,
myocardial infarction, or death at 90 days (HR 3.16, 95% CI 2.0 to
5.2, P<0.001), followed by the presence of silent
ischemia during the first 24 hours of the Holter
recording (HR 1.39, 95% CI 1.02 to 2.84, P=0.026)
(Table 4).
|
Incremental Value of CRP
The area of the ROC curve of the prognostic model increased from
0.68±0.06 to 0.79±0.05 (P=0.047) when CRP values were
added to the model including clinical, ECG, Holter, and 2D
echocardiographic variables. When repeated in
reverse order, the addition of the clinical model to the CRP data did
not significantly improve the ROC area (0.84±0.05 and 0.83±0.05,
P=NS).
Validation Set
Table 1 describes the baseline characteristics of the
derivation and validation sets. Median and 25th to 75th percentile
baseline CRP values were similar in both sets (0.60, 0.30 to 0.90
versus 0.50, 0.20 to 0.90, P=NS). In the ROC curve of the
validation set, a CRP value of 1.5 mg/dL at discharge was also
associated with the best likelihood ratio of major events at 90
days.
Although there was no statistically significant association, a trend was noted between CRP levels >1.5 mg/dL on admission and in-hospital prognosis (refractory angina, acute myocardial infarction, or death 50% versus 21%, P=0.12). A CRP value >1.5 mg/dL at admission was significantly associated with a worse 90-day outcome (100% versus 44.6%, P<0.01).
A strong relation was observed between CRP >1.5 mg/dL at discharge and 90-day outcome (95.2% versus 8.3%, P<0.001), similar to that shown in the derivation set. In the validation set, CRP at discharge remained the strongest independent prognostic marker of 90-day outcome (HR 3.3, 95% CI 2.0 to 7.69, P<0.001).
Incremental Value of CRP
The addition of CRP data to the non-CRP model significantly
increased the area of the ROC curve from 0.78±0.06 to 0.97±0.02
(P=0.0097). Conversely, no significant differences in the
ROC areas were observed when the non-CRP model was added to the CRP
values.
The overall predictive performance of the multivariate model elaborated with the CRP value at discharge was also confirmed (area of ROC curves for the derivation and validation sets 0.79±0.05 and 0.97±0.02, respectively; P=0.0007).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Our data indicate that patients with unstable angina who have serum CRP levels >1.5 mg/dL have a significantly worse outcome. Another important finding of this study is that CRP adds independent prognostic information to that provided by the clinical, ECG, Holter, and 2D-echocardiographic variables. We also demonstrate that compared with CRP at admission, CRP at discharge has the strongest association with 90-day evolution in a multivariate model.
Several prior studies have reported elevated CRP values in patients with unstable coronary artery disease.14 15 However, variations in CRP levels during in-hospital treatment were not previously analyzed in detail. According to our data, 2 distinctive patterns have a different prognostic message can be described: a benign pattern, consisting of either persistently normal or decreasing values from admission through discharge, and an adverse pattern, represented by those patients with persistently elevated or increasing values from admission to discharge. These variations in CRP levels cannot be explained by different in-hospital treatment because the use of anti-ischemic and antithrombotic medications was similar in patients with CRP levels above and below 1.5 mg/dL. Persistently elevated or "crescendo" patterns may represent either an ongoing inflammatory process or, in some cases, the presence of subtle myocardial necrosis. All our patients had normal serial CK-MB values; however, the latter possibility may not be excluded because of the lack of troponin measurements.
Although all CRP determinations were significantly associated with 90-day outcome, those performed at discharge showed a better relation with prognosis. Our data indicate that the persistence of elevated CRP despite intense hospital treatment and waning of symptoms could be a strong marker of persistent plaque instability and increased subsequent risk.
There are no good gold standards for risk stratification of unstable angina after the completion of in-hospital treatment.18 19 20 Although the exploration of coronary reserve is routinely used for this purpose, we must remember that the presence of an unstable plaque without an underlying fixed component capable of significantly reducing coronary reserve may also explain the development of ischemic complications after discharge in many cases.19 20 These data emphasize the importance of methods that demonstrate the presence of persistently active plaques in patients who are clinically stable.
A problem of circular reasoning may arise when findings are used both as prognostic and diagnostic criteria. This is a well-known limitation of the prognostic information provided by stress tests. In contrast, this limitation is absent in the present study, because the treatment of all patients was pursued without any knowledge regarding CRP values.
Comparison With Other Studies of Unstable Angina
Liuzzo and coworkers14 found a higher incidence of
ischemic episodes in patients with elevated CRP; however, in
contrast to the results of our study, theirs did not demonstrate a
relation with other clinically important end points such as myocardial
infarction or death. Another difference from the previous observation
by Liuzzo and coworkers is that the present study did not show a
relation between CRP on admission and in-hospital outcome. Morrow and
colleagues,21 using a cutoff point of 1.5 mg/dL, observed
that an elevated CRP level at admission was associated with a higher
mortality rate at 14 days, but they did not include data about the
relation of CRP with in-hospital prognosis. Haverkate and
colleagues22 reached similar conclusions. Conversely, in
the study by Montalescot and coworkers,23 CRP level at
entry was not associated with 14-day outcome. These differences can be
attributed to the use of different cutoff points and inclusion
criteria, but they also may be explained by the smaller sample size of
all these studies.
Study Limitations
A limitation of this study is the lack of troponin determinations.
Morrow and coworkers21 reported that the probability of a
positive troponin T assay increased with rising concentrations of CRP,
and in their study, the combination of troponin T and CRP was found to
have additive prognostic value. In addition, as previously discussed,
the role of myocardial necrosis in CRP elevation cannot be fully
analyzed without troponin T measurements.
Conclusions
Elevation of CRP is common in unstable angina and probably
indicates the presence of evolving inflammation at the coronary
plaque or myocardial necrosis. In patients who have overcome the acute
phase and are clinically stabilized, the finding of elevated CRP levels
at hospital discharge suggests persistent instability of the disrupted
plaque and is strongly related to the occurrence of subsequent
ischemic complications. Conversely, a low CRP level after
in-hospital treatment could be an indicator of quiescence of the
injured plaque. This information may be very useful for the selection
of patients who are potential candidates for more aggressive
therapy.
|
Acknowledgments |
|---|
We thank the medical residents, nurses, and laboratory staff of the coronary care unit of the Hospital Italiano for their collaborations in this trial and Dr Marcus Flather for his careful revision of the manuscript.
Received May 20, 1999; revision received July 7, 1999; accepted July 13, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Constantinides P. Plaque fissures in human
coronary thrombosis. J Atheroscler Res. 1966;6:1–17.
-
Davies JM, Thomas AC. Thrombosis and acute
coronary artery lesion in sudden cardiac ischemic
death. N Engl J Med. 1984;310:1137–1140.[Abstract]
-
Falk E. Unstable angina with fatal outcome: dynamic
coronary thrombosis leading to infarction and/or sudden death:
autopsy evidence of recurrent mural thrombosis with
peripheral embolization culminating in total vascular
occlusion. Circulation. l985;50:127–134.
-
Fuster V, Badimon L, Badimon JJ, Chesebro JH. The
pathogenesis of coronary artery disease and the acute
coronary syndromes. N Engl J Med. 1992;326:242–250.[Medline]
[Order article via Infotrieve]
-
Van der Wal AC, Becker AE, van der Los CH, Das PK.
Site of intimal rupture or erosion of thrombosed coronary
atherosclerotic plaques is characterized by an inflammatory process
irrespective of the dominant plaque morphology. Circulation. 1994;89:36–44.
[Abstract/Free Full Text]
-
Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V,
Fallon JT. Macrophage infiltration in acute coronary
syndromes: implications for plaque rupture. Circulation. 1994;90:775–778.
[Abstract/Free Full Text]
-
Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A,
Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V. Human
monocyte-derived macrophages induce collagen breakdown in
fibrous caps of atherosclerotic plaques: potential role of
matrix-degrading metalloproteinases and implications for plaque
rupture. Circulation. 1995;92:1565–1569.
-
Mazzone A, De Servi S, Ricevuti G, Mazzucchelli I,
Fossati G, Pasotti F, Specchia G, Notario A. Increased expression of
neutrophil and monocyte adhesion molecules in unstable coronary
artery disease. Circulation. 1993;22:358–363.
-
Biasucci LM, D’Onofrio G, Liuzzo G, Zini G, Caligiuri
G, Monaco C, Rebuzzi AG, Bizzi RB, Maseri A. Intracellular neutrophil
myeloperoxidase is reduced in unstable angina and acute myocardial
infarction, but its reduction is not related to ischemia.
J Am Coll Cardiol. 1996;27:611–616.[Abstract]
-
Berck BC, Weintraub W, Alexander RW. Elevation of C
reactive protein in "active" coronary disease.
Am J Cardiol. 1990;65:168–172.[Medline]
[Order article via Infotrieve]
-
Braunwald E. Unstable angina: a classification.
Circulation.. 1989;80:410–414.
[Free Full Text]
-
US Department of Health and Human Services, Public
Health Service. Unstable Angina: Diagnosis and Management.
Clinical Practice Guidelines, No. 10. Rockville, Md: Agency
for Health Care Policy and Research and National Heart, Lung, and Blood
Institute; 1994.
-
Bazzino O, Tajer C, Paviotti C, Mele E, Trivi M, Piombo
A, Hirshon Prado A, Paolasso E. Clinical predictors of in-hospital
prognosis in unstable angina: ECLA 3. Am Heart J. 1999;137:322–331.[Medline]
[Order article via Infotrieve]
-
Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi
AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and
serum amyloid A protein in severe unstable angina. N Engl
J Med. 1994;331:417–424.
[Abstract/Free Full Text]
-
Toss H, Lindhal 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.
[Abstract/Free Full Text]
-
Ridker PM, Cushmen M, Stampfer MJ, Tracy R, Hennekens
CH. Inflammation, aspirin, and the risk of
cardiovascular disease in apparently healthy men.
N Engl J Med. 1997;336:973–1014.
[Abstract/Free Full Text]
-
American Society of
Echocardiography Committee on Standards,
Subcommittee on Quantitation of Two-Dimensional Echocardiograms.
Recommendations for quantitation of the left ventricle by 2-dimensional
echocardiography. J Am Soc
Echocardiogr. 1989;2:358–367.[Medline]
[Order article via Infotrieve]
-
Coplan NL, Wallach ID. The role of exercise testing for
evaluating patients with unstable angina. Am Heart J. 1992;124:252–256.[Medline]
[Order article via Infotrieve]
-
Moss AJ, Goldstein RE, Jackson Hall W, Bigger T, Fleiss
JL, Greenberg H, Bodenheimer M, Kroner RJ, Marcus FI, Wackers FJ,
Gillespie JA, Gregory JJ, Kleiger R, Lichstein E, Parker JO, Raubertas
RF, Stern S, Tzivoni D, van Voorhees L. Detection and significance of
myocardial ischemia in stable patients after recovery from an
acute coronary event. JAMA. 1993;269:2379–2385.[Abstract]
-
Lauer MS. Noninvasive risk stratification after
myocardial infarction: which test is best? Am Heart J. 1998;136:565–569.[Medline]
[Order article via Infotrieve]
-
Morrow DA, Rifai N, Antman AN, Weiner DL, McCabe CH,
Cannon CP, Braunwald E. C-reactive protein is a potent predictor of
mortality independently or in combination with troponin T in acute
coronary syndromes: a TIMI 11 substudy. J Am Coll
Cardiol. 1998;31:1460–1465.
[Abstract/Free Full Text]
-
Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys
MB. Production of C-reactive protein and risk of
coronary events in stable and unstable angina: European
Concerted Action on Thrombosis and Disabilities Angina Pectoris Study
Group. Lancet. 1997;349:462–466.[Medline]
[Order article via Infotrieve]
-
Montalescot G, Philippe F, Ankri A, for the French
Investigators of the ESSENCE Trial. Early increase of von
Willebrand Factor predicts adverse outcome in unstable
coronary artery disease. Circulation. 1998;98:294–299.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  P. Bogaty, L. Boyer, S. Simard, F. Dauwe, R. Dupuis, B. Verret, T. Huynh, F. Bertrand, G. R. Dagenais, and J. M. Brophy Clinical utility of C-reactive protein measured at admission, hospital discharge, and 1 month later to predict outcome in patients with acute coronary disease. The RISCA (recurrence and inflammation in the acute coronary syndromes) study. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2339 - 2346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Norja, L. Nuutila, P. J Karhunen, and S. Goebeler C-reactive protein in vulnerable coronary plaques J. Clin. Pathol., May 1, 2007; 60(5): 545 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, and R. H. Christenson National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Circulation, April 3, 2007; 115(13): e356 - e375. [Full Text] [PDF]
|
|
|
|
 |
|
 NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, R. H. Christenson, NACB COMMITTEE MEMBERS, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Clin. Chem., April 1, 2007; 53(4): 552 - 574. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ziakas, S. Gavrilidis, G. Giannoglou, E. Souliou, K. Gemitzis, D. Kalampalika, M. A. Vayona, I. Pidonia, G. Parharidis, and G. Louridas In-Hospital and Long-Term Prognostic Value of Fibrinogen, CRP, and IL-6 Levels in Patients with Acute Myocardial Infarction Treated with Thrombolysis Angiology, May 1, 2006; 57(3): 283 - 293. [Abstract] [PDF]
|
|
|
|
|
|
E. J. Armstrong, D. A. Morrow, and M. S. Sabatine Inflammatory Biomarkers in Acute Coronary Syndromes: Part II: Acute-Phase Reactants and Biomarkers of Endothelial Cell Activation Circulation, February 21, 2006; 113(7): e152 - e155. [Full Text] [PDF]
|
|
|
|
|
|
S. De Servi, M. Mariani, G. Mariani, and A. Mazzone C-Reactive Protein Increase in Unstable Coronary Disease: Cause or Effect? J. Am. Coll. Cardiol., October 18, 2005; 46(8): 1496 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Biasucci CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical Use of Inflammatory Markers in Patients With Cardiovascular Diseases: A Background Paper Circulation, December 21, 2004; 110(25): e560 - e567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Milani, C. J. Lavie, and M. R. Mehra Reduction in C-reactive protein through cardiac rehabilitation and exercise training J. Am. Coll. Cardiol., March 17, 2004; 43(6): 1056 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Arroyo-Espliguero, P. Avanzas, J. Cosin-Sales, G. Aldama, C. Pizzi, and J. C. Kaski C-reactive protein elevation and disease activity in patients with coronary artery disease Eur. Heart J., March 1, 2004; 25(5): 401 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P L Sanchez, J L Morinigo, P Pabon, F Martin, I Piedra, I F Palacios, and C Martin-Luengo Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome Heart, March 1, 2004; 90(3): 264 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H C Routledge, J G Ayres, and J N Townend Why cardiologists should be interested in air pollution Heart, December 1, 2003; 89(12): 1383 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 R. Nijmeijer, W. K. Lagrand, Y. T. P. Lubbers, C. A. Visser, C. J. L. M. Meijer, H. W. M. Niessen, and C. E. Hack C-Reactive Protein Activates Complement in Infarcted Human Myocardium Am. J. Pathol., July 1, 2003; 163(1): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Koenig C-reactive protein and cardiovascular risk: an update on what is going on in cardiology Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1039 - 1041. [Full Text] [PDF]
|
|
|
|
|
|
G. G. L. Biondi-Zoccai, A. Abbate, G. Liuzzo, and L. M. Biasucci Atherothrombosis, inflammation, and diabetes J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Oldgren, L Wallentin, L Grip, R Linder, B.L Norgaard, and A Siegbahn Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease Eur. Heart J., January 1, 2003; 24(1): 86 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.R. Ferreiros, R. Kevorkian, J.J. Fuselli, J. Guetta, C.P. Boissonnet, D. di Toro, R. Cragnolino, O. Masoli, A. Cagide, and J. Krauss First national survey on management strategies in non ST-elevation acute ischaemic syndromes in Argentina. Results of the STRATEG-SIA study Eur. Heart J., July 1, 2002; 23(13): 1021 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.J. de Winter, G.S. Heyde, K.T. Koch, J. Fischer, J.P. van Straalen, M. Bax, C.E. Schotborgh, K.J. Mulder, G.T. Sanders, J.J. Piek, et al. The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty Eur. Heart J., June 2, 2002; 23(12): 960 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.F. Riesen, H. Engler, M. Risch, W. Korte, and G. Noseda Short-term effects of atorvastatin on C-reactive protein Eur. Heart J., May 2, 2002; 23(10): 794 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Zebrack, J. B. Muhlestein, B. D. Horne, J. L. Anderson, and Intermountain Heart Collaboration Study Group C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina J. Am. Coll. Cardiol., February 20, 2002; 39(4): 632 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nijmeijer, W. K Lagrand, A. Baidoshvili, Y. T.P Lubbers, W. T. Hermens, C. J.L.M Meijer, C. A Visser, C.E. Hack, and H. W.M Niessen Secretory type II phospholipase A2 binds to ischemic myocardium during myocardial infarction in humans Cardiovasc Res, January 1, 2002; 53(1): 138 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Blackburn, P. Giral, E. Bruckert, J.-M. Andre, S. Gonbert, M. Bernard, M. J. Chapman, and G. Turpin Elevated C-Reactive Protein Constitutes an Independent Predictor of Advanced Carotid Plaques in Dyslipidemic Subjects Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1962 - 1968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.C. Kaski and E.G. Zouridakis Inflammation, infection and acute coronary plaque events Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I10 - I15. [Abstract] [PDF]
|
|
|
|
|
|
V. K BHATIA and D. O HASKARD Markers of inflammation in unstable angina Heart, June 1, 2001; 85(6): 603 - 604. [Full Text]
|
|
|
|
|
|
V. Pasceri, J. Chang, J. T. Willerson, and E. T. H. Yeh Modulation of C-Reactive Protein-Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti-Atherosclerosis Drugs Circulation, May 29, 2001; 103(21): 2531 - 2534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Navab, J. A. Berliner, G. Subbanagounder, S. Hama, A. J. Lusis, L. W. Castellani, S. Reddy, D. Shih, W. Shi, A. D. Watson, et al. HDL and the Inflammatory Response Induced by LDL-Derived Oxidized Phospholipids Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 481 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rifai and P. M. Ridker High-Sensitivity C-Reactive Protein: A Novel and Promising Marker of Coronary Heart Disease Clin. Chem., March 1, 2001; 47(3): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
|