Cardiovascular Research

Cardiovascular Research 1999 42(1):240-245; doi:10.1016/S0008-6363(99)00018-8
© 1999 by European Society of Cardiology

This Article Abstract FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by de Winter, R. J Articles by Sanders, G. T Search for Related Content PubMed PubMed Citation Articles by de Winter, R. J Articles by Sanders, G. T Social Bookmarking          What's this?

Copyright © 1999, European Society of Cardiology

Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non-Q-wave myocardial infarction

Robbert J de Winter^a,*, Radha Bholasingh^a, Jeroen G Lijmer^c, Rudolph W Koster^a, Jozef P.M.C Gorgels^b, Yvonne Schouten^b, Frans J Hoek^b and Gerard T Sanders^b

^aDepartment of Cardiology, Room B2-125, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
^bDepartment of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
^cDepartment of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

r.j.dewinter{at}amc.uva.nl

^* Corresponding author. Tel.: +31-20-5669111; fax: +31-20-6962609

Received 5 November 1998; accepted 15 January 1999

	Abstract

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
Objectives: Elevated concentrations of C-reactive protein (CRP), a non-specific acute phase reactant, and troponin I (TnI), a cardiac-specific marker of myocardial damage, have been found to be associated with a higher risk for cardiac events in patients with an acute coronary syndrome. We evaluated CRP alone and in combination with TnI for predicting the incidence of major cardiac complications within 6 months in patients with unstable angina or non-Q-wave infaction (NQMI). Methods: CRP and TnI was measured on admission in patients with unstable angina or NQMI, but results were kept blinded. Patients were treated according to a conservative management strategy, and the incidence of major cardiac events within 6 months was assessed. Results: An abnormal CRP (>5 mg/l) and an abnormal TnI (>0.4 µg/l) were more frequent in patients that suffered a major cardiac event (CRP: 93 vs. 35%, P<0.0001; TnI: 73 vs. 26%, P<0.001). The incidence of major cardiac events was higher in patients with an abnormal CRP than in patients with a normal CRP, both when TnI was abnormal (42 vs. 4.5%, P=0.003) and when TnI was normal (11 vs. 0%, P=0.014). Mean event-free survival was excellent in patients with both a normal CRP and TnI, whereas survival was poorest in patients with both an abnormal CRP and TnI (121±16 vs. 180 days, P<0.0001). Conclusions: An abnormal CRP on admission in patients with unstable angina or NQMI is associated with increased incidence of major cardiac events within 6 months, both in patients with normal and abnormal TnI. CRP and TnI have independent and additive prognostic value in this patient group, and the combination may be useful for early risk stratification.

KEYWORDS Acute coronary syndromes; Prognosis; C-reactive protein; Troponin I

	1. Introduction

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
Patients with an acute coronary syndrome, either severe unstable angina (UA) or non-Q-wave myocardial infarction (NQMI), have a high risk of suffering a subsequent cardiac events [1–3]. Several studies have shown that in about one third of these patients, an elevated troponin T [4–7] or troponin I (TnI) [8,9], can be found, and these elevations are an indicator of a poor prognosis. Other studies have shown that an increase in circulating concentrations of acute phase reactants such as C-reactive protein (CRP) and interleukin-6 (IL-6) are strong predictors of adverse outcome in patients with an acute coronary syndrome [10–12]. It has been demonstrated that an elevated CRP is not necessarily induced by ischemic injury, as normal CRP levels were measured after an episode of ischemia in patients with variant angina without atherosclerotic coronary artery disease [12]. Moreover, although myocardial necrosis can cause an acute phase reaction by itself, Liuzzo et al. reported an elevation of CRP in UA patients without an abnormal troponin T [10]. Finally, myocardial necrosis was an unlikely cause of a modest elevation of CRP in a large group of patients with stable angina in the ECAT study, although no marker of necrosis was measured [13]. Thus, both CRP and troponin T or I are prognostic indicators in patients with unstable angina and NQMI, and may have independent and additive prognostic value.

The aim of this study was to asses the prognostic value of CRP and troponin I in patients with unstable angina or NQMI for the occurrence of major cardiac events within 6 months.

	2. Methods

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
2.1 Patients
Consecutive patients presenting at the cardiac emergency room of the Academic Medical Center with typical chest pain of <8 h duration were eligible for the study. Patients were included if they had either diagnostic ST-segment depression or T-wave changes characteristic of myocardial ischemia. CK-MB was measured on admission, and at 5, 7 and 10 h after the onset of symptoms and, when CK-MB mass was abnormal, at frequent intervals thereafter. The diagnosis for AMI was established according to the WHO criteria [14], with a peak CK-MB above 14 µg/l (twice the upper limit of normal). Non-Q-wave AMI was considered present when peak CK-MB exceeded 14 µg/l and no new Q-waves developed on the electrocardiogram. Patients with a peak CK-MB above the upper limit of normal (7.0 µg/l), but below the predefined limit for AMI were classified as unstable angina, as were patients without CK-MB elevation.

Patients with ST-elevations on the admission-electrocardiogram that were candidates for reperfusion therapy (either primary PTCA or thrombolytic therapy) were excluded. Patients were also excluded when the evolution of the electrocardiogram showed the development of new left bundle branch block or new Q-waves. Other exclusion criteria were a known or suspected infectious or inflammatory condition and a scheduled revascularization procedure. The protocol was approved by the institutions Medical Ethics Committee and all patients gave informed consent. The investigation conforms with the principles outlined in the Declaration of Helsinki.

2.2 Assays
CRP and TnI were measured from samples drawn on admission, and results were kept blinded from the physicians treating the patients. Blood samples were drawn in vacuum tubes containing lithium heparin, centrifuged, and remaining plasma stored at –70°C for later measurements. Patients were treated with aspirin, heparin i.v., nitrates i.v., β-blockers etc. according to a conservative management strategy as outlined in the TIMI IIb trial [15].

CRP was measured with a nephelometric assay (Behring Diagnostics, Marburg, Germany). The detection limit was 0.2 mg/l, linearity was from 0.2–230 mg/l, and the coefficient of variation (C.V.) was <3% at a concentration of 2 mg/l. The 95th percentile in 120 healthy donors in our institution was established at 5.0 mg/l.

TnI was measured with the fluorometric enzyme immunoassay on the Stratus II (Dade, Miami, FL, USA). The lower detection limit was 0.35 µg/l, linearity was from 0.35 to 50 µg/l, C.V. was 11.7% in the concentration range of 1.4 µg/l. The upper limit of normal as previously established [8] and according to the manufacturer was 0.4 µg/l.

CK-MB was measured with the Immuno-1 (Bayer, Leverkusen, Germany). The upper limit of normal was 7.0 µg/l, C.V. at 5.0 µg/l was 2.5%.

2.3 Follow-up
A 6-month follow-up was assessed by telephone interview, either with the patient, the cardiologist or general practitioner caring for the patient, or the patient’s relatives. Primary outcome was defined as cardiac death, recurrent non-fatal AMI or recurrent hospital admission for severe unstable angina (defined as recurrent unstable angina at rest with diagnostic ST-segment depression or T-wave changes characteristic of myocardial ischemia). Secondary outcome was defined as (the need for) percutaneous transluminal coronary angioplasty or coronary bypass grafting. Patients underwent revascularization only when they did not respond to optimal medical therapy. Physicians caring for the patients during follow-up who were responsible for scheduled revascularization procedures, were unaware of the CRP or TnI results.

2.4 Statistical analysis
CRP and TnI were treated as a dichotomous variable (either elevated or normal) with cut-off value for CRP: 5.0 mg/l and for TnI: 0.4 µg/l. Two-by-two contingency tables for the primary outcome were constructed for CRP > 5.0 mg/l, TnI >0.4 µg/l or both elevated. The prognostic value of CRP and TnI was assessed in a multivariate logistic regression model with the primary outcome as the dependent variable. Models with age, gender, history of hypertension, diabetes mellitus, previous myocardial infarction and ‘aspirin use’ in combination with either an abnormal CRP, an abnormal TnI or both were compared with a log likelihood test. [16,17] To assess event-free survival, Kaplan–Meier curves were constructed both for the primary outcome and for all outcome including revascularizations, and differences in mean survival were compared using the log-rank test. Calculations were done with a statistical software package (SPSS 6.01 for windows, SPSS, USA). All statistical comparisons were two-tailed, and a P value of <0.05 was considered statistically significant.

	3. Results

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
A total of 150 patients were included in the study, 115 patients with unstable angina and 35 patients with non-Q-wave AMI. The patients’ characteristics are summarized in Table 1, comparing patients that reached a primary endpoint with the other patients. Follow-up at six month was 100% complete. There were 15 major cardiac events (10%) and 28 revascularizations (19%), listed in Table 2 One patient died from lung cancer 30 days after admission and this patient was censored at day 30. CRP values ranged from 0.0 to 76.1 mg/l (median 3.35; 25th and 75th percentiles 1.4 and 8.85 mg/l, respectively). An abnormal CRP (>5.0 mg/l) was present in 61 patients (41%), median CRP for the 15 patients with a major cardiac event was 12.5 mg/l (range 3.0–57.1 mg/l), compared to 3.0 mg/l (range 0–76.1 mg/l) for the 135 patients without a major cardiac event. TnI values ranged from 0.0 to 41.4 µg/l (median 0.0 µg/l; 25th and 75th percentiles 0.0 and 0.83 µg/l, respectively). An abnormal TnI (>0.4 µg/l) was present in 44 patients (29%), median TnI for the 15 patients with a major cardiac event was 2.4 µg/l (range 0.0 to 13.4 µg/l) compared to 0.0 µg/l (range 0.0 to 41.3 µg/l) for the 135 patients without a major cardiac event.

View this table: [in this window] [in a new window]   Table 1 Baseline characteristicsa

 

View this table: [in this window] [in a new window]   Table 2 Events during 6 months follow-up in 150 patients with unstable angina or NQMIa

 
Patients with a major cardiac event were older, and more frequently had an elevated CRP or TnI. In addition, patients with a primary event were more often already on aspirin. The incidence of a major cardiac event was significantly higher among patients with CRP >5.0 mg/l than in other patients (23 (13–36%) vs. 1.1 (0–6%), P=0.00001), and this was evident both in patients with an elevated TnI (42 (22–63%) vs. 4.5 (0–23%), P=0.003) and in patients without an elevated TnI (0 vs. 11 (3–25%), P=0.014) (Fig. 1). The multivariate logistic regression model with age, gender, history of infarction, hypertension, aspirin use and diabetes significantly improved when either an abnormal CRP or an abnormal TnI or both were included in the model (–2 log LR for CRP and TnI: 11.915 and 10.060 respectively, P<0.001), demonstrating the additive prognostic value of both markers. A multivariate model including both markers showed improved performance in comparison with models with a single marker (P<0.001), demonstrating their independent predictive value.

View larger version (18K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 Incidence of major cardiac complications by normal or abnormal CRP concentration in all patients and in those with a normal and abnormal TnI concentration. Primary outcome was defined as cardiac death, non-fatal acute myocardial infarction or admission for recurrent unstable angina. Statistical comparison was made by 2 test of Fisher exact test.

 
Table 3 shows the event rate and mean event free survival for patients having both CRP and TnI elevated, either CRP or TnI elevated or no CRP or TnI elevation. Primary outcome was significantly more frequent in patients having both CRP/TnI elevated (10/24) than patient having either (5/58) or none elevated (0/68) (both vs. either: P<0.0001; both vs. none: P<0.0001; either vs. none: P=0.015). Kaplan–Meier survival analysis showed that mean event-free survival for the primary outcome was significantly lower in patients having both CRP/TnI elevated versus patients with either CRP/TnI elevated or no elevations (Fig. 2a, P<0.0001 and P=0.0226, respectively). Incidence of the combined endpoint cardiac death, non-fatal AMI, recurrent severe unstable angina and the need for revascularizations was no longer statistically significantly different (Table 3). However, mean event free survival was still significantly different between both CRP and TnI elevated vs. no elevations and between either elevated vs. no elevations (Table 3, Fig. 2b P=0.0015).

View this table: [in this window] [in a new window]   Table 3 Number of events and event free survival in patients with no CRP or TnI elevations, either CRP or TnI elevated or both CRP and TnI elevateda

 

View larger version (20K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 2 (a) Kaplan–Meier survival curves for 150 patients with unstable angina or non-Q-wave infarction during a follow-up of 6 months. Patient groups were defined as having both an abnormal CRP (>5.0 mg/l) and an abnormal TnI (>0.4 µg/l), either an abnormal CRP or TnI, or both CRP and TnI normal. Major cardiac events were defined as cardiac death, recurrent non-fatal acute myocardial infarction or recurrent admission for severe unstable angina. Differences in survival were compared with the Log rank test (Table 3). Mean event-free survival for the primary outcome was significantly lower in patients having both CRP/TnI elevated versus patients with either CRP/TnI elevated or no elevations (P<0.0001 and P=0.0226 respectively). (b) Kaplan–Meier survival curves for 150 patients with unstable angina or non-Q-wave infarction during a follow-up of 6 months. Event free survival was assessed for all outcome including (the need for) revascularization, i.e. either PTCA or CABG. Differences in survival were compared with the Log rank test (Table 3). Mean event free survival was significantly different between patients with both CRP and TnI elevated versus no elevations and between either elevated versus no elevations (P=0.0015). There was no significant difference between patients with either CRP/TnI elevated versus no CRP/TnI elevations (P=0.379).

 

	4. Discussion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
The present study confirms earlier studies, showing that both CRP, a non-specific acute phase reactant, and TnI, a cardiac specific marker of myocardial damage, are elevated early in a substantial number of patients with unstable angina and non-Q-wave AMI. It shows that CRP and TnI are independent prognostic indicators of adverse outcome. The incidence of a major cardiac event was 23% in patients with an abnormal CRP vs. 1.1% in patients with a normal CRP. Moreover, in patients without a TnI elevation, a CRP >5.0 mg/l carried a significantly higher risk for a major cardiac event within 6 months (11 vs. 0%). Patients with both CRP and TnI elevated had the highest incidence of cardiac death, recurrent AMI or admission for recurrent unstable angina within 6 months, and had a poor mean event free survival. The difference in the incidence of events is apparent within the first two weeks, but the survival curves continue to diverge during the subsequent 6-month follow-up (Fig. 2). In contrast, patients with both a normal CRP and TnI have an excellent prognosis. In this patient group there were no cardiac deaths, recurrent AMIs or recurrent admissions for unstable angina during the 6 months follow-up.

Our study confirms and extends the findings of one recent report from the TIMI 11A substudy investigators, which demonstrated independent and combined prognostic value of an abnormal CRP and a positive rapid troponin T test for the prediction of 14-day mortality in patients with acute coronary syndromes [18]. Although the patient group differed due to different enrollment and timing of blood samples, the troponin measured was I instead of T, and the follow-up period was different, the results of our study are consistent with the findings of the TIMI 11A substudy.

In a substudy of the FRISC study, Toss et al. [19] could not demonstrate a worse outcome in patients with unstable angina with increased CRP but no troponin T elevation. This may have been caused by the large proportion of patients with an elevated troponin T in the FRISC study which used a cut-off value 1 µg/l. In contrast, Liuzzo et al. [10] demonstrated that CRP elevation in patients with unstable angina, without evidence of myocardial damage as assessed with troponin T, is associated with poor outcome. In addition, in another paper, Liuzzo et al. showed that severe myocardial ischemia in patients with variant angina without atherosclerotic coronary artery disease does not by itself induce an increase in plasma CRP [12]. Therefore, it is likely that CRP elevations are due to activation of inflammation. It has been shown that other pro-inflammatory cytokines such as interleukin-6, interleukin-8 and TNF- are elevated on admission in patients with acute coronary syndromes [11,20,21], and that these elevations may be associated with a worse outcome [11]. We have previously shown that IL-6 has equivalent discriminatory capacity to the pro-coagulant factor fibrinopeptide A to distinquish between patients with stable and unstable coronary artery disease [22].

Whether CRP elevations are causal to the initiation of an episode of unstable coronary artery disease is unknown. It has been shown that CRP stimulates production of tissue factor by mononuclear cells, the main initiator of blood coagulation [23]. In addition, it has been suggested that CRP together with phospholipase A2 may cause complement activation and promote phagocytosis of damaged cells by activated neutrophils [24]. Unstable atherosclerotic plaques have an increased number of macrophages that seem to be most abundant in the vulnerable shoulder region of the fibrous cap overlying the core of atheroma within the vessel wall [25]. Therefore, it is conceivable that an elevated CRP signifies ongoing activation of inflammation that characterizes unstable coronary artery disease and indeed may be one of the causal factors of instability.

Limitations of the study are the relatively small number of patients and the relatively few events. Separate analysis of the patients with unstable angina or non-Q-wave AMI gave comparable results, but in order to increase study population size the two patient groups were considered together. However, even in this relatively small patient group, differences between patients with and without CRP or TnI elevations are striking. Together with another report [18], our findings suggest the possibility for risk stratification with the combination of these two markers.

In conclusion, our study demonstrates the independent prognostic value of CRP and TnI in patients with unstable angina or NQMI, for long term adverse outcome. Incidence of events was high and mean event-free survival was low in patients with combined elevation of CRP and TnI, whereas prognosis is excellent for patients without elevations of CRP and TnI. These findings suggest that the effects of a comprehensive treatment, e.g. with IIb/IIIa antagonists, of patients with both markers elevated or early discharge of patients with both a normal CRP and TnI could be studied in a prospective study.

Time for primary review 33 days.

	Acknowledgements

 
We are thankful to the physicians and nursing staff of the Cardiac Emergency Room and the Coronary Care Unit of the Academic Medical Center for their efforts in completing this study. Special thanks is due to Mariandl vt Hof for all the work involved in completing the follow-up.

	References

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 

1. The RISC group. Wallentin L. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet (1990) 336:827–830.[CrossRef][Web of Science][Medline]
2. Theroux P., Waters D., Qui S., McCans J., de Guise P., Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation (1993) 88:2045–2048.[Abstract/Free Full Text]
3. TIMI IIIB Investigators. Braunwald E. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB trial. Circulation (1994) 89:1545–1556.[Abstract/Free Full Text]
4. Hamm C.W., Ravkilde J., Gerhardt W., et al. The prognostic value of serum troponin T in unstable angina. New Engl J Med (1994) 327:146–150.
5. Stubbs P., Collinson P., Moseley D., Greenwood T., Noble M. Prognostic significance of admission troponin T concentrations in patients with myocardial infarction. Circulation (1996) 94:1291–1297.[Abstract/Free Full Text]
6. Lindahl B., Venge P., Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. Circulation (1996) 93:1651–1657.[Abstract/Free Full Text]
7. Ohman E.M., Armstrong P.W., Christenson R.H., et al. Cardiac troponin T levels for risk stratification in acute myocardial infarction. New Engl J Med (1996) 335:1333–1341.[Abstract/Free Full Text]
8. Antman E.M., Tanasijevic M.J., Thompson B., et al. Cardiac specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. New Engl J Med (1996) 335:1342–1349.[Abstract/Free Full Text]
9. Galvani M., Ottani F., Ferrini D., et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation (1997) 95:2053–2059.[Abstract/Free Full Text]
10. Liuzzo G., Biasucci L.M., Gallimore J.R., et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. New Eng J Med (1994) 331:417–424.[Abstract/Free Full Text]
11. Biasucci L.M., Vitelli A., Liuzzo G., et al. Elevated levels of interleukin-6 in unstable angina. Circulation (1996) 94:874–877.[Abstract/Free Full Text]
12. Liuzzo G., Biasucci L.M., Rebuzzi A.G., et al. Plasma protein acute-phase response in unstable angina is not induced by ischemic injury. Circulation (1996) 94:2373–2380.[Abstract/Free Full Text]
13. Haverkate F., Thompson S.G., Pyke S.D.M., Gallimore J.R., Pepys M.B. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet (1997) 349:462–466.[CrossRef][Web of Science][Medline]
14. World Health Organization criteria for the diagnosis of acute myocardial infarction. Proposal for the multinational monitoring of trends and determinants in cardiovascular disease. Geneva: Cardiovascular Disease Unit of WHO, 1981.
15. TIMI II Investigators. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) Phase II Trial. New Engl J Med (1989) 320:618–627.[Abstract]
16. Hosmer D.W. Jr., Lemeshow S. Applied logistic regression. (1989) New York: Wiley. 30–33.
17. Boyd J.C. Mathematical tools for demonstrating the clinical usefulness of biochemical markers. Scan J Clin Lab Invest (1997) 57(Suppl_227):46–63.[Web of Science]
18. Morrow D.A., Rifai N., Antman E.M., et al. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: A TIMI 11A substudy. J Am Coll Cardiol (1998) 31:1460–1465.[Abstract/Free Full Text]
19. Toss H., Lindahl B., Siegbahn A., Wallentin L. for the FRISC study group. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. Circulation (1997) 96:4204–4210.[Abstract/Free Full Text]
20. Kanda T., Hirao Y., Oshima S., et al. Interleukin-8 as a sensitive marker of unstable coronary artery disease. Am J Cardiol (1996) 77:304–307.[CrossRef][Web of Science][Medline]
21. Maury C.P.J., Teppo A.M. Circulating tumor necrosis factor-alpha (cachectin) in myocardial infarction. J Int Med (1989) 225:333–336.[Web of Science][Medline]
22. Manten A., DeWinter R.J., Minnema M.C., et al. Procoagulant and proinflammatory activity in acute coronary syndromes. Cardiovasc Res (1998) 40:389–395.[Abstract/Free Full Text]
23. Cermak J., Key N.S., Bach R.R., Balla J., Jacob H.S., Vercelotti G.M. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood (1993) 82:513–520.[Abstract/Free Full Text]
24. Hack C.E., Wolbink G.J., Schalkwijk C., Speijer H., Hermens W.T., van den Bosch H. A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells. [Review]. Immunol Today (1997) 18:111–115.[CrossRef][Web of Science][Medline]
25. van der Wal A., Becker A.E., van der Loos C., Das P.K. 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]

CiteULike    Connotea    Del.icio.us    What's this?

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]

				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]

				J. T. Wu and L. L. Wu Association of Soluble Markers with Various Stages and Major Events of Atherosclerosis Ann. Clin. Lab. Sci., January 1, 2005; 35(3): 240 - 250. [Abstract] [Full Text] [PDF]

				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]

				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]

				S Kennon, A D Timmis, R Whitbourn, and C Knight C reactive protein for risk stratification in acute coronary syndromes? Verdict: unproven Heart, November 1, 2003; 89(11): 1288 - 1290. [Abstract] [Full Text] [PDF]

				L.K Newby, M.V Bhapkar, H.D White, E.J Topol, F.C Dougherty, R.A Harrington, M.C Smith, L.F Asarch, R.M Califf, and for the SYMPHONY and 2nd SYMPHONY Investigators Predictors of 90-day outcome in patients stabilized after acute coronary syndromes Eur. Heart J., January 2, 2003; 24(2): 172 - 181. [Abstract] [Full Text] [PDF]

				P J Sheridan and D C Crossman Critical review of unstable angina and non-ST elevation myocardial infarction Postgrad. Med. J., December 1, 2002; 78(926): 717 - 726. [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]

				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]

				S. Kennon, C. P. Price, P. G. Mills, K. Ranjadayalan, J. Cooper, H. Clarke, and A. D. Timmis The effect of aspirin on C-reactive protein as a marker of risk in unstable angina J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1266 - 1270. [Abstract] [Full Text] [PDF]

				K. A. HERZIG, D. M. PURDIE, W. CHANG, A. M. BROWN, C. M. HAWLEY, S. B. CAMPBELL, J. M. STURTEVANT, N. M. ISBEL, D. L. NICOL, and D. W. JOHNSON Is C-Reactive Protein a Useful Predictor of Outcome in Peritoneal Dialysis Patients? J. Am. Soc. Nephrol., April 1, 2001; 12(4): 814 - 821. [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]

				W. L. Roberts, L. Moulton, T. C. Law, G. Farrow, M. Cooper-Anderson, J. Savory, and N. Rifai Evaluation of Nine Automated High-Sensitivity C-Reactive Protein Methods: Implications for Clinical and Epidemiological Applications. Part 2 Clin. Chem., March 1, 2001; 47(3): 418 - 425. [Abstract] [Full Text] [PDF]

				B. Lindahl, H. Toss, A. Siegbahn, P. Venge, L. Wallentin, and The FRISC Study Group Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease N. Engl. J. Med., October 19, 2000; 343(16): 1139 - 1147. [Abstract] [Full Text] [PDF]

				R. J. de Winter, J. Fischer, R. Bholasingh, J. P. van Straalen, T. de Jong, J. G.P. Tijssen, and G. T. Sanders C-Reactive Protein and Cardiac Troponin T in Risk Stratification: Differences in Optimal Timing of Tests Early after the Onset of Chest Pain Clin. Chem., October 1, 2000; 46(10): 1597 - 1603. [Abstract] [Full Text] [PDF]

				W. L. Roberts, R. Sedrick, L. Moulton, A. Spencer, and N. Rifai Evaluation of Four Automated High-Sensitivity C-Reactive Protein Methods: Implications for Clinical and Epidemiological Applications Clin. Chem., April 1, 2000; 46(4): 461 - 468. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by de Winter, R. J Articles by Sanders, G. T Search for Related Content PubMed PubMed Citation Articles by de Winter, R. J Articles by Sanders, G. T Social Bookmarking          What's this?

Online ISSN 1755-3245 - Print ISSN 0008-6363

Copyright © 2009 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics