Predischarge C-Reactive Protein and 1-year Outcome After Acute Coronary Syndromes
Article Outline
Abstract
Purpose
To investigate the relationship between high-sensitivity C-reactive protein and cardiovascular events following acute coronary syndrome.
Methods
This nationwide, cross-sectional, prospective study involved 439 patients with an acute coronary syndrome who presented to the hospital within 24 hours of symptom onset. Patients with a concomitant inflammatory process were excluded. Predischarge C-reactive protein samples were measured using a high-sensitivity method in a core laboratory. The outcome was the composite of death, acute myocardial infarction, stroke/transient ischemic attack, urgent hospitalization for unstable angina, and urgent revascularization within 1 year.
Results
At 1 year, event rates were 10.2% for the lowest, 8.2% for the middle, and 11.0% for the highest C-reactive protein tertiles (P = .75) with similar event-free survival (P = .70). The hazard ratio (HR) for event rates between the highest and lowest tertiles was 1.10 (95% confidence interval [CI]: 0.54 to 2.20) There was marked overlap of C-reactive protein values between patients with and without events (median [interquartile range]: 8.39 [3.27 to 32.63] vs 9.55 [4.07 to 24.02], respectively; P = .91). C-reactive protein was not an independent predictor of 1-year events (HR for highest tertile: 1.19; 95% CI: 0.58 to 2.43; P = .64) and performed poorly on receiver operating characteristic curve analysis (C statistic = 0.51).
Conclusion
Predischarge high-sensitivity C-reactive protein level is a poor predictor of cardiovascular events at 1 year after acute coronary syndrome.
Keywords: High-sensitivity C-reactive protein, Acute coronary syndromes, Cardiovascular events, Outcomes
Elevated high-sensitivity C-reactive protein levels are independently associated with the risk of death or myocardial infarction in healthy individuals,1, 2, 3 and provide incremental information to that afforded by lipids.4 Studies have suggested that high-sensitivity C-reactive protein levels at admission are predictive of early and late outcomes in patients with an acute coronary syndrome.5, 6, 7, 8 One study suggested that high-sensitivity C-reactive protein level at discharge was strongly predictive of cardiac events after an acute coronary syndrome,9 whereas other studies have failed to demonstrate a consistent relation between C-reactive protein and hospital outcome in patients with an acute coronary syndrome.10, 11, 12
C-reactive protein measured 25 days after an acute myocardial infarction has been shown to be associated with long-term mortality.13 However, in another study, C-reactive protein measured 2 months after myocardial infarction was not an independent marker for recurrent events.14 Thus it remains uncertain whether predischarge C-reactive protein can discriminate individuals at higher risk of recurrent cardiac events from those at low risk.
The aim of this prospective study was to assess whether predischarge high-sensitivity C-reactive protein levels are predictive of cardiac events in unselected acute coronary syndrome patients receiving “contemporary” management, particularly in ST-segment elevation myocardial infarction patients, who have been excluded from many previous studies.
Methods
This nationwide, cross-sectional, prospective study involved patients admitted to coronary care units for suspected acute coronary syndrome. All coronary care units in France were approached to participate. Each site was requested to recruit a minimum of 4 consecutive patients. The population included patients aged ≥18 years with a presumptive diagnosis of acute coronary syndrome who presented within 24 hours of symptom onset.
Patients had to have symptoms consistent with acute myocardial ischemia and at least one of the following: electrocardiographic changes with dynamic ST or T-wave changes, new Q waves or new R waves in V1, or left bundle branch block; documented coronary artery disease (myocardial infarction, angina, ischemic congestive heart failure, or history of sudden death; history of new positive stress test; prior or new cardiac catheterization with coronary artery disease; prior or new percutaneous coronary intervention or coronary artery bypass graft); and any increase in cardiac enzymes (creatine kinase-MB, troponin I, troponin T). Patients had to be permanent residents in France and be able to provide a contact address at 6 months and 1 year after discharge. Patients were included if their stay in hospital before discharge home or to a convalescent center was anticipated to be no longer than 14 days.
Patients were excluded if they had any coexisting medical condition that could increase C-reactive protein levels (eg, pneumonia, sepsis, cancer, rheumatoid arthritis), if they underwent coronary artery bypass grafting during hospitalization, or were in cardiogenic shock or had iatrogenic acute coronary syndrome at admission. Patients transferred from a medical intensive care unit or from a surgery department and those with hepatitis or cirrhosis were excluded.
All patients provided written informed consent before participating in the study. The study protocol was reviewed by the Institutional Review Board of Hôpital La Pitié-Salpêtrière on August 22, 2001 using the French centralized nationwide Institutional Review Board approval procedure, and was performed in accordance with French law.
Two blood samples were drawn, the first following admission and within 24 hours of symptom onset and the second when the patient was stable and within 48 hours preceding planned discharge. Thus, patients were screened at inclusion but were enrolled only if they fulfilled all selection criteria at discharge and had undergone the second blood sampling. Standard lipid profiles and high-sensitivity C-reactive protein levels were measured at admission; C-reactive protein was measured predischarge. Quantitative high-sensitivity C-reactive protein determination was carried out at the core laboratory (MDS Pharma Services, Baillet en France, France) using a latex particle-enhanced immunoturbidometric assay (Kamiya, Seattle, WA). The assay was cross-validated in a subset of patients using the Dade Behring nephelometric technique with a high degree of correlation (Pearson correlations and probabilities = 0.99 [<.001]). Investigators and adjudication committee members were blinded to the C-reactive protein results. Because the predictive value of C-reactive protein is likely to be affected by revascularization and because a high rate of revascularization was anticipated, predischarge C-reactive protein (as opposed to admission value) was chosen as the primary variable of interest.
The primary endpoint was the composite of death, acute myocardial infarction, urgent revascularization, hospitalization for unstable angina, or stroke/transient ischemic attack. The secondary endpoints were death or acute myocardial infarction, or death, acute myocardial infarction or stroke/transient ischemic attack. Death and all cardiovascular events were censored at 1 year and were adjudicated by an independent critical event committee blinded to the C-reactive protein results.
Follow-up events at 6 and 12 months were ascertained through hospital consultations, review of medical records, interviews with primary care physicians or nonhospital cardiologists, or by direct contact with either the patient or a close relative. Case report forms and source documents were compared. Queries relating to missing or incoherent data were followed-up by telephone, facsimile or letter.
Sample Size and Statistical Analysis
A sample size of 438 patients was estimated to have 80% power at a 2-sided significance level of .05 to demonstrate a difference between 15% and 5% in the proportion of patients with major cardiovascular events between the highest and the lowest tertiles of C-reactive protein.
For the primary outcome variable, a χ2 or Fisher’s exact test was used to compare the proportion of patients who died or had one of the primary endpoint events within the year following hospital discharge in the highest and the lowest tertiles of predischarge C-reactive protein.
A Cox proportional hazard model multivariable analysis was carried out to predict the combined endpoint of death, myocardial infarction, urgent revascularization, rehospitalization for unstable angina and stroke/transient ischemic attack. The analysis was censored at 1 year after discharge. Age was systematically included in the model. Other prognostic factors with at least 10 patients in each category of each variable were retained from a first Kaplan-Meier analysis if they were statistically significant at a 5% type I risk error for all event definitions. Two proportional hazard model multivariable analyses were performed: the first analysis included all selected factors; the second included all selected factors and added C-reactive protein tertiles. Global Wald tests are provided for each multivariable model. All calculations used SAS 8.2 for Windows statistical package (SAS Institute Inc., Cary, NC).
Results
A total of 551 patients were pre-enrolled by 105 investigators at 93 sites (30 university hospitals, 63 non-university hospitals; Figure 1). Eighty-three sites were public, 8 were private, and 2 were military hospitals. The majority (65%) of hospitals had onsite percutaneous coronary intervention facilities and 40% had coronary artery bypass graft facilities. The median recruitment rate was 4 per site (range 1 to 33).
Figure 1.
Study flow chart. ACS = acute coronary syndrome; CABG = coronary artery bypass graft surgery; CRP = C-reactive protein; hs-CRP = high-sensitivity C-reactive protein; ICU, intensive care unit.
Of the 551 pre-enrolled patients, 455 had a predischarge CRP sample drawn (on average 5.8 ± 3.36 days after admission, median 5 days) and were enrolled into the study. Blood samples were drawn, immediately spun and shipped overnight for analysis by the core laboratory. Data were analyzed from 439 of the 551 pre-enrolled patients; the remaining 112 patients were excluded (Figure 1). The overall median age of the patients was 61 years, and 77% were men (Table 1). Sixty percent of the patients were diagnosed with ST-segment elevation myocardial infarction/left bundle branch block, 30% with non-ST-segment elevation myocardial infarction, and 10% with unstable angina. Patients with ST-segment elevation myocardial infarction were younger and more likely to be male than those with non-ST elevation acute coronary syndrome, and were less likely to have a history of diabetes, hypertension, hypercholesterolemia, or myocardial infarction, or to have undergone a prior intervention (Table 1). The median duration of hospitalization was 7 days.
Table 1. Baseline Characteristics of Study Population
| Characteristic | STEMI (n = 263) | NSTEMI/UA (n = 176) | Total (n = 439) | P Value (STEMI vs NSTEMI/UA) |
|---|---|---|---|---|
| Age, median in years (range) | 58 (23-91) | 65(25-90) | 61(23-91) | <.001⁎ |
| Male sex | 212(81) | 125(71) | 337(77) | .020† |
| Weight, median in kg (range) | 78(40-140) | 76(39-123) | 77(39-140) | .274⁎ |
| BMI, median (range) | 27(16-43) | 27(18-38) | 27(16-43) | .858⁎ |
| Current smoker | 123(47) | 67(38) | 190(43) | .063† |
| History of diabetes | 31(12) | 41(23) | 72(16) | .002† |
| History of hypertension | 92(35) | 92(52) | 184(42) | <.001† |
| Hypercholesterolemia | 81(31) | 82(47) | 163(37) | .001† |
| Family history CAD | 52(20) | 36(21) | 88(20) | .808† |
| Prior CABG | 1(0) | 11(6) | 12(3) | <.001† |
| Serum creatinine levels, median in mg/dL (range) | 88(44-213) | 89(48-277) | 88(44-277) | .157⁎ |
| Total cholesterol, median in mmol/l (range)‡ | 5.3(2.9-14.6) | 5.2(2.7-8.0) | 5.3(2.7-14.6) | .130⁎ |
| LDL Cholesterol, median in mmol/L (range)‡ | 3.2(1.1-8.3) | 2.9(1.0-5.5) | 3.1(1.0-8.3) | .002⁎ |
| Triglycerides, median in mmol/L (range)‡ | 1.4(0.4-12.2) | 1.8(0.4-19.1) | 1.6(0.4-19.1) | <.001⁎ |
| Prior PCI | 19(7) | 45(26) | 64(15) | <.001† |
| Prior MI | 23(9) | 34(19) | 57(13) | .003† |
⁎Wilcoxon test. |
†Fisher’s exact test. |
‡Determined by the core laboratory. |
The rates of coronary angiography and percutaneous coronary intervention were high (91% and 71%, respectively) and were consistently higher in patients with ST-segment elevation myocardial infarction (92% and 78%) compared with non-ST elevation acute coronary syndrome (89% and 61%). In-hospital recurrent ischemia was less frequent among patients with ST-segment elevation myocardial infarction than those with non-ST elevation acute coronary syndrome (Table 2). Congestive heart failure occurred more frequently in patients with ST elevation myocardial infarction.
Table 2. In-Hospital Outcomes
| Outcome | STEMI (n = 263) | NSTEMI/UA (n = 176) | Total (n = 439) | P Value⁎ |
|---|---|---|---|---|
| Recurrent ischemia | 11(4) | 14(8) | 25(6) | .140 |
| New myocardial infarction | 7(3) | 6(3) | 13(3) | .776 |
| Cardiac arrest | 2(1) | 0 | 2(<1) | .517 |
| Congestive heart failure | 21(8) | 8(5) | 29(7) | .173 |
| Stroke/TIA | 1(<1) | 1(<1) | 2(<1) | 1.00 |
⁎Fisher’s exact test. |
The overall rate of prescription at discharge of 3 of the 4 evidence-based cardiac medications was high (85%; Table 3), and 49% of the patients received all four classes of medication.
Table 3. Discharge Medications
| Therapy | STEMI (n = 263) | NSTEMI/UA (n = 176) | Total (n = 439) | P Value⁎ |
|---|---|---|---|---|
| Aspirin | 253(96) | 162(92) | 415(95) | .085 |
| Thienopyridine | 216(82) | 126(72) | 342(78) | .01 |
| Any antiplatelet therapy (thienopyridine or aspirin) | 260(99) | 173(98) | 433(99) | .688 |
| Beta-blocker | 228(87) | 143(81) | 371(85) | .139 |
| ACE-I | 183(70) | 80(46) | 263(60) | <.001 |
| ARB | 4(2) | 11(6) | 15(3) | .013 |
| Statin | 243(92) | 144(82) | 387(88) | .001 |
| Patients given 3 of 4 medications† | 240(91) | 135(77) | 375(85) | <.001 |
| Patients given all 4 medications† | 154(59) | 61(35) | 215(49) | <.001 |
⁎Fisher’s exact test. |
†Any antiplatelet therapy (thienopyridine or aspirin), beta-blocker, ACE-I, or statin. |
The median C-reactive protein level predischarge was 9.5 mg/L (mean 20.0 mg/L; Figure 2). The three tertiles of C-reactive protein were defined as <5.2 mg/L, 5.2 to 17.4 mg/L, or >17.4 mg/L. C-reactive protein levels were higher in patients with ST-elevation or non-ST-segment elevation myocardial infarction compared with those with unstable angina (11.3, 10.0 and 4.0 mg/L, respectively; P <.01).
Figure 2.
C-reactive protein level at discharge from hospital. Mean (standard) 20.0 (28.4) mg/L; range 0.20-280.60 mg/L. Q25 4.01, Q50 9.50, Q75 24.67 mg/L. Q33.3 5.20, Q66.6 17.37 mg/L. hs-CRP = high-sensitivity C-reactive protein.
The median length of follow-up was 375 days (mean 405 days; range 153 to 701). Follow-up data were available in 99.3% (436 of 439) of patients. Overall, 55 events were accrued in 439 patients. Event rates at 1 year were 7.6%, 13.6%, and 11.4% for ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina, respectively (P = .014). Freedom from the primary endpoint survival curves for each of the C-reactive protein tertiles are displayed in Figure 3, and show the marked overlap of tertiles (P = .67 by log-rank). Similar results were observed for death and myocardial infarction, and for death, myocardial infarction and stroke/transient ischemic attack (data not shown). Binary primary event rates at 1 year according to tertile were similar (10.2%, 8.2%, and 11.0% for the lowest, medium and highest tertiles, respectively; P = .75, Fisher’s exact test) (Figure 4). One-year individual event rates according to tertile are shown in Table 4. The hazard ratio (HR) for primary events between the highest and the lowest tertiles was 1.09 (95% confidence interval [CI], 0.54 to 2.20; P =.82). The distribution of predischarge C-reactive protein shows the marked overlap between patients with and without events in the year following discharge (Figure 5), with median values of 8.39 (interquartile range: 3.27 to 32.63) for patients with and 9.55 (interquartile range: 4.07 to 24.02; P = .91, Wilcoxon’s test) for those without events.
Figure 3.
Postdischarge outcomes at 1 year by predischarge C-reactive protein tertile. Log-rank test P = .6979.
Figure 4.
Binary primary endpoints at 1 year by C-reactive protein tertile.
Table 4. Individual Event Rates at 1 Year Following Discharge According to C-Reactive Protein Tertile
| Outcome† | 1st tertile (n = 147) | 2nd tertile (n = 146) | 3rd tertile (n = 146) | P Value⁎ |
|---|---|---|---|---|
| Death | 2(1.4) | 1(0.7) | 6(4.1) | .134 |
| Non-fatal MI | 7(4.8) | 7(4.8) | 6(4.1) | 1.000 |
| Stroke/TIA | 0 | 2(1.4) | 3(2.1) | .214 |
| Urgent revascularization | 6(4.1) | 2(1.4) | 2(1.4) | .319 |
| Unstable angina | 7(4.8) | 2(1.4) | 2(1.4) | .125 |
| Any event | 15(10.2) | 12(8.2) | 16(11.0) | .745 |
⁎Fisher’s exact test. |
†Patients may have experienced more than one event. |
Figure 5.
Distribution of hs-C-reactive protein values in patients with versus without outcome events (death, myocardial infarction, unstable angina, revascularization, stroke or transient ischemic attack). Box shows mean, upper and lower quartiles; whiskers show highest and lowest observations. All outliers are represented by small boxes.
Receiver operating characteristic curve analysis showed that C-reactive protein at discharge performed poorly for predicting the primary endpoint at 1 year (C statistic = 0.51; Figure 6). Importantly, admission C-reactive protein (5.7, 4.7 and 2.4 mg/L in ST-segment elevation, non-ST-segment elevation myocardial infarction, and unstable angina patients, respectively) also had no relation to 1-year major adverse cardiac events regardless of whether in-hospital events were included in the analysis or not. Likewise, changes between admission and discharge, categorized in stable high, stable low, increasing, or decreasing, had no relation to postdischarge events up to 1 year (data not shown). Finally, although the power of such subgroup analyses is limited, separate analysis of each of the three diagnostic categories did not suggest any difference in the relation between admission or predischarge C-reactive protein and 1-year outcomes (data not shown).
Figure 6.
Receiver operating characteristic analysis for prediction of the primary endpoint at 1 year. C statistic = 0.5129.
Multivariable analysis, adjusting for factors having a prognostic value (age [<65 years or ≥65 years], treated diabetes, treated hypertension, history of myocardial infarction and aspirin prescription at discharge), showed that diabetes (HR 2.17; 95% CI, 1.10 to 4.26), lack of aspirin at discharge, and a history of myocardial infarction (HR 2.45; 95% CI, 1.22 to 4.90) were the main independent predictors of the postdischarge combined endpoint (Table 5). C-reactive protein was not an independent predictor of the 1-year composite endpoint. When forced into the model, C-reactive protein did not improve its ability to predict the primary endpoint (Wald P = .00002 without C-reactive protein, changing to P = .00006 after inclusion of C-reactive protein). The adjusted HR of events for the highest tertile of C-reactive protein (using the lowest tertile as reference value) was 1.19 (95% CI, 0.58 to 2.43; P = 0.64).
Table 5. Prediction of Death, Myocardial Infarction, Urgent Revascularization, Hospitalization for Unstable Angina, or Stroke/Transient Ischemic Attack
| Parameter | With hs-CRP in the model Global Wald Test: P = .00006 | Without hs-CRP in the model Global Wald Test: P = .00002 | ||||
|---|---|---|---|---|---|---|
| χ2 | Probability | Hazard ratio (95% confidence interval) | χ2 | Probability | Hazard ratio (95% confidence interval) | |
| CRP 2nd tertile | 0.455 | 0.500 | 0.766(0.353-1.662) | – | – | – |
| CRP 3rd tertile | 0.222 | 0.638 | 1.188(0.581-2.430) | – | – | – |
| History of MI | 6.273 | 0.012 | 2.444(1.214-4.917) | 6.407 | 0.011 | 2.450(1.224-4.903) |
| Treated diabetes | 5.395 | 0.020 | 2.228(1.133-4.379) | 5.055 | 0.025 | 2.170(1.104-4.263) |
| Hypertension | 2.561 | 0.110 | 1.703(0.887-3.267) | 2.388 | 0.122 | 1.670(0.872-3.199) |
| Age ≥65 years | 0.005 | 0.943 | 0.975(0.495-1.922) | 0.005 | 0.943 | 0.976(0.500-1.905) |
| Aspirin at discharge | 2.941 | 0.086 | 0.448(0.179-1.121) | 3.455 | 0.063 | 0.427(0.174-1.047) |
Discussion
The results from this prospective registry show that, after hospitalization for an acute coronary syndrome, elevated predischarge C-reactive protein level is not associated with a significantly increased risk of death or major cardiovascular events at 1 year in unselected patients who undergo “contemporary” management. The absolute levels of C-reactive protein were higher than reported previously (median 9.5 mg/L; mean 20 mg/L) and may reflect the fact that most patients had acute myocardial infarction (predominantly ST-segment elevation), a departure from most previous studies. This high proportion of ST elevation may be related to some selection by centers that enrolled a low number of patients.
In the study by Ferreiros et al,9 a predischarge C-reactive protein level >15 mg/L was associated with a highly significant increase at 90 days in the combined endpoint of death, myocardial infarction, or refractory angina in patients with unstable angina. However, this study differs markedly from the present study because it included patients with non-ST elevation acute coronary syndrome, only 6.7% underwent revascularization, and almost 40% of patients had a major cardiac event within 90 days of discharge.9
Whereas most studies of C-reactive protein and outcomes are based on patients enrolled in randomized clinical trials, our study involved unselected patients admitted to coronary care units. Therefore, the results are more applicable to the spectrum of patients treated in clinical practice. Furthermore, the data are based on adverse events that occurred after hospital discharge rather than the cumulative figure for in-hospital and postdischarge outcomes. Although there was important dispersion of predischarge C-reactive protein values (Figure 2), this distribution represents a “real-life” attempt at excluding patients with known or suspected extracardiac causes of elevated C-reactive protein; therefore, we chose not to exclude patients with exceedingly high baseline values when no known or suspected condition would have prompted a priori exclusion.
Although the results of this study fail to show an association between predischarge C-reactive protein levels and cardiac events at 1 year in acute coronary syndrome patients, they absolutely cannot exclude an important role for C-reactive protein in the prediction of cardiovascular events in this population. During the early days of hospitalization, C-reactive protein values are likely to be confounded by any interventions performed,15 as well as by the inflammatory process related to myocardial infarction. Zebrack et al16 reported that C-reactive protein measured shortly after acute myocardial infarction was not predictive of death or nonfatal myocardial infarction, whereas it was predictive in patients with stable or unstable angina.10
Benamer et al reported an increase in C-reactive protein levels during the first days of hospitalization in patients with an acute coronary syndrome and elevated biomarkers of necrosis.10 More recently, Yip et al reported a prognostic value of C-reactive protein in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.17 C-reactive protein measured at later time-points appears to have an important role in prognostic assessment after acute coronary syndrome. Indeed, recent data from the PROVE-IT-TIMI 22 (PRavastatin Or AtorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial show that patients who achieve lower C-reactive protein levels on statin therapy 30 days after an acute coronary syndrome have better clinical outcomes than those with higher levels.18 Finally, some previous studies have suggested that C-reactive protein particularly correlates with long-term risk of subsequent death,6, 8 an endpoint that cannot be reliably assessed in our relatively small study in which postdischarge mortality was low. Therefore, our study does not preclude an association between C-reactive protein level and subsequent cardiac mortality in coronary artery disease patients as was seen in large studies powered to detect differences in mortality.6, 7, 8, 19 What these results do show is that, in patients with acute coronary syndrome who are treated aggressively with revascularization and evidence-based therapies, who are discharged alive without having a coronary artery bypass graft and without inflammatory disease, predischarge C-reactive protein probably cannot discriminate individuals at risk of major adverse cardiac events in the year following discharge. This is probably because it is confounded by the inflammatory process related to infarction and to percutaneous intervention. Given the small size of our study and the lower than anticipated event rate, it does not rule out a real impact of C-reactive protein on mortality or adverse outcomes in larger cohorts, but the clinical significance of a reduced difference between patients with high versus low C-reactive protein values is probably limited for individual patient management. The frank overlap between values from patients experiencing or not experiencing events suggests that it is probably premature to base individual treatment decisions on predischarge C-reactive protein.
Conclusions
In the context of modern interventional therapy for acute coronary syndrome, predischarge high-sensitivity C-reactive protein in patients with acute myocardial infarction cannot predict 1-year outcome on an individual basis. C-reactive protein levels probably should not be drawn routinely as a basis for making clinical decisions affecting patient care. This does not exclude the epidemiological value of high-sensitivity C-reactive protein levels in patients with unstable angina or, if measured at later time-points, in predicting the likelihood of adverse outcomes, particularly death, after discharge.
Acknowledgments
The authors thank the physicians and nurses who participated in the study, and Sophie Rushton-Smith, PhD, for editorial assistance.
Appendix.
Principal Investigator: P.G. Steg
Steering Committee: P. Ravaud, A. Tedgui
Critical Events Committee: J. Puel (Chair), G. Finet, J.P. Monassier
Core Laboratory (MDS Pharma Services, France): C. Taveau, E. Vinchon
Logistical Coordination: K. Chevassut, P. Marie (Bristol-Myers Squibb)
Statistics and Data Management: E. Curaudeau, A. Gaudichet, N. Schmidely (Bristol-Myers Squibb)
D. Moyse, A. Richardot
The ELISCOR investigators are (in alphabetical order): E. Abitbol, Créteil; L. Aguirre, Marseille; B. Al Jouma, Chaumont; A. Amiar, Maubeuge; JM. Aubert, Lille; D. Baborier, Lons Le Saunier; T. Badoual, Créteil; JP. Baguet, La Tronche; JM. Baisset, Rennes; J. Ballout, Nevers; JL. Banos, Pau; S. Banoun, Lagny Sur Marne; P. Barnay, Marseille; H. Belfaqih, Le Coudray; T. Benard, Angers; N. Benazza, Bar Le Duc; P. Bernardet, Libourne; D. Berville, Poissy; G. Bessede, Gueret; P. Bonnet, Montvilliers; C. Boukerche, Montfermeil; JM. Bouvier, Cholet; M. Burban, Saint Herblain; I. Canavy, Toulon; J. Cassagnes, Clermont Ferrand; AG. Casu, Agen; A. Cerisier, Saint Etienne; JM. Chevalier, Villeneuve D’ornon; P. Coste, Pessac; Y. Cottin, Dijon; V. Cratère, Vienne; B. De Breyne, Bron; JP. De Pasquale, Feurs; T. Dechery, Montlucon; N. Delarche, Pau; P. Delmas, Lisieux; JL Dequeker, Bayonne; S. Destrac, St Jean De Verges; R. Deturck, Lens; J. Dewilde, Quimper; C. D’hoine, Arras; E. Donal, Poitiers; R. Douillet, Vannes; M. Elbaz, Toulouse; M. Eldakouri, Metz; O. Fondard, Montreuil Sous Bois; L. Fourcade, Marseille; M. Fratu, Niort; O. Gaday, Agen; E. Garbarz, Paris; M. Ghanem, Montmorency; H. Gorka, Paris; Y. Gottwalles, Colmar; C. Haffner, Strasbourg; P. Hainaut, Clichy; A. Koubbi, Compiègne; B. Koujan, Chateauroux; M. Lang, Blois; M. Latrèche, Avignon; Y. Laurent, Massy; R. Le Bouar, Mulhouse; P. Legalery, Besançon; G. Legros, Lens; JP. Lhosnot, Paris; I. L’huillier, Dijon; N. Lotfi-Brilland, Suresnes; V. Lucke-Simandoux, Saint Michel; N. Mansencal, Boulogne; CJ. Mariottini, St Laurent Du Var; M. Martelet, Langres; B. Mban, Saint Brieuc; R. Megbemado, Bry Sur Marne; P. Meimoun, Compiègne; D. Mery, Arles; C. Minifie, Bordeaux; M. Mokhtari, Clamart; M. Montout Hedreville, Chambray Les Tours; R. Mossaz, Fréjus; J. Mouawad, Fréjus; O. Nguyen-Khac, La Roche Sur Yon; A. Noury, Cambrai; F. Paganelli, Marseille; F. Paillard, Rennes; E. Philip, Marseille; C. Pigale, Orléans; R. Piquemal, Vandoeuvre; JE. Poulard, Abbeville; N. Poulos, Gonesse; E. Prétorian, Dechy; F.Prunier, Angers; J. Quilici, Marseille; P. Raisky, Paris; D. Raufast, Toulon; F. Revault D’allonnes, Saint Malo; C. Richard, Saumur; A. Sangaré, Montereau; C. Saunier, La Tronche; A. Scheublé, Paris; N. Schiano, Nice; J. Schwob, Le Chesnay; P. Sosner, Poitiers; K. Taghipour, Arras; J. Taieb, Aix En Provence; V. Thuus, Epinal; X. Tran-Thanh, Longjumeau; O. Tricot, Dunkerque; G. Verdier, Caen; F. Vochelet, Elbeuf.
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Supported by an unrestricted grant from Bristol-Myers Squibb, France. ELISCOR was supported by an unrestricted grant from Bristol-Myers Squibb, Rueil-Malmaison, France.The complete list of ELISCOR Investigators is in the Appendix.
PII: S0002-9343(06)00202-6
doi:10.1016/j.amjmed.2006.02.018
© 2006 Elsevier Inc. All rights reserved.
