Eur J Cardiothorac Surg 2006;29:983-985
© 2006 Elsevier Science NL
Preoperative C-reactive protein is predictive of long-term outcome after coronary artery bypass surgery
Olli-Pekka Kangasniemi,
Fausto Biancari
*
,
Johannes Luukkonen,
Sailaritta Vuorisalo
1
,
Jari Satta,
Risto Pokela,
Tatu Juvonen
Division of Cardio-thoracic and Vascular Surgery, Department of Surgery, Oulu University Hospital, P.O. Box 21, 90029 Oulu, Finland
Received 8 December 2005;
received in revised form 25 January 2006;
accepted 9 February 2006.
* Corresponding author. Tel.: +358 8 315 2813/40 733973; fax: +358 8 315 2577. (Email: faustobiancari{at}yahoo.it).
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Abstract
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Background: Increased levels of C-reactive protein (CRP) are associated with the presence and severity of atherosclerosis, and with increased risk of coronary events as well as of cardiac events after coronary percutaneous intervention. Methods: We have investigated whether preoperative CRP had an impact on the long-term outcome of 843 patients who underwent on-pump coronary artery bypass surgery (CABG). Results: Among operative survivors, patients with preoperative CRP <1.0 mg/dL had significantly better 12-year overall survival rate (74.1% vs 63.0%, p
= 0.004) and survival freedom from fatal cardiac event (86.7% vs 78.1%). Multivariate analysis including patients’ age, extracardiac arteriopathy, urgent/emergent operation, recent myocardial infarction, congestive heart failure, left ventricular ejection fraction, atrial fibrillation, transient ischemic attack/stroke, number of distal anastomoses, diabetes, and preoperative CRP 
1.0 mg/dL or <1.0 mg/dL, showed that the latter was an independent predictor of late all-cause mortality (p
= 0.017, RR 1.60, 95% CI 1.09–2.35). Its impact on overall survival was particularly evident in patients with left ventricular ejection fraction <50% (CRP < 1.0 mg/dL: 58.7% vs CRP 1.0 mg/dL: 43.7%, p
< 0.00001). Conclusions: Increased preoperative levels of CRP are associated with significantly decreased overall survival after primary on-pump CABG.
Key Words: Coronary artery bypass surgery • C-reactive protein • Survival
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1. Introduction
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Increased levels of C-reactive protein (CRP) are associated with the presence and severity of atherosclerosis, and with increased risk of coronary events as well as of cardiac events after coronary percutaneous intervention [1]. CRP is also a major prognostic factor in patients with chronic heart failure [2]. It is also predictive of immediate postoperative outcome after coronary artery bypass surgery (CABG) [3]. However, to the best of our knowledge, there is no data about the possible impact of CRP on the long-term outcome after CABG. This issue has been investigated in the present study.
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2. Material and methods
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Between January 1992 and December 1993, 1098 patients undergoing isolated on-pump CABG were considered for prospective studies evaluating antibiotic prophylaxis strategies [4]. Patients with signs and/or symptoms of infection, on antibiotic treatment or with antibiotic allergy as well as patients undergoing redo cardiac surgery have been excluded from this study. CRP was measured by the immunoturbimetric CRP method (Orion Diagnostica, Finland). In most of cases, the precise CRP value was not specified when <1.0 mg/dL. Thus, herein, CRP was considered as a dichotomous variable (CRP <1.0 mg/dL and 1.0 mg/dL). Eighty-seven patients had a preoperative CRP 1.0 mg/dL). In overall, 843 patients were included in the present analysis and risk factors in patients with preoperative CRP <1.0 mg/dL and 1.0 mg/dL are summarized in Table 1
. Causes of late death have been obtained from a national registry (Tilastokeskus).
Statistical analysis was performed using SPSS statistical software (SPSS v. 10.0.5, SPSS Inc., Chicago, IL, USA). The Fisher's exact test and the Mann–Whitney test were used for univariate analysis. The Kaplan–Meier and Cox regression methods were used to evaluate the impact of variables on the long-term outcome. Cox regression with the help of backward selection was used for multivariate analysis. Only preoperative variables whose p
< 0.05 at univariate analysis were considered for inclusion in the regression model. A p-value of <0.05 was considered statistically significant.
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3. Results
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During the in-hospital stay, 12 patients (1.4%) had stroke, 1 (0.1%) TIA, 276 (32.7%) atrial fibrillation, 17 (2.0%) pneumonia, and 2 (0.2%) low cardiac output syndrome. Three patients (0.4%) died during the immediate postoperative period, all of them having preoperative CRP <1.0 mg/dL. Preoperative CRP did not have any significant impact on the occurrence of major immediate postoperative morbidity or mortality.
Among operative survivors (753 patients in the low CRP group and 87 in the high CRP group), patients with preoperative CRP <1.0 mg/dL had significantly better 12-year overall survival rate (74.1% vs 63.0%, p
= 0.004) and survival freedom from fatal cardiac event (86.7% vs 78.1%, p
= 0.008). Multivariate analysis including patients’ age, extracardiac arteriopathy, urgent/emergent operation, recent myocardial infarction, congestive heart failure, left ventricular ejection fraction, atrial fibrillation, transient ischemic attack/stroke, number of distal anastomoses, diabetes, and preoperative CRP 1.0 mg/dL or <1.0 mg/dL, showed that the latter was an independent predictor of late all-cause mortality (p
= 0.017, RR 1.60, 95% CI 1.09–2.35; Fig. 1
). Its impact on overall survival was particularly evident in patients with left ventricular ejection fraction <50% (CRP <1.0 mg/dL: 58.7% vs CRP 1.0 mg/dL: 43.7%, p
< 0.00001; Fig. 2
).
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Fig. 1. Adjusted 12-year overall survival among operative survivors with preoperative CRP <1.0 mg/dL and those with C-reactive protein 1.0 mg/dL (p
= 0.017, RR 1.60, 95% CI 1.09–2.35).
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Fig. 2. Interactions between preoperative levels of C-reactive protein (CRP) and preoperative left ventricular ejection fraction (LVEF) and their impact on long-term all-cause mortality (785 patients included in the analysis; log-rank: p
< 0.00001).
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Multivariate analysis including patients’ age, extracardiac arteriopathy, recent myocardial infarction, congestive heart failure, left ventricular ejection fraction, atrial fibrillation, diabetes, and preoperative CRP 1.0 mg/dL or <1.0 mg/dL, showed that the latter tended to predict late cardiac death (p
= 0.075, RR 1.65, 95% CI 0.95–2.88), but its impact was not statistically significant.
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4. Discussion
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This study confirmed that CRP is a relevant marker of severity of coronary artery disease as it was significantly increased in patients with unstable angina, recent myocardial infarction and decreased left ventricular ejection fraction. Indeed, CRP has been shown to be a relevant predictor of outcome in patients with heart failure, an observation herein confirmed by the higher prevalence of patients with left ventricular ejection fraction <50% having increased preoperative CRP. Although the difference in survival was not impressive, CRP retained its significance as a predictor of all-cause long-term mortality when adjusted for other important variables. This observation suggests that this inflammatory marker can be an important therapeutic target also in CABG patients as recently recognized in medically treated patients with acute coronary syndromes [5].
Preoperative CRP 1.0 mg/dL tended also to be associated with fatal cardiac events 12-year after CABG, but its impact was not statistically significant. This finding can be related to a nonperfect definition of cardiac event in the discharge records. It has been shown in 1997 that the positive predictive value of the International Classification of Diseases code for acute myocardial infarction compared with the FINMONICA definite/possible acute myocardial infarction category was about 90%, but the sensitivity varied from 50% at local hospitals to 80% at central hospitals [6]. These figures for the definition of myocardial infarction were not much improved in a more recent analysis [7].
The present study has several limitations. Beside its retrospective nature, the lack of specified CRP levels below 1.0 mg/dL prevented the analysis of CRP as a continuous variable and thus the identification of a possibly better cut-off value that the present one. On the other hand, this series provided a unique possibility to evaluate this parameter excluding from the analysis those patients with clinical signs/symptoms of infection or on antibiotic treatment, furthermore, during a period in which statins were not yet in use. This has lead to exclusion from the analysis of a few patients with acute coronary syndrome and/or heart failure-related infection (i.e. pneumonia), and to inclusion of patients with ‘pure’ coronary artery disease. This explains the observed low operative mortality and morbidity rates and the fact that CRP was not predictive of these immediate postoperative adverse events. The latter do not conflict with our previous findings since our most recent series was unselected and having a markedly higher postoperative mortality and morbidity rates [3].
In conclusion, increased preoperative levels of CRP are associated with significantly decreased overall survival after primary on-pump CABG.
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Footnotes
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1 Present address: Department of Vascular Surgery, Helsinki University Hospital, Helsinki, Finland. 
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References
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Abstract
1. Introduction
