Prognostic importance of creatine kinase and creatine kinase–MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction

doi:10.1016/j.ahj.2007.11.004

American Heart Journal

Volume 155, Issue 4, April 2008, Pages 673-679

https://doi.org/10.1016/j.ahj.2007.11.004 Get rights and content

Background

Although the prognostic significance of creatine kinase (CK) and creatine kinase–MB (CK-MB) after myocardial infarction has been established after thrombolysis or no reperfusion therapy, there is limited evidence of the prognostic importance after primary percutaneous coronary intervention (PCI).

Methods

In this prospective, observational study, individual data from all patients who survived at least 2 days after primary PCI between 1991 and 2004 in our hospital were recorded. The association between enzymatic infarct size (examined by peak CK and peak CK-MB levels, each divided into tertiles) and both left ventricular ejection fraction (LVEF) and 1-year mortality was evaluated.

Results

In the study group of 4670 patients, mean peak CK was 2327 U/L (SD 2008) and mean peak CK-MB was 244 U/L (SD 208). Both increased CK and CK-MB were associated with a lower LVEF. A total of 252 patients (5.4%) died between 2 days and 1 year after admission. Both peak CK and peak CK-MB were higher in those who died. Particularly, patients in the highest tertile of either peak CK or peak CK-MB had increased mortality, whereas the differences between the lower tertiles were not significant. In 2738 patients, after multivariable analysis including LVEF, the hazard ratio for 1-year mortality in patients in the highest CK tertile was 2.28 (95% CI 1.32-3.91) and for CK-MB, 1.91 (95% CI 1.11-3.26), compared to those in the other tertiles.

Conclusions

According to this large-scale study, peak CK and peak CK-MB are comparable independent predictors of LV function and 1-year mortality in patients after primary PCI.

Section snippets

Population

From January 1991 to December 2004, individual patient data from all patients with admission diagnosis of STEMI admitted for primary PCI at the Isala klinieken (Zwolle, Netherlands) were prospectively recorded. Patients who died during the first 2 days were not included in this substudy because many of these patients died before peak CK was recorded. Furthermore, patients with peak CK values >10 000 U/L were excluded because these high elevations of CK were probably at least partly due to

Baseline characteristics

Of the 4670 included patients, mean age was 60.8 years (SD 11.8) and 1102 patients (24%) were female. Data on peak CK and peak CK-MB were available in all patients. Mean peak CK was 2327 U/L (SD 2008) and mean CK-MB, 244 (SD 208). The range in the 3 tertiles was <1080 U/L, 1080 to 2660 U/L, and >2660 U/L, respectively, for CK; and <120 U/L, 120 to 281 U/L, and >281 U/L, respectively, for CK-MB. Differences of the baseline characteristics between the tertiles of CK are summarized in Table I and

Discussion

The present study shows that both peak CK and peak CK-MB are comparable independent predictors of LVEF and 1-year mortality in patients after primary PCI for STEMI. Furthermore, particularly patients in the highest tertiles of either CK or CK-MB had a poor prognosis, whereas the differences between the lower tertiles were less clear.

Conclusions

Our study shows an independent association between either peak CK or CK -MB and both LV function and mortality in patients undergoing primary PCI. Accordingly, the worldwide use of these 2 biomarkers seems to be justified, also in patients with TIMI-3 flow after mechanical reperfusion therapy. Future efforts should be aimed toward how to improve treatment in high-risk patients, as identified by peak CK(-MB).

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Randomized Control of Sympathetic Drive With Continuous Intravenous Esmolol in Patients With Acute ST-Segment Elevation Myocardial Infarction: The BEtA-Blocker Therapy in Acute Myocardial Infarction (BEAT-AMI) Trial
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Biomarker evaluation is a limitation of the study due to indirect estimation of myocardial damage. On the other hand, all the evaluated biomarkers—troponin (37–41), CK (42,43), CKMB (38,44), and NT-proBNP (45–48)—have been identified as strong prognostic indicators in patients with AMI. In the BEAT-AMI trial, all four evaluated biomarkers were significantly lowered by esmolol-induced heart rate control, indicating a protective effect of acute intravenous esmolol.
This study sought to evaluate the role of esmolol-induced tight sympathetic control in patients with ST-segment elevation myocardial infarction (STEMI).
Elevated sympathetic drive has a detrimental effect on patients with acute STEMI. The effect of beta-blocker-induced heart rate mediated sympathetic control on myocardial damage is unknown.
The authors conducted a prospective, randomized, single-blind trial involving patients with STEMI and successful percutaneous intervention (Killip class I and II). Patients were randomly allocated to heart rate control with intravenous esmolol for 24 h or placebo. The primary outcome was the maximum change in troponin T release as a prognostic surrogate marker for myocardial damage. A total of 101 patients were enrolled in the study.
There was a significant difference between patients allocated to placebo and those who received sympathetic control with esmolol in terms of maximum change in troponin T release: the median serum troponin T concentration increased from 0.2 ng/ml (interquartile range [IQR] 0.1 to 0.7 ng/ml) to 1.3 ng/ml (IQR: 0.6 to 4.7 ng/ml) in the esmolol group and from 0.3 ng/ml (IQR: 0.1 to 1.2 ng/ml) to 3.2 ng/ml (IQR: 1.5 to 5.3 ng/ml) in the placebo group (p = 0.010). The levels of peak creatine kinase (CK), CK subunit MB (CK-MB), and n-terminal brain natriuretic peptide (NT-proBNP) were lower in the esmolol group compared with placebo (CK 619 U/l [IQR: 250–1,701 U/l] vs. 1,308 U/l [IQR: 610 to 2,324 U/l]; p = 0.013; CKMB: 73.5 U/l [IQR: 30 to 192 U/l] vs. 158.5 U/l [IQR: 74 to 281 U/l]; p = 0.005; NT-proBNP: 1,048 pg/ml (IQR: 623 to 2,062 pg/ml] vs. 1,497 pg/ml [IQR: 739 to 3,318 pg/ml]; p = 0.059). Cardiogenic shock occurred in three patients in the placebo group and in none in the esmolol group.
Esmolol treatment statistically significantly decreased troponin T, CK, CK-MB and NT-proBNP release as surrogate markers for myocardial injury in patients with STEMI. (Heart Rate Control After Acute Myocardial Infarction; DRKS00000766)
Renal dysfunction and hsCRP predict long-term outcomes of percutaneous coronary intervention in acute myocardial infarction
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The authors also analyzed serum biomarkers frequently assessed in clinical practice, such as CTnI, CK and CK-MB. These have been shown to reliably predict infarct size and prognosis in patients with MI.34 Nienhuis et al34 showed that both peak CK and peak CK-MB levels could independently predict mortality and LVEF at 1 year in patients with STEMI who had undergone primary PCI.
This study assessed the combined utility of estimated glomerular filtration rate (eGFR) and serum high-sensitivity C-reactive protein (hsCRP) levels to predict long-term mortality and cardiovascular outcomes of patients with acute sT-segment elevation myocardial infarction (sTEMi) undergoing primary percutaneous coronary intervention (PCI). Elevated CRP levels and renal dysfunction have both been shown to independently and jointly predict mortality and cardiovascular outcomes after PCI in the short term. However, long-term results in patients with acute STEMI undergoing PCI have not been reported.
A total of 262 patients with acute STEMI undergoing primary PCI were classified at admission into quartiles according to eGFR (< 60, 60-70, 70-80 and ≥ 80 mL · min^–1 · 1.73 m^–2) and hsCRP (< 3 and ≥ 3 mg/L). Mortality, nonfatal myocardial infarction (MI) and major adverse cardiac events (MACEs) were compared among the groups.
During a median follow-up of 48.3 months, the composite of all-cause mortality and nonfatal MI (mortality + MI) was significantly higher (35.09%) in the group with the lowest eGFR compared with that of the other 3 eGFR groups (14.29%, 3.77% and 9.43%, respectively, P < 0.0001) and the group with elevated hsCRP (34.29%) versus that with hsCRP < 3 mg/L (4.41%, P < 0.0001). A combined analysis showed an exaggerated hazard in patients with the lowest eGFR and highest hsCRP (hazard ratio: 44.658; 95% confidence interval: 5.955–111.890).
Renal dysfunction and elevated hsCRP predict a high long-term incidence of MACE in patients with acute STEMI undergoing primary PCI, with the combination being of prognostic significance for long-term mortality and MI in these patients.
Effects of Prolastin C (plasma-derived alpha-1 antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study)
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There were no clinically significant changes in blood pressure, heart rate, and temperature during infusions (Table 2). Peak creatine kinase-MB, an estimate of infarct size,7 was remarkably similar between patients treated with AAT (123 [48 to 183] ng/ml) and historical placebo controls (123 [77 to 189] ng/ml, p = 0.85). The use of guideline-recommended treatments at discharge was not different comparing Prolastin C versus placebo controls (Supplementary Table 2).
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Citation Excerpt :
In an analysis of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications trial, peak CK concentration after primary PCI was shown to be a powerful predictor of 1-year mortality independent of other clinical and angiographic measures.13 In a large prospective cohort study of 4,670 patients from a single center, Nienhuis et al14 demonstrated that peak CK and CK-MB measurements were independent predictors of left ventricular function and 1-year mortality in primary PCI–treated acute MI. Our study of a multicenter primary PCI–treated STEMI cohort with systematically collected core laboratory–determined CK-MB measurements further extends these findings by quantifying the strength of this association.
Peak creatine kinase (CK)–MB concentration is related to reperfusion success and clinical outcomes after fibrinolytic therapy for acute myocardial infarction. However, prognostic implications of CK-MB measurements after primary percutaneous coronary intervention (PCI), which provides more predictable and consistent reperfusion, are unknown.
We pooled 2,042 primary PCI–treated ST-segment elevation myocardial infarction (STEMI) patients from 3 trials with serial core laboratory–determined CK-MB measurements; 1,799 patients (88.1%) who survived to 36 hours and had ≥4 CK-MB measurements were studied. Cox regression modeling was performed to quantify the association between peak CK-MB concentration (and area under the time-concentration curve [AUC]) and mortality at 6 months, and death or congestive heart failure at 90 days.
The median (25th-75th percentiles) peak CK-MB concentration and AUC measurement through 36 hours were 239 (109-429) ng/mL and 4,263 (2,081-7,124) ng/(mL h), respectively. By multivariable analysis, peak CK-MB concentration and AUC measurement were independently associated with 6-month mortality (adjusted hazard ratio [HR] 1.15, 95% CI 1.05-1.25, per 100-ng/mL increase, P = .002; and adjusted HR 1.09, 95% CI 1.03-1.14, per 1,000-ng/[mL h] increase, P < .001, respectively) and 90-day death or congestive heart failure (adjusted HR 1.26, 95% CI 1.18-1.34, P < .001; and adjusted HR 1.15, 95% CI 1.11-1.19, P < .001, respectively).
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Clinical InvestigationsInterventional CardiologyPrognostic importance of creatine kinase and creatine kinase–MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction

Background

Methods

Results

Conclusions

Section snippets

Population

Baseline characteristics

Discussion

Conclusions

Am Heart J

J Am Coll Cardiol

Am J Cardiol

Am Heart J

Am Heart J

J Am Coll Cardiol

Am J Cardiol

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

Atherosclerosis

J Am Coll Cardiol

Estimation of infarct size in man and its relation to prognosis

Circulation

Enzymatic indices of myocardial necrosis: influence on short- and long-term prognosis after myocardial infarction

Circulation

Clinical Investigations
Interventional Cardiology
Prognostic importance of creatine kinase and creatine kinase–MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction