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CLINICAL STUDY

The prognostic value of creatine kinase elevations extends across the whole spectrum of acute coronary syndromes

Stefano Savonitto, MD^*,*, Christopher B. Granger, MD, FACC, Diego Ardissino, MD, Laura Gardner, BSPH, Claudio Cavallini, MD^||, Marcello Galvani, MD^¶, Filippo Ottani, MD^#, Harvey D. White, DSc, FACC^**, Paul W. Armstrong, MD, FACC, E. Magnus Ohman, MD, FACC, Karen S. Pieper, MSc, Robert M. Califf, MD, FACC, Eric J. Topol, MD, FACC GUSTO-IIb Investigators

^* Department of Cardiology, Niguarda Hospital, Milan, Italy
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
Division of Cardiology, Ospedali Riuniti di Parma, Parma, Italy
Duke Clinical Research Institute, Durham, North Carolina, USA
^|| Division of Cardiology, Presidio Ospedaliero Ca’ Foncello, Treviso, Italy
^¶ Division of Cardiology, Ospedale Morgagni-Pierantoni, Forlí, Italy
^# Division of Cardiology, Ospedale Civile, Bentivoglio, Italy
^** Cardiology Department, Green Lane Hospital, Auckland, New Zealand
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Department of Cardiology, Cleveland Clinic, Cleveland, Ohio, USA

Manuscript received April 18, 2001; revised manuscript received August 29, 2001, accepted September 7, 2001.

^* Reprint requests and correspondence: Dr. Stefano Savonitto, Divisione di Cardiologia, Ospedale Niguarda Ca’ Granda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
ssavoni{at}tin.it

OBJECTIVES: The study investigated the relationship among creatine kinase (CK) elevations, clinical characteristics and cardiac events across the whole spectrum of acute coronary syndromes (ACS).

BACKGROUND: Elevated serum levels of cardiac enzymes have been shown to be a major prognostic determinant in acute myocardial ischemia. Yet prior to this report, the relation between cardiac enzyme levels and other prognostic determinants across the entire spectrum of ACS has not been explored by a large clinical study.

METHODS: We evaluated the relation between the maximum CK ratio (CK level/upper limit of normal) in the early hours following admission and cardiac events at six months in 11,725 patients enrolled in a large trial of ACS.

RESULTS: Patients with higher risk characteristics, such as older age, female gender, hypertension, diabetes, prior coronary events or heart failure, more frequently presented without ST-segment elevation on the electrocardiogram and tended to develop lesser enzyme elevations. After adjusting for significant baseline predictors of cardiac events, a continuous correlation was observed between the CK ratio and death (chi-square 63.04, p < 0.0001) and (re)infarction or death (chi-square 55.48, p < 0.0001). This correlation was similar for patients with and without ST-segment elevation. The adjusted incidence of cardiac events at follow-up began to rise even for CK levels within the normal range, the steepest part of the curve residing between one and three times the upper limit of normal. In patients with a CK ratio of >1 to 2 compared with those within the normal range, the adjusted odds ratio for death was 1.26 (95% confidence interval [CI] 0.98 to 1.63), and 1.59 (95% CI 1.38 to 1.90) for (re)infarction and death. For all CK levels, the event rate was higher among patients without ST-segment elevation.

CONCLUSIONS: Although high-risk patients with ACS often develop lesser CK elevations, this study demonstrated that even minor enzyme elevations appear to have important and independent prognostic implications.

Abbreviations and Acronyms   ACS   acute coronary syndromes   CK   creatine kinase   CK-MB   creatine kinase-myocardial band   ECG   electrocardiogram/electrocardiographic   GUSTO-IIb   Global Use of Strategies to Open Occluded Coronary Arteries-IIb trial   MI   myocardial infarction   PTCA   percutaneous transluminal coronary angioplasty

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