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Role of Creatine Kinase in the Troponin Era: A Systematic Review

ABSTRACT:

Introduction

The diagnosis of non-ST-elevated myocardial infarction (NSTEMI) depends on a combination of history, electrocardiogram, and cardiac biomarkers. The most sensitive and specific biomarkers for cardiac injury are the troponin assays. Many hospitals continue to automatically order less sensitive and less specific biomarkers such as creatine kinase (CK) alongside cardiac troponin (cTn) for workup of patients with chest pain. The objective of this systematic review was to identify whether CK testing is useful in the workup of patients with NSTEMI symptoms.

Methods

We undertook a systematic review to ascertain whether CK ordered as part of the workup for NSTEMI was useful in screening patients with cardiac chest pain. The MEDLINE, Embase, and Cochrane databases were searched from January 1995–September 2020. Additional papers were added after consultation with experts. We screened a total of 2,865 papers, of which eight were included in the final analysis. These papers all compared CK and cTn for NSTEMI diagnosis.

Results

In each of the eight papers included in the analysis, cTn showed a greater sensitivity and specificity than CK in the diagnosis of NSTEMI. Furthermore, none of the articles published reliable evidence that CK is useful in NSTEMI diagnosis when troponin was negative.

Conclusion

There is no evidence to continue to use CK as part of the workup of NSTEMI acute coronary syndrome in undifferentiated chest pain patients. We conclude that CK should not be used to screen patients presenting to the emergency department with chest pain.

SUBMITTER: Beamish D

PROVIDER: S-EPMC8597688 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Creatine kinase (CK) is an energy storage enzyme that plays an important role in energy metabolism. CK/phosphocreatine functions as an energy buffer and links ATP production sites with ATP utilization sites. Several key mutations in the ?A-crystallin (cryaa) and ?B-crystallin (cryab) genes have been linked with autosomal-dominant, hereditary human cataracts. The cryaa-R49C mutation was identified in a four-generation Caucasian family. We previously identified an increase in the quantity of CK complexed with ?-crystallin in the lenses of knock-in mice expressing the cryaa-R49C mutation using proteomic analyses. Increased levels of CK in postnatal cataractous lenses may indicate increased ATP requirements during early cataract development. To gain a further understanding of the relationship between CK and ?-crystallin, we investigated whether ?-crystallin interacts with and forms complexes with CK, in vitro. Isothermal titration calorimetry (ITC) showed that each CK dimer bound to 28 ?-crystallin subunits, with a Kd of 3.3 × 10-7 M, and that the interaction between ?-crystallin and CK was endothermic, thermodynamically favorable, and entropy-driven. High-salt concentrations did not affect the interaction between CK and ?-crystallin, suggesting that the interaction between CK and ?-crystallin is primarily hydrophobic. Gel permeation chromatography (GPC) detected water-soluble ?-crystallin and CK complexes, as determined by increased light scattering after complex formation. In addition, CK and ?-crystallin formed partially-water-insoluble, high-molecular-mass complexes. Enzyme-linked immunosorbent assay (ELISA)-based enzymatic activity analyses of lens homogenates showed a 17-fold increase in CK activity in the postnatal lenses of cryaa-R49C knock-in mice. These studies indicate that the interaction between ?-crystallin and CK is functionally important and that increased CK levels may be necessary to meet the increased ATP demands of ATP-dependent functions in cataractous lenses.

Project description:BackgroundCreatine kinase plays a key role in cellular energy transport. The enzyme transfers high-energy phosphoryl groups from mitochondria to subcellular sites of ATP hydrolysis, where it buffers ADP concentration by catalyzing the reversible transfer of the high-energy phosphate moiety (P) between creatine and ADP. Cellular creatine uptake is competitively inhibited by beta-guanidinopropionic acid. This substance is marked as safe for human use, but the effects are unclear. Therefore, we systematically reviewed the effect of beta-guanidinopropionic acid on energy metabolism and function of tissues with high energy demands.MethodsWe performed a systematic review and searched the electronic databases Pubmed, EMBASE, the Cochrane Library, and LILACS from their inception through March 2011. Furthermore, we searched the internet and explored references from textbooks and reviews.ResultsAfter applying the inclusion criteria, we retrieved 131 publications, mainly considering the effect of chronic oral administration of beta-guanidinopropionic acid (0.5 to 3.5%) on skeletal muscle, the cardiovascular system, and brain tissue in animals. Beta-guanidinopropionic acid decreased intracellular creatine and phosphocreatine in all tissues studied. In skeletal muscle, this effect induced a shift from glycolytic to oxidative metabolism, increased cellular glucose uptake and increased fatigue tolerance. In heart tissue this shift to mitochondrial metabolism was less pronounced. Myocardial contractility was modestly reduced, including a decreased ventricular developed pressure, albeit with unchanged cardiac output. In brain tissue adaptations in energy metabolism resulted in enhanced ATP stability and survival during hypoxia.ConclusionChronic beta-guanidinopropionic acid increases fatigue tolerance of skeletal muscle and survival during ischaemia in animal studies, with modestly reduced myocardial contractility. Because it is marked as safe for human use, there is a need for human data.