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The prognostic value of elevated creatine kinase to predict poor outcome in patients with COVID-19 - A systematic review and meta-analysis.
Akbar, MR, Pranata, R, Wibowo, A, Lim, MA, Sihite, TA, Martha, JW
Diabetes & metabolic syndrome. 2021;(2):529-534
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Abstract
BACKGROUND AND AIMS Creatine kinase (CK), a marker of muscle damage, is potentially associated with a more severe COVID-19. In this systematic review and meta-analysis, we aim to evaluate the association between the elevated CK and severity and mortality in COVID-19. METHODS We performed a systematic literature search on PubMed, Scopus, and Embase up until January 26, 2020. The main outcome was poor outcome, a composite of mortality and severe COVID-19. RESULTS There are 2471 patients from 14 studies included in this systematic review and meta-analysis. The incidence of elevated CK in this pooled analysis was 17% (11%, 22%) and the incidence of poor outcome in this pooled analysis was 27% (19%, 34%). Elevated CK was associated with poor outcome in patients with COVID-19 (OR 3.01 [2.21, 4.10], p < 0.001; I2: 10.2%). The effect estimate did not vary with age (p = 0.610), male (p = 0.449), hypertension (p = 0.490), and diabetes (p = 0.457). Elevated CK has a sensitivity of 0.24 (0.17, 0.32), specificity of 0.91 (0.86, 0.94), PLR of 2.6 (1.9, 3.7), NLR of 0.84 (0.78, 0.90), DOR of 3 (2, 5), and AUC of 0.62 (0.57, 0.66) for predicting poor outcome in patients with COVID-19. In this pooled analysis, elevated CK confers to a 49% probability for poor outcome and a non-elevated CK confers to a 24% probability. Subgroup analysis and univariate meta-regression indicates that the sensitivity and specificity does not vary with age, male, hypertension, and diabetes. CONCLUSION Elevated CK was associated with increased mortality and severity in patients with COVID-19. PROSPERO CRD42021233435.
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Phototherapy on Management of Creatine Kinase Activity in General Versus Localized Exercise: A Systematic Review and Meta-Analysis.
Machado, AF, Micheletti, JK, Lopes, JSS, Vanderlei, FM, Leal-Junior, ECP, Netto Junior, J, Pastre, CM
Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. 2020;(3):267-274
Abstract
OBJECTIVE The main focus of this systematic review was to determine the efficacy of phototherapy in the management of creatine kinase (CK) activity after exercise and furthermore to identify for which exercise model protocol phototherapy provides the best results. DESIGN Meta-analysis comparing phototherapy with a control condition. SETTING The MEDLINE, EMBASE, SPORTDiscus, PEDro, and CENTRAL databases were searched from their earliest records to October 03, 2016. Data were pooled in a meta-analysis and described as standardized mean difference (SMD) with 95% confidence intervals (CIs) using a random effects model. PARTICIPANTS Healthy subjects (no restrictions were applied, eg, age, sex, and exercise level). INTERVENTION Phototherapy (low-level laser therapy and/or light-emitting diode therapy) before or after exercise and a placebo or control condition. MAIN OUTCOME MEASURES Creatine kinase activity (no restriction to any analysis, eg, serum, plasma, or capillary blood). RESULTS Fourteen studies were included for review. The results revealed that phototherapy has a more positive effect than control condition in management of CK activity [SMD = 0.77, 95% CI (0.32 to 1.22); P = 0.0007; I = 72%]. In exploratory analysis, the results showed that phototherapy was effective only in the exercise protocol with localized exercise with large effect size [localized exercise: SMD = 0.89, 95% CI (0.26 to 1.51); P = 0.0002; I = 76%; general exercise: SMD = 0.61, 95% CI (-0.05 to 1.26); P = 0.07; I = 67%]. CONCLUSIONS The available evidence suggest that phototherapy has beneficial effects on the management of CK activity and demonstrate a possible relationship based on damage caused by exercise, providing a greater effect in studies that used localized exercise.
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Creatine kinase, neuromuscular fatigue, and the contact codes of football: A systematic review and meta-analysis of pre- and post-match differences.
Hagstrom, AD, Shorter, KA
European journal of sport science. 2018;(9):1234-1244
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Physiological or performance tests are routinely utilised to assess athletes' recovery. At present, the ideal tool to assess recovery remains unknown. Therefore, the aim of this systematic review was to examine the change in creatine kinase (CK) and neuromuscular function as measured via a countermovement jump (CMJ) following a match in the contact codes of football. A comprehensive search of databases was undertaken with RevMan (V 5.3) used for statistical analysis. Our results demonstrated that CK pre- versus post-match (standardised mean difference (SMD) = 0.90, 95% CI = 0.50 to 1.31, p < .0001), CK pre- versus 24 h post-match (SMD = 1.50, 95% CI = 1.12 to 1.88, p < .00001), and CK pre- versus 48 h post-match all increased significantly (SMD = 0.90, 95% CI = 0.50 to 1.31, p < .0001), while CMJ peak power (PP) pre- versus post-match (SMD = -0.59, 95% CI = -1.12 to -0.06, p = .03), and pre- versus 24 h post-match (SMD = -0.80, 95% CI = -1.31 to -0.28, p = .002) decreased significantly. There was a significant relationship between the change in CK and the change in CMJ PP from immediately pre to immediately post (r = -0.924, p = .025), and between CMJ immediately following a match and 24 h CK change (r = -0.983, p = .017). In conclusion, CK levels increase and performance in the CMJ decreases following a match of a contact code of football. The identification of this relationship may allow coaching staff to implement a standalone measure of recovery.
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The value of serum creatine kinase in predicting the risk of rhabdomyolysis-induced acute kidney injury: a systematic review and meta-analysis.
Safari, S, Yousefifard, M, Hashemi, B, Baratloo, A, Forouzanfar, MM, Rahmati, F, Motamedi, M, Najafi, I
Clinical and experimental nephrology. 2016;(2):153-61
Abstract
INTRODUCTION Identifying the potential effective factors of rhabdomyolysis-induced acute kidney injury (AKI) is of major importance for both treatment and logistic concerns. The present study aimed to evaluate the value of creatine kinase (CK) in predicting the risk of rhabdomyolysis-induced AKI through meta-analysis. METHODS Two reviewers searched the electronic databases of Medline, EMBASE, Cochrane library, Scopus, and Google Scholar. Data regarding study design, patient characteristics, number of cases, mean and screening characteristics of CK, and final patient outcome were extracted from relevant studies. Pooled measures of standardized mean difference, OR, and diagnostic accuracy were calculated using STATA version 11.0. RESULT 5997 non-redundant studies were found (143 potentially relevant). 27 articles met the inclusion criteria but 9 were excluded due to lack of data. The correlation between serum CK and AKI occurrence was stronger in traumatic cases (SMD = 1.34, 95 % CI = 1.25-1.42, I(2) = 94 %; p < 0.001). This correlation was more prominent in crush-induced AKI (adjusted OR = 14.7, 95 % CI = 7.63-28.52, I(2) = 0.0 %; p = 0.001). Area under the ROC curve of CK in predicting AKI occurrence was 0.75 (95 % CI = 0.71-0.79). CONCLUSION The results of this meta-analysis declared the significant role of rhabdomyolysis etiology (traumatic/non-traumatic) in predictive performance of CK. There was a significant correlation between mean CK level and risk of crush-induced AKI. The pooled OR of CK was considerable, but its screening performance characteristics were not desirable.
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Clinical Inquiry: when you suspect ACS, which serologic marker is best?
Mitchell, J, Mounsey, A, Mackler, L
The Journal of family practice. 2014;(2):106-20
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Creatine and creatine analogues in hypertension and cardiovascular disease.
Horjus, DL, Oudman, I, van Montfrans, GA, Brewster, LM
The Cochrane database of systematic reviews. 2011;(11):CD005184
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BACKGROUND The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a target for pharmacologic intervention. OBJECTIVES To systematically evaluate evidence regarding the effectiveness of interventions directly targeting the creatine kinase system as compared to placebo control in adult patients with essential hypertension or cardiovascular disease. SEARCH METHODS Electronic databases searched: Medline (1950 - Feb 2011), Embase (up to Feb 2011), the Cochrane Controlled Trials Register (issue 3, Aug 2009), Latin-American/Caribbean databank Lilacs; references from textbooks and reviews; contact with experts and pharmaceutical companies; and searching the Internet. There was no language restriction. SELECTION CRITERIA Randomized controlled trials comparing creatine, creatine phosphate, or cyclocreatine (any route, dose or duration of treatment) with placebo; in adult patients with essential hypertension, heart failure, or myocardial infarction. We did not include papers on the short-term use of creatine during cardiac surgery. DATA COLLECTION AND ANALYSIS The outcomes assessed were death, total myocardial infarction (fatal or non-fatal), hospitalizations for congestive heart failure, change in ejection fraction, and changes in diastolic and systolic blood pressure in mm Hg or as percent change. MAIN RESULTS Full reports or abstracts from 1164 papers were reviewed, yielding 11 trials considering treatment with creatine or creatine analogues in 1474 patients with heart failure, ischemic heart disease or myocardial infarction. No trial in patients with hypertension was identified. Eleven trials (1474 patients, 35 years or older) comparing add-on therapy of the creatine-based drug on standard treatment to placebo control in patients with heart failure (6 trials in 1226 / 1474 patients ), or acute myocardial infarction (4 trials in 220 / 1474 patients) or 1 in ischemic heart disease (28 / 1474 patients) were identified. The drugs used were either creatine, creatine phosphate (orally, intravenously, or intramuscular) or phosphocreatinine. In the trials considering heart failure all three different compounds were studied; creatine orally (Gordon 1995, Kuethe 2006), creatine phosphate via intravenous infusion (Ferraro 1996, Grazioli 1992), and phosphocreatinine orally (Carmenini 1994, Maggi 1990). In contrast, the acute myocardial infarction trials studied intravenous creatine phosphate only. In the ischemic heart disease trial (Pedone 1984) creatine phosphate was given twice daily through an intramuscular injection to outpatients and through an intravenous infusion to inpatients. The duration of the study intervention was shorter for the acute patients, from a two hour intravenous infusion of creatine phosphate in acute myocardial infarction (Ruda 1988, Samarenko 1987), to six months in patients with heart failure on oral phosphocreatinine therapy (Carmenini 1994). In the acute myocardial infarction patients the follow-up period varied from the acute treatment period (Ruda 1988) to 28 days after start of the symptoms (Samarenko 1987) or end of the hospitalization period (Zochowski 1994). In the other trials there was no follow-up after discontinuation of treatment, except for Gordon 1995 which followed the patients until four days after stopping the intervention.Only two out of four trials in patients with acute myocardial infarction reported mortality outcomes, with no significant effect of creatine or creatine analogues (RR 0.73, CI: 0.22 - 2.45). In addition, there was no significance on the progression of myocardial infarction or improvement on ejection fraction. The main effect of the interventions seems to be on improvement of dysrhythmia. AUTHORS' CONCLUSIONS This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations.
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Impact of statin dosing intensity on transaminase and creatine kinase.
Dale, KM, White, CM, Henyan, NN, Kluger, J, Coleman, CI
The American journal of medicine. 2007;(8):706-12
Abstract
PURPOSE Higher intensity statin therapy reduces cardiovascular events more than lower intensity therapy, but the safety impact of higher intensity therapy is unknown. We performed a meta-analysis of randomized controlled trials comparing higher versus lower intensity therapy on liver and muscle safety. METHODS A systematic literature search through January 2006 was conducted to identify randomized trials comparing higher versus lower intensity statin therapy meeting our criteria. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (random-effects model). Statistical heterogeneity scores were assessed with the Q statistic and L'Abbe plots. Publication bias was assessed with the Egger weighted regression and funnel plots. RESULTS Higher intensity statin therapy increased the incidence of transaminase elevations (RR 3.10 [95% Confidence Interval [CI], 0.88-7.85]) versus lower intensity statin therapy. When studies of hydrophilic and lipophilic statins were evaluated separately, higher intensity hydrophilic statin therapy increased the risk for transaminase elevations (RR 3.54 [95% CI, 1.83-6.85]), but higher intensity lipophilic therapy did not (RR 1.58 [95% CI, 0.81-3.08]). The risk of creatine kinase (CK) elevations showed a trend toward an increase (RR 2.63 [95% CI, 0.88-7.85]) with higher intensity therapy. No occurrences of CK elevations occurred in studies evaluating hydrophilic statins, whereas lipophilic statins showed an increased risk with higher intensity therapy (RR 6.09 [95% CI, 1.36-27.35]). CONCLUSIONS More aggressive statin therapy increases the incidence of transaminase elevations in clinical trials versus lower intensity therapy. Increases in transaminases may be more problematic when hydrophilic statins are used aggressively, whereas CK elevations are more problematic with higher intensity lipophilic statin therapy.
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Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous coronary intervention.
Ioannidis, JP, Karvouni, E, Katritsis, DG
Journal of the American College of Cardiology. 2003;(8):1406-11
Abstract
OBJECTIVES The aim of this study was to assess whether small creatine kinase-MB isoenzyme (CK-MB) elevations after percutaneous coronary intervention (PCI) affect the subsequent mortality risk. BACKGROUND Several studies have evaluated the relationship of CK-MB levels after PCI with the subsequent risk of death. While there is consensus that elevations exceeding 5 times the upper limit of normal increase mortality significantly, there is uncertainty about the exact clinical impact of smaller CK-MB elevations. METHODS We performed a meta-analysis of seven studies with CK-MB measurements and survival outcomes on 23230 subjects who underwent PCI. Data were combined with random effects models. RESULTS Mean follow-up was 6 to 34 months per study. By random effects, 19% (95% confidence interval [CI], 16% to 23%) had one- to five-fold CK-MB elevations, while only 6% (95% CI, 5% to 9%) had >5-fold elevations. Compared with subjects with normal CK-MB, there was a dose-response relationship with relative risks for death being 1.5 (95% CI, 1.2 to 1.8, no between-study heterogeneity) with one- to three-fold CK-MB elevations, 1.8 (95% CI, 1.4 to 2.4, no between-study heterogeneity) with three- to five-fold CK-MB elevations, and 3.1 (95% CI, 2.3 to 4.2, borderline between-study heterogeneity) with over five-fold CK-MB elevations (p < 0.001 for all). CONCLUSIONS Any increase in CK-MB after PCI is associated with a small, but statistically and clinically significant, increase in the subsequent risk of death.
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Accuracy of biomarkers to diagnose acute cardiac ischemia in the emergency department: a meta-analysis.
Balk, EM, Ioannidis, JP, Salem, D, Chew, PW, Lau, J
Annals of emergency medicine. 2001;(5):478-94
Abstract
STUDY OBJECTIVE We sought to evaluate quantitatively the evidence on the diagnostic performance of presentation and serial biochemical markers for emergency department diagnosis of acute cardiac ischemia (ACI), including acute myocardial infarction (AMI) and unstable angina. METHODS We conducted a systematic review and meta-analysis of the English-language literature published between 1966 and December 1998. We examined the diagnostic performance of creatine kinase, creatine kinase-MB, myoglobin, and troponin I and T testing. Diagnostic performance was assessed by using estimates of test sensitivity and specificity and was summarized by summary receiver-operating characteristic curves. RESULTS Only 4 studies were found that evaluated all patients with ACI; 73 were found that focused only on a diagnosis of AMI. To diagnose ACI, presentation biomarker tests had sensitivities of 16% to 19% and specificities of 96% to 100%; serial biomarker tests had sensitivities of 31% to 45% and specificities of 95% to 98%. Considering only the diagnosis of AMI, presentation biomarker tests had summary sensitivities of 37% to 49% and summary specificities of 87% to 97%; serial biomarker tests had summary sensitivities of 79% to 93% and summary specificities of 85% to 96%. Variation of test sensitivity was best explained by test timing. Longer symptom duration or time between serial tests yielded higher sensitivity. CONCLUSION The limited evidence available to evaluate the diagnostic accuracy of biomarkers for ACI suggests that biomarkers have very low sensitivity to diagnose ACI. Thus, biomarkers alone will greatly underdiagnose ACI and will be inadequate to make triage decisions. For AMI diagnosis alone, multiple testing of individual biomarkers over time substantially improves sensitivity, while retaining high specificity, at the expense of additional time. Further high-quality studies are needed on the clinical effect of using biomarkers for patients with ACI in the ED and on optimal timing of serial testing and in combination with other tests.