Creatine kinase during non-ST-segment elevation acute coronary syndromes is associated with major bleeding

BackgroundIt was recently reported that highly elevated plasma activity of the ADP-scavenging enzyme creatine kinase (CK), to >10 times the upper reference limit (URL), is independently associated with fatal or non-fatal bleeding during treatment for ST-segment elevation myocardial infarction (OR 2.6 (95% CI, 1.8 to 2.7)/log CK increase). Evidence indicates that CK attenuates ADP-dependent platelet aggregation. This study investigates whether moderately elevated CK in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is associated with major bleeding.MethodsThe Thrombolysis In Myocardial Ischemia (TIMI) 3B trial compared recombinant tissue-type plasminogen activator (rt-PA) (35–80 mg) with placebo and early catheterisation with conservative management in patients with NSTE-ACS. Main outcomes of the current study are the independent association of peak plasma CK (CKmax) with adjudicated fatal or non-fatal major bleeding (primary) and with combined major bleeding, stroke and hospital death (secondary), with covariables including age, sex, body mass index, systolic blood pressure, creatinine and assignment to add-on rt-PA versus placebo. Discrimination was assessed with C-statistics.ResultsThe study included 1473 patients (66% men, 80% white, mean age 59 years, SE 0.3). CKmax ranged between 15 and 19 045 IU/L (mean (SE), 450 (24) IU/L; two times URL). Major bleeding occurred in 2.0% (mean age 65 (1.3) years; mean CKmax 1015 (319) IU/L; six times URL), and the combined outcome in 4.3% of the patients, adjusted OR per log CK increase, respectively, 3.1 (1.6 to 5.9) for major bleeding and 3.9 (2.5 to 6.1) for the combined outcome; C-index 0.8 for both outcomes. The association between CK and bleeding was independent of the use of thrombolytic therapy.DiscussionThe presented data add to the existing evidence that proportionate to its plasma activity, the ADP-binding enzyme CK is strongly and independently associated with non-fatal and fatal major bleeding during treatment for NSTE-ACS. CK might increase the accuracy of prediction models for major bleeding in patients with NSTE-ACS.Trial registration numberNCT00000472.

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Creatine Kinase during Non-ST-Segment Elevation Acute Coronary Syndromes is Associated with Major Bleeding

10.1101/2020.02.28.20029108 ◽

2020 ◽

Author(s):

Lizzy M. Brewster ◽

Jim D. Fernand

Keyword(s):

Creatine Kinase ◽

Major Bleeding ◽

Acute Coronary Syndromes ◽

Prediction Models ◽

Peak Plasma ◽

St Segment Elevation ◽

Reference Limit ◽

St Segment ◽

Coronary Syndromes ◽

Plasma Activity

AbstractBackgroundIt was recently reported that highly elevated plasma activity of the ADP-scavenging enzyme creatine kinase (CK), to >10 times the upper reference limit (URL), is independently associated with fatal or non-fatal bleeding during treatment for ST-segment elevation myocardial infarction (OR 2.6 [95% CI, 1.8 to 2.7]/log CK increase). Evidence indicates that CK attenuates ADP-dependent platelet aggregation. This study investigates whether moderately elevated CK in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) is associated with major bleeding.MethodsThe Thrombolysis In Myocardial Ischemia (TIMI) 3B trial compared rt-PA (35 to 80 mg) with placebo, and early catheterization with conservative management in patients with NSTE-ACS. Main outcomes of the current study are the independent association of peak plasma CK (CKmax) with adjudicated fatal or non-fatal major bleeding (primary), and with combined major bleeding, stroke, and all-cause mortality (secondary) in multivariable binomial logistic regression analysis, with co-variables including age, sex, BMI, SBP, creatinine, and treatment assignment. Discrimination was assessed with C-statistics.ResultsThe study included 1473 patients (66% men, 80% white, mean age 59 y, SE 0.3). CKmax ranged between 15 and 19045 IU/L (mean (SE), 450(24) IU/L; i.e. 2 times URL). Major bleeding occurred in 2.0% (mean age 65(1.3) y; mean CKmax 1015(318) IU/L; 6 times URL), and the combined outcome in 4.3% of the patients, adjusted OR per log CK increase respectively 3.1 [1.6 to 5.8] for major bleeding, and 3.9 [2.5 to 6.1] for the combined outcome; C-index 0.8 for both outcomes.DiscussionThe presented data add to the existing evidence that proportionate to its plasma activity, the ADP-binding enzyme CK is strongly and independently associated with non-fatal and fatal major bleeding during ACS treatment. CK might increase the accuracy of prediction models for major bleeding in patients treated with antithrombotic or thrombolytic drugs for ACS.ClinicalTrials.gov identifierNCT00000472

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Relationship between creatine kinase and major bleeding in patients with non-ST-segment elevation acute coronary syndrome

10.32592/ircmj.2021.23.9.741 ◽

2021 ◽

Keyword(s):

Acute Coronary Syndrome ◽

Creatine Kinase ◽

Major Bleeding ◽

Characteristic Curve ◽

Area Under The Curve ◽

St Segment Elevation ◽

Coronary Syndrome ◽

St Segment ◽

Elevation Acute Coronary Syndrome ◽

The Relationship

Objective: To investigate the relationship between creatine kinase (CK) and major bleeding in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients during hospitalization, and to analyze the predictive value of CK for major bleeding in NSTE-ACS patients during treatment. Methods: A total of 1469 NSTE-ACS patients admitted to our hospital from January 2017 to December 2019 were collected, including 1024 unstable angina pectoris patients and 445 non-ST-segment elevation myocardial infarction patients. Plasma CK and hemoglobin concentrations were measured after admission. The patients were divided into major bleeding group (n=31) and non-major bleeding group (n=1438) according to Thrombolysis In Myocardial Ischemia bleeding classification standard, and they were given routine treatment. Results: During the treatment period, major bleeding occurred in 31 of 1469 NSTE-ACS patients, accounting for 2.11%. CK value in major bleeding group was higher than that in non-major bleeding group (P<0.001). According to the quartile, CK was divided into groups Q1-Q4, and the incidence of major bleeding in group Q4 was higher than that of the other three groups (P<0.001). Plasma CK was positively correlated with major bleeding in NSTE-ACS patients (r=0.59, P<0.001). Receiver operating characteristic curve analysis showed that the area under the curve of baseline CK value was 0.793 (SE=0.062, P=0.001, 95％CI 0.711-0.872) in NSTE-ACS patients during treatment. Conclusion: CK was associated with major bleeding in NSTE-ACS patients.

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Comparison of Site-Reported and Core Laboratory-Reported Creatine Kinase-MB Values in Non–ST-Segment Elevation Acute Coronary Syndrome (from the International Trial SYNERGY)

The American Journal of Cardiology ◽

10.1016/j.amjcard.2009.06.056 ◽

2009 ◽

Vol 104 (10) ◽

pp. 1330-1335 ◽

Cited By ~ 2

Author(s):

Jason P. Linefsky ◽

Min Lin ◽

Karen S. Pieper ◽

Craig J. Reist ◽

Lisa G. Berdan ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Creatine Kinase ◽

St Segment Elevation ◽

International Trial ◽

Coronary Syndrome ◽

St Segment ◽

Creatine Kinase Mb ◽

Elevation Acute Coronary Syndrome

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Demographics, practice patterns and long-term outcomes of patients with non–ST-segment elevation acute coronary syndrome in the past two decades: the CREDO-Kyoto Cohort-2 and Cohort-3

BMJ Open ◽

10.1136/bmjopen-2020-044329 ◽

2021 ◽

Vol 11 (2) ◽

pp. e044329

Author(s):

Yasuaki Takeji ◽

Hiroki Shiomi ◽

Takeshi Morimoto ◽

Yusuke Yoshikawa ◽

Ryoji Taniguchi ◽

...

Keyword(s):

Stent Thrombosis ◽

Major Bleeding ◽

Cardiac Death ◽

Cardiovascular Death ◽

Coronary Revascularisation ◽

St Segment Elevation ◽

Coronary Syndrome ◽

The Past ◽

St Segment ◽

Definite Stent Thrombosis

ObjectivesTo evaluate patient characteristics and long-term outcomes in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) in the past two decades.DesignMulticenter retrospective study.SettingThe Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) Registry Cohort-2 (2005–2007) and Cohort-3 (2011–2013).Participants3254 patients with NSTEACS who underwent first coronary revascularisation.Primary and secondary outcome measuresThe primary outcome was all-cause death. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, any coronary revascularisation and target vessel revascularisation.ResultsPatients in Cohort-3 were older and more often had heart failure at admission than those in Cohort-2. The prevalence of PCI, emergency procedure and guideline-directed medical therapy was higher in Cohort-3 than in Cohort-2. In patients who received PCI, the prevalence of transradial approach, drug-eluting stent use and intravascular ultrasound use was higher in Cohort-3 than in Cohort-2. There was no change in 3-year adjusted mortality risk from Cohort-2 to Cohort-3 (HR 1.00, 95% CI 0.83 to 1.22, p=0.97). Patients in Cohort-3 compared with those in Cohort-2 were associated with lower adjusted risks for stroke (HR 0.65, 95% CI 0.46 to 0.92, p=0.02) and any coronary revascularisation (HR 0.76, 95%CI 0.66 to 0.87, p<0.001), but with higher risk for major bleeding (HR 1.25, 95% CI 1.06 to 1.47, p=0.008). The unadjusted risk for definite stent thrombosis was lower in Cohort-3 than in Cohort 2 (HR 0.29, 95% CI 0.11 to 0.67, p=0.003).ConclusionsIn the past two decades, we did not find improvement for mortality in patients with NSTEACS. We observed a reduction in the risks for definite stent thrombosis, stroke and any coronary revascularisation, but an increase in the risk for major bleeding.

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Factor V Leiden Does Not Modify the Phenotype of Acute Coronary Syndrome or the Extent of Myocardial Necrosis

Journal of the American Heart Association ◽

10.1161/jaha.120.020025 ◽

2021 ◽

Author(s):

Bakhtawar K. Mahmoodi ◽

Niclas Eriksson ◽

Gerrit J. A. Vos ◽

Karina Meijer ◽

Agneta Siegbahn ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Creatine Kinase ◽

Factor V Leiden ◽

High Sensitivity ◽

Factor V ◽

St Segment Elevation ◽

Coronary Syndrome ◽

High Sensitivity Troponin ◽

St Segment ◽

Elevation Acute Coronary Syndrome

Background The prothrombotic defect factor V Leiden (FVL) may confer higher risk of ST‐segment–elevation myocardial infarction (STEMI), compared with non–ST‐segment–elevation acute coronary syndrome, and may be associated with more myocardial necrosis caused by higher thrombotic burden. Methods and Results Patients without history of cardiovascular disease were selected from 2 clinical trials conducted in patients with acute coronary syndrome. FVL was defined as G‐to‐A substitution at nucleotide 1691 in the factor V (factor V R506Q) gene. Odds ratios were calculated for the association of FVL with STEMI adjusted for age and sex in the overall population and in the subgroups including sex, age (≥70 versus <70 years), and traditional cardiovascular risk factors. The peak biomarker levels (ie, creatine kinase‐myocardial band and high‐sensitivity troponin I or T) after STEMI were contrasted between FVL carriers and noncarriers. Because of differences in troponin assays, peak high‐sensitivity troponin levels were converted to a ratio scale. The prevalence of FVL mutation was comparable in patients with STEMI (6.0%) and non–ST‐segment–elevation acute coronary syndrome (5.8%). The corresponding sex‐ and age‐adjusted odds ratio was 1.06 (95% CI, 0.86–1.30; P =0.59) for the association of FVL with STEMI. Subgroup analysis did not show any differences. In patients with STEMI, neither the median peak creatine kinase‐myocardial band nor the peak high‐sensitivity troponin ratio showed any differences between wild‐type and FVL carriers ( P for difference: creatine kinase‐myocardial band=0.33; high sensitivity troponin ratio=0.54). Conclusions In a general population with acute coronary syndrome, FVL did not discriminate between a STEMI or non–ST‐segment–elevation acute coronary syndrome presentation and was unrelated to peak cardiac necrosis markers in patients with STEMI. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT00391872 and NCT01761786.

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