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

BACKGROUND: It 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. METHODS: The 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. RESULTS: The 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. DISCUSSION: The 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 NUMBER: NCT00000472.

Creatine kinase is associated with bleeding after myocardial infarction.

BACKGROUND: The ADP-scavenging enzyme creatine kinase (CK) is reported to reduce ADP-dependent platelet activation. Therefore, we studied whether highly elevated CK after ST-elevation myocardial infarction (STEMI) is associated with bleeding. METHODS: Data of the Thrombolysis in Myocardial Infarction Study Group phase II trial on the efficacy of angioplasty, following intravenous recombinant tissue-type plasminogen activator (rt-PA), are used to assess whether peak plasma CK (CKmax) is independently associated with adjudicated fatal or non-fatal bleeding (primary) and combined bleeding/all-cause mortality (secondary) in multivariable binomial logistic regression analysis, adjusting for baseline and treatment allocation covariates. RESULTS: The included patients (n=3339, 82% men, 88% white, mean age 57 years, SE 0.2) had a history of angina pectoris (55%), hypertension (38%) and/or diabetes mellitus (13%). CKmax ranged from 16 to 55 890 IU/L (mean 2389 IU/L, SE 41), reached within 8 hours in 51% of the patients (93% within 24 hours). Adjudicated fatal/non-fatal bleeding occurred in 30% of the patients (respectively 26% in the low vs 34% in the high CK tertile), and bleeding/all-cause mortality in 35% (29% in the low vs 40% in the high CK tertile). In multivariable regression analysis, the adjusted OR for fatal/non-fatal bleeding (vs not bleeding and survival) was 2.6 (95% CI 1.8 to 3.7)/log CKmax increase, and 3.1 (2.2 to 4.4) for bleeding/all-cause mortality. CONCLUSION: Highly elevated plasma CK after myocardial infarction might be an independent predictor of bleeding and haemorrhagic death. This biologically plausible association warrants further prospective study of the potential role of extracellular CK in ADP-dependent platelet activation and bleeding.

Hypertension prevalence, awareness, treatment, and control in Surinamese living in Suriname and The Netherlands: the HELISUR and HELIUS studies.

We studied hypertension prevalence, awareness, treatment, and control among persons living in a middle-income country compared with those of similar ethnicity living in a high-income country. Data from the cross-sectional HELISUR and HELIUS studies were used among 1000 Surinamese and 6971 Surinamese migrants living in The Netherlands (18-70 years), respectively. Groups were formed based on country and self-defined ethnicity, and stratified by sex. Age-adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated for hypertension prevalence, awareness, treatment, and control. Subsequently, we focused on hypertension prevalence and adjusted for risk factors for hypertension: BMI and waist circumference (model 2), educational level, physical activity, and smoking (model 3). After adjustment for age, no significant differences in hypertension prevalence, awareness, treatment, and control between countries were seen in men. However, women in Suriname were more often hypertensive with lower levels of awareness and control than those in The Netherlands (African: OR 1.54 [95% CI 1.19, 2.00]; South-Asian: 1.90 [1.35, 2.67]; awareness: 0.62 [0.43, 0.88] in African women; control: 0.48 [0.28, 0.84] in South-Asian women). Higher hypertension prevalence was explained by differences in BMI and waist circumference in African women (adjusted OR 1.26 [0.96, 1.65]) and by education, physical activity, and smoking in South-Asian women (adjusted OR 1.29 [0.87, 1.89]). Particularly, women in Suriname bear a relatively high hypertension burden with lower levels of awareness and control. As the higher hypertension prevalence was mainly explained by lifestyle-related risk factors, health promotion interventions may reduce the hypertension burden in Suriname.