Dataset Information

Interleukin-18 in patients with acute coronary syndromes.

ABSTRACT: BACKGROUND:We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS). HYPOTHESIS AND METHODS:Plasma IL-18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT-hs, NT-proBNP, cystatin C, CRP-hs, and GDF-15). RESULTS:Median IL-18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320?ng/L (n = 16?636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF-15, and CRP-hs were independently associated with higher IL-18 levels. Higher baseline IL-18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02-1.07 and HR 1.10, 95% CI 1.06-1.14, respectively, per 25% increase of IL-18 levels). Associations remained significant after adjustment for clinical variables but became non-significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98-1.04 and HR 1.04, 95% CI 1.00-1.08, respectively). There were no associations with sMI. CONCLUSIONS:In ACS patients, IL-18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL-18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.

SUBMITTER: Akerblom A

PROVIDER: S-EPMC6906991 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interleukin-18 in patients with acute coronary syndromes.

Åkerblom Axel A James Stefan K SK Lakic Tatevik G TG Becker Richard C RC Cannon Christopher P CP Steg Philippe G PG Himmelmann Anders A Katus Hugo A HA Storey Robert F RF Wallentin Lars L Weaver W Douglas WD Siegbahn Agneta A

Clinical cardiology 20191009 12

<h4>Background</h4>We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS).<h4>Hypothesis and methods</h4>Plasma IL-18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarc ...[more]

PMID: 31596518

Similar Datasets

Project description:RATIONALE:Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE:We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. METHODS AND RESULTS:In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. CONCLUSIONS:CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.

Project description:• Population pharmacokinetics and pharmacodynamics of rivaroxaban have been characterized in healthy subjects and in patients with total venous thromboembolism, deep vein thrombosis or atrial fibrillation.• This article is the first description of the population pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in patients with acute coronary syndrome (ACS). It is the largest population pharmacokinetic and pharmacodynamic study on rivaroxaban conducted to date (n= 2290). The PK and PK-PD relationship of rivaroxaban in patients with ACS were similar to those in other patient populations. In addition, model-based simulations showed that the influence of renal function and age on the exposure to rivaroxaban in the ACS population were similar to the findings from Phase 1 special population studies. These findings suggest that rivaroxaban has highly predictable PK-PD and may provide a consistent anticoagulant effect across the studied patient populations, which allows an accurate prediction of the dose to control anticoagulation optimally.The aim of this analysis was to use a population approach to facilitate the understanding of the pharmacokinetics and pharmacodynamics of rivaroxaban in patients with acute coronary syndrome (ACS) and to evaluate the influence of patient covariates on the exposure of rivaroxaban in patients with ACS. METHODS A population pharmacokinetic model was developed using pharmacokinetic samples from 2290 patients in Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 46. The relationship between pharmacokinetics and the primary pharmacodynamic end point, prothrombin time, was evaluated.The pharmacokinetics of rivaroxaban in patients with ACS was adequately described by an oral one-compartment model. The estimated absorption rate, apparent clearance and volume of distribution were 1.24 h(-1) (interindividual variability, 139%), 6.48 l h(-1) (31%) and 57.9 l (10%), respectively. Simulations indicate that the influences of renal function, age and bodyweight on exposure in ACS patients are consistent with the findings in previous Phase 1 studies. Rivaroxaban plasma concentrations exhibit a close-to-linear relationship with prothrombin time in the ACS population, with little interindividual variability. The estimated pharmacokinetic and pharmacodynamic parameters for the ACS patients were comparable to those for venous thromboembolism prevention, deep vein thrombosis and atrial fibrillation patients.The similarity in pharmacokinetics/pharmacodynamics of rivaroxaban among different patient populations and the low interindividual variability in the exposure-prothrombin time relationship indicate that the anticoagulant effect of rivaroxaban is highly predictable and consistent across all the patient populations studied.

Project description:BackgroundPublished data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.ObjectivesThe purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts.MethodsFrom March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).ResultsIn 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).ConclusionsIn this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.

Project description:BackgroundThe Coronary Psychosocial Evaluation Studies trial demonstrated promising results for enhanced depression treatment to reduce cardiovascular risk of patients with acute coronary syndrome and comorbid depression, but the long-term effectiveness of this intervention is unclear.MethodsA total of 157 participants with persistent depression after hospitalization for acute coronary syndromes were enrolled in the Coronary Psychosocial Evaluation Studies trial. A total of 80 participants were allocated to 6 months of enhanced depression treatment, and 77 participants were allocated to usual care. We report on an additional 12 months of observational follow-up for the composite outcome of death or first hospitalization for myocardial infarction or unstable angina.ResultsAlthough the intervention was previously shown to have favorable cardiovascular effects during the treatment period, we observed a significant time-by-treatment group interaction during extended follow-up (P = .008). Specifically, during the 6-month treatment period, death or hospitalization for myocardial infarction/unstable angina occurred in 3 participants (4%) in the treatment group compared with 11 participants (14%) in the usual care group (hazard ratio, 0.25; 95% confidence interval, 0.07-0.90; P = .03). In contrast, during 12 months of additional observational follow-up, 11 participants (14%) in the treatment group experienced the composite outcome of death or hospitalization for myocardial infarction/unstable angina compared with 3 participants (4%) in the usual care group (hazard ratio, 2.91; 95% confidence interval, 0.80-10.56; P = .10).ConclusionsEnhanced depression treatment was associated with a reduced risk of death or hospitalization for myocardial infarction/unstable angina during active treatment, but this effect did not persist after treatment ceased. Future research is needed to confirm our findings and to determine the optimal duration of depression treatment in patients with depression after acute coronary syndromes.

Dataset Information

Interleukin-18 in patients with acute coronary syndromes.

Publications

Interleukin-18 in patients with acute coronary syndromes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets