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131.
  • Åkerblom, Axel, 1977-, et al. (författare)
  • Cystatin C and Estimated Glomerular Filtration Rate as Predictors for Adverse Outcome in Patients with ST-Elevation and Non-ST-Elevation Acute Coronary Syndromes : Results from the Platelet Inhibition and Patient Outcomes Study
  • 2012
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 58:1, s. 190-199
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:We evaluated the predictive ability of cystatin C and creatinine-based estimations of glomerular filtration rate (eGFR), including the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, in acute coronary syndrome (ACS) patients with (STE-ACS) or without (NSTE-ACS) ST elevation in a large contemporary ACS population.METHODS:Concentrations of cystatin C and creatinine, as well as eGFR at randomization, were measured in 16 401 patients in the Platelet Inhibition and Patient Outcomes (PLATO) study and evaluated as predictors of the composite end point of cardiovascular death or myocardial infarction within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro-B-type natriuretic peptide, troponin I, and C-reactive protein.RESULTS:The median cystatin C value was 0.83 mg/L. Increasing quartiles of cystatin C were strongly associated with poor outcome (6.9%, 7.1%, 9.5%, and 16.2%). The fully adjusted hazard ratios per SD of cystatin C in the NSTE-ACS and STE-ACS populations were 1.12 (95% CI 1.04-1.20) (n = 8053) and 1.06 (95% CI 0.97-1.17) (n = 5278), respectively. There was no significant relationship of cystatin C with type of ACS (STE or NSTE). c Statistics ranged from 0.6923 (cystatin C) to 0.6941 (CKD-EPI).CONCLUSIONS:Cystatin C concentration contributes independently in predicting the risk of cardiovascular death or myocardial infarction in NSTE-ACS, with no interaction by type of ACS. CKD-EPI exhibited the largest predictive value of all renal markers. Nevertheless, the additive predictive value of cystatin C or creatinine-based eGFR measures in the unselected ACS patient is small.
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132.
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133.
  • Åkerblom, Axel, et al. (författare)
  • Interleukin-18 in patients with acute coronary syndromes.
  • 2019
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:12, s. 1202-1209
  • Tidskriftsartikel (refereegranskat)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.
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134.
  • Åkerblom, Axel, 1977-, et al. (författare)
  • Polymorphism of the cystatin C gene in patients with acute coronary syndromes : Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study
  • 2014
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:1, s. 96-102
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: Plasma cystatin C is independently associated with cardiovascular (CV) risk in non-ST-elevation acute coronary syndromes (NSTE-ACS). The effect of genetic variability on cystatin C concentrations and outcome is unclear.Methods: Plasma cystatin C concentrations were measured in blood, obtained within 24 hours of admission, in 16279 ACS patients from the PLATelet inhibition and patient Outcomes trial. 9978 patients were genome-wide genotyped with up to 2.5 million SNPs. The first occurrence of CV death or myocardial infarction (MI) within one year was evaluated by multivariable (clinical variables and biomarkers) Cox regression analysis and c-statistics both overall (all ACS) and in NSTE-ACS.Results: We observed SNPs association with cystatin C levels (up to p=7.82 x 10-16). The most significant SNP (rs6048952) was adjacent the CST3 gene with additive effect on cystatin C concentrations: 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G and G/G genotypes respectively. Multivariable c-statistics regarding the combined endpoint (CV death or MI) was 0.6619. Adding cystatin C concentrations or genetically adjusted cystatin C levels, exhibited c-statistics of 0.6705 and 0.6703, respectively.The overall hazard ratio for rs6048952 was 0.93 (95%CI 0.82-1.04) regarding the CV death or MI while 0.85 (95%CI 0.70-1.03) regarding CV death in all ACS patients. In the NSTE-ACS subgroup, the hazard ratio for rs6048952 was 0.72 (95%CI 0.54-0.95).Conclusions: Genetic polymorphism, independently of kidney function, affects cystatin C concentrations, but does not appear to influence ischemic outcome in an overall ACS population. However, genetic variation appears to affect cardiovascular mortality in moderate-to-high risk NSTE-ACS patients.
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135.
  • Åkerblom, Axel, 1977-, et al. (författare)
  • Prevalence and relevance of abnormal glucose metabolism in acute coronary syndromes : insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
  • 2019
  • Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer. - 0929-5305 .- 1573-742X. ; 48:4, s. 563-569
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes mellitus (DM) and abnormal glucose metabolism are associated with cardiovascular (CV) disease. We investigated the prevalence and prognostic importance of dysglycaemia in patients with acute coronary syndromes (ACS) in the PLATelet inhibition and patient Outcomes (PLATO) trial. Diabetes was defined as known diabetes or HbA1c >= 6.5% or non-fasting glucose >= 11.1 mmol/L on admission, prediabetes as HbA1c >= 5.7% but < 6.5%, and no diabetes as HbA1c < 5.7%. The primary endpoint was the composite of CV death, spontaneous myocardial infarction type 1 (sMI) or stroke at 12 months. Multivariable Cox regression models, adjusting for baseline characteristics, and biomarkers NT-proBNP and troponin I, were used to explore the association between glycaemia and outcome. On admission, 16,007 (86.1%) patients had HbA1c and/or glucose levels available and were subdivided into DM 38.5% (6160) (1501 patients had no previous DM diagnosis), prediabetes 38.8% (6210), and no DM 22.7% (3637). Kaplan Meier event rates at 12 months for CV death, sMI or stroke per subgroups were 14.5% (832), 9.0% (522), and 8.5% (293), respectively with multivariable adjusted HRs, versus no diabetes, for diabetes: 1.71 (1.50-1.95) and for prediabetes 1.03 (0.90-1.19). Corresponding event rates for CV death were 6.9% (391), 3.4% (195) and 3.0% (102), respectively, with adjusted HRs for patients with DM of: 1.92 (1.42-2.60) and for prediabetes 1.02 (0.79-1.32). Abnormal glucose metabolism is common in ACS patients, but only patients with definite DM have an increased CV risk, indicating that prediabetes is not immediately associated with worse CV outcomes.
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136.
  • Åkerblom, Axel, 1977-, et al. (författare)
  • Ticagrelor in patients with heart failure after acute coronary syndromes - Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
  • 2019
  • Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 213, s. 57-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown.Methods: We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission. The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF.Results: Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF. Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276).Conclusions: In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.
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