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Sökning: WFRF:(Ghukasyan Tatevik)

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1.
  • Andersen, Thomas, et al. (författare)
  • C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes
  • 2019
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 39:11, s. 2402-2410
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.Approach and Results:Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.Conclusions:In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.
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2.
  • Batra, Gorav, et al. (författare)
  • Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome
  • 2021
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 6:12, s. 1440-1445
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease.Objective: To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function.Design, Setting, and Participants: This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020.Exposures: Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs ≥2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [≥90 mL/min/1.73 m2], mildly decreased eGFR level [60-90 mL/min/1.73 m2], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m2]).Main Outcomes and Measures: Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke.Results: This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (≥2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]).Conclusions and Relevance: In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.
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4.
  • Franchi, Francesco, et al. (författare)
  • Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial
  • 2019
  • Ingår i: Journal of the American Heart Association. - 2047-9980 .- 2047-9980. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM+/CKD- and DM-/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P-interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P-interaction=0.288). Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
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5.
  • Gregersen, Ida, et al. (författare)
  • Legumain in Acute Coronary Syndromes : A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial
  • 2020
  • Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980 .- 2047-9980. ; 9:17
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The cysteine protease legumain is increased in patients with atherosclerosis, but its causal role in atherogenesis and cardiovascular disease is still unclear. The aim of the study was to investigate the association of legumain with clinical outcome in a large cohort of patients with acute coronary syndrome. METHODS AND RESULTS : Serum levels of legumain were analyzed in 4883 patients with acute coronary syndrome from a substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Levels were analyzed at admission and after 1 month follow-up. Associations between legumain and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and its individual components were assessed by multivariable Cox regression analyses. At baseline, a 50% increase in legumain level was associated with a hazard ratio (HR) of 1.13 (95% CI, 1.04-1.21),P=0.0018, for the primary composite end point, adjusted for randomized treatment. The association remained significant after adjustment for important clinical and demographic variables (HR, 1.10; 95% CI, 1.02-1.19;P=0.013) but not in the fully adjusted model. Legumain levels at 1 month were not associated with the composite end point but were negatively associated with stroke (HR, 0.62; 95% CI, 0.44-0.88;P=0.0069), including in the fully adjusted model (HR, 0.57; 95% CI, 0.37-0.88;P=0.0114). CONCLUSIONS: Baseline legumain was associated with the primary outcome in patients with acute coronary syndrome, but not in the fully adjusted model. The association between high levels of legumain at 1 month and decreased occurrence of stroke could be of interest from a mechanistic point of view, illustrating the potential dual role of legumain during atherogenesis and acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00391872.
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6.
  • Hilvo, Mika, et al. (författare)
  • Prediction of Residual Risk by Ceramide-Phospholipid Score in Patients With Stable Coronary Heart Disease on Optimal Medical Therapy
  • 2020
  • Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980 .- 2047-9980. ; 9:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Identification of patients with stable coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced ceramide-and phospholipid-based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable coronary heart disease on optimal medical therapy and to identify biological processes that contribute to the CERT2 score. METHODS AND RESULTS: Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were analyzed using a tandem liquid chromatography-mass spectrometry method. STABILITY was a trial in patients with stable coronary heart disease randomized to the lipoprotein-associated phospholipase A2 inhibitor darapladib or placebo on optimized medical therapy at baseline, with a median follow-up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25-1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35-1.59) for cardiovascular death, 1.32 (95% CI, 1.16-1.49) for stroke, 1.23 (95% CI, 1.14-1.33) for myocardial infarction, and 1.56 (95% CI, 1.39-1.76) for hospitalization due to heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P<0.001, r>0.2) with inflammatory markers high-sensitivity C-reactive protein, interleukin 6, the heart failure marker N-terminal pro-B-type natriuretic peptide, and low-density lipoprotein cholesterol. After also adjusting for levels of other prognostic biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. CONCLUSIONS: The CERT2 risk score can detect residual risk in patients with stable coronary heart disease and is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia.
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7.
  • Hjort, Marcus, 1988-, et al. (författare)
  • Biomarker Concentrations and Their Temporal Changes in Patients With Myocardial Infarction and Nonobstructive Compared With Obstructive Coronary Arteries : Results From the PLATO Trial
  • 2023
  • Ingår i: Journal of the American Heart Association. - : American heart association. - 2047-9980 .- 2047-9980. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights.Methods and Results: In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs‐cTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hs‐CRP (high‐sensitivity C‐reactive protein), and GDF‐15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1‐month follow‐up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow‐up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short‐ and long‐term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs‐cTnT (GMR, 0.77 [95% CI, 0.68–0.88]) but higher hs‐CRP (GMR, 1.21 [95% CI, 1.08–1.37]) and GDF‐15 concentrations (GMR, 1.06 [95% CI, 1.02–1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT‐proBNP concentrations were similar. Temporal decreases in hs‐cTnT, NT‐proBNP, and hs‐CRP concentrations until 1‐month follow‐up were more pronounced in patients with MINOCA. At follow‐up, patients with MINOCA had lower concentrations of hs‐cTnT (GMR, 0.71 [95% CI, 0.60–0.84]), NT‐proBNP (GMR, 0.45 [95% CI, 0.36–0.56]), and hs‐CRP (GMR, 0.68 [95% CI, 0.53–0.86]). One‐month GDF‐15 concentrations were similar between both groups with MI.Conclusions: Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial recovery.CLINICAL TRAIL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
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8.
  • Kontny, Frederic, et al. (författare)
  • Pentraxin-3 vs C-reactive protein and other prognostic biomarkers in acute coronary syndrome : A substudy of the Platelet Inhibition and Patients Outcomes (PLATO) trial
  • 2020
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:4, s. 313-322
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: We investigated the dynamics, associations with patient characteristics, other biomarkers, and clinical outcomes of pentraxin 3 in acute coronary syndrome.METHODS AND RESULTS: In multivariate analyses, pentraxin 3 measured in 5154 patients randomised in the Platelet Inhibition and Patients Outcomes (PLATO) trial (NCT00391872) was compared with leukocytes, high-sensitivity C-reactive protein, interleukin-6, cystatin C, N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15 concerning prediction of clinical outcome. Pentraxin 3 peaked earlier than high-sensitivity C-reactive protein and was more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein. The frequency of cardiovascular death, spontaneous myocardial infarction or stroke by quartiles of pentraxin 3 at admission was 6.1%, 7.3%, 9.7% and 10.7%, respectively ( p<0.0001). The hazard ratio per 50% increase of pentraxin 3 was 1.13 (95% confidence interval: 1.07-1.19), p<0.0001. This association remained significant after stepwise adjustments for leukocytes/high-sensitivity C-reactive protein (1.09 (1.02-1.15)), p=0.009, interleukin-6 (1.07 (1.01-1.14)), p=0.026, and cystatin C (1.07 (1.00-1.13)), p=0.044, but not after adjustment for N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15. Admission pentraxin 3 was also associated with several of the individual endpoint components (cardiovascular death/spontaneous myocardial infarction; p=0.008, cardiovascular death; p=0.026, and spontaneous myocardial infarction; p=0.017), but not with stroke. Pentraxin 3 measured in the chronic phase (i.e. at one month) was still predictive of the composite endpoint in univariate analysis (1.12 (1.04-1.20) per 50% increase) p=0.0024, but not after adjustment for the other biomarkers.CONCLUSION: Admission level of pentraxin 3 is a modestly stronger predictor than high-sensitivity C-reactive protein and interleukin-6, but not than N-terminal prohormone brain natriuretic peptide or high-sensitivity troponin T, concerning cardiovascular outcome in acute coronary syndrome. Pentraxin 3 is more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein.
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9.
  • Nelson, Thomas A, et al. (författare)
  • Differential effect of clopidogrel and ticagrelor on leukocyte count in relation to patient characteristics, biomarkers and genotype : a PLATO substudy.
  • 2022
  • Ingår i: Platelets. - : Taylor & Francis. - 0953-7104 .- 1369-1635. ; 33:3, s. 425-431
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation plays a key role in cardiovascular disease by contributing to atherothrombosis. The PLATelet inhibition and patient Outcomes (PLATO) study (NCT00391872) compared ticagrelor to clopidogrel in patients with acute coronary syndromes and demonstrated fewer cardiovascular events with ticagrelor but lower white blood cell counts (WBC) with clopidogrel. In this further analysis of the PLATO biomarker substudy, we assessed associations between WBC and clinical characteristics, biomarker levels, and CYP2C19 polymorphisms.On-treatment mean (SD) WBC in the clopidogrel group was mildly reduced at each stage of follow-up compared with either the ticagrelor group (1 month: 7.27 (2.1) and 7.67 (2.23) x109/L for clopidogrel and ticagrelor, respectively; p < .001) or following cessation of clopidogrel (7.23 (1.97) x109/L, at 6 months vs 7.56 (2.28) x109/L after treatment cessation; P < .001). This occurred independently of baseline biomarkers and CYP2C19 genotype (where known). Adjusting for clinical characteristics and other biomarkers, no significant interaction was detected between clinical risk factors and the observed effect of clopidogrel on WBC.Clopidogrel weakly suppresses WBC, independent of clinical characteristics, baseline inflammatory biomarker levels, and CYP2C19 genotype. Further work is required to determine the mechanism for this effect and whether it contributes to clopidogrel's efficacy as well as therapeutic interaction with anti-inflammatory drugs.
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10.
  • Thomas, Mark R., et al. (författare)
  • Prognostic impact of baseline inflammatory markers in patients with acute coronary syndromes treated with ticagrelor and clopidogrel.
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 10:2, s. 153-163
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Inflammation plays a major role in the pathophysiology of coronary artery disease. We aimed to determine whether baseline inflammatory markers were associated with clinical outcomes and the observed superiority of ticagrelor compared to clopidogrel in patients with acute coronary syndromes in the PLATO study.METHODS: Blood samples were collected from 16,400 patients within 24 hours of the onset of acute coronary syndrome, at the time of random assignment to ticagrelor or clopidogrel in the PLATO study and prior to invasive procedures. The differential white blood cell count and plasma levels of C-reactive protein, interleukin-6 and interleukin-10 were determined and their relationships with clinical outcomes were assessed according to quartiles and using continuous models. The substudy primary endpoint was a composite of cardiovascular death and myocardial infarction.RESULTS: Compared to the lowest quartile, the risk of the primary endpoint was significantly elevated in patients in the highest quartile of white blood cell count (hazard ratio (HR) 1.30; P=0.01), neutrophil count (HR 1.33; P=0.007), monocyte count (HR 1.24; P=0.004), C-reactive protein (HR 1.93; P<0.001) and interleukin-6 (HR 2.29; P<0.001). This was predominantly driven by an association with cardiovascular death. Following adjustment for clinical characteristics, troponin, cystatin C and N-terminal pro-brain-type natriuretic peptide, only white blood cell count and neutrophil count maintained a significant association with the primary endpoint. Ticagrelor had a consistent relative cardiovascular benefit compared to clopidogrel in each quartile of each of the inflammatory markers.CONCLUSIONS: Acute coronary syndrome patients with elevated levels of baseline inflammatory markers are at increased risk of adverse cardiovascular events, particularly cardiovascular death. The consistent cardiovascular benefit of ticagrelor compared to clopidogrel tended to confer a greater absolute risk reduction in patients with the highest levels of inflammatory markers, as they were at highest risk.
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