| 1. |
- Batra, Gorav, et al.
(author)
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Effects of early myocardial reperfusion and perfusion on myocardial necrosis/dysfunction and inflammation in patients with ST-segment and non-ST-segment elevation acute coronary syndrome : results from the PLATelet inhibition and patients Outcomes (PLATO) trial
- 2022
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In: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 11:4, s. 336-349
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Journal article (peer-reviewed)abstract
- Aims Restoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade (TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown. Methods and results Among 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis [troponin T (TnT)], myocardial dysfunction [N-terminal prohormone brain natriuretic peptide (NT-proBNP)], inflammation [interleukin-6 (IL-6) and C-reactive protein (CRP)], and oxidative stress/ageing/inflammation [growth differentiation factor-15 (GDF-15)] were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann-Whitney-Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01). Conclusions Successful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS.
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| 2. |
- Kontny, Frederic, et al.
(author)
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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
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In: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:4, s. 313-322
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Journal article (peer-reviewed)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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| 3. |
- Schunk, Stefan J., et al.
(author)
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Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
- 2021
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
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Journal article (peer-reviewed)abstract
- AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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