Is the increase in eltrombopag dose cause of myocardial infarction?
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ABSTRACT:
SUBMITTER: Ozgunoglu EC
PROVIDER: S-EPMC8274900 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (?30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.
| S-EPMC4599491 | biostudies-literature
Project description:Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy.This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival.A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences.Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome.These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (The PACE-MI Registry Study-Outcomes of Beta-blocker Therapy After Myocardial Infarction [OBTAIN]: NCT00430612).
| S-EPMC4583654 | biostudies-literature
Project description:PurposePrevious reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD). This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI).Methods and materialsA nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009. Cases were 183 patients with MI as their first heart disease after BC. One control per case was selected and matched on age and BC diagnosis date. Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts. Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan.ResultsMedian age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7). Median time to MI was 13.6 years (interquartile range, 9.9-18.1). Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy). MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%). Patients receiving ?20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients. ERRs were higher for younger women, with borderline significance (ERR<45years, 24.2%/Gy; ERR?50years, 2.5%/Gy; Pinteraction = .054). Whole heart dose-volume parameters did not modify the dose-response relationship significantly.ConclusionsMI rate after radiation for BC increases linearly with MWHD. Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.
| S-EPMC6361769 | biostudies-literature
Project description:BackgroundWhether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown.ObjectiveTo assess whether oral multivitamins reduce cardiovascular events and are safe.DesignDouble-blind, placebo-controlled, 2 x 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) SETTING: 134 U.S. and Canadian academic and clinical sites.Patients1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 mol/L (2.0 mg/dL) or less.InterventionPatients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo.MeasurementsThe primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina.ResultsThe median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events.LimitationThere was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety).ConclusionHigh-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.Primary funding sourceNational Institutes of Health.
| S-EPMC4143134 | biostudies-literature
Project description:Coronary artery disease (CAD) is characterised by progressive atherosclerotic plaque leading to flow-limiting stenosis, while myocardial infarction (MI) occurs due to plaque rupture or erosion with abrupt coronary artery occlusion. Multiple inflammatory pathways influence plaque stability, but direct assessment of endothelial inflammation at the site of coronary artery stenosis has largely been limited to pathology samples or animal models of atherosclerosis. We describe a technique for isolating and characterising endothelial cells (ECs) and EC microparticles (EMPs) derived directly from the site of coronary artery plaque during balloon angioplasty and percutaneous coronary intervention. Coronary artery endothelial cells (CAECs) were identified using imaging flow cytometry (IFC), and individual CAEC and EMP expression of the pro-atherogenic adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) was assessed immediately following angioplasty. Patients with MI registered 73?% higher VCAM-1 expression on their CAECs and 79?% higher expression on EMPs compared to patients with stable CAD. In contrast, VCAM-1 expression was absent on ECs in the peripheral circulation from these same subjects. VCAM-1 density was significantly higher on CAECs and EMPs among patients with MI and positively correlated with markers of myocardial infarct size. We conclude that increased VCAM-1 expression on EC and formation of EMP at the site of coronary plaque is positively correlated with the extent of vascular inflammation in patients with myocardial infarction.
| S-EPMC4479188 | biostudies-literature
Project description:Depression and stress have each been found to be associated with poor prognosis in patients with coronary heart disease. A recently offered psychosocial perfect storm conceptual model hypothesizes amplified risk will occur in those with concurrent stress and depressive symptoms. We tested this hypothesis in a large sample of US adults with coronary heart disease.Participants included 4487 adults with coronary heart disease from the REasons for Geographic and Racial Differences in Stroke study, a prospective cohort study of 30,239 black and white adults. We conducted Cox proportional hazards regression with the composite outcome of myocardial infarction or death and adjustment for demographic, clinical, and behavioral factors. Overall, 6.1% reported concurrent high stress and high depressive symptoms at baseline. During a median 5.95 years of follow-up, 1337 events occurred. In the first 2.5 years of follow-up, participants with concurrent high stress and high depressive symptoms had increased risk for myocardial infarction or death (adjusted hazard ratio, 1.48 [95% confidence interval, 1.08-2.02]) relative to those with low stress and low depressive symptoms. Those with low stress and high depressive symptoms (hazard ratio, 0.92 [95% confidence interval, 0.66-1.28]) or high stress and low depressive symptoms (hazard ratio, 0.86 [95% confidence interval, 0.57-1.29]) were not at increased risk. The association on myocardial infarction or death was not significant after the initial 2.5 years of follow-up (hazard ratio, 0.89 [95% confidence interval, 0.65-1.22]).Our results provide initial support for a psychosocial perfect storm conceptual model; the confluence of depressive symptoms and stress on medical prognosis in adults with coronary heart disease may be particularly destructive in the shorter term.
| S-EPMC4366334 | biostudies-literature
Project description:This study sought to assess whether plasminogen, which is homologous to lipoprotein (a) [Lp(a)], contains proinflammatory oxidized phospholipids (OxPL) and whether this has clinical relevance.OxPL measured on apolipoprotein B-100 (OxPL/apoB), primarily reflecting OxPL on Lp(a), independently predict cardiovascular disease (CVD) events.The authors examined plasminogen from commercially available preparations and plasma from chimpanzees; gorillas; bonobos; cynomolgus monkeys; wild-type, apoE(-/-), LDLR(-/-), and Lp(a)-transgenic mice; healthy humans; and patients with familial hypercholesterolemia, stable CVD, and acute myocardial infarction (AMI). Phosphocholine (PC)-containing OxPL (OxPC) present on plasminogen were detected directly with liquid chromatography-mass spectrometry (LC-MS/MS) and immunologically with monoclonal antibody E06. In vitro clot lysis assays were performed to assess the effect of the OxPL on plasminogen on fibrinolysis.LC-MS/MS revealed that OxPC fragments were covalently bound to mouse plasminogen. Immunoblot, immunoprecipitation, density gradient ultracentrifugation, and enzyme-linked immunosorbent assay analyses demonstrated that all human and animal plasma samples tested contained OxPL covalently bound to plasminogen. In plasma samples subjected to density gradient fractionation, OxPL were present on plasminogen (OxPL/plasminogen) in non-lipoprotein fractions but on Lp(a) in lipoprotein fractions. Plasma levels of OxPL/apoB and OxPL/apo(a) varied significantly (>25×) among subjects and also strongly correlated with Lp(a) levels. In contrast, OxPL/plasminogen levels were distributed across a relatively narrow range and did not correlate with Lp(a). Enzymatic removal of OxPL from plasminogen resulted in a longer lysis time for fibrin clots (16.25 vs. 11.96 min, p = 0.007). In serial measurements over 7 months, OxPL/plasminogen levels did not vary in normal subjects or in patients with stable CVD, but increased acutely over the first month and then slowly decreased to baseline in patients following AMI.These data demonstrate that plasminogen contains covalently bound OxPL that influence fibrinolysis. OxPL/plasminogen represent a second major plasma pool of OxPL, in addition to those present on Lp(a). OxPL present on plasminogen may have pathophysiological implications in AMI and atherothrombosis.
| S-EPMC3333481 | biostudies-literature
Project description:BACKGROUND:Coronary artery calcification (CAC) and atherosclerotic inflammation associate with increased risk of myocardial infarction (MI). Vascular calcification is regulated by osteogenic proteins (OPs). It is unknown whether an association exists between CAC and plasma OPs and if they are affected by atherothrombotic inflammation. We tested the association of osteogenic and inflammatory proteins with CAC and assessed these biomarkers after MI. METHODS:Circulating OPs (osteoprotegerin, RANKL, fetuin-A, Matrix Gla protein [MGP]) and inflammatory proteins (C-reactive protein, oxidized-LDL, tumoral necrosis factor-?, transforming growth factor [TGF]-?1) were compared between stable patients with CAC (CAC ? 100 AU, n = 100) and controls (CAC = 0 AU, n = 30). The association between biomarkers and CAC was tested by multivariate analysis. In patients with MI (n = 40), biomarkers were compared between acute phase and 1-2 months post-MI, using controls as a baseline. RESULTS:MGP and fetuin-A levels were higher within individuals with CAC. Higher levels of MGP and RANKL were associated with CAC (OR 3.12 [95% CI 1.20-8.11], p = 0.02; and OR 1.75 [95% CI 1.04-2.94] respectively, p = 0.035). After MI, C-reactive protein, OPG and oxidized-LDL levels increased in the acute phase, whereas MGP and TGF-?1 increased 1-2 months post-MI. CONCLUSIONS:Higher MGP and RANKL levels associate with CAC. These findings highlight the potential role of these proteins as modulators and markers of CAC. In addition, the post-MI increase in OPG and MGP, as well as of inflammatory proteins suggest that the regulation of these OPs is affected by atherothrombotic inflammation.
| S-EPMC6107213 | biostudies-literature
Project description:Very low-dose (VLD) factor Xa (FXa) inhibition, in combination with acetylsalicylic acid (ASA) and clopidogrel, is associated with improved outcomes in patients with acute coronary syndrome (ACS) with a tolerable bleeding risk profile. To date, there are no data documenting platelet inhibition and the anticoagulatory effects of VLD FXa inhibition on top of guideline-adherent dual-antiplatelet therapy (DAPT) in patients with ACS. Patients with non-ST-elevation myocardial infarction (NSTEMI) receiving oral DAPT (ASA + clopidogrel, n = 20; or ASA + ticagrelor, n = 20) were prospectively enrolled in a nonrandomized study. Coagulation- and platelet-dependent thrombin generation (TG), measured by means of the calibrated automated thrombogram, were significantly decreased after in vitro and in vivo addition of rivaroxaban. As shown by a total thrombus-formation analysis approach, rivaroxaban treatment led to a significantly decreased coagulation-dependent (AR-chip) thrombus formation in patients treated with ASA plus P2Y12 inhibitor (clopidogrel/ticagrelor), whereas the pure platelet-dependent (PL-chip) thrombus formation was not affected at all. Adjunctive rivaroxaban therapy was not associated with significant differences in platelet aggregation assessed by light-transmission aggregometry (LTA). Nevertheless, according to fluorescence-activated cell sorter analysis, VLD rivaroxaban treatment resulted in a significantly reduced expression of platelet HMGB-1, whereas P-selectin exposure was not affected. Furthermore, an enhanced effect of rivaroxaban on total thrombus formation and TG was observed in particular in clopidogrel nonresponder patients defined as adenosine 5'-diphosphate-induced LTA ?40%. VLD rivaroxaban reduces thrombus formation and platelet-dependent TG in patients with ACS receiving DAPT, which can be of potential ischemic benefit. This trial was registered at www.clinicaltrials.gov as #NCT01417884.
| S-EPMC5873232 | biostudies-literature
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to use RNA-seq to compare ILC1s gene expression in ST segmment elevation myocardial infarction patient compared with healthy control. Results: Using an optimized data analysis workflow, More than 70 million clean reads were obtained from each sample group after elimination of low-quality reads. A total of 4204 DEGs were found up-regulated and 4712 DEGs down-regulated on comparison of ILC1s from STEMI patients and controls. Conclusion: The dynamic number and gene expression changes in the subtype ILC1s indicate the role of ILCs in STEMI.
2020-02-23 | GSE127853 | GEO