Aim: Elevation of Troponin after scheduled percutaneous coronary intervention (PCI) is a recognized consequence. We sought to evaluate the prognostic significance and impact of the newly published ...definition of PCI-related myocardial infarction (MI) according to which any troponin elevation >3 times the upper reference limit identify a peri-procedural MI. Methods: Search of BioMedCentral, CENTRAL, mRCT and PubMed (updated May 2008). Outcomes of interest were: MACE the composite of all cause death, MI, repeat target vessel PCI (re-PCI) and coronary artery bypass grafting (CABG); single end points were also assessed. Results: Fifteen studies have been included totalling 7578 patients. Troponin elevation occurred in 28.7% of the procedures. The incidence of PCI-related MI according to the new definition was 14.5%. During the hospitalization, any level of raised troponin was associated with an increased risk of MACE OR 11.29 (3.00–42.48), Number needed to harm (NNH) 5, death OR 7.16 (1.95–26.27), NNH = 100, MI OR 30.85 (6.05–157.38), NNH = 4 and re-PCI OR 4.13 (1.23–13.88), NNH = 50. Patients with PCI-related MI had an increased risk of death OR 17.25 (2.71–109.96), NNH = 100 and re-PCI OR 10.86 (3.2–36.94), NNH = 25. At follow up of 18 months any troponin elevation was associated with an increased risk of MACE OR 1.48 (1.12–1.96), NNH = 20, death OR 2.19 (1.59–3.00), NNH = 50, MI OR 3.29 (2.71–6.31), NNH = 33 and re-PCI OR 1.47 (1.06–2.03), NNH = 25. In patients with PCI-related MI the risk of MACE was further increased: OR 2.25 (1.26–4.00), NNH = 3. An increase of the troponin level below the cut-off was not associated with MACE. Conclusion: A diagnosis of MI according to the new guidelines applies to 15% of patients undergoing PCI and these patients are at high risk of further adverse events both during the hospital stay and at 18 months.
We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-of-hospital cardiac arrest (OHCA) of various aetiologies.
We ...analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3–5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs 95% confidence intervals) and compared these with a bootstrap method.
Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146–1804) pg/mL vs. 31 (17–61) pg/mL at 24 h and 1162 (147–4360) pg/mL vs. 36 (21–87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2–27.3) µg/L vs. 8.5 (5.8–13.2) µg/L at 24 h and 20.4 (8.1–56.6) µg/L vs. 8.2 (5.9–12.1) µg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86–0.94) for NfL vs. 0.65 (0.58–0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83–0.93) for NfL and 0.73 (0.66–0.81) for NSE at 48 h, p < 0.001.
Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.
Loss of ABI gene family member 3-binding protein (ABI3BP) expression may be functionally involved in the pathogenesis of cancer. Previous reports have indicated a loss of expression in lung cancer ...and a presumed role in inducing cellular senescence. We show here that ABI3BP expression is significantly decreased in most malignant thyroid tumors of all types. To better understand ABI3BP's role, we created a model by re-expressing ABI3BP in two thyroid cancer cell lines. Re-expression of ABI3BP in thyroid cells resulted in a decrease in transforming activity, cell growth, cell viability, migration, invasion, and tumor growth in nude mice. ABI3BP re-expression appears to trigger cellular senescence through the p21 pathway. Additionally, ABI3BP induced formation of heterochromatin 1-binding protein gamma-positive senescence-associated (SA) heterochromatin foci and accumulation of SA beta-galactosidase. The combination of a decrease in cell growth, invasion, and other effects upon ABI3BP re-expression in vitro helps to explain the large reduction in tumor growth that we observed in nude mice. Together, our data provide evidence that the loss of ABI3BP expression could play a functional role in thyroid tumorigenesis. Activation of ABI3BP or its pathway may represent a possible basis for targeted therapy of certain cancers.
. Latini R, Masson S, Pirelli S, Barlera S, Pulitano G, Carbonieri E, Gulizia M, Vago T, Favero C, Zdunek D, Struck J, Staszewsky L, Maggioni AP, Franzosi MG, Disertori M on the behalf of the ...GISSI‐AF Investigators (Istituto di Ricerche Farmacologiche “Mario Negri”, Milan; Istituti Ospitalieri, Cremona; POL Madonna della Consolazione, Reggio Calabria; Ospedale Nuovo Girolimo Fracastoro, San Bonifacio; Ospedale Garibaldi‐Nesima, Catania; Ospedale Luigi Sacco, Milan, Italy; Roche Diagnostics, Rotkreuz, Switzerland; B.R.A.H.M.S. AG, Henningsdorf, Germany; ANMCO Research Center, Florence; and Ospedale Santa Chiara, Trento, Italy). Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI‐Atrial Fibrillation Trial. J Intern Med 2011; 269: 160–171.
Objective. We evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF).
Background. Predicting long‐term maintenance of sinus rhythm in patients with AF is difficult.
Methods. Plasma concentrations of three specific cardiac markers high‐sensitivity troponin T (hsTnT), N‐terminal probrain natriuretic peptide (NT‐proBNP) and mid‐regional proatrial natriuretic peptide (MR‐proANP) and three stable fragments of vasoactive peptides mid‐regional proadrenomedullin (MR‐proADM), copeptin (CT‐proAVP) and CT‐proendothelin‐1 (CT‐proET‐1) were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI‐AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models.
Results. Mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) 95% confidence intervals (CIs) for 1 SD increment (1.15 1.04–1.28, P = 0.007), MR‐proANP (1.15 1.01–1.30, P = 0.04), NT‐proBNP (1.24 1.11–1.39, P = 0.0001) and CT‐proET‐1 (1.16 1.01–1.33, P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR‐proANP tended to predict subsequent recurrence (adjusted HR 95%CI) (1.53 0.98–2.37, P = 0.06).
Conclusion. Circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.
Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but ...there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis.
Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS).
Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE OR 0.64 (0.44, 0.94, P=0.02. Compared to warfarin, NOA were associated with a significantly reduced risk of HS OR 0.43 (0.34, 0.55), P<0.001, NNT to avoid a HS 153 and all cause death OR 0.90 0.84, 0.96, P=0.03, NNT to save one fatality 43. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps>0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA.
Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.
Aims This ancillary analysis of the GISSI-HF database aims at assessing the effect of rosuvastatin on the occurrence of atrial fibrillation (AF) in patients with chronic heart failure (HF) who were ...not in AF at study entry. Methods and results GISSI-HF was a double-blind, placebo-controlled trial testing n-3 PUFA and rosuvastatin vs. corresponding placebos in patients with chronic HF. Atrial fibrillation occurrence was defined as the presence of AF in the electrocardiogram (ECG) performed at each visit during the trial or AF as a cause of worsening HF or hospital admission or as an event during hospitalization. Among the 3690 patients (80.7%) without AF on their baseline ECG, 15.0% developed AF during a median follow-up period of 3.7 years, 258 randomized to rosuvastatin (13.9%) vs. 294 allocated to placebo (16.0%). Although the difference was not significant at unadjusted analysis (P = 0.097) and multivariable analysis adjusting for clinical variables (P = 0.067), it became significant after adjustment for clinical variables and laboratory examinations (P = 0.039), and for clinical variables, laboratory examinations, and background therapies (P = 0.038). Conclusion This study shows that there is some evidence of a beneficial effect of rosuvastatin in terms of reduction of AF occurrence in patients with HF. Larger populations are needed to provide a definite answer to the question. ClinicalTrials.gov Identifier: NCT00336336
•Incretin-based drugs have been suggested to increase the risk of hospitalization for heart failure in clinical trials.•Incretin-based drugs are not associated with an increased risk of ...hospitalization for HF in real-world data from Italy.•These data support the cardiovascular safety of incretin-based drugs in the clinical practice.
There are concerns that incretin-based antidiabetic drugs – including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists – increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting.
Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry.
The multivariate odds ratios (ORs) of HF in relation to current use of incretin-based drugs as compared to current use of two or more oral antidiabetics was 1.06 (95% confidence interval, CI, 0.83–1.35), with no evidence of a trend in risk with increasing duration of use. The corresponding ORs were 1.10 (95% CI 0.85–1.41) for DPP-4 inhibitors and 0.84 (95% CI 0.48–1.47) for GLP-1 receptor agonists. Estimates were consistent in various sensitivity analyses.
This study indicates that incretin-based drugs are not associated with an increased risk of hospitalization for HF, thus providing further reassurance on the cardiovascular safety of these antidiabetic drugs in the clinical practice.
Objectives
Fibroblast growth factor‐23 (FGF‐23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the ...relationships between levels of vitamin D or FGF‐23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community‐dwelling elderly subjects.
Design and Setting
Plasma levels of FGF‐23 and vitamin D were measured in 1851 men and women (65–84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All‐cause mortality or hospitalizations were available after a median follow‐up of 47 months with record linkage of administrative data.
Results
Vitamin D deficiency (<20 ng mL−1) was found in 72.3% of subjects, but FGF‐23 levels were normal 74 (58–97) RU per mL. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF‐23 were associated with a higher left ventricular (LV) mass index. Levels of FGF‐23 hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28–2.28), P < 0.0001 but not vitamin D 0.76 (0.57–1.01), P = 0.08 were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N‐terminal pro‐brain natriuretic peptide and high‐sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF‐23 and below median values of vitamin D had greater LV hypertrophy and higher mortality.
Conclusions
In community‐dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF‐23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.
Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown.
The present study ...investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP). We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent.
We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression.
Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.
PDF
