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Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI. APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power. The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone. ClinicalTrials.gov Identifier: NCT05077683. [ABSTRACT FROM AUTHOR]

[Display omitted] • Young women with AMI had suboptimal treatment, with fewer PCIs than young men. • Young women were less likely to receive secondary prevention treatments. • Ten-year survival was similar in young men and young women. • Long-term morbidity did not differ between young men and young women. Conflicting data exists about long-term outcomes in young women and men experiencing acute myocardial infarction (AMI). The FAST-MI program consists of three nationwide French surveys carried out 5 years apart from 2005 to 2015, including consecutive patients with AMI over a 1-month period with up to 10-year follow-up. The present analysis focused on adults ≤ 50 yo according to their gender. Women accounted for 17.5% (335) of the 1912 patients under 50 yo and had a similar age as men (43.9 ± 5.1 vs. 43.9 ± 5.5 years, P = 0.92). They received less percutaneous coronary interventions (PCI) than men (85.9% vs. 91.3%, P = 0.005), even in ST-elevation myocardial infarction (83.6% vs. 93.5%, P < 0.001). Recommended secondary prevention medications were less frequently prescribed at discharge in women (40.6% vs. 52.8%, P < 0.001), a trend that persisted in 2015 (59.1% vs. 72.8% in 2015, P < 0.001). Still, ten-year survival was similar in men (90.5%) and women (92.3%) (crude HR: 0.86 [95% CI: 0.55–1.35], P = 0.52, adjusted HR: 0.63 [95% CI: 0.38–1.07], P = 0.09); similar results were found for ten-year survival among hospital survivors (91.2% in men vs. 93.7% in women, adjusted HR: 0.87 [95% CI: 0.45–1.66], P = 0.66). Of the 1684 patients alive at hospital discharge with morbidity follow-up ≥ 6 months available, death, AMI or stroke at 8 years occurred in 12.9% men and 11.2% in women (adjusted HR: 0.90 [95% CI: 0.60–1.33], P = 0.59). Young women with AMI undergo less cardiac interventions and are less often prescribed secondary prevention treatment than men, even when significant coronary artery disease is present, but keep a similar long-term prognosis after AMI. Optimal management of these young patients, regardless of gender, is necessary to ensure best outcomes after this major cardiovascular event. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.Methods: We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints.Conclusions: The MINT trial will inform RBC transfusion practice in patients with acute MI. [ABSTRACT FROM AUTHOR]

▪ • The optimal timing of revascularization of non-infarct related artery (IRA) in ST-elevation myocardial infarction (STEMI) with multivessel disease is debated. • Our trial show that staged non-IRA complete revascularization was the preferred strategy by operators. • This strategy was however not superior compared to an immediate revascularization in terms of major adverse cardiovascular events at one year. In patients with ST-segment elevation myocardial infarction and multivessel disease, percutaneous coronary intervention for non-culprit lesions is superior to treatment of the culprit lesion alone. The optimal timing for non-infarct-related artery revascularization – immediate versus staged – has not been investigated adequately. We aimed to assess clinical outcomes at 1 year in patients with ST-segment elevation myocardial infarction with multivessel disease using immediate versus staged non-infarct-related artery revascularization. Outcomes were analysed in patients from the randomized FLOWER-MI trial, in whom, after successful primary percutaneous coronary intervention, non-culprit lesions were assessed using fractional flow reserve or angiography during the index procedure or during a staged procedure during the initial hospital stay, ≤ 5 days after the index procedure. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction and unplanned hospitalization with urgent revascularization at 1 year. Among 1171 patients enrolled in this study, 1119 (96.2%) had complete revascularization performed during a staged procedure, and 44 (3.8%) at the time of primary percutaneous coronary intervention. During follow-up, a primary outcome event occurred in one of the patients (2.3%) with an immediate strategy and in 55 patients (4.9%) with a staged strategy (adjusted hazard ratio 1.44, 95% confidence interval 0.39–12.69; P = 0.64). Staged non-infarct-related artery complete revascularization was the strategy preferred by investigators in practice in patients with ST-segment elevation myocardial infarction with multivessel disease. This strategy was not superior to immediate revascularization, which, in the context of this trial, was used in a small proportion of patients. Further randomized studies are needed to confirm these observational findings. [ABSTRACT FROM AUTHOR]

Background: The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population.Methods: The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted.Results: Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (Pinteraction = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (Pinteraction = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; Pinteraction = .012).Conclusions: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• Dual-antiplatelet therapy (DAPT) ≥1 year post myocardial infarction reduces major adverse cardiovascular events but increases bleeding. • Appropriate patient selection for DAPT ≥1 year post myocardial infarction is important to avoid undue bleeding complications. • In contemporary practice, DAPT use ≥1 year post myocardial infarction is prevalent and associated with patient and index event characteristics. • There are marked geographical variations in DAPT use ≥1 year post myocardial infarction. • Further clinical initiatives are needed to optimize patient selection for DAPT ≥1 year post myocardial infarction. Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS. We used multivariable logistic regression to identify determinants of DAPT use at 396 days post-MI (365 days plus a 31day overrun period to account for intended DAPT discontinuation at 1 year). Patients treated with an oral anticoagulant were excluded. Of 7708 patients (median age 67 years, women 25%, ST-elevation MI 50%), 39% and 16% were on DAPT at 396 days and 5 years post-MI, respectively. DAPT use at 396 days post-MI was more prevalent in patients <65 years of age, treated with percutaneous coronary intervention (versus coronary artery bypass grafting or medical therapy), and with multivessel disease or a history of angina. Additional clinical determinants of ischemic and/or bleeding events following MI (diabetes, second prior MI, hypertension, peripheral artery disease, heart failure, smoking, and renal insufficiency) were not independently associated with DAPT use at 396 days. There were geographic variations in the use of DAPT at 396 days (p <0.001), with the lowest use in Europe and the highest in Asia and Australia. In a contemporary patient cohort, DAPT use beyond 1 year post MI was prevalent and associated with patient and index event characteristics. There were marked geographical variations in DAPT use beyond 1 year post MI. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease (MVD), recent studies have demonstrated the superiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions compared to culprit lesion treatment-only therapy. FFR- and angio-guided PCI have however never been compared in STEMI patients.Trial Design: FLOWER-MI is an open-label multicenter national randomized clinical trial. The aim is to investigate FFR-guided complete revascularization in comparison to angio-guided complete revascularization in STEMI patients with successful PCI of the culprit lesion and ≥50% stenosis in at least one additional non-culprit lesion requiring PCI. Eligible patients will be randomized after successful primary PCI in a 1:1 fashion to either FFR-guided or angio-guided complete revascularization during the index procedure or a staged procedure before discharge (≤5 days). Patients assigned to FFR guidance first have FFR measured in each non-culprit vessel and only undergo PCI if FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac events, including all-cause death, non-fatal MI, and unplanned hospitalization leading to urgent revascularization at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, and 3-year outcomes. Based on estimated event rates, a sample size of 1170 patients is needed to show superiority of the FFR-guided revascularization with 80% power.Conclusion: The aim of FLOWER-MI trial is to assess whether FFR-guided complete revascularization in the acute setting is superior angio-guided complete revascularization. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The increased use of reperfusion therapy in ST-segment-elevation myocardial infarction (STEMI) patients in the past decades is generally considered the main determinant of improved outcomes. The aim was to assess 20-year trends in profile, management, and one-year outcomes in STEMI patients in relation with use or non-use of reperfusion therapy (primary percutaneous coronary intervention (pPCI) or fibrinolysis).Methods: We used data from 5 one-month French nationwide registries, conducted 5 years apart from 2005 to 2015, including 8579 STEMI patients (67% with and 33% without reperfusion therapy) admitted to cardiac intensive care units in France.Results: Use of reperfusion therapy increased from 49% in 1995 to 82% in 2015, with a shift from fibrinolysis (37.5% to 6%) to pPCI (12% to 76%). Early use of evidence-based medications gradually increased over the period in both patients with and without reperfusion therapy, although it remained lower at all times in those without reperfusion therapy. One-year mortality decreased in patients with reperfusion therapy (from 11.9% in 1995 to 5.9% in 2010 and 2015, hazard ratio [HR] adjusted on baseline profile 0.40; 95% CI: 0.29-0.54, P < .001) and in those without reperfusion therapy (from 25.0% to 18.2% in 2010 and 8.1% in 2015, HR: 0.33; 95% CI: 0.24-0.47, P < .001).Conclusions: In STEMI patients, one-year mortality continues to decline, both related to increased use of reperfusion therapy and progress in overall patient management. In patients with reperfusion therapy, mortality has remained stable since 2010, while it has continued to decline in patients without reperfusion therapy. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. This study sought to determine the effect of ticagrelor on limb events. Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; P interaction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (P interaction = 0.40) or TIMI major bleeding (P interaction = 0.3239). Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795) [Display omitted] [ABSTRACT FROM AUTHOR]

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Introduction: Estrogens and progesterone play critical roles in angiogenesis and vasodilation. Moreover, placental aromatase deficiency is detected in women with preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis occurs much earlier than typical PE diagnosis. Thus, we investigated whether the circulating steroid profile was already disturbed at 24-29 weeks of gestation in women with subsequent PE, and compared the profile with that of women with "placental" small gestational age (SGA) without PE.Methods: We selected nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25), SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas chromatography/mass spectrometry and to measure placental growth factor and soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated in a new set of women.Results: Compared with that of controls, the women with PE had a significantly lower estrone/androstenedione ratio, and exhibited a decreasing trend for estradiol and estrone levels. Lower estriol levels were observed in the SGA group compared to the NP group. Compared with that of controls, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group.Discussion: Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE diagnosis, highlighting potential new biomarkers of PE. [ABSTRACT FROM AUTHOR]

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Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme that catalizes the degradation of tryptophan along the kynurenine pathway. Here, we show that Ido1 activity sustains an immunostimulatory potential through inhibition of interleukin (Il)10. In atherosclerosis, Ido1-dependent inhibition of Il10 translates into disease exacerbation. The resistance of Ido1-deficient mice to enhanced immune activation is broken in Ido1/Il10 double-deficient mice, which show exaggerated immune responses and develop severe spontaneous colitis. We demonstrate that Ido1 activity is required for the regulation of Il10 and that kynurenic acid (Kna), an Ido1-derived metabolite, is responsible for reduced Il10 production through activation of a cAMP-dependent pathway and inhibition of Erk1/2 phosphorylation. Resupplementation of Ido1-deficient mice with Kna limits Il10 expression and promotes atherosclerosis. In human atherosclerotic lesions, increased levels of Kna are associated with an unstable plaque phenotype, and its blood levels predict death and recurrent myocardial infarction in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.Background: Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.Methods: We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.Results: PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.Conclusions: Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Background: Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods: We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. Results: PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. Conclusions: Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. [Copyright &y& Elsevier]

BACKGROUND & AIMS: There is an unclear risk of colonic high-grade dysplasia (HGD) and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) treated with immunosuppressants. We analyzed data on CRC development among patients with IBD enrolled in the observational cohort Cancers et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME). METHODS: We followed and collected data from 19,486 patients with IBD (60.3% with Crohn's disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and June 2005, and followed them until December 2007. When the study began, 2841 patients (14.6%) were characterized as having long-standing extensive colitis (ie, >10 years and involving ≥50% of the colon). Early lesions (HGD and CRC) were defined as those diagnosed within 10 years after diagnosis of IBD. RESULTS: Thirty-seven patients developed CRC during the follow-up period, and 20 developed colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD patients (95% confidence interval [CI]: 1.5-3.0; P < .0001), 7.0 for patients with long-standing extensive colitis (95% CI: 4.4-10.5; P < .001), and 1.1 for patients without long-standing extensive colitis (95% CI: 0.6-1.8; P = .84). Among patients with long-standing extensive colitis, the multivariate adjusted hazard ratio for colorectal HGD and cancer was 0.28 for those who received thiopurines compared with those who never received thiopurine therapy (95% CI: 0.1-0.9; P = .03). Twenty-two patients developed early lesions; 7 of these were related to IBD, based on histologic analysis. CONCLUSIONS: Patients with IBD and long-standing extensive colitis are at increased risk for CRC, although the risk is lower among patients receiving thiopurine therapy. Patients without long-standing extensive colitis have a risk for CRC similar to that of the general population, but they can develop IBD-related lesions within 10 years after diagnosis of IBD. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to assess the impact of invasive strategy (IS) versus a conservative strategy (CS) on in-hospital complications and 3-year outcomes in patients with non–ST-segment elevation myocardial infarction (NSTEMI) from the FAST-MI (French Registry of Acute Coronary Syndrome). Background: Results from randomized trials comparing IS and CS in patients with NSTEMI are conflicting. Methods: Of the 3,670 patients in FAST-MI, which included patients with acute myocardial infarction (within 48 h) over a 1-month period in France at the end of 2005, 1,645 presented with NSTEMI. Results: Of the 1,645 patients analyzed, 80% had an IS. Patients in the IS group were younger (67 ± 12 years vs. 80 ± 11 years), less often women (29% vs. 51%), and had a lower GRACE (Global Registry of Acute Coronary Events) risk score (137 ± 36 vs. 178 ± 34) than patients treated with CS. In-hospital mortality and blood transfusions were significantly more frequent in patients with CS versus IS (13.1% vs. 2.0%, 9.1% vs. 4.6%). Use of IS was associated with a significant reduction in 3-year mortality and cardiovascular death (17% vs. 60%, adjusted hazard ratio [HR]: 0.44, 95% confidence interval [CI]: 0.35 to 0.55 and 8% vs. 36%, adjusted HR: 0.37, 95% CI: 0.27 to 0.50). After propensity score matching (181 patients per group), 3-year survival was significantly higher in patients treated with IS. Conclusions: In a real-world setting of patients admitted with NSTEMI, the use of IS during the initial hospital stay is an independent predictor of improved 3-year survival, regardless of age. (French Registry of Acute Coronary Syndrome [FAST-MI]; NCT00673036) [Copyright &y& Elsevier]

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Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Little is known of the influence of nutritional status on cytochrome P450 (CYP) 1A2 activity in elderly patients. Thirty elderly institutionalised patients with malnutrition (group A, aged 88 ± 5 years) and 24 without (group B, aged 81 ± 9 years) were included. Malnutrition was defined as weight loss of >10% over the previous 6 months and/or a body mass index (BMI) <21 kg/m2 and albuminaemia ≤32 g/L. CYP1A2 activity was evaluated by the plasma paraxanthine/caffeine (PAX/CAF) metabolic ratio. The plasma PAX/CAF metabolic ratio was similar in both groups regardless of nutritional status (0.34 ± 0.13 [A] versus 0.30 ± 0.11 [B]; p = 0.11). The CYP1A2 metabolic ratio was not correlated to either BMI, serum albumin or renal clearance. CYP1A2 activity, as measured by the plasma PAX/CAF ratio, was not influenced by nutritional status in elderly patients. Keywords: cytochrome P450 1A2, caffeine, human, elderly patients, malnutrition Résumé L’influence de la malnutrition protéinocalorique, fréquente chez le sujet âgé hospitalisé, sur l’activité du cytochrome P450 (CYP) 1A2 n’est pas connue. La malnutrition était définie par une perte de poids > 10 % en 6 mois, et/ou un indice de masse corporelle (IMC) < 21 kg/m2, et une albuminémie ≤ 32 g/L. Trente patients dénutris (âge moyen : 88 ± 5 ans) et 24 patients témoins (âge moyen 81 ± 9 ans) ont été inclus. L’activité du CYP1A2, mesurée par le rapport métabolique plasmatique paraxanthine/caféine, n’était pas significativement différente selon le statut nutritionnel (0,34 ± 0,13 dans le groupe dénutri versus 0,30 ± 0,11 dans le groupe témoin ; p = 0,11). Aucune corrélation n’a été retrouvée entre l’activité du CYP1A2 et les facteurs tels que l’IMC, l’albuminémie ou la clairance rénale. L’activité du CYP1A2 n’est pas modifiée par la malnutrition protéinocalorique. Mots clés : cytochrome P450 1A2, caféine, gériatrie, malnutrition Texte reçu le 29 juillet 2003 ; accepté le 2 décembre 2003 [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system, and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through fecal microbiota transplantation (FMT) is a promising approach for the treatment of CD. We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species and link these events to the maintenance of remission in CD. We found that FMT had a significant long-term effect on patient microbial compositions, although this was primarily driven by the engraftment of donor species, which remained at low abundance. Thirty-eight percent of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods, such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, and transmission of Bacteroidetes was deleterious. Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD. [ABSTRACT FROM AUTHOR]

Patients with familial hypercholesterolemia (FH) are prone to develop acute myocardial infarction (AMI) at a younger age. The aim of the present study was to assess 5-year outcomes after AMI according to the presence of FH in a large multicenter cohort of patients. The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction consists of nationwide surveys recruiting patients over a 1- to 2-month period every 5 years. Patients recruited in 2005 and 2010 were followed up to 5 years. Of 5147 patients discharged alive and in whom FH status could be assessed, 2.8% had probable/definite FH, using an adapted Dutch Lipid Clinic score. They were 12 years younger, on average, than non-FH patients. Before adjustment, their 5-year survival and event-free survival did not differ from non-FH patients. After adjustment, however, both mortality (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.15–2.89; P =.011) and the combined endpoint of death, AMI, or stroke (HR 2.22, 95% CI: 1.51–3.26; P <.001) were higher in FH patients. The higher risk in FH patients was also present in patients receiving high-intensity lipid-lowering therapy at discharge: adjusted HR for mortality 2.29, 95% CI: 1.18 to 4.47, P =.015; HR for cardiovascular events 2.57, 95% CI: 1.48 to 4.48, P =.001. Concordant results were observed in propensity score–marched cohorts. The risk of long-term mortality and cardiovascular events is twice as high in FH than in non-FH patients, when adjusted on baseline characteristics, even for those receiving high-intensity lipid-lowering therapy. Additional therapeutic measures are needed in these patients. • Familial hypercholesterolemia is present in ≈3% of myocardial infarction patients. • Those with familial hypercholesterolemia are 12 years younger than other patients. • Crude 5-year survival is similar in patients with familial hypercholesterolemia. • After adjustment, their risk is twice that of non-FH patients. • Increased risk is also present when high-dose lipid-lowering therapy is used. [ABSTRACT FROM AUTHOR]

Study Objective: This study compares the effectiveness and cost-effectiveness of nurse-driven targeted HIV screening alongside physician-directed diagnostic testing (intervention strategy) with diagnostic testing alone (control strategy) in 8 emergency departments.Methods: In this cluster-randomized, 2-period, crossover trial, 18- to 64-year-old patients presenting for reasons other than potential exposure to HIV were included. The strategy applied first was randomly assigned. During both periods, diagnostic testing was prescribed by physicians following usual care. During the intervention periods, patients were asked to complete a self-administered questionnaire. According to their answers, the triage nurse suggested performing a rapid test to patients belonging to a high-risk group. The primary outcome was the proportion of new diagnoses among included patients, which further refers to effectiveness. A secondary outcome was the intervention's incremental cost (health care system perspective) per additional diagnosis.Results: During the intervention periods, 74,161 patients were included, 16,468 completed the questionnaire, 4,341 belonged to high-risk groups, and 2,818 were tested by nurses, yielding 13 new diagnoses. Combined with 9 diagnoses confirmed through 97 diagnostic tests, 22 new diagnoses were established. During the control periods, 74,166 patients were included, 92 were tested, and 6 received a new diagnosis. The proportion of new diagnoses among included patients was higher during the intervention than in the control periods (3.0 per 10,000 versus 0.8 per 10,000; difference 2.2 per 10,000, 95% CI 1.3 to 3.6; relative risk 3.7, 95% CI 1.4 to 9.8). The incremental cost was €1,324 per additional new diagnosis.Conclusion: The combined strategy of targeted screening and diagnostic testing was effective. [ABSTRACT FROM AUTHOR]

Background: Fetuin-A is an ubiquitary anti-inflammatory protein that counteracts CRP effects and has a protective effect against inflammation and myocardial ischemia. Low fetuin-A has been found to be associated with cardiovascular death in patients with end-stage renal failure disease. Low fetuin-A combined with high CRP level may be used to severe inflammatory imbalance and to predict outcome in acute coronary syndromes (ACS). Methods: We measured admission plasma fetuin-A and CRP level in 748 consecutive patients (65±13 years, sex, 389 with ST and 337 without ST elevation) included in the ACS French registry (Fast MI) and correlated these data with the outcome. Tertile was used to define low fetuin-A (tertile 1) and high CRP level (tertile 3). Results: Plasma fetuin-A and CRP concentrations at admission averaged 95±27mg/L and 11±16UI, respectively with low fetuin-A defined as <69mg/L and high CRP level as 25UI. At one year follow up (n=726, 97%), cardiovascular mortality (n=50, 7%) was 16% (18/111), 9% (21/250) and 3% (11/365) in patients with low fetuin-A/high CRP (n=111), either low fetuin or high CRP (n=250) and high fetuin-A/low CRP (n=365), respectively. By multivaritate analysis low fetuin-A/high CRP level remained independently predictive of outcome (OR=3.4 [1.6–7.3], p=0.001, Figure 1) after adjustment to ST elevation, GRACE score and medical treatment. In contrast, CRP and fetuin-A alone failed to predict outcome. Conclusions: Inflammatory imbalance assessed by combining fetuin-A and CRP values is an important predictor of cardiovascular death in ACS patients. Display Omitted [ABSTRACT FROM AUTHOR]

Background and aim Familial hypercholesterolemia (FH) is at very high risk of early myocardial infarction (MI). The prevalence of FH, which is estimated to be at least 1:500 in the general population, remains unclear in patients with acute MI. From databases of 3 French regional and nationwide registries of acute MI (RICO and FAST-MI 2005 and 2010, respectively), we aimed to determine FH prevalence by developing a specific algorithm. Methods and results Consecutive patients with AMI ≤48 hours of onset included 1) in FAST-MI : during a one-month period in 223 institutions at the end of 2005 and 213 institutions at the end of 2010, and 2) in RICO :from January 2001 – December 2013 (≈ 13 y), were considered in the 3 databases. The algorithm was adapted from Dutch lipid clinic network criteria and was build upon 4 variables (i.e. LDL level and previous use of lipid lowering medications, premature and family history) to identify FH probability. The LDL level was adjusted on each type of lipid lowering medications and the probability of FH was defined taking into account missing data rate. Among the 7484 patients included in the RICO registry, 29.1% had premature vascular disease, 29.7% had familial history, 19.9% were under lipid lowering medications and 9.7% had LDL ≥5 mmol/L. FH prevalence was calculated as unlikely (72.6%), possible (24.6%) and probable /definite (2.8%). From the 1957 patients from FAST-MI 2005 with all data available, 29.7% had premature CV disease, 23% had a family history, 26.6% were on LLDs, and 5.4% had LDL ≥5 mmol/l. FH prevalence was calculated as unlikely (77.9%), possible (19.4%) and probable /definite (2.7%). In the 2223 patients from FASTMI 2010, 32.2% had premature CV disease, 24.9% had a family history, 28.1% were on LLDs, and 5.0% had LDL ≥5 mmol/l. FH prevalence was calculated as unlikely (75.7%), possible (21.5%) and probable /definite (2.7%). Conclusion Our 4-variable algorithm yielded concordant results to determine FH probability in 3 different cohorts of AMI patients. In this large population reflecting routine clinical practice in acute MI, a high prevalence of FH was found, suggesting the opportunity for prevention strategies. The author hereby declares no conflict of interest [ABSTRACT FROM AUTHOR]

Background: An association between transfusion during index hospitalization and increased subsequent mortality has been reported in acute myocardial infarction (AMI). Whether this reflects the prognostic role of transfusion per se, or the impact of the index event leading to transfusion, remains unclear. We sought to evaluate the impact of transfusion on mortality in patients with AMI.Methods: Using the nationwide FAST-MI 2005 AMI registry, we recorded anemia on admission, Thrombolysis in Myocardial Infarction major or minor bleeding, and transfusions during hospital stay. Multivariable analyses were performed to identify independent predictors of in-hospital and 5-year mortality. Cohorts of patients matched for propensity to receive transfusion were compared.Results: Among 3541 patients with AMI, 827 (23.4%) had anemia on admission, 114 (3.2%) had minor or major bleeding, and 151 (4.3%) underwent transfusion. After multivariable analysis, both anemia and bleeding were independently associated with 5-year mortality (hazard ratio [HR] 1.4, 95% CI 1.2-1.6 and HR 1.4, 95% CI 1.1-1.8, respectively), whereas transfusion did not appear to be an independent predictor (HR 1.1, 95% CI 0.8-1.5). Mortality at 5 years did not differ between cohorts matched for propensity to receive transfusion.Conclusions: In this cohort, anemia on admission and bleeding during hospitalization were both associated with increased 5-year mortality in patients with myocardial infarction. Conversely, transfusion per se was not associated with lower survival. Further work is needed to clarify the optimal transfusion strategy in patients with bleeding or anemia and myocardial infarction. [ABSTRACT FROM AUTHOR]

We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, −2.0, (95% CI, −10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice. [ABSTRACT FROM AUTHOR]

Purpose The beneficial effect of a high dose of statin (HDS) compared with lower doses is controversial in secondary prevention. We studied factors impacting the prescription of a HDS at discharge after an Acute Myocardial Infarction [AMI], and assessed effects of this HDS on mortality and cardiovascular morbidity. Methods Participants were 2240 survivors of a STEMI or NSTEMI from the French FAST-MI registry conducted in 2005, with a known statin dose at discharge. Rosuvastatin at any dose, atorvastatin ≥20 mg/d and Simvastatin 40 mg/d were considered as HDS. Factors related to HDS prescription were studied using logistic regression. Impact of HDS prescription on occurrence of death or major cardiovascular events [MACE] (MI, stroke or revascularisation) was studied using a Cox proportional hazards model after propensity score matching. Results 54.5% of the patients had a HDS prescription at discharge. In crude risk analyses, HDS prescription was associated with a lower risk of death or MACE (HR=0.84 [0.71-0.98], p<0.03). However, patients already under treatment with a HDS before the ACS, patients managed in a university hospital, located in a large city, with a younger age, a STEMI, a high blood pressure at entry (≥140 mmHg) and who were discharged rapidly after their AMI were more likely to benefit from a HDS prescription at discharge. After propensity score matching, the dose of statin the patients received at discharge was not related to death or MACE occurrence in the following 3 years (HR=1.04 [0.77-1.36], p=0.87). Using a more stringent definition for HDS (atorvastatin ≥40 mg or rosuvastatin ≥20 mg) yielded similar results. Conclusions The issue of long term benefit of HDS therapy compared with lower ones after an AMI remains unanswered in an observational context, because in this “real life” large registry, high doses were preferentially prescribed to patients with a low risk profile, but less commonly to patients with a high risk profile. [ABSTRACT FROM AUTHOR]

Background & Aims: Patients with inflammatory bowel disease (IBD) who have been exposed to thiopurines might have an increased risk of skin cancer. We assessed this risk among patients in France. Methods: We performed a prospective observational cohort study of 19,486 patients with IBD, enrolled from May 2004 to June 2005, who were followed up until December 31, 2007. The incidence of nonmelanoma skin cancer (NMSC) in the general population, used for reference, was determined from the French Network of Cancer Registries. Results: Before the age of 50 years, the crude incidence rates of NMSC among patients currently receiving or who previously received thiopurines were 0.66/1000 and 0.38/1000 patient-years, respectively; these values were 2.59/1000 and 1.96/1000 patient-years for the age group of 50 to 65 years and 4.04/1000 and 5.70/1000 patient-years for patients older than 65 years. Among patients who had never received thiopurines, the incidence of NMSC was zero before the age of 50 years, 0.60/1000 for the ages of 50 to 65 years, and 0.84/1000 for those older than 65 years. A multivariate Cox regression model stratified by propensity score quintiles showed that ongoing thiopurine treatment (hazard ratio [HR], 5.9; 95% confidence interval [CI], 2.1–16.4; P = .0006) and past thiopurine exposure (HR, 3.9; 95% CI, 1.3–12.1; P = .02) were risk factors for NMSC. They also identified age per 1-year increase as a risk factor for NMSC (HR, 1.08; 95% CI, 1.05–1.11; P < .0001). Conclusions: Ongoing and past exposure to thiopurines significantly increases the risk of NMSC in patients with IBD, even before the age of 50 years. These patients should be protected against UV radiation and receive lifelong dermatologic screening. [ABSTRACT FROM AUTHOR]