Infarction Mortality Research Articles

NOX2-mediated reactive oxygen species are double-edged swords in focal cerebral ischemia in mice

BackgroundReactive oxygen species (ROS) often promote acute brain injury after stroke, but their roles in the recovery phase have not been well studied. We tested the hypothesis that ROS activity mediated by NADPH oxidase 2 (NOX2) contributes to acute brain injury but promotes functional recovery during the delayed phase, which is linked with neuroinflammation, autophagy, angiogenesis, and the PI3K/Akt signaling pathway.MethodsWe used the NOX2 inhibitor apocynin to study the role of NOX2 in brain injury and functional recovery in a middle cerebral artery occlusion (MCAO) stroke mouse model. Infarct size, neurological deficits and behavior were evaluated on days 3, 7, 10 and 14 after reperfusion. In addition, dynamic NOX2-induced ROS levels were measured by dihydroethidium (DHE) staining. Autophagy, inflammasomes, and angiogenesis were measured by immunofluorescence staining and western blotting. RNA sequencing was performed, and bioinformatics technology was used to analyze differentially expressed genes (DEGs), as well as the enrichment of biological functions and signaling pathways in ischemia penumbra at 7 days after reperfusion. Then, Akt pathway-related proteins were further evaluated by western blotting.ResultsOur results showed that apocynin injection attenuated infarct size and mortality 3 days after stroke but promoted mortality and blocked functional recovery from 5 to 14 days after stroke. DHE staining showed that ROS levels were increased at 3 days after reperfusion and then gradually declined in WT mice, and these levels were significantly reduced by the NOX2 inhibitor apocynin. RNA-Seq analysis indicated that apocynin activated the immune response under hypoxic conditions. The immunofluorescence and western blot results demonstrated that apocynin inhibited the NLRP3 inflammasome and promoted angiogenesis at 3 days but promoted the NLRP3 inflammasome and inhibited angiogenesis at 7 and 14 days after stroke, which was mediated by regulating autophagy activation. Furthermore, RNA-Seq and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that apocynin injection resulted in PI3K–Akt signaling pathway enrichment after 7 days of MCAO. We then used an animal model to show that apocynin decreased the protein levels of phosphorylated PI3K and Akt and NF-κB p65, confirming that the PI3K–Akt–NF-κB pathway is involved in apocynin-mediated activation of inflammation and inhibition of angiogenesis.ConclusionsNOX2-induced ROS production is a double-edged sword that exacerbates brain injury in the acute phase but promotes functional recovery. This effect appears to be achieved by inhibiting NLRP3 inflammasome activation and promoting angiogenesis via autophagy activation.

CHA2DS2-VASc score as an independent outcome predictor in patients hospitalized with acute ischemic stroke.

PurposeAtrial fibrillation (AF) is a significant independent risk factor for 1-year mortality in patients with first acute ischemic stroke (AIS). The CHA2DS2-VASc score was initially developed to assess the risk of stroke in patients with AF. Recently, this scoring system has been demonstrated to have clinical value for predicting long-term clinical outcomes in AIS but the evidence is insufficient. This large-scale prospective cohort study investigated the independent predictive value of the score in such patients.MethodsWe included patients with AIS from the Taiwan Stroke Registry (TSR) during 2006–2016 as the present study population. Patients were divided into those with high (≥2) and low (<2) CHA2DS2-VASc scores. We further analyzed and classified patients according to the presence of AF. The clinical endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year after the index AIS.ResultsA total of 62,227 patients with AIS were enrolled. The median age was 70.3 years, and 59% of the patients were women. After confounding factors were controlled, patients with high CHA2DS2-VASc scores had significantly higher incidence of 1-year MACCEs (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.52, 1.76), re-stroke (adjusted HR = 1.28; 95% CI = 1.16, 1.42), and all-cause mortality (adjusted HR = 2.03; 95% CI = 1.83, 2.24) than those with low CHA2DS2-VASc scores did. In the comparison between AF and non-AF groups, the AF group had increased MACCEs (adjusted HR = 1.74; 95% CI = 1.60, 1.89), myocardial infarction (adjusted HR = 4.86; 95% CI = 2.07, 11.4), re-stroke (adjusted HR = 1.47; 95% CI = 1.26, 1.71), and all-cause mortality (adjusted HR = 1.90; 95% CI = 1.72, 2.10). The Kaplan–Meier curve revealed that both CHA2DS2-VASc scores and AF were independent risk predictors for 1-year MACCEs and mortality.ConclusionsThe CHA2DS2-VASc score and AF appeared to consistently predict 1-year MACCEs of AIS patients and provide more accurate risk stratification. Therefore, increased use of the CHA2DS2-VASc score may help improve the holistic clinical assessment of AIS patients with or without AF.

Effects of immune-mediated inflammatory diseases on cardiovascular diseases in patients with type 2 diabetes: a nationwide population-based study

Both type 2 diabetes and immune-mediated inflammatory diseases (IMIDs), such as Crohn’s disease (CD), ulcerative colitis, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis (PsO) are risk factors of cardiovascular disease. Whether presence of IMIDs in patients with type 2 diabetes increases their cardiovascular risk remains unclear. We aimed to investigate the risk of cardiovascular morbidity and mortality in patients with type 2 diabetes and IMIDs. Patients with type 2 diabetes without cardiovascular disease were retrospectively enrolled from nationwide data provided by the Korean National Health Insurance Service. The primary outcome was cardiovascular mortality, and the secondary outcomes were myocardial infarction (MI), stroke, and all-cause mortality. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each IMID. Overall 2,263,853 patients with type 2 diabetes were analyzed. CD was associated with a significantly higher risk of stroke (IPTW-adjusted HR: 1.877 [95%CI 1.046, 3.367]). UC was associated with a significantly higher risk of MI (1.462 [1.051, 2.032]). RA was associated with a significantly higher risk of cardiovascular mortality (2.156 [1.769, 2.627]), MI (1.958 [1.683, 2.278]), stroke (1.605 [1.396, 1.845]), and all-cause mortality (2.013 [1.849, 2.192]). AS was associated with a significantly higher risk of MI (1.624 [1.164, 2.266]), stroke (2.266 [1.782, 2.882]), and all-cause mortality (1.344 [1.089, 1.658]). PsO was associated with a significantly higher risk of MI (1.146 [1.055, 1.246]), stroke (1.123 [1.046, 1.205]) and all-cause mortality (1.115 [1.062, 1.171]). In patients with type 2 diabetes, concomitant IMIDs increase the risk of cardiovascular morbidity and mortality. Vigilant surveillance for cardiovascular disease is needed in patients with type 2 diabetes and IMIDs.

High Risk of Cardiovascular Events in Patients, Biosynthesis of Aspirin-Resistant Thromboxane And The Risk Of Stroke, Myocardial Infarction Or Death

In a higher-risk group, we investigated if aspirin resistance, which is defined as inability to reduce production of thromboxane, enhanced the risk for cardiovascular disease. Methods: The Cardiac Outcome Preventive Assessment Study collected baseline urine samples from 5000 patients. A level of urinary 11-dehydro-thromboxane B2 was measured, which is a marker of within vitro cell generation of thromboxane, in 400 cured patients with aspirin having a cardiovascular death, stroke and infarction, stroke during a 5-year follow-up and in 400 age - and matching sex control subjects, which did not have an event, using a nested case-control design. Result: After accounting for baseline differences, the risks of infarction, strokes, or cardiac mortality rose with every fourth of 11-dihydro-thromboxane B2, with individuals in the top fourth section having a 1.9-fold greater threat than those from the lower portion (“OR, 1.9; 95% CI, 1.3 to 2.8; p=0.009). The upper quartile showed a 2-fold increased myocardial infarction risk ("OR, 2.1; 95% CI, 1.3 to 3.5; p=0.07) and a 3.6-fold elevated risk of cardiac death ("OR, 3.6; 95% CI, 1.78to 7.5; p=0.01) than the lower quartile. Conclusions: the 11-dehydro thromboxane B2 level in urine, better determine the risk of cardiovascular events or cardiovascular death in aspirin-treated patients. These findings also depicts that patients with elevated urine 11-dehydro thromboxane B2 concentrations are more impervious to aspirin, and could profit from greater antiplatelet medications or therapies that even more efficiently stop thromboxane generation in vivo or activities.

Effects of exercise initiation and smoking cessation after new-onset type 2 diabetes mellitus on risk of mortality and cardiovascular outcomes

Lifestyle changes after a diagnosis of type 2 diabetes mellitus (DM) can affect vascular health outcomes. The objective of this study was to investigate the effects of changes in smoking and exercise on the risk of cardiovascular disease (CVD) and mortality in patients with newly diagnosed DM. Data were analyzed for 181,591 people with newly diagnosed type 2 DM who underwent 2 serial health examinations within 2 years before and after DM diagnosis. The study population was followed from the baseline to the date of death or cardiovascular events, or until December 31, 2018 and median follow-up was 6.07 years. Based on the change in status from before to after the diagnosis, participants were grouped into smoking groups (continuous smokers, quitters, new smokers, and nonsmokers) and exercise groups (constant exercisers, new exercisers, exercise dropouts, and nonexercisers). Compared with the nonexercisers, those who initiated exercise after their DM diagnosis had a lower risk of myocardial infarction (MI), stroke, and all-cause mortality: the hazard ratio (HR; 95% confidence interval [CI]) was 0.85 (0.76–0.94) for MI, 0.86 (0.78–0.94) for stroke, and 0.84 (0.89–0.90) for all-cause mortality. Quitters had a higher risk of MI, stroke, and all-cause mortality than nonsmokers, but their risk level was much lower than that in continuous smokers. When the group of continuous smokers and nonexercisers was considered as the reference group, participants who quit smoking and remained nonexercisers had a 21% lower risk of CVD (HR 0.79; 95% CI 0.70–0.90). Those who quit smoking and started exercising had a 46% reduced risk of CVD (HR 0.54; 95% CI 0.41–0.71) and a 22% reduced risk in all-cause mortality (HR 0.78; 95% CI 0.63–0.96). Smoking cessation and exercise initiation after a diagnosis of new-onset type 2 DM was associated with a reduced risk of CVD and all-cause mortality.

High serum uric acid trajectories are associated with risk of myocardial infarction and all-cause mortality in general Chinese population

BackgroundLong-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all-cause mortality.MethodsWe included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006–2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all-cause mortality.ResultsWe identified three SUA trajectories during 2006–2012: low-stable (n=44,124, mean SUA: 236–249 μmol/L), moderate-stable (n=34,431, mean SUA: 324–354 μmol/L) and high-stable (n=6,984, mean SUA: 425–463 μmol/L). During a median follow-up of 6.8 years, we documented 817 (0.96%) incident MI and 6498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07–1.71) and all-cause mortality (HR, 1.22; 95% CI, 1.12–1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all-cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged <60 years (P-interaction<0.0001), respectively.ConclusionsHigher SUA trajectories were associated with altered risk of MI and all-cause mortality, suggesting that monitoring SUA trajectory may assist in identifying subpopulations at higher risk of MI and all-cause mortality.

179-OR: Cardiovascular Effectiveness of Empagliflozin vs. Glucagon-Like Peptide-1 Receptor Agonists or Liraglutide in the EMPRISE Study

Within the EMPRISE® monitoring program, we evaluated the cardiovascular effectiveness of empagliflozin (EMPA) vs. glucagon-like peptide-1 receptor agonists (GLP1RA) or liraglutide using data from Medicare and 2 U.S. commercial claims databases [2014- (2018 for Medicare) ]. We identified patients ≥18 years with type 2 diabetes initiating (i) EMPA vs. GLP1-RA or (ii) EMPA vs. liraglutide. Primary outcomes were hospitalization for heart failure (HHF) , myocardial infarction (MI) , stroke, and all-cause mortality (Medicare only) . After 1:1 propensity score matching, we estimated pooled HR (95% CI) overall and in subgroups of patients with and without baseline cardiovascular disease (CVD) . We identified 105,955 pairs of EMPA vs. GLP1RA initiators and 72,498 pairs of EMPA vs. liraglutide initiators (Table) . Relative to GLP1RA, EMPA had a lower risk of HHF [HR:0.62 (95% CI, 0.53, 0.71) ] and a similar risk of MI [0.95 (0.85, 1.07) ], stroke [1. (0.94, 1.27) ], and mortality [0.91 (0.77, 1.08) ]. Results were consistent for patients with and without CVD. When we compared EMPA vs. liraglutide, estimates were similar to those from GLP1 RA, both overall and across subgroups. Among real-world patients, EMPA was associated with a reduced risk of HHF, but with similar risk of MI, stroke, and mortality, across the broad spectrum of CVD, compared with GLP-1RA overall or liraglutide. Disclosure P.T.Htoo: Employee; Johnson &amp; Johnson. S.Schneeweiss: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. H.Tesfaye: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. M.Najafzadeh: None. R.Glynn: Research Support; Amarin Corporation, AstraZeneca, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. A.Deruaz-luyet: Employee; Boehringer Ingelheim International GmbH, Other Relationship; IQVIA Inc., Sanofi. S.F.Fazeli farsani: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

MO533: Safety of Roxadustat versus Erythropoiesis-Stimulating Agents for Treatment of Anemia in Patients With Chronic Kidney Disease Incident to or not Receiving Dialysis: Pooled Analysis of Four Phase 3 Studies

Abstract BACKGROUND AND AIMS Patients with late-stage chronic kidney disease (CKD) who are non–dialysis-dependent (NDD) or incident to dialysis (ID) (e.g. initiated dialysis within the last 4 months) or dialysis-dependent (DD) represent a vulnerable population at increased risk for morbidity and mortality despite significant clinical advancements in recent years. The safety of roxadustat in patients with NDD or ID-DD CKD requires further elucidation. METHOD In this post-hoc exploratory analysis, safety results from eligible patients with anemia of CKD enrolled in four phase 3, randomized, open-label studies [NDD (DOLOMITES) or ID-DD (SIERRAS, HIMALAYAS, ROCKIES)] were pooled and compared roxadustat to an erythropoiesis-stimulating agent (ESA). Endpoints were time to major adverse cardiovascular event [MACE; myocardial infarction, stroke and all-cause mortality (ACM)] and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE + were evaluated for non-inferiority using hazard ratios (HRs) at 1.8 and 1.3-upper margins, respectively, and 95% confidence intervals (CIs). TEAEs were descriptively summarized. RESULTS In total, 2142 patients were evaluated (1083 roxadustat; 1059 ESA; 616 NDD; 1526 ID-DD). Roxadustat was non-inferior to ESA for risk of MACE [HR 0.79 (95% CI 0.61–1.02)] and MACE+ [HR 0.78, (95% CI 0.62–0.98)] with a consistent finding for ACM [HR 0.78 (95% CI 0.57–1.05)]. TEAEs were generally comparable between roxadustat and ESA groups, including any TEAE [incidence rate per 100 patient-exposure years (IR/100 PEY) 56.1 versus 53.5], TEAEs leading to discontinuation of study drug (IR/100 PEY 6.7 versus 5.1) and TEAEs leading to death (IR/100 PEY 6.9 versus 7.4). The most frequent (IR/100 PEY) TEAEs were hypertension (roxadustat 12.8, ESA 12.3), end-stage kidney disease (roxadustat 6.6, ESA 6.1), diarrhea (roxadustat 7.1, ESA 4.8) and hyperkalemia (roxadustat 4.3, ESA 4.8). CONCLUSION There was no evidence of an increased risk of cardiovascular events or mortality with roxadustat compared with ESA in patients with anemia who have NDD or ID-DD CKD. Although TEAE development occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued a study drug because of an adverse event.

Clinical features and predictors of outcome in patients with acute myocardial infarction complicated by out-of-hospital cardiac arrest

BackgroundAlthough short-term mortality of acute myocardial infarction (AMI) has decreased dramatically in the past few decades, sudden cardiac arrest remains a serious complication. The aim of the study was to assess the clinical characteristics and predictors of prognosis in AMI patients who experienced out-of-hospital cardiac arrest (OHCA).MethodsWe retrospectively registered consecutive AMI patients who were treated with emergency percutaneous coronary intervention (PCI) between 2004 and 2017. Clinical characteristics and outcomes were compared between patients with OHCA and those without OHCA.ResultsAmong 2101 AMI patients, 95 (4.7%) presented with OHCA. Younger age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.93–0.97; p < 0.0001), absence of diabetes mellitus (OR, 0.51; 95% CI, 0.30–0.85; p = 0.01) or dyslipidemia (OR, 0.56; 95% CI, 0.36–0.88; p = 0.01), left main trunk (LMT) or left anterior descending artery (LAD) as the culprit lesion (OR, 3.26; 95% CI, 1.99–5.33; p < 0.0001), and renal deficiency (OR, 3.64; 95% CI, 2.27–5.84; p < 0.0001) were significantly associated with incidence of OHCA. Thirty-day mortality was 32.6% in patients with OHCA and 4.5% in those without OHCA. Multivariate logistic analysis revealed LMT or LAD as the culprit lesion (OR, 12.18; 95% CI, 2.27–65.41; p = 0.004), glucose level (OR, 1.01; 95% CI, 1.00–1.01; p = 0.01), and renal deficiency (OR, 3.35; 95% CI, 1.07–10.53; p = 0.04) as independent predictors of 30-day mortality among AMI patients with OHCA.ConclusionsIn patients with AMI who underwent emergency PCI, 30-day mortality was six times greater in those having presented initially with OHCA compared with those without OHCA. Younger age, absence of diabetes mellitus or dyslipidemia, LMT or LAD as the culprit lesion, and renal deficiency were independent predictors of OHCA. OHCA patient with higher blood glucose level on admission, LMT or LAD as the culprit lesion, or renal deficiency showed worse clinical outcomes.

Influence of air pollutants on circulating inflammatory cells and microRNA expression in acute myocardial infarction

Air pollutants increase the risk and mortality of myocardial infarction (MI). The aim of this study was to assess the inflammatory changes in circulating immune cells and microRNAs in MIs related to short-term exposure to air pollutants. We studied 192 patients with acute coronary syndromes and 57 controls with stable angina. For each patient, air pollution exposure in the 24-h before admission, was collected. All patients underwent systematic circulating inflammatory cell analyses. According to PM2.5 exposure, 31 patients were selected for microRNA analyses. STEMI patients exposed to PM2.5 showed a reduction of CD4+ regulatory T cells. Furthermore, in STEMI patients the exposure to PM2.5 was associated with an increase of miR-146a-5p and miR-423-3p. In STEMI and NSTEMI patients PM2.5 exposure was associated with an increase of miR-let-7f-5p. STEMI related to PM2.5 short-term exposure is associated with changes involving regulatory T cells, miR-146a-5p and miR-423-3p.

A systematic review and meta-analysis of percutaneous coronary intervention compared to coronary artery bypass grafting in non-ST-elevation acute coronary syndrome

Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment [i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS. MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed. We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint [CABG vs. PCI, incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.70; 1.23]. CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio 1.36, 95% CI 0.94; 1.95). For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

Objective risk assessment vs standard care for acute coronary syndromes\u2014The Australian GRACE Risk tool Implementation Study (AGRIS): a process evaluation

BackgroundStructured risk-stratification to guide clinician assessment and engagement with evidence-based therapies may reduce care variance and improve patient outcomes for Acute Coronary Syndrome (ACS). The Australian Grace Risk score Intervention Study (AGRIS) explored the impact of the GRACE Risk Tool for stratification of ischaemic and bleeding risk in ACS. While hospitals in the active arm had a higher overall rate of invasive ACS management, there was neutral impact on important secondary prevention prescriptions/referrals, hospital performance measures, myocardial infarction and 12-month mortality leading to early trial cessation. Given the Grace Risk Tool is under investigation internationally, this process evaluation study provides important insights into the possible contribution of implementation fidelity on the AGRIS study findings.MethodsUsing maximum variation sampling, five hospitals were selected from the 12 centres enrolled in the active arm of AGRIS. From these facilities, 16 local implementation stakeholders (Cardiology advanced practice nurses, junior and senior doctors, study coordinators) consented to a semi-structured interview guided by the Theoretical Domains Framework. Directed Content Analysis of qualitative data was structured using the Capability/Opportunity/Motivation-Behaviour (COM-B) model.ResultsPhysical capability was enhanced by tool usability. While local stakeholders supported educating frontline clinicians, non-cardiology clinicians struggled with specialist terminology. Physical opportunity was enhanced by the paper-based format but was hampered when busy clinicians viewed risk-stratification as one more thing to do, or when form visibility was neglected. Social opportunity was supported by a culture of research/evidence yet challenged by clinical workflow and rotating medical officers. Automatic motivation was strengthened by positive reinforcement. Reflective motivation revealed the GRACE Risk Tool as supporting but potentially overriding clinical judgment. Divergent professional roles and identity were a major barrier to integration of risk-stratification into routine Emergency Department practice. The cumulative result revealed poor form completion behaviors and a failure to embed risk-stratification into routine patient assessment, communication, documentation, and clinical practice behaviors.ConclusionsNumerous factors negatively influenced AGRIS implementation fidelity. Given the prominence of risk assessment recommendations in United States, European and Australian guidelines, strategies that strengthen collaboration with Emergency Departments and integrate automated processes for risk-stratification may improve future translation internationally.

Temporal Trends of Major Bleeding and Its Prediction by the Academic Research Consortium-High Bleeding Risk Criteria in Acute Myocardial Infarction.

Limited data exist on the temporal trend of major bleeding and its prediction by the Academic Research Consortium-High Bleeding Risk (ARC-HBR) criteria in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). We investigated 10-year trends of major bleeding and predictive ability of the ARC-HBR criteria in AMI patients. In a multicenter registry of 10,291 AMI patients undergoing PCI between 2004 and 2014 the incidence of Bleeding Academic Research Consortium (BARC) 3 and 5 bleeding was assessed, and, outcomes in ARC-defined HBR patients with AMI were compared with those in non-HBR. The primary outcome was BARC 3 and 5 bleeding at 1 year. Secondary outcomes included all-cause mortality and composite of cardiovascular death, myocardial infarction, or ischemic stroke. The annual incidence of BARC 3 and 5 bleeding in the AMI population has increased over the years (1.8% to 5.8%; p < 0.001). At 1 year, ARC-defined HBR (n = 3371, 32.8%) had significantly higher incidence of BARC 3 and 5 bleeding (9.8% vs. 2.9%; p < 0.001), all-cause mortality (22.8% vs. 4.3%; p < 0.001) and composite of ischemic events (22.6% vs. 5.8%; p < 0.001) compared to non-HBR. During the past decade, the incidence of major bleeding in the AMI population has increased. The ARC-HBR criteria provided reliable predictions for major bleeding, mortality, and ischemic events in AMI patients.

Long-term risk of adverse outcomes according to atrial fibrillation type

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE.

Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients.

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

Abstract 10158: Clinical Features and Outcome-Predictors of Patients with Out-of-Hospital Cardiac Arrest Complicating Acute Myocardial Infarction

Background: Although short-term mortality of acute myocardial infarction (AMI) has decreased dramatically, sudden cardiac arrest is still one of serious complication. We assessed the clinical characteristics and prognosis’ predictors of AMI patients with out-of-hospital cardiac arrest (OHCA). Methods: We retrospectively analyzed consecutive patients with AMI who were treated with emergency percutaneous coronary intervention between 2004 and 2017. Patients with OHCA were compared with those without OHCA. Results: Among 2,101 AMI patients, 95 (4.7%) presented OHCA. Younger age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.93-0.97; p&lt;0.0001), absence of coronary risk factors such as, diabetes mellitus (OR: 0.51; 95% CI: 0.30-0.85; p=0.01) or dyslipidemia (OR: 0.56; 95% CI: 0.36-0.88; p=0.01), left main trunk (LMT) and left anterior descending artery (LAD) as culprit lesion (OR: 3.26; 95% CI: 1.99-5.33; p&lt;0.0001), and renal deficiency (OR: 3.64; 95% CI: 2.27-5.84; p&lt;0.0001) were significantly associated with incidence of OHCA. The 30-day mortality of patients with OHCA was more than 5-hold higher compared with those without OHCA (32.6% vs. 4.5%, p&lt;0.0001). In multivariate logistic regression analysis, LMT or LAD as culprit lesion (OR: 12.18; 95% CI: 2.27-65.41; p=0.04), glucose level (OR: 1.01; 95% CI: 1.00-1.01; p=0.01) and renal deficiency (OR: 3.35; 95% CI: 1.07-10.53; p=0.04) were found as independent predictors of 30-day mortality among AMI patients with OHCA. Conclusions: About 1 of 20 AMI patients presented with OHCA and younger age, absence of coronary risk factors, and anterior wall infarction were associated with OHCA occurrence.

Abstract 10348: Incidence and Characterization of Inpatient Complications Occurring More Than 48 Hours Post Stemi

Background: With continued reductions in ST-elevation myocardial infarction (STEMI) mortality and an interest in reducing length of stay (LOS), the question of which patients require extended inpatient monitoring remains uncertain. Methods: We present a single center retrospective study of consecutive patients admitted with STEMI undergoing emergent percutaneous intervention (PCI) from 2009-2018 (n=500). We identified subjects using the catheterization lab database and then reviewed the medical record for the following events occurring 48 hours or more following PCI: acute kidney injury (AKI), stent thrombosis, acute bleeding, falls with injury, use of mechanical support, use of vasopressors, cardiogenic shock, arrhythmias, ventricular rupture, papillary muscle rupture, pericarditis, heart failure requiring intravenous diuresis, re-admission within 48 hours of admission, and death. We hypothesized that elderly patients with multiple comorbidities would be at increased risk of late inpatient complications. Results: The average length of stay was 3.9 days and 384/500 patients stayed longer than 48 hours. Predictors of LOS beyond 48 hours included a left-anterior descending (LAD) culprit lesion (p= 0.04) and chronic kidney disease (CKD) (p=0.03). Risk factors for complications occurring beyond 48 hours included PCI of the LAD (increased risk of heart failure, p=0.003), older age (increased risk of cardiogenic shock, p=0.02), male sex (increased risk of requiring intravenous diuresis, p=0.01) and an initial Thrombolysis in Myocardial Infarction (TIMI) flow of 0 (increased risk of requiring vasopressors, p=0.005). Conclusion: In our sample, STEMI involving the LAD and CKD were associated with a prolonged hospital stay. Patients undergoing PCI of the LAD, and those with initial TIMI 0 flow, older age, and male sex should be strongly considered for extended inpatient monitoring.

Abstract 10242: Single versus Dual Antiplatelet Post Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis

Introduction: Perioperative use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) remains controversial. This meta-analysis compares the safety and efficacy of single anti-antiplatelet therapy (SAPT) versus DAPT after TAVR in patients with no indications for long-term anticoagulation. Hypothesis: The use of SAPT is safe and efficacious in TAVR patients. Methods: Electronic databases were queried for randomized controlled trials (RCTs) and observational studies matching the inclusion criteria. The safety endpoints included bleeding and major vascular complications. The efficacy outcomes included myocardial infarction (MI), stroke, short and long-term all-cause mortality. The ratio risk ratio (RR) with 95% confidence interval (CI) was computed using a random-effect model. Results: A total of 4 RCTs and 2 observational studies (n=1,417) were included in the final analysis. There were decreased rates of bleeding (life-threatening or major) (RR: 0.44; CI: 0.31-0.63) with aspirin only therapy. However, there was no difference of MI (RR: 0.73; CI: 0.28-1.87), stroke (RR: 0.92; CI: 0.55-1.54), major vascular complications (RR: 0.61; CI: 0.35-1.07), short-term mortality (&gt;30 days) (RR: 0.82; CI: 0.45-1.49), and long-term mortality (&gt;30 days) (RR: 1.13; CI: 0.73-1.76). Conclusions: This analysis showed lower rates of bleeding and composite of bleeding/thromboembolic events with aspirin only compared to dual antiplatelet amongst patients that underwent TAVR for aortic stenosis.

Relationship between blood pressure levels and ischemic stroke, myocardial infarction, and mortality in very elderly patients taking antihypertensives: a nationwide population-based cohort study

BackgroundIn the very elderly, “the lower the better” hypothesis has constantly been contradicted by randomized control trials and various cohort studies, but inconsistency in results led to unclear blood pressure treatment targets. This study aimed to assess the relationship between baseline blood pressure (BP) and ischemic stroke, myocardial infarction, and all-cause mortality in very elderly people treated for hypertension.MethodsThis large population-based retrospective cohort study was based on the national claims database of the Korean National Health Insurance System, which covers the entire Korean population. 374,250 participants aged ≥ 75 years taking antihypertensive agents were recruited, excluding patients with a history of previous ischemic stroke or myocardial infarction.ResultsSystolic BP (SBP) followed a J curve for ischemic stroke and a U curve for all-cause mortality, with nadir ranges of 120 to 129 mmHg and 140 to 149 mmHg, respectively. While increasing diastolic BP (DBP) generally resulted in higher HRs for ischemic stroke, HRs for myocardial infarction and all-cause mortality significantly increased only when DBP was ≥ 80 mmHg and ≥ 90 mmHg, respectively. The SBP/DBP combination analysis showed that even with SBP < 130 mmHg, higher DBP ≥ 90 mmHg had higher HRs for all three outcomes compared to the reference group (130 to 149 / < 80 mmHg).ConclusionsThere were no further benefits or even harm below certain BP levels for ischemic stroke, myocardial infarction, and all-cause mortality in very elderly hypertensive patients.

Long-term trends in treatment and outcomes of patients with diabetes and acute coronary syndromes: insights from the nationwide AMIS plus registry

Abstract Background Although impressive advances in the treatment of patients with acute coronary syndromes (ACS) have been achieved over the last decades, morbidity and mortality of patients with diabetes and ACS remain substantial. This study aimed at investigating long-term trends in treatment and outcomes of patients with diabetes and ACS, using data from a large, prospective, nation-wide database. Methods Patients with ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) enrolled in the prospective AMIS Plus registry between 01/2003 and 12/2018 and available data on diabetes diagnosis were included in the analysis. Major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, and cerebrovascular events were assessed for each 3-year period. Results Out of 49'413 ACS patients, 10'200 (20.6%) had diabetes (29.4% women). In diabetic patients, the percentage of women decreased from 32.3% in 2002–2004 to 25.9% in 2017–2019 (p&amp;lt;0.001). Diabetic patients were older (p&amp;lt;0.001), more frequently women (p&amp;lt;0.001), and had a higher body mass index (p&amp;lt;0.001). They less often underwent percutaneous coronary intervention (p&amp;lt;0.001) and were more frequently treated by coronary artery bypass grafting (p&amp;lt;0.001). Over the 18-year period, the percentage of diabetic patients undergoing PCI or CABG increased (p&amp;lt;0.001). While treatment with glycoprotein IIb/IIIa inhibitors, low-molecular weight heparin, and beta blockers decreased over time, administration of aspirin, P2Y12 inhibitors, lipid-lowering drugs, and unfractionated heparin increased. Rates of MACE were 9.5% and 5.2% in diabetic and non-diabetic patients (p&amp;lt;0.001). Rates of mortality (7.7% versus 4.1%, p&amp;lt;0.001), recurrent myocardial infarction (1.5% versus 0.9%, p&amp;lt;0.001), and cerebrovascular events (1.2% versus 0.6%, p&amp;lt;0.001) were higher in diabetic as compared with non-diabetic patients, with highest rates of MACE, mortality, and myocardial infarction observed in diabetic women. Rates of MACE decreased from 11.8% in 2002–2004 to 7.5% in 2017–2019 in diabetic patients (p for trend &amp;lt;0.001). While rates of mortality (9.4% to 5.9%, p for trend =0.001) and rates of recurrent myocardial infarction (3.4% to 0.9%, p for trend &amp;lt;0.001) decreased over time, rates of cerebrovascular events remained stable (p for trend =0.34). Trends were the same in diabetic women and men. Conclusions Rates of MACE significantly decreased over the 18-year period in both diabetic women and men, with highest rates observed in diabetic women. Despite the observed improvements, rates of MACE remained 50% higher in diabetic as compared with non-diabetic patients. These findings emphasize that advanced strategies particularly targeting the vulnerable high-risk diabetic patient population are warranted to further improve quality of care in ACS. Funding Acknowledgement Type of funding sources: None.