Risk Of MACE Research Articles

Sex differences in acute myocardial infarction - Preliminary results from an umbrella review

Abstract Background Cardiovascular disease (CVD) is the leading cause of premature death among women, and the negative impact on public health is profound. Women have higher rates of comorbidities, complications such as stroke, in addition to higher mortality compared to men (1-6) and targeting sex-related differences regarding the treatment of CVD in women is of great importance to prevent the number of CVD events. The purpose of this study was to get an overview of the systematic reviews and meta-analyses investigating sex differences in patients with acute myocardial infarction (AMI) the past 10 years. Methods A systematic search was carried out in Epistemonikos, the largest database of systematic reviews that screens PubMed, Cochrane, Embase, CINAHL, PsycInfo and others (i.e., currently nine databases) (7, 8). The search was conducted 12 January 2024, with the general search strings: (1) sex differences OR gender differences AND myocardial infarction, (2) sex differences OR gender differences OR women OR female AND myocardial infarction. The search was restricted to systematic reviews conducted the last 10 years. Results Forty-nine (search 1: 19, search 2: 30) systematic reviews and meta-analyses were identified, and five studies investigating sex differences in relation to AMI were included. Two systematic reviews, Babioakis (2021) and Meer (2015), reported of longer door-to-balloon (D2B) time and/or symptom-to-balloon (S2B) time in female patients presenting with STEMI and referred for PCI, compared to male patients (9). Chaudhary (2022) investigated adverse event of MINOCA (more commonly in women/ younger age (51-59 years) and reported higher risk of MACE among women than men (10.1% vs. 9.1%, OR 1.15, 1.04-1.23), in addition to higher incidence of stroke (3.5% vs. 2.2%, OR 1.3, 1.01-1.68), however no significantly differences were observed for all-cause mortality, non-fatal AMI, and cardiovascular readmissions between the groups (10). Three systematic reviews reported of higher risk of mortality after STEMI among women, compared to men (11-13). Xi (2022) reported of higher risk of short-term mortality (RR, 1.73; 95% CI 1.53 to 1.96)) (adjusted RR, 1.24; 95% CI 1.11 to 1.38) (13), Pancholy (2014) reported of higher risk of in-hospital mortality (RR, 1.93; 95% CI, 1.75-2.14) (adjusted RR, 1.48; 95% CI, 1.07-2.05) (11), and van der Meer (2015) reported of higher crude short- and long-term mortality in women, in addition to less use of GP IIb/IIIa inhibitors in women, compared to men (women 51%, men 57%) (12). Conclusions Our umbrella review revealed that women had longer timeline for treatment in AMI, had less use of medication and higher risk of mortality and MACE compared to men. Clinical practice needs further improvements in management in female patients.

Long non-coding RNA SNHG7 serves as a diagnostic biomarker for acute coronary syndrome and its predictive value for the clinical outcome after percutaneous coronary intervention

BackgroundAcute coronary syndrome (ACS) is one of the common causes of cardiovascular death. The related lncRNAs were novel approaches for early diagnosis and intervention. This paper focused on the clinical function of SNHG7 for patients after PCI.MethodsThe expression of SNHG7 was assessed in ACS patients. The predictive roles of SNHG7 were unveiled by the ROC curve. The relationship between SNHG7 and Gensini scores was judged by Pearson analysis. One-year follow-up was conducted and all patients were catalogued into different groups based on the prognosis. The qRT-PCR, K-M curve, and Cox regression analysis were performed to document the prognostic significance of SNHG7.ResultsSNHG7 was highly expressed in ACS and its three subtypes. SNHG7 showed a certain value in predicting ACS, UA, NSTEMI, and STEMI. Gensini is a closely correlated indicator of SNHG7. The declined expression of SNHG7 was observed in the non-MACE and survival groups. The risk of MACE and death was increased in the group with high expression of SNHG7. SNHG7 was an independent biomarker in patients with ACS after PCI.ConclusionsSNHG7 might be a diagnostic and prognostic tool for ACS patients.

ST-segment depression and left ventricular systolic function recovery post-atrial fibrillation ablation in heart failure.

Catheter ablation (CA) of atrial fibrillation (AF) improves left ventricular ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction (HFrEF). The impact of ST-segment depression before CA on LVEF recovery and clinical outcomes remains unknown. In the present study, we aimed to investigate the relationship between ST-segment depression during AF rhythm before CA and improvement in the LVEF and clinical outcomes in persistent atrial fibrillation (PerAF) patients with HFrEF. The present study included 122 PerAF patients (male; 98 patients, 80%, mean age: 69 [56, 76] years) from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry who had LVEF<50% and underwent an initial ablation. The patients who underwent percutaneous coronary intervention or coronary artery bypass grafting within the past 1month were not included in the enrolled patients. We assigned the patients based on the presence of ST-segment depression before CA during AF rhythm and evaluated improvement in the LVEF (LVEF≥15%) 1year after CA and the relationship between ST-segment depression and heart failure (HF) hospitalization/major adverse cardiovascular events (MACE), which are defined as a composite of HF hospitalization, cardiovascular death, hospitalization due to coronary artery disease, ventricular arrhythmia requiring hospitalization and stroke. The percentage of patients with improvement in the LVEF 1year after CA was significantly lower in the patients with ST-segment depression than those without (58.6% vs. 79.7%, P=0.012). Multiple regression analysis showed ST-segment depression was independently and significantly associated with improvement in the LVEF 1year after CA (HR: 0.35; 95% CI: 0.129-0.928, P=0.035). Kaplan-Meier analysis showed that the patients with ST-segment depression significantly had higher risk of HF hospitalization and MACE than those without (log rank P=0.022 and log rank P=0.002, respectively). Multivariable Cox proportional hazards analysis showed that ST-segment depression was independently and significantly associated with a higher risk of MACE (HR: 2.82; 95% CI: 1.210-6.584, P=0.016). ST-segment depression before CA during AF rhythm was useful prognostic predictor of improvement in the LVEF and clinical outcomes including HF hospitalization and MACE in PerAF patients with HFrEF.

Predictors and prognostic value of coronary computed tomography angiography for unrecognized myocardial infarction in patients with chronic coronary syndrome

ObjectiveUnrecognized myocardial infarction (UMI) on delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) and coronary computed tomography angiography (CCTA) derived high-risk features provide prognostic information in patients with chronic coronary syndrome (CCS). The study aimed to assess the prognostic value of UMI and predictors of UMI using CCTA in patients with CCS who underwent elective percutaneous coronary intervention (PCI). MethodsThis study enrolled 181 patients with CCS who underwent DE-CMR and CCTA before elective PCI. The CCTA-derived predictors of UMI and the association of baseline clinical characteristics, CCTA findings, and CMR-derived factors, including UMI, with MACEs, defined as death, nonfatal myocardial infarction, unplanned late revascularization, hospitalization for congestive heart failure, and stroke, were investigated. ResultsUMI was detected in 57 (31.5%) patients. ROC analysis revealed that the optimal cut-off values of Agatston score and mean peri-coronary fat attenuation index (FAI) for predicting the presence of UMI were 397 and −69.8, respectively. The multivariable logistic regression analysis revealed that left ventricular mass, Agatston score >397, mean FAI >−69.8, positive remodeling of the target lesion, and CCTA-derived stenosis severity were independent predictors of UMI. Kaplan–Meier analysis revealed that patients with UMI were associated with increased risk of MACEs. The Cox proportional hazards analysis showed post-PCI minimum lumen diameter and the presence of UMI were independent predictors of MACEs. The risk of MACEs significantly increased according to the number of four preprocedural CCTA-relevant features of UMI. ConclusionPreprocedural comprehensive CCTA analysis may help predict the presence of UMI and provide prognostic information in patients with CCS who underwent PCI.

Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Low platelet count at admission has an adverse impact on outcome in patients with acute coronary syndromes: from the START Antiplatelet registry

Some previous observations suggest that a low platelet count is associated with an increased risk of adverse outcomes in patients with acute coronary syndromes (ACS). However, most of the data come from post-hoc analyses of randomized controlled trials and from studies including thrombocytopenia developed during hospital stay. Our aim was to assess the impact of low platelet count at admission on cardiovascular outcomes and treatment approach in patients hospitalized for ACS in a current real-life setting in Italy. Patients admitted to Italian coronary care units for ACS were enrolled in the START-ANTIPLATELET registry. Baseline clinical characteristics and treatment at discharge were recorded. Patients were followed-up at 6 months, 1 year and yearly thereafter. Low platelet count was defined as a count at admission < 150 > 100 k/µl or < 100 k/µL. Among 1894 enrolled patients, 157 (8.3%) had a platelet count < 150 > 100 k/µl and 30 (1.6%) < 100 k/µl. The median follow-up was 12.3 months (0.4–50.1). patients with low platelets were older (72 ± 10.4 vs 66 ± 12.4 years, p = 0.006), more frequently males (82.9 vs 72.1%, p = 0.001), hypertensive (90.0% vs 70.4%, p = 0.03), with non-valvular atrial fibrillation (NVAF) (17.1 vs 8.6%, p = 0.02), and peripheral arterial disease (11.5 vs 6.2% p = 0.01) and/or had a previous myocardial infarction (40 vs 18.7%, p = 0.008) and/or a PCI (14.6 vs 7.8%, p = 0.001) than patients with normal platelets. A slightly, but significantly, lower percentage of thrombocytopenic patients were treated with primary PCI (78.1 vs 84.4%, p = 0.04) and they were more frequently discharged on aspirin plus clopidogrel rather than aspirin plus newer P2Y12 antagonists (51.9 vs 65.4%, p = 0.01). MACE-free survival was significantly shorter in thrombocytopenic patients compared to patients with normal platelets (< 150 > 100 k/µl: 37.6 vs 41.8 months, p = 0.002; HR = 2.7, 95% CIs 1.4–5.2; < 100 k/µl: 31.7 vs 41.8 months, p = 0.01; HR = 6.5, 95% CIs 1.5–29.1). At multivariate analysis, low platelet count, age at enrollment, low glomerular filtration rate, low ejection fraction, a previous ischemic stroke and NVAF were independent predictors of MACE. A low platelet count at admission identifies a subgroup of ACS patients with a significantly increased risk of MACE and these patients should be managed with special care to prevent excess adverse outcomes.

Assessing the Role of Bioelectrical Impedance Vector Analysis in Prognosis and Prevention of Contrast-Associated Acute Kidney Injury After Percutaneous Coronary Intervention.

This study evaluated the impact of Bioelectrical Impedance Vector Analysis (BIVA)-guided hydration therapy on contrast-associated acute kidney injury (CA-AKI) in patients undergoing percutaneous coronary intervention (PCI). From April 2022 to January 2023, this prospective study at the Eastern General Hospital of the Chinese People's Liberation Army involved 902 adults with stable coronary artery disease (CAD) scheduled for PCI. BIVA measurements were performed pre-contrast, followed by a standard hydration regimen. The study focused on the development of CA-AKI and major adverse cardiovascular events (MACE, including all-cause death, nonfatal myocardial infarction, and target vessel revascularization) within 1year post-PCI. Among the 902 patients (average age: 60.8 years, 65.2% men), CA-AKI post-PCI was observed in 10.8%. Those with CA-AKI had more comorbidities and higher baseline creatinine levels. The contrast volume-to-estimated Glomerular Filtration Rate (eGFR) ratio was higher in CA-AKI patients, with a significantly increased resistance/height ratio (R/H). High R/H values correlated with a greater risk of MACE and all-cause mortality within a year. The study underscores the importance of BIVA-guided hydration therapy and R/H ratio in predicting CA-AKI in PCI patients with stable CAD. Incorporating R/H ratio assessments may enhance pre-procedural risk assessment and improve long-term outcomes (P = .0017).

Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.

End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. Out of 69368 incident dialysis patients, 22326, 5020, 2853, and 39169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and≥6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.

Effects of newer anti-hyperglycemic agents on cardiovascular outcomes in older adults: Systematic review and meta-analysis

AimTo demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups. MethodsPubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years). ResultsFor SGLT-2is, five CVOTs (46,969 patients, 45–50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85–0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73–0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79–0.93]) with no difference in subgroups <65 or ≥65 years.For GLP-1RAs, nine CVOTs (n = 64,236, 34–75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83–0.95]), stroke (RR; 0.86 [CI, 0.76–0.97]) and ACM (RR; 0.90 [CI, 0.83–0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years.Four CVOTs (n = 33,063; 35–58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups. ConclusionThe overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals.

Predicting cardiovascular disease risk using photoplethysmography and deep learning.

Cardiovascular diseases (CVDs) are responsible for a large proportion of premature deaths in low- and middle-income countries. Early CVD detection and intervention is critical in these populations, yet many existing CVD risk scores require a physical examination or lab measurements, which can be challenging in such health systems due to limited accessibility. We investigated the potential to use photoplethysmography (PPG), a sensing technology available on most smartphones that can potentially enable large-scale screening at low cost, for CVD risk prediction. We developed a deep learning PPG-based CVD risk score (DLS) to predict the probability of having major adverse cardiovascular events (MACE: non-fatal myocardial infarction, stroke, and cardiovascular death) within ten years, given only age, sex, smoking status and PPG as predictors. We compare the DLS with the office-based refit-WHO score, which adopts the shared predictors from WHO and Globorisk scores (age, sex, smoking status, height, weight and systolic blood pressure) but refitted on the UK Biobank (UKB) cohort. All models were trained on a development dataset (141,509 participants) and evaluated on a geographically separate test (54,856 participants) dataset, both from UKB. DLS's C-statistic (71.1%, 95% CI 69.9-72.4) is non-inferior to office-based refit-WHO score (70.9%, 95% CI 69.7-72.2; non-inferiority margin of 2.5%, p<0.01) in the test dataset. The calibration of the DLS is satisfactory, with a 1.8% mean absolute calibration error. Adding DLS features to the office-based score increases the C-statistic by 1.0% (95% CI 0.6-1.4). DLS predicts ten-year MACE risk comparable with the office-based refit-WHO score. Interpretability analyses suggest that the DLS-extracted features are related to PPG waveform morphology and are independent of heart rate. Our study provides a proof-of-concept and suggests the potential of a PPG-based approach strategies for community-based primary prevention in resource-limited regions.

New-onset atrial fibrillation, cardiovascular outcomes and all-cause mortality in patients with newly diagnosed cancer: A large population-based matched cohort study.

11184 Background: Studies have shown an association between atrial fibrillation (AF) and cancer, but the relationship is incompletely studied. there is also a paucity of data regarding the specific association between cancer type and AF risk . Notably, the longitudinal associations of new-onset AF with adverse cardiovascular (ACV) outcomes in Newly Diagnosed Cancer Patients remain unclear. Thus, through a comprehensive nationwide population-based study, we assessed the associations between new-onset AF and subsequent risks of ACV events and all-cause mortality. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adults (&gt;18 years) with any new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients without AF. The primary outcome was new ACV events like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), ischemic heart disease (IHD), and cerebrovascular events (CVE; cerebral infarction, carotid intervention, stroke, transient ischemic attack. The secondary outcome was all-cause mortality. Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare group outcomes. Results: Among the new diagnoses, 52,606 developed AF, and 374,959 remained AF free during the follow-up. After PSM, both cohorts (51,567 each) were well-matched. The mean follow-up duration was 4.8 (± 2.7) years. Among newly diagnosed cancer patients, those with incident AF had higher risk of MACE (HR 1.56; 95% CI 1.49–2.16), HF (HR 3.10; 95% CI 2.76–4.36), IHD (HR 1.68; 95% CI 1.41–2.01), CVE (HR 2.93; 95% CI 2.13–4.04), and all-cause mortality (HR 2.56; 95% CI 1.89–3.78) compared with those without incident AF. We noted a higher incidence rate during the initial months after the diagnosis of AF for both sexes. During the first year, the association with any ACV events (men: HR 2.78, 95% CI, 1.85–3.20; women: HR 1.81, 95% CI, 1.31–2.67) was more substantial than that following AF diagnosis for both sexes. New ‐onset AF was strongly associated with metastatic cancer. In sensitivity analysis, we excluded individuals with &lt;1 year of follow-up results were consistent, and all statistically significant associations remained unchanged. Conclusions: cancer patients who developed AF had significantly higher risks of subsequent adverse cardiovascular events and greater all-cause mortality. AF was strongly associated with metastatic disease. Our findings highlight the importance of strategies for AF prevention to mitigate macrovascular complications in all newly diagnosed cancer patients.

Angiogenesis inhibitors and cardiovascular outcomes in cancer: Real-world, population-based, matched cohort study.

e24024 Background: Angiogenesis inhibitors (AI) have vascular side effects and are now recognized forcardiovascular adverse events (CVAEs). Clinical trial outcomes can underestimate treatment-related adverse events due to restrictive eligibility criteria, limited sample size, and failure to anticipate specific toxicities. In contrast, observational studies have small sample sizes and insufficient adjustment of confounding covariates. In addition, prospective high-quality evidence in real-world settings is scarce. We evaluated the incidence of CVAEs in real-world populations on AI therapy. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adult patients ( &gt; 18 years) with new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients never treated with AIs. The primary outcome was the new incidence of CVAEs-like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), arrhythmia, ischemic heart disease (IHD), venous thromboembolism (VT), and cerebrovascular events (CVE cerebral infarction, carotid intervention, stroke, transient ischemic attack). Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare the AI therapy association with incident CVAEs. Results: We identified 1,170,667 patients with diagnoses of colorectal, cervical, kidney, liver, nonsmall cell lung, or ovarian cancer between 2010 and 2022. Among these, 59,890 had an AI treatment history, and 110,777 did not, with a median follow-up time of 3.1 years. After PSM, both cohorts (59545 each) were well-matched. In the adjusted analysis, AI therapy was associated with higher risks of MACE (HR, 1.23; 95% CI 1.16 -1.31), HF (HR, 1.16; 95% CI 1.08 - 1.25), and VT (HR 2.07; 95% CI 1.95 - 2.19), IHD (HR 1.23; 95% CI 1.16- 1.31), arrhythmias (HR 1.19; 95% CI 1.12-1.27), CVEs (HR, 1.30; 95% CI 1.21- 1.40) at 1 year of exposure. These outcomes were still significantly higher “increased,” suggesting causation; this is an association at follow-up by increasing the lag exposure. Sensitivity analysis results were consistent, and all statistically significant associations remained unchanged. Conclusions: Angiogenesis inhibitor treatment was associated with a significantly higher risk of CVAEs and various malignancies. The increased risk ranges from approximately 1.16 to 2.07 fold, indicating a substantial elevation in risk. These findings highlight the importance of risk stratification and cardiovascular monitoring during and after AI therapy. There is an unmet need to define strategies for CVAE prevention in this high-risk population.

Annual vascular and bleeding outcomes in East Asian poststenting patients with acute coronary syndrome: The BRIC-ACS II trial

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): no Objective We aim to determine the incidence of events in the ‘real-world’ ACS Chinese patients over 1-year after PCI. Methods and Results From November 2017 till April 2020, we enrolled post-stenting ACS patients (n=5515) from 30 hospitals with the strict 1-year follow-up (n=5150). Only 153(3.0%) patients developed MACE (a composite of all-cause death, myocardial infarction, ischemic stroke, or urgent coronary revascularization). The cumulative incidence of annual bleeding (BARC≥2) was 5.8% (298/5150). The BARC≥2 bleeding was higher 298 (5.8%) and was not associated with worsened MACE (P =0.52). Patients treated with ticagrelor (n=1620, 6.0%) had a significantly increased risk of bleeding than those treated with clopidogrel (n=2331; 4.1%) (HR=1.486; 95% CI:1.12-1.97; P=0.006), but similar risk of vascular MACE (2.7% vs 2.8%; HR= 0.94; 95% CI:0.64-1.38; P=0.747).The factors independently associated with the comprehensive risk of BARC≥2 bleeding and MACE, including female gender, renal insufficiency, peptic ulcer, atrial fibrillation, continuous use of ticagrelor and non-continuous DAPT. The discrimination of the nomogram model was further tested by the ROC curve (AUC value:0.610 (95% CI, 0.577-0.642)). Conclusions The annual incidence of BARC≥2 bleeding in ACS patients treated with PCI in China was higher (5.8%) than MACE (3.0%). DAPT with ticagrelor increased the bleeding rates with no trend towards MACE reduction.

Mortality, Hepatic Decompensation, and Cardiovascular- and Renal-Related Outcomes in Lean Versus Non-lean Patients Hospitalized With Metabolic Dysfunction-Associated Steatohepatitis (MASH).

Metabolic dysfunction-associated steatohepatitis (MASH) is an important cause of cirrhosis and end-stage liver disease. In addition, there have been reports of worse extrahepatic outcomes, especially cardiovascular events, in patients with lean patients' fatty liver disease compared to the non-lean group.There is limited data on hepatic, cardiac, and renal outcomes in lean compared to non-lean patients with MASH. This study aims to evaluate the cardiovascular, renal, and hepatic outcomes in hospitalized US adults with MASH, focusing on a comprehensive comparison between lean and non-lean patients. The National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalizations with MASH. Hospitalizations with a history of overweight and obesity (lean body mass index (BMI) <25 vs. lean BMI >25) were also identified. The primary outcome was in-hospital mortality. Secondary outcomes were major adverse cardiovascular outcomes (MACE: a composite of acute myocardial infarction, cardiac arrest, stroke, heart failure, and atrial fibrillation); major adverse kidney outcome (MAKE: a composite outcome of acute kidney injury (AKI), renal replacement therapy, and renal cancer), and hepatic decompensation (esophageal varices with bleeding, ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and hepatorenal syndrome) Multivariate logistic regression analysis was used to derive risk ratios for clinical outcomes. We included 539,275 MASH patients in our sample; 324,330 (60%) were lean. The included patients were mostly female (61%), the mean age was 64 years, and 76% were White. At baseline, non-lean patients had a higher prevalence of heart failure, hypertension, and hyperlipidemia. There was no difference in the prevalence of smoking among both groups.In a multivariate analysis, with adjustment for age, sex, race, sarcopenia, cardiometabolic risk factors, hospital characteristics, admission type, socioeconomic factors, and all comorbidities (including 31 Elixhauser comorbidities), lean status was associated with a 40% increased risk of mortality(adjusted odds ratio (aOR) 1.40, confidence interval (CI) 1.29-1.53), 19% increased risk of MACE (aOR 1.19; 95% CI 1.14-1.24), 20% increased risk of renal decompensation (aOR 1.25; 95% CI 1.20-1.30), and 33% increased risk of hepatic decompensation (aOR 1.33 CI 1.28-1.38). Lean patients with MASH are at higher risk of cardiovascular and renal outcomes and may benefit from enhanced screening for early identification and treatment to improve outcomes.

#1259 Relationship between renal dysfunction, non-obstructive ACS and in-hospital prognosis: findings from the CCC-ACS project

Abstract Background and Aims Acute coronary syndrome (ACS) is an acute and critical condition of coronary heart disease (CHD) with high mortality and poor prognosis. The prevalence of non-obstructive ACS is about 5% ∼ 15%. Among patients with non-obstructive ACS, which patients are more prone to poor prognosis is a concern. Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease, and due to its special pathophysiological mechanism, non-obstructive ACS may not be uncommon in CKD patients. Therefore, the aim of this study was to investigate the relationship between renal function, the occurrence and prognosis of non-obstructive ACS. Method Improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS), a hospital-based medical quality improvement project, is a hospital-based medical quality improvement project to improve the compliance of ACS guidelines in China and improve the prognosis of patients. It was jointly sponsored by the American Heart Association (AHA) and the Chinese Society of Cardiology (CSC) in 2014, with 240 hospitals participating, representing different levels of ACS management in Chinese hospitals. We analyzed patients who underwent coronary angiography from November 2014 to July 2019 in CCC-ACS. Patients were divided into eGFR &amp;lt;60 ml/min·1.73 m² and eGFR≥60 ml/min·1.73 m² groups according to estimated glomerular filtration rate (eGFR) calculated by the EPI formula. According to the results of coronary angiography, the patients were divided into obstructive ACS group and non-obstructive ACS group (obstructive ACS group was defined as at least one coronary artery stenosis ≥ 50%; the others were non-obstructive ACS group). Outcome was defined as in-hospital all-cause mortality and in-hospital MACEs. Results A total of 77 586 patients were included, including 2 292 patients (3.0%) with non-obstructive ACS and 75 294 patients (97.0%) with obstructive ACS. After adjusting for confounding factors using a multivariate logistic regression model, patients with eGFR&amp;lt;60 ml/min·1.73 m² had an approximately 20% increased risk of non-obstructive ACS compared with patients with eGFR≥60 ml/min·1.73 m². The comparison of in-hospital outcomes between the patients with non-obstructive ACS and obstructive ACS is shown in Fig. 1. In-hospital outcomes showed that although the obstructive ACS group had a worse in-hospital prognosis than the non-obstructive ACS group, and the eGFR&amp;lt;60 ml/min·1.73 m² group had a worse in-hospital prognosis than the eGFR≥60 ml/min·1.73 m² group, further grouping of patients showed that the non-obstructive ACS group with eGFR&amp;lt;60 ml/min·1.73 m² had a worse prognosis than the obstructive ACS group with eGFR≥60 ml/min·1.73 m². Confounding factors adjusted for non-obstructive ACS showed that lower eGFR was associated with a higher risk of in-hospital MACEs. After analyzing the in-hospital medication and discharge medication of patients, it was found that the standardized cardiovascular drug therapy was inadequate in patients with non-obstructive ACS. Conclusion Patients with non-obstructive ACS have worse renal function than patients with obstructive ACS, and the proportion of patients with eGFR&amp;lt;60 ml/min·1.73 m² is higher. In patients with non-obstructive ACS, the risk of in-hospital MACEs significantly increased as eGFR decreased. This suggests that we may consider giving standardized cardiovascular drug therapy to patients with non-obstructive ACS, especially those with non-obstructive ACS combined with abnormal renal function, in order to improve the prognosis of patients. This needs to be confirmed by more randomized controlled trial results.

#2219 Glycemic control and adverse outcomes in patients with diabetes and CKD stage 4-5: a nationwide cohort study

Abstract Background and Aims Although poor glycemic control is strongly associated with adverse clinical outcomes, few studies have evaluated their risk across the full glycemic spectrum in patients with moderate to advanced chronic kidney disease (CKD). Guidelines for HbA1c targets are mainly derived from extrapolation of trials conducted in people with normal or mildly reduced kidney function. In non-dialysis CKD individualized targets are recommended, often aiming for less strict glycemic control, due to lack of evidence for the efficacy of lower HbA1c, and potentially greater harm. In this study, we analyzed long-term outcomes across the full spectrum of HbA1c in CKD stage 4-5. Method Using data from the Swedish Renal Registry, we included patients with diabetes and CKD stages 4-5. Adjusted cause-specific Cox models were used to analyze associations between the one-year baseline mean HbA1c level (&amp;lt;43, 43-52 [reference], 53-64, 65-74, 75-89, ≥90 mmol/mol) and the occurrence of major adverse cardiovascular events (MACE, a composite of cardiovascular death, hospitalization for myocardial infarction or stroke), kidney replacement therapy (KRT), all-cause mortality, and hospitalization/death due to hypoglycemia. Results We included 2571 patients (71 years, 64% men, eGFR 20 mL/min per 1.73m², HbA1c 59.7 mmol/mol [7.6%], 75% insulin users). At baseline, patients with a higher HbA1c level were younger, had a higher prevalence of cardiovascular disease and were more likely prescribed insulin. Kidney function and malnutrition-inflammation markers were, however, not different between groups. Over a median follow-up of 4.9 [4.6;5.2] years, 939 (37%) KRT, 1078 (42%) MACE, and 1523 (59%) deaths occurred. Increasing HbA1c was gradually associated with the risk of MACE (adjusted HR from 0.76 [95% CI: 0.60-0.96] for HbA1c &amp;lt;43 mmol/mol to 1.39 [1.01-1.92] for HbA1c ≥ 90 mmol/mol) (Fig.). In contrast, a J-shaped relationship was observed for the risk of all-cause mortality. Compared to the reference group (43-52 mmol/mol; 5-year absolute risk 52% [48-56]), a HbA1c &amp;lt;43 mmol/mol was not associated with a higher mortality (adjusted HR 1.03 [0.86-1.23], 5-year absolute risk 57% [51-63]), while any HbA1c above 75 mmol/mol was associated with a higher risk of death. The risks of KRT and severe hypoglycemia were not different across HbA1c levels. Conclusion In CKD stage 4-5, HbA1c above the general recommendation for non-CKD patients (43-52 mmol/mol) is associated with a higher risk of MACE and all-cause mortality, but not KRT, without increased risk of severe hypoglycemia. This suggests that targeting a lower HbA1c, together with other cardio-reno-metabolic prevention strategies, might contribute to improve health outcomes in this very high-risk population.

#2063 Safety and efficacy of vadadustat vs darbepoetin alfa in patients on maintenance dialysis by prespecified subgroups of baseline ESA dose

Abstract Background and Aims Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in Europe, Australia, Japan for the treatment of anemia in patients with dialysis-dependent (DD)-CKD. In the INNO2VATE global phase 3 trials in patients with DD-CKD, including 2 separate trials in patients new to dialysis [NCT02865850] and on maintenance dialysis [NCT02892149], vadadustat was noninferior to the erythropoiesis -stimulating agent (ESA) darbepoetin alfa for cardiovascular safety and hemoglobin efficacy. Among patients with DD-CKD, high ESA dose requirements have been associated with an increased risk of cardiovascular complications. In this secondary analysis, we compared cardiovascular safety and hematological efficacy of vadadustat and darbepoetin alfa across baseline ESA dose categories. Method In the INNO2VATE trials, 3554 patients on maintenance dialysis were randomized 1:1 to vadadustat or darbepoetin alfa, stratified according to geographic region, New York Heart Association heart failure classification, and hemoglobin concentration at trial entry. Data were analyzed for prespecified subgroups of patients categorized by their baseline ESA (epoetin alfa/equivalents) dose: low (&amp;lt;90 U/kg/week), intermediate (90-299 U/kg/week), or high (≥300 U/kg/week). Within these dose subgroups, the key safety endpoint was the first occurrence of an adjudicated major adverse cardiovascular event (MACE: first occurrence of all-cause mortality, nonfatal myocardial infarction [MI], or nonfatal stroke) using a time-to-event analysis. Primary and secondary efficacy endpoints were mean change in hemoglobin concentration from baseline during the primary (weeks 24-36) and secondary (weeks 40-52) evaluation periods, respectively. Results More participants were in the low (vadadustat: n = 916 [53%], darbepoetin alfa: n = 968 [55%]) and intermediate (vadadustat: n = 724 [42%], darbepoetin alfa: n = 693 [39%]) than in the high (vadadustat: n = 102 [6%], darbepoetin alfa: n = 98 [6%]) baseline ESA dose subgroups. Hazard ratios for the occurrence of first MACE between vadadustat and darbepoetin alfa in the 3 baseline ESA dose subgroups were as follows: low dose, 0.99 (95% CI, 0.81 to 1.23); intermediate dose, 0.93 (95% CI, 0.74 to 1.18); and high dose, 0.62 (95% CI, 0.34 to 1.14) (Fig.). Similar results were observed for other key MACE-related endpoints, including all-cause mortality, MACE plus hospitalizations for heart failure or thromboembolic events, cardiovascular MACE (first occurrence of cardiovascular mortality, nonfatal MI, or nonfatal stroke), and cardiovascular death. Mean hemoglobin concentrations increased in both treatment groups throughout the trial period. The least squares mean treatment difference (vadadustat compared to darbepoetin alfa) for change in hemoglobin concentration from baseline to the primary efficacy period was –0.10 g/dL (95% CI, –0.19 to –0.02), –0.20 g/dL (95% CI, –0.30 to –0.09), and –0.39 g/dL (95% CI, –0.67 to –0.11) for the low, intermediate, and high baseline ESA dose subgroups, respectively. Similar results were observed for the secondary efficacy period. Across baseline ESA dose subgroups, the proportion of patients whose average hemoglobin concentration was within target range was similar between the vadadustat and darbepoetin alfa arms during the primary efficacy period (low: odds ratio [OR], 0.89; 95% CI, 0.74, 1.08; intermediate: OR, 0.87; 95% CI, 0.70, 1.09; high: OR, 0.90; 95% CI 0.49, 1.64). Similar results were observed during the secondary efficacy period. Conclusion The cardiovascular safety and efficacy of vadadustat was similar to darbepoetin alfa in patients with DD-CKD irrespective of baseline ESA dose. In patients requiring higher ESA doses at baseline, the risk of MACE was numerically (but not significantly) lower in vadadustat-treated patients. Further investigation is required to confirm or refute this trend.

D-dimer and fibrinogen indicate ischemic risk in patients with atrial fibrillation after percutaneous coronary intervention

BackgroundThis study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).MethodsIn this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1–3 after PCI. Dilute Russell’s viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-β2-Glycoprotein 1 (aβ2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis.Results158 patients were enrolled between May 2020 and May 2021 on day 1–3 after PCI. The median age was 78 years (interquartile range [IQR] 72–82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39–5.49], p = 0.579), nor bleeding (HR 1.07 [0.30–3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09–23.41], p = 0.038) and major bleeding (HR 7.04 [1.58–31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60–0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70–0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11–11.96], p = 0.033).ConclusionBiomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.

Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus

ObjectiveCardiovascular disease (CVD) risk is increased in SLE and underestimated by general population prediction algorithms. We aimed to develop a novel SLE-specific prediction tool, SLECRISK, to provide a more accurate estimate of CVD risk in SLE. MethodsWe studied patients in the Brigham and Women's Hospital SLE cohort. We collected one-year baseline data including the presence of traditional CVD factors and SLE-related features at cohort enrollment. Ten-year follow-up for the first major adverse cardiovascular event (MACE; myocardial infarction (MI), stroke, or cardiac death) began at day +1 following the baseline period (index date). ICD-9/10 codes identified MACE were adjudicated by board-certified cardiologists. Least absolute shrinkage and selection operator regression selected SLE-related variables to add to the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equations 10-year risk Cox regression model. Model fit statistics and performance (sensitivity, specificity, positive/negative predictive value, c-statistic) for predicting moderate/high 10-year risk (≥7.5 %) of MACE were assessed and compared to ACC/AHA, Framingham risk score (FRS), and modified FRS (mFRS). Optimism adjustment internal validation was performed using bootstrapping. ResultsWe included 1,243 patients with 90 MACEs (46 MIs, 36 strokes, 19 cardiac deaths) over 8946.5 person-years of follow-up. SLE variables selected for the new prediction algorithm (SLECRISK) were SLE activity (remission/mild vs. moderate/severe), disease duration (years), creatinine (mg/dL), anti-dsDNA, anti-RNP, lupus anticoagulant, anti-Ro positivity, and low C4. The sensitivity for detecting moderate/high-risk (≥7.5 %) of MACE using SLECRISK was 0.74 (95 %CI: 0.65, 0.83), which was better than the sensitivity of the ACC/AHA model (0.38 (95 %CI: 0.28, 0.48)). It also identified 3.4-fold more moderate/high-risk patients than the ACC/AHA. Patients who were moderate/high-risk according to SLECRISK but not ACC/AHA, were more likely to be young women with severe SLE and few other traditional CVD risk factors. Model performance between SLECRISK, FRS, and mFRS were similar. ConclusionThe novel SLECRISK tool is more sensitive than the ACC/AHA for predicting moderate/high 10-year risk for MACE and may be particularly useful in predicting risk for young females with severe SLE. Future external validation studies utilizing cohorts with more severe SLE are needed.

Association between the triglyceride-glucose index and in-hospital major adverse cardiovascular events in patients with acute coronary syndrome: results from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome project

ObjectiveAlthough the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization.MethodsWe recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups.ResultsA total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121–1.400 and HR = 1.604, 95% CI 1.437–1.791, respectively; p value for trend < 0.001], especially in patients with STEMI or renal insufficiency. Moreover, we found interactions between the TyG index and age, sex, diabetes status, renal insufficiency status, and previous PCI (all p values for interactions < 0.05).ConclusionsIn patients with ACS, the TyG index was an independent predictor of in-hospital MACEs. Special vigilance should be exercised in females, elderly individuals, and patients with renal insufficiency.