Subsequent Major Adverse Cardiovascular Events Research Articles

Patient acceptance and adherence to the COMPASS trial drug recommendations following symptomatic carotid endarterectomy.

IntroductionThe COMPASS trial demonstrated that in patients with atherosclerotic diseases, low-dose rivaroxaban and aspirin provides greater protection against subsequent major adverse cardiovascular events (MACE) than mono-antiplatelet therapy (MAPT) alone. Drug acceptance and adherence maximises this benefit. We have assessed drug acceptance and adherence to the COMPASS drug regime in patients following carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. MethodsFollowing CEA, the views of 63 patients on the COMPASS drug regime were assessed using the Beliefs about Medicine Questionnaire (BMQ) and drug adherence was determined using the Sidorkiewicz scoring system. These views were compared with those of 54 patients on MAPT. Side effects (bleeding and drug reactions) and new MACE were recorded. ResultsPost-CEA patients on the COMPASS drug regimen had strong positive views on the necessity to take these drugs (Necessity Scale 19.6 +/- 3.6). Although there were some concerns about the COMPASS drug regimen, these were not strongly held (Concern Scale 11.8 +/-4.9) and the Necessity-Concerns Differential was positive (7.8 +/- 6.2). The Drug Adherence Score was “High” to “Good” (level of drug adherence 1.7+/-1.0). The BMQ scales and Drug Adherence Score of post-CEA patients on the COMPASS drug regimen were similar to those on MAPT. The incidence of post-CEA MACE and side effects were similar for those on the COMPASS drug regimen and MAPT. ConclusionsPost-CEA patients on the COMPASS drug regimen had positive views on taking the drugs and drug adherence was high. We did not identify any patient-related barriers to the use of the COMPASS drug regimen to further reduce cardiovascular events.

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Nomograms based on ratio indexes to predict severity and prognosis in immune checkpoint inhibitors-related myocarditis: a retrospective analysis

PurposeImmune checkpoint inhibitors-related myocarditis (ICI-M) is one of the immune-related adverse events (irAEs), which is rare and highly lethal. This study aimed to establish nomograms based on ratio biomarkers to predict the severity and prognosis of ICI-M.MethodsWe retrospectively examined patients with advanced cancers who were also diagnosed with ICI-M at the Fourth Hospital of Hebei Medical University. The patients of ICI-M were divided into mild and severe groups and a 40-day following up was carried out. The major adverse cardiovascular events(MACEs) were regarded as the endpoint. Nomogram-based models were established and validated.ResultsSeventy-seven patients were involved, including 31 severe cases(40.3%). Lactate dehydrogenase-to-albumin ratio(LAR) combined with the change rate from baseline to onset of LAR(▵\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ riangle$$\\end{document}LAR) which performed best to diagnose the severe ICI-M was identified to establish the nomogram-based model. The bootstrap-corrected concordance index [0.752 95% confidence interval (CI): 0.635-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$-$$\\end{document}0.866] and calibration plot with good degree of fitting confirmed this diagnostic model. Neutrophil-to-high-density lipoprotein cholesterol ratio(NHR) and LAR were also screened into the nomogram-based model for 40-day MACEs after ICI-M, which performed well by validating for concordance index(0.779 95% CI: 0.677-\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$-$$\\end{document}0.865)and calibration plots after being bootstrap-corrected. Moreover, a ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document}101% increase in LAR significantly separated patients in MACE-free survival.ConclusionRatio indexes at onset and their change rates from baseline showed good diagnostic value for the severity of ICI-M and prognostic value for subsequent MACEs, particularly LAR, NHR and their change rates. The nomogram-based models of ratio indexes could provide a potential choice for early detection and monitor of the severe ICI-M and subsequent MACEs.Graphical abstract

#2379 Acute kidney injury as a key predictor of major adverse cardiovascular events in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) significantly raises cardiovascular event risks. The influence of acute-on-chronic kidney incidents is less understood. This study examines the link between acute kidney injury (AKI) episodes and subsequent Major Adverse Cardiovascular Events (MACE) in CKD patients. Method From 2013 to 2016, the CKD-REIN cohort enrolled 3033 adults with CKD stages 3-5 (average age 67; 66% male; mean eGFR 33 mL/min/1.73m²) from 40 French outpatient nephrology clinics, reflecting national geographic and legal diversity. During a 5-year follow-up, all AKI episodes, whether inpatient or outpatient, were identified, confirmed, and categorized per KDIGO-AKI standards by an expert panel. Cardiovascular events were evaluated using clinical trial Cardiovascular and Stroke Endpoint Definitions. MACE cumulative incidences (myocardial infarction, stroke, heart failure hospitalization, cardiovascular death) post-AKI were calculated using Aalen-Johansen methods, accounting for kidney failure and death risks. The impact of the first AKI episode on MACE risk was analyzed using a multivariable Cox model, treating AKI as a time-variable and stratifying by characteristics (in/outpatient status, AKI stage, pre-renal causes, renal recovery at discharge). Factors like demographics, cardiovascular risks, CKD severity, and treatments were considered. Interaction and sensitivity analyses were performed, excluding those with prior AKI or cardiovascular disease. Results During a median follow-up of 5.2 years, 530 patients experienced an incident AKI episode. The cumulative incidence of MACE at 1 year following this initial episode of AKI was 8.1% [95% confidence interval, 6.1; 10.8], with a median time to occurrence of 6.7 months after AKI. After adjustment for multiple confounders, we observed a substantial increased hazard of MACE associated with a first episode of AKI (HR = 5.99 [4.63; 7.76], p &amp;lt; 0.001), and this association remained significant for each MACE component (Fig. 1A). A dose-response relationship was observed, with higher risks in more severe AKI cases (KDIGO grades 2-3) and among hospitalized versus non-hospitalized patients (Fig. 1B). This association was also observed across all subgroups, without any interaction with age, sex, nor major comorbidities (diabetes, history of AKI, or cardiovascular events), as well as in various sensitivity analyses. Overall, we estimated an attributable risk fraction of 18.1% [13.6; 22.4] for MACE associated with AKI episodes within this population. Conclusion Our study highlights a strong dose-response relationship between incident AKI events and the risk of subsequent major cardiovascular events in CKD patients. These findings suggest that AKI may not only be a marker of increased cardiovascular risk but also a potential mediator of this risk. From a clinical perspective, these results underscore the importance of close monitoring and management of AKI in CKD patients to reduce the risk of MACE. This study improves our understanding of the interplay between renal and cardiovascular health, emphasizing the need for integrated care approaches in this high-risk population.

Risk of Major Adverse Cardiovascular Events After Emergency Department Visits for Hypertensive Urgency.

Chronic hypertension is an established long-term risk factor for major adverse cardiovascular events (MACEs). However, little is known about short-term MACE risk after hypertensive urgency, defined as an episode of acute severe hypertension without evidence of target-organ damage. We sought to evaluate the short-term risk of MACE after an emergency department (ED) visit for hypertensive urgency resulting in discharge to home. We performed a case-crossover study using deidentified administrative claims data. Our case periods were 1-week intervals from 0 to 12 weeks before hospitalization for MACE. We compared ED visits for hypertensive urgency during these case periods versus equivalent control periods 1 year earlier. Hypertensive urgency and MACE components were all ascertained using previously validated International Classification of Diseases, Tenth Revision Clinical Modification codes. We used McNemar test for matched data to calculate risk ratios. Among 2 225 722 patients with MACE, 1 893 401 (85.1%) had a prior diagnosis of hypertension. There were 4644 (0.2%) patients who had at least 1 ED visit for hypertensive urgency during the 12 weeks preceding their MACE hospitalization. An ED visit for hypertensive urgency was significantly more common in the first week before MACE compared with the same chronological week 1 year earlier (risk ratio, 3.5 [95% CI, 2.9-4.2]). The association between hypertensive urgency and MACE decreased in magnitude with increasing temporal distance from MACE and was no longer significant by 11 weeks before MACE (risk ratio, 1.2 [95% CI, 0.99-1.6]). ED visits for hypertensive urgency were associated with a substantially increased short-term risk of subsequent MACE.

Imaging of the brain-heart axis: prognostic value in a European setting.

Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe. In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from 'at-risk' to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis. Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05-2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96-3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments. In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging.

Association between lipoprotein(a), LPA genetic risk score, aortic valve disease, and subsequent major adverse cardiovascular events.

Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and Lp(a). As Lp(a) is almost entirely genetically determined, in this study, we aim to determine whether Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascular events (MACEs). Patients undergoing coronary angiography between January 2012 and May 2013 were invited to participate in the study. Of 752 analysable participants, 446 had their Lp(a) measured and 703 had a calculable LPA genetic risk score (GRS). The primary outcomes were the presence of CAVD at baseline and MACE over a 7-year follow-up. The GRS explained 45% of variation in Lp(a). After adjustment for cardiac risk factors and coronary artery disease (CAD), the odds of CAVD increased with increasing Lp(a) [odds ratio (OR) 1.039 per 10-unit increase, 95% confidence interval (CI) 1.022-1.057, P < 0.001] and GRS (OR 1.054 per 10-unit increase, 95% CI 1.024-1.086; P < 0.001). Lipoprotein(a) and the GRS as continuous variables were not associated with subsequent MACEs. A dichotomized GRS (>54) was associated with MACE, but this relationship became non-significant when CAD classification was added into the model (OR 1.333, 95% CI 0.927-1.912; P = 0.12). An LPA GRS can explain 45% of variation in Lp(a) levels, and both Lp(a) and the GRS are associated with CAVD. An elevated GRS is associated with future cardiac events in a secondary risk setting, but, if the CAD status is known, it does not provide additional prognostic information.

Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase.

The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7days), subacute (1month after pPCI), and chronic phases (6months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. Among the 200 analyzed patients (182 men; median age, 61years; age range, 50-66years), 37 (18.5%) encountered MACE during a median follow-up of 31.2months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: A cohort study from the UK Biobank

Background and aimsElevated lipoprotein(a) [Lp(a)] is a genetic driver for atherosclerotic cardiovascular disease (ASCVD). We aimed to provide novel insights into the associated risk of elevated versus normal Lp(a) levels on major adverse cardiovascular events (MACE) in an incident ASCVD cohort. MethodsThis was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a). ResultsThe study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period. ConclusionsThe association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help identify and better manage these higher-risk individuals.

Risk Factors Associated with Major Adverse Cardiovascular Events after Ischemic Stroke: A Linked Registry Study

Introduction: Survivors of stroke are at risk of experiencing subsequent major adverse cardiovascular events (MACE). We aimed to determine the incidence of, and risk factors for, MACE after first-ever ischemic stroke, by age group (18–64 years vs. ≥65 years). Methods: Observational cohort study using patient-level data from the Australian Stroke Clinical Registry (2009–2013), linked with hospital administrative data. We included adults with first-ever ischemic stroke who had no previous acute cardiovascular admissions and followed these patients for 2 years post-discharge, or until the first post-stroke MACE event. A Fine-Gray sub-distribution hazard model, accounting for the competing risk of non-cardiovascular death, was used to determine factors for incident post-stroke MACE. Results: Among 5,994 patients with a first-ever ischemic stroke (median age 73 years, 45% female), 17% were admitted for MACE within 2 years (129 events per 1,000 person-years). The median time to first post-stroke MACE was 117 days (89 days if aged <65 years vs. 126 days if aged ≥65 years; p = 0.025). Among patients aged 18–64 years, receiving intravenous thrombolysis (sub-distribution hazard ratio [SHR] 0.51 [95% CI, 0.28–0.92]) or being discharged to inpatient rehabilitation (SHR 0.65 [95% CI, 0.46–0.92]) were associated with a reduced incidence of post-stroke MACE. In those aged ≥65 years, being unable to walk on admission (SHR 1.33 [95% CI 1.15–1.54]), and history of smoking (SHR 1.40 [95% CI 1.14–1.71]) or atrial fibrillation (SHR 1.31 [95% CI 1.14–1.51]) were associated with an increased incidence of post-stroke MACE. Acute management in a large hospital (>300 beds) for the initial stroke event was associated with reduced incidence of post-stroke MACE, irrespective of age group. Conclusions: MACE is common within 2 years of stroke, with most events occurring within the first year. We have identified important factors to consider when designing interventions to prevent MACE after stroke, particularly among those aged <65 years.

Chronic kidney disease's impact on revascularization and subsequent major adverse cardiovascular events in patients with chronic coronary syndrome

ObjectiveTo determine the impact of CKD on the completeness of revascularization and major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Patients and methodsThe study enrolled 400 CCS patients who underwent revascularization by PCI. They were separated into two categories according to their eGFR levels: the control group: 200 patients with eGFR ≥60mL/min/1.73m2, and the CKD Group: 200 patients with eGFR< 60ml/min/1.73m.2 Patients were reclassified according to revascularization into complete and incomplete revascularization groups with one-year follow-up to assess the MACE. ResultsCKD patients were significantly older (65.78 ± 6.41 vs. 56.70 ± 9.20 years, P=<0.001). They had higher syntax scores (P = 0.005), CIN (P = 0.001), all-cause mortality (P = 0.02), MACE (P = 0.037), and heart failure (P = 0.014). After reclassification according to revascularization. GFR was significantly reduced among patients with incomplete revascularization (51.08 ± 28.15 vs. 65.67 ± 26.62, respectively, P =<0.001). Repeated revascularization (P < 0.001), STEMI (P = 0.003), stent thrombosis (P = 0.015), MACE (P < 0.001), stroke (P < 0.001), and all-cause mortality (P < 0.001) were more prevalent among patients with incomplete revascularization. Multivariate regression analysis revealed eGFR (P = 0.001) and Syntax score (SS) (P=<0.001) as independent predictors of incomplete revascularization. The optimal eGFR cutoff value for predicting partial revascularization is 49.50mL/min/1.73m2, with 58.8% sensitivity and 69.3 % specificity. ConclusionChronic kidney disease is associated with a higher syntax score and incomplete revascularization prevalence in CCS patients. Additionally, incomplete revascularization is associated with an increased incidence of major adverse cardiac events. In patients with CCS, CKD predicts partial revascularization and subsequent MACE.

Prevalence and outcomes of familial hypercholesterolemia in young patients undergoing coronary bypass surgery

Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism, with elevated low-density lipoprotein cholesterol (LDL) levels and increased risk of premature coronary disease. Appropriate management substantially reduces the risk of adverse events; however, FH is frequently under-recognised and under-treated. The prevalence of FH amongst younger patients undergoing coronary bypass surgery, as well as their clinical outcomes, has not been described. Purpose This study aimed to determine the prevalence of FH in patients undergoing coronary bypass surgery prior to age 60 years. The association of FH on attainment of LDL targets and subsequent adverse cardiovascular events was also determined. Methods A retrospective analysis of all patients undergoing coronary bypass surgery prior to the age of 60 years was conducted at an Australian tertiary hospital during the period April 2008 and July 2022. Exclusion criteria were severe renal or hepatic impairment, uncontrolled malignancy, severe inflammatory or infectious disease, or lipid data unavailable. Baseline demographics and risk factors at the time of surgery were identified by a search of the Statewide Cardiothoracic Database. Blood lipid levels (highest, pre-surgery and most recent) and clinical outcomes were obtained from digital medical records. Dutch Lipid Clinic Network Scores (DLCNS) were calculated for all patients and grouped as ‘unlikely FH’ (DLCNS &amp;lt;3), ‘possible FH’ (DLCNS 3 – 5), or ‘probable / definite FH’ (DLCNS ³ 6). Attainment of LDL targets (&amp;lt;1.8mmol/L and &amp;lt;1.4mmol/L) and subsequent major adverse cardiovascular events (MACE) were compared between the ‘unlikely’ and ‘probable / definite’ FH groups. Results During the study period, 683 patients underwent coronary bypass procedures prior to the age of 60. 93 were excluded, leaving a study population of 590, with a median follow up of 7.9 years [IQR 4.7, 12.1]. Baseline characteristics are outlined in table 1. 80 patients (13.6%) were classified as ‘definite/probable FH’, 249 (42.2%) as ‘possible FH’ and 261 (44.2%) ‘unlikely FH’. As observed in table 2, patients with definite/probable FH had a significantly higher prevalence of uncontrolled lipids (81.2%) and MACE (21.3%) compared to patients with unlikely FH. For MACE, this result remained statistically significant after adjusting for age, sex, smoking status, hypertension, diabetes and surgery type (elective vs urgent) - OR 2.52 [95% CI 1.0 - 6.4]. Conclusion FH is highly prevalent in young patients undergoing coronary bypass surgery. These patients are less likely to achieve LDL targets and are more likely to suffer adverse cardiovascular events in the years following surgery. Detection of these patients may improve LDL management and clinical outcomes as well as the yield of new cases through cascade testing of close relatives.Table 1:Baseline CharacteristicsTable 2:Outcomes

Abstract 13567: Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES

Background: Baseline (BL) lipoprotein(a) (Lp(a)) concentration is similarly related to cardiovascular (CV) risk when measured in either mass or molar units by immunoassay (IA). Because of Lp(a) isoform variation in mass, differences may exist between Lp(a) measurement methods in terms of relating change to risk reduction. We determined whether the reduction in major adverse cardiovascular events (MACE) by PCSK9 inhibitor alirocumab (ALI) had a similar relationship to the reduction in Lp(a) concentration as measured by 3 different methods. Methods: Lp(a) was measured by IA-mass (Siemens), IA-molar (Roche), and mass spectrometry (MS)-molar assays at BL and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial which compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome. Changes in Lp(a) from BL to M4 were related to subsequent risk of MACE (coronary heart disease (CHD) death, nonfatal myocardial infarction (NFMI), fatal + nonfatal ischemic stroke, or unstable angina hospitalization) in the ALI group. Proportional hazards models were adjusted for BL Lp(a), BL LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay. All analyses were by intention-to-treat. Results: Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE. Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while change in IA-molar concentration was marginally significant; associations were more evident with CHD death + NFMI ( Figure ). MACE HRs for median change were similar across tests. Conclusion: With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, 3 Lp(a) assay methods appeared similarly predictive of ALI MACE reduction.

Mitochondrial metabolites predict adverse cardiovascular events in individuals with diabetes.

Metabolic mechanisms underlying the heterogeneity of major adverse cardiovascular (CV) event (MACE) risk in individuals with type 2 diabetes mellitus (T2D) remain unclear. We hypothesized that circulating metabolites reflecting mitochondrial dysfunction predict incident MACE in T2D. Targeted mass-spectrometry profiling of 60 metabolites was performed on baseline plasma samples from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS; discovery cohort) and Exenatide Study of Cardiovascular Event Lowering (EXSCEL; validation cohort) biomarker substudy cohorts. A principal components analysis metabolite factor comprising medium-chain acylcarnitines (MCACs) was associated with MACE in TECOS and validated in EXSCEL, with higher levels associated with higher MACE risk. Meta-analysis showed that long-chain acylcarnitines (LCACs) and dicarboxylacylcarnitines were also associated with MACE. Metabolites remained associated with MACE in multivariate models and favorably changed with exenatide therapy. A third cohort (Cardiac Catheterization Genetics [CATHGEN]) with T2D was assessed to determine whether these metabolites improved discriminative capability of multivariate models for MACE. Nine metabolites (MCACs and LCACs and 1 dicarboxylacylcarnitine) were associated with time to MACE in the CATHGEN cohort. Addition of these metabolites to clinical models minimally improved the discriminative capability for MACE but did significantly down reclassify risk. Thus, metabolites reporting on dysregulated mitochondrial fatty acid oxidation are present in higher levels in individuals with T2D who experience subsequent MACE. These biomarkers may improve CV risk prediction models, be therapy responsive, and highlight emerging risk mechanisms.

Cardiac magnetic resonance left ventricular filling pressure is linked to symptoms, signs and prognosis in heart failure.

Left ventricular filling pressure (LVFP) can be estimated from cardiovascular magnetic resonance (CMR). We aimed to investigate whether CMR-derived LVFP is associated with signs, symptoms, and prognosis in patients with recently diagnosed heart failure (HF). This study recruited 454 patients diagnosed with HF who underwent same-day CMR and clinical assessment between February 2018 and January 2020. CMR-derived LVFP was calculated, as previously, from long- and short-axis cines. CMR-derived LVFP association with symptoms and signs of HF was investigated. Patients were followed for median 2.9years (interquartile range 1.5-3.6years) for major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, HF hospitalization, non-fatal stroke, and non-fatal myocardial infarction. The mean age was 62±13years, 36% were female (n=163), and 30% (n=135) had raised LVFP. Forty-seven per cent of patients had an ejection fraction<40% during CMR assessment. Patients with raised LVFP were more likely to have pleural effusions [hazard ratio (HR) 3.2, P=0.003], orthopnoea (HR 2.0, P=0.008), lower limb oedema (HR 1.7, P=0.04), and breathlessness (HR 1.7, P=0.01). Raised CMR-derived LVFP was associated with a four-fold risk of HF hospitalization (HR 4.0, P<0.0001) and a three-fold risk of MACE (HR 3.1, P<0.0001). In the multivariable model, raised CMR-derived LVFP was independently associated with HF hospitalization (adjusted HR 3.8, P=0.0001) and MACE (adjusted HR 3.0, P=0.0001). Raised CMR-derived LVFP is strongly associated with symptoms and signs of HF. In addition, raised CMR-derived LVFP is independently associated with subsequent HF hospitalization and MACE.

Poor recognition and undertreatment of anemia in patients with chronic kidney disease managed in primary care.

Anemia is a common complication of chronic kidney disease (CKD), but limited awareness and treatment options may hinder its management among CKD patients followed in primary care. We evaluated adults with CKD stages 3-5 attending primary care in Stockholm, Sweden, 2012-2018. We assessed the incidence of anemia, clinical reactions, and association with subsequent major adverse cardiovascular events (MACE) and death. We identified 45,637 patients with CKD stages 3-5 free from anemia (mean age 78 years; 64% females; 79% CKD stage 3b). During a median follow-up of 2.4 years, 26% of patients developed anemia, and 10.4% developed severe anemia (hemoglobin <10g/dL). Within 6 months from the anemia event, iron tests were infrequent; ferritin and transferrin saturation were tested in 27% and 11% of anemia cases, respectively, and 49% and 24% of severe anemia cases. Few patients were recognized with a clinical diagnosis (15% of anemia cases; 68% of severe anemias). Only 19% of patients with anemia received treatment, primarily iron (10%) and blood transfusions (7%); erythropoietin-stimulating agent use was anecdotal (∼1%). Treatment rates for severe anemia were higher, but 43% of patients still failed to receive treatment. Developing anemia was associated with a higher risk of MACE and death. Anemia was common and associated with adverse outcomes among patients with CKD stages 3-5 managed in primary care. Iron stores were infrequently tested, and a large proportion of patients with anemia remained untreated/under-recognized.

Association Between Lipoprotein(A), LPA Genetic Risk Score, Aortic Valve Disease, and Subsequent Major Adverse Cardiovascular Events

Cohort studies have demonstrated associations between calcific aortic valve disease (CAVD) and lipoprotein(a) [Lp(a)]. As Lp(a) is almost entirely genetically determined, with the increasing clinical availability of genetic information, this study aimed to determine whether Lp(a), when predicted from genetic data, is associated with CAVD and major adverse cardiovascular events (MACE). Consecutive patients undergoing coronary angiography were invited to participate in the study. Of 752 analysable participants, 446 had Lp(a) measured and 703 had a calculable LPA genetic risk score (GRS). Calcific aortic valve disease was categorised as absent/present and by severity. The primary outcomes were presence of CAVD at baseline, and MACE over 7 years of follow-up. The GRS explained 45% of the variation in Lp(a). After adjustment for cardiac risk factors and coronary artery disease, the odds of CAVD increased with Lp(a) (OR 1.039 per 10-unit increase, 95% CI 1.022–1.057; p<0.001) and GRS (OR 1.054 per 10-unit increase, 95% CI 1.024–1.086; p<0.001). Lp(a) and the GRS as continuous variables were not associated with subsequent MACE. Dichotomised GRS (>54) was associated with MACE, but this relationship became non-significant when coronary artery disease classification was added into the model (OR 1.33, 95% CI 0.93–1.91; p=0.12). An LPA GRS can explain 45% of the variation in Lp(a) levels. Both Lp(a) and an LPA GRS are associated with CAVD. An elevated GRS appears to be associated with future cardiac events in a secondary risk setting, but, if coronary artery disease status is known, it does not provide additional prognostic information.

Factors Associated with Increased Risk of Major Cardiovascular Events for Patients Undergoing CAR T Therapy

Introduction: Chimeric antigen receptor (CAR)-T cell therapy use has increased exponentially following its approval for multiple indications in non-Hodgkin lymphomas, multiple myeloma, and acute lymphoblastic leukemia. While cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias are well-described and frequently encountered side effects, a significant proportion of patients experience major adverse cardiovascular events (MACE). This study investigates factors associated with increased risk for MACE. Methods: We performed a retrospective analysis of a consecutive cohort of patients treated with CAR-T therapy at our center between 2018 and 2022. Clinical, laboratory, and imaging parameters were collected. MACE were defined as acute myocardial infarction (AMI), stroke or transient ischemic attack, cardiovascular death, unstable angina, life-threatening arrhythmias, and heart failures. Data was analyzed using SPSS v23. Categorical variables were compared using univariate chi-square test. Results: A total of 126 patients were included. Of these, ten patients (12.5%) had a MACE event. Baseline characteristics including age, sex, body mass index, coronary artery calcium, lipid profile, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, CRS, ICANS, and tocilizumab use are summarized in Table. The median follow-up period was 8.9 months. Patients who experienced MACE versus no MACE had a significantly higher age at CAR-T cell therapy (74.5 years vs. 64.9 years, p = .009), higher peak C-reactive protein (CRP) with a median of 116.7 mg/dL versus 73.85 mg/dL, p = 0.006 respectively. CRS and ICANS grades were associated with MACE events (p = 0.008 and 0.005, respectively). No echocardiographic differences were found. No progression free or overall survival differences were observed in the groups (p = 0.67 and 0.16, respectively). Conclusions: Our results indicate that patients undergoing CAR-T cell therapy who are older and who experience an increased degree of inflammatory response, reflected by peak CRP level, were associated with MACE. These data suggest that inflammatory markers may be clinically relevant predictors of subsequent MACE in CAR-T therapy-treated patients. Prospective inflammation monitoring combined with trials incorporating anti-inflammatory strategies may mitigate the risk of MACE in this patient population. Keywords: Cellular therapies, Diagnostic and Prognostic Biomarkers, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. G. Kaur Consultant or advisory role: SANOFI, BMS, Janssen, Cellectar, Arcellx Y. F. Madanat Consultant or advisory role: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Honoraria: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Educational grants: Blueprint Medicines and Morphosys.

Risk of Major Adverse Cardiovascular Event Following Incident Hospitalization for Acute Gout: A Western Australian Population-Level Linked Data Study.

Cardiovascular disease is the most common cause of death in people with gout. Acute inflammation, which is a characteristic of gout, may have a mechanistic role in major adverse cardiovascular events (MACEs). We aimed to examine the relationship between admissions to a hospital with acute gout and MACEs in a large population-based data set. We extracted data from the Hospital Morbidity Data Collection and Death Registrations of the Western Australian Rheumatic Disease Epidemiology Registry. We identified patients admitted to hospital with incident acute gout and who had admissions or a death record because of MACEs. We compared the risk of MACEs during the postdischarge period (1-30 days after acute gout admission) and control period (365 days prior to admission and 365 days after the postdischarge period) using a self-controlled case-series (SCCS) design, which is a within-person design that controls for time-invariant patient-specific confounding. We performed conditional fixed-effects Poisson regression to obtain rate ratios (RRs). We identified 941 patients (average age: 76.4 years; SD: 12.6; 66.7% male) with an incident acute gout admission and documented MACEs during the control and/or postdischarge periods. Of the 941 patients, 898 (95%) experienced MACEs during the combined control period (730-day period) and 112 (12%) during the postdischarge period (30-day period). The rates of MACEs during the total control and postdischarge periods were 0.84 and 1.45 events per person-year, respectively. Regression analysis confirmed increased rate during the postdischarge period (RR: 1.67; 95% CI: 1.38-2.03) compared with the control period. Sensitivity analyses indicated that our results were robust in relation to known limitations of the SCCS design. We report an increased risk of MACEs in the first 30 days after an incident hospital admission with acute gout, suggesting a temporal association between acute inflammation and subsequent MACEs in patients with gout.

Atrial high-rate episodes intensify R2CHA2DS2-VASc score for prognostic stratification in pacemaker patients

Patients with device detected atrial high-rate episodes (AHRE) have an increased risk of MACE. The R2CHA2DS2-VASc, CHADS2, R2CHADS2 and CHA2DS2-VASc score have been investigated for predicting major adverse cardiovascular events (MACE) in different groups of patients. We aimed to evaluate the R2CHA2DS2-VASc score in combination with AHRE ≥ 6 min for predicting MACE in patients with dual-chamber PPM but no prior atrial fibrillation (AF). We retrospectively enrolled 376 consecutive patients undergoing dual-chamber PPM implantation and no prior AF. The primary endpoint was subsequent MACE. For all patients in the cohort, CHADS2, R2CHADS2, CHA2DS2-VASc, R2CHA2DS2-VASc scores and AHRE ≥ or < 6 min were determined. AHRE was recorded as a heart rate > 175 bpm (Medtronic) or > 200 bpm (Biotronik) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine the independent predictors of MACE. ROC-AUC analysis was performed for CHADS2, R2CHADS2, CHA2DS2-VASc, and R2CHA2DS2-VASc scores and then adding AHRE ≥ 6 min to the four scores. The median age was 77 years, and 107 patients (28.5%) developed AHRE ≥ 6 min. After a median follow-up of 32 months, 46 (12.2%) MACE occurred. Multivariate Cox regression analysis showed that R2CHA2DS2-VASc score (HR, 1.485; 95% CI, 1.212–1.818; p < 0.001) and AHRE ≥ 6 min (HR, 2.125; 95% CI, 1.162–3.887; p = 0.014) were independent predictors for MACE. The optimal R2CHA2DS2-VASc score cutoff value was 4.5 (set at ≥ 5), with the highest Youden index (AUC, 0.770; 95% CI, 0.709–0.831; p < 0.001). ROC-AUC analysis of the four risk scores separately combined with AHRE ≥ 6 min all showed better discriminatory power than the four scores alone (All Z-statistic p < 0.05). In patients with PPM who develop AHRE ≥ 6 min, it is crucial to perform risk assessment with either four scores to further stratify risk for MACE.