Subsequent Cardiovascular Events Research Articles

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.

Immune Checkpoint Inhibitors and the Risk of Cardiovascular Adverse Events: A Pooled Clinical Trial Database Analysis

Introduction Immune checkpoint inhibitors (ICIs) are a highly effective class of cancer immunotherapy, but their use has been limited by immune-related adverse events (irAEs) affecting various organ systems. Recent real-world studies have shown higher incidence rates of cardiovascular (CV) events in patients with cancer who are treated with ICIs compared to those treated with conventional chemotherapy (Laenens et al, J Clin Oncol 2022). Studies suggest that the underlying mechanism involves a pro-inflammatory response causing unintended vascular compromise, but there have been limited data on ICI-related cardiotoxicity across pooled datasets. Given that ICIs have been applied to lung cancer treatment in recent years, we use it as an example indication to study clinical trial (CT) patients with advanced non-small cell lung cancer (aNSCLC) randomized to either a first-line (1L) ICI-containing regimen or to 1L chemotherapy alone (chemo) to evaluate for potential differential rates of CV events. Methods We pooled patient-level, phase 3 CT data on aNSCLC patients treated with ICI or chemo from the Medidata Enterprise Data Store. Treatment assignment was the main variable of interest. The primary outcome was a composite CV event (acute coronary syndrome, heart failure, stroke, transient ischemic attack), occurring between the start of study treatment (index date) and 30 days following the last dose of study treatment. Incidence rates and the relative hazard of a CV event by treatment assignment were estimated. Additionally, the risk of CV event with non-CV death treated as a competing risk was estimated using the Fine-Gray model. In a post-hoc subgroup analysis we explored the impact of treatment assignment on overall survival (OS) among patients with and without baseline vascular disease. OS was defined as the time from the index date until the date of death (all-cause). Patients alive at the end of CT follow-up were censored. Results A total of 1862 patients were included in this analysis, with 1128 (60.6%) randomized to ICI and 734 (39.4%) to chemo. Baseline demographics and comorbidities were balanced across treatment groups. Forty-six (2.5%) patients experienced at least 1 CV event. The incidence rate of CV events was 2.48 times (95% CI: 1.10, 6.57) higher among patients treated with ICI compared to chemo. The unadjusted hazard of composite CV event, estimated using Kaplan-Meier, differed significantly by treatment assignment (p= 0.008) ( Figure 1). After adjusting for baseline demographics and comorbidities, the hazard of a composite CV event remained higher for patients treated with ICI compared to chemo (aHR 2.68, 95% CI: 1.19-6.06) ( Table 1). Baseline vascular disease history (N=359; 19.3%) was also associated with an increased hazard of a CV event (aHR: 2.40; 95% CI: 1.25-4.60). Similar results were found in the competing risk analysis. In the subgroup analysis, patients without baseline vascular disease history had a significant OS benefit from an ICI compared to chemo (aHR 0.84, 95% CI: 0.75-0.95), whereas patients with baseline vascular disease did not (aHR 1.00, 95% CI: 0.78-1.27). Conclusion Though ICIs enhance the body's immune responses against cancer, it is important to study the associated effect of irAEs on off-target tissues. These analyses of historical CT data suggest a positive association between 1L treatment of aNSCLC with ICI and subsequent composite CV events compared with chemo alone. Given the high prevalence of morbidity among patients with lung cancer, the use of concomitant cardioprotective therapies may be an important consideration when treating cancer populations with ICIs. Pooling CT data increases the power to detect clinically important differences in rare toxicities and may inform future research and patient-physician decision-making regarding the suitability of ICI use in aNSCLC treatment. Furthermore, this research highlights the potential clinical utility of drug repurposing: expanding the use of drugs approved to treat CV events and exploring their use in patients with vascular disease who are also being treated with ICIs. As cell-mediated immune responses play a key role in the potential CV effects of ICI treatments, future studies are needed to define the underlying mechanisms of ICI-related dysregulation of the immune system to better monitor patients and improve clinical outcomes in the context of immunotherapy for aNSCLC and other cancer types.

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.

Role of Soluble Urokinase-Type Plasminogen Activator Receptor in Cardiovascular Disease.

Chronic inflammation is a major contributor to cardiovascular disease (CVD) risk. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived glycoprotein that is strongly associated with atherosclerotic disease. This review summarizes evidence on suPAR's role in CVD pathogenesis and its potential as a prognostic indicator and therapeutic target. Clinical, genetic, and experimental evidence supports suPAR's role as a pathogenic factor in atherosclerosis. suPAR promotes atherosclerosis through modulation of monocyte activation and function. Clinically, elevated suPAR levels are linked to increased cardiovascular risk across diverse populations. Ongoing clinical trials are evaluating therapies targeting suPAR signaling. Current evidence positions suPAR as a regulator of myeloid cell function that contributes to vascular inflammation and subsequent cardiovascular events. Additional research is needed to determine whether suPAR measurement can improve CVD risk prediction and enable personalized management. Overall, suPAR is a promising immune-derived biomarker and target for reducing inflammation and cardiovascular risk.

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

Arterial inflammation induced by immune checkpoint inhibitors assessed on 18F-FDG PET-CT scans in stage III/IV melanoma patients

Abstract Background In recent years, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, as they lead to a substantial improvement in the prognosis of cancer patients. In high-grade melanoma patients, ICIs have doubled the three-year survival rate. However, ICIs may not only increase the immune response to tumor cells, but also to non-tumor cells, potentially inducing pro-atherogenic effects that can result in increased vascular inflammation and subsequent cardiovascular events. Purpose The objective of this study is to assess differences in vascular inflammation in the large arteries, as detected by 18F-FDG PET-CT scans, between stage III/IV melanoma patients receiving ICI therapy compared to stage III/IV melanoma patients not treated with ICIs. Methods The study population consisted of a cohort stage III/IV melanoma patients who underwent PET-CT scans at baseline, defined as &amp;lt; 1 year after diagnosis of stage III/IV melanoma and at T1 and T2, 6 months and 18 months after the baseline scan respectively. Patients with a history of cardiovascular events, treated with statins or corticosteroids (prednisolone &amp;gt; 10 mg per day) were excluded. Vascular inflammation was evaluated in the following eight arterial segments: the left and right carotid artery, ascending aorta, aortic arch, thoracic descending aorta, abdominal aorta and the left and right iliac artery. For each segment, the maximum standardized uptake value (SUV) for 18F-FDG uptake was derived and target-to-background ratio (TBR) was calculated from the ratio of the maximum SUV of the segment and the mean SUV of the superior and inferior vena cava. Vascular inflammation was defined as the total TBR per patient, calculated by sum of the TBR values of the eight arterial segments. The study endpoint was the difference in the increase in total TBR between patients treated with ICIs (exposure group) and patients without ICI treatment (control group). Results A total of 70 stage III/IV melanoma patients of whom 46 received ICIs and 24 did not receive ICI therapy were analyzed in this study. The median age at diagnosis was 61 years [IQR: 49-69] and 37 patients (52.9%) were female. The exposure group had a median ICI treatment of 9 [6-13] cycles. The results showed a significant difference in the TBR between the baseline PET-CT scan and T1 between the two groups. The control group showed a decrease in TBR by -0.33 [95% CI: -0.66 – 0.01], whereas the exposure group showed an increase in TBR by 0.17 [-0.14 – 0.49] (p = 0.045). No differences in TBR were found between T1 and T2. Conclusion The present study demonstrated that in stage III/IV melanoma patients treated with ICIs, there was a significant increase in vascular inflammation assessed by PET-CT in the large arteries during the first six months after treatment initiation, as compared to a control group without ICI treatment.∆TBR on PET-CT between baseline and T1∆TBR on PET-CT between T1 and T2

Reduction of perivascular inflammation following long-term statin treatment - a coronary CT follow-up study using Fat Attenuation Index

Abstract Background Perivascular fat attenuation index (FAI) assessed by coronary computed tomography (CCTA) has been demonstrated to represent a reliable marker of coronary inflammation. Several studies have explored the potential anti-inflammatory effects of statins in reducing the risk of plaque rupture and subsequent cardiovascular events. However, the effect of statin therapy on FAI has not been clearly demonstrated so far. Purpose Our objective was to investigate the changes in perivascular FAI at the level of coronary lesions, as measured by coronary computed tomography (CCTA), following long-term high-dose statin therapy. Methods This study includes 23 patients who presented with typical chest pain, had a low to intermediate likelihood of coronary artery disease, and underwent a CCTA examination which revealed the existence of at least one coronary atheromatous plaque. Statin therapy was initiated in all patients according to guidelines. The CCTA was repeated after a time interval ranging from 1.5 to 3 years. Lesion-specific perivascular FAI, together with different plaque characteristics, were measured at both baseline and follow-up using a new AI-powered medical device called CaRi-Heart®. Results The mean age of the participants was 61.72 ± 8.86 at the time of the first scan, and 65.21% (n = 15) of them were male. At baseline, the CT density of the adipose tissue (ranging from -190 to -30 HU), was not significantly different between the two groups. A significant decrease in serum lipids following statin therapy was recorded during follow-up: from 193.4 ± 47.09 to 145.2 ± 34.7, p = 0.04 for total cholesterol, and from 101.77 ± 25.20 to 86.41 ± 21.09, p = 0.02 for LDL cholesterol. The FAI-score consistently decreased from baseline to follow-up, especially in the left anterior descending artery: from 15.87 ± 9.32 vs. 12.40 ± 7.55, p = 0.04, while there was no significant decrease in coronary inflammation at the level of left circumflex artery (13.98 ± 6.16 vs. 13.10 ± 6.59, p = ns), or right coronary artery (20.53 ± 13.74 vs. 19.96 ± 16.24, p = ns). Similarly, the FAI-Score Centile values were lower during the second scan, specifically for LAD (0.51 ± 0.28 vs. 0.69 ± 0.29, p = 0.04), while there were no significant differences of FAI score centile in the LCX (0.72 ± 0.28 vs. 0.74 ± 0.26, p = ns) and RCA (0.71 ± 0.32 vs. 0.78 ± 0.21, p = ns). Conclusion CaRi-Heart® mapping technology revealed a significant decrease of coronary inflammation, as expressed by the FAI-score, as a result of high-dose statin treatment especially at the level of the LAD. This indicates a potential role of local factors related to coronary circulation in the complex process of plaque inflammation. The perivascular FAI-score and FAI-score centile may serve as promising imaging biomarkers for monitoring the anti-inflammatory response to statin treatments.Color-coded FAI MappingPVAT-FAI Score of Coronary Inflammation

Effects of once-weekly semaglutide on major adverse cardiovascular events in patients with type 2 diabetes and polyvascular disease: a post hoc analysis of the SUSTAIN 6 trial

Abstract Background The presence of polyvascular disease (defined as atherosclerosis involving ≥2 distinct vascular territories) is a strong, independent predictor of subsequent cardiovascular (CV) events in patients with type 2 diabetes (T2D). In the SUSTAIN 6 trial, the glucagon-like peptide-1 receptor agonist once-weekly (OW) subcutaneous semaglutide reduced major adverse cardiovascular events (MACE; a composite of death from CV causes, non-fatal myocardial infarction and non-fatal stroke) in patients with T2D at high CV risk. Purpose This analysis of SUSTAIN 6 assessed the effect of OW semaglutide on MACE in patients with T2D, stratified by the number of atherosclerotic vascular territories at baseline. Methods Patients in SUSTAIN 6 were randomised to receive 0.5 or 1.0 mg OW subcutaneous semaglutide or placebo. The median follow-up was 2.1 years. In this post hoc analysis, the SUSTAIN 6 population was stratified according to documented atherosclerosis: polyvascular disease (≥2 vascular territories), single vascular disease (1 vascular territory) or no atherosclerotic cardiovascular disease (ASCVD). Time to first MACE was analysed using a stratified Cox proportional hazards model, with pooled treatment by vascular risk group as fixed factors. Results In SUSTAIN 6, 640 patients (19.4%) had polyvascular disease, 1821 patients (55.2%) had vascular disease in one arterial bed and 836 patients (25.4%) had no ASCVD at baseline. Demographic and clinical characteristics at baseline are presented in the Table. In the total population, the presence of polyvascular disease and single vascular disease was associated with a greater risk of MACE, compared with no ASCVD (hazard ratio [HR]: 2.25 [95% confidence interval – CI: 1.47;3.52] and HR: 1.64 [95% CI: 1.11;2.48], respectively). In the SUSTAIN 6 trial, OW semaglutide significantly reduced the risk of MACE vs placebo (HR: 0.74 [95% CI: 0.58;0.95]). In this analysis, the risk of MACE was consistently lower with OW semaglutide vs placebo across those with polyvascular disease, single vascular disease and no ASCVD (pinteraction=0.98) (Figure). The absolute risk reductions for OW semaglutide vs placebo at 2 years were 3.37% [95% CI: –1.28;8.02] (number needed to treat [NNT] 30) in patients with polyvascular disease, 2.02% [95% CI: –0.30;4.34] (NNT 50) in patients with single vascular disease and 0.78% [95% CI: –1.96;3.52] (NNT 128) in patients with no ASCVD. Conclusion Patients with polyvascular disease in the SUSTAIN 6 trial population are at over two times greater risk of MACE than those without ASCVD. The MACE risk reduction with OW semaglutide vs placebo is consistent across people with T2D and polyvascular disease, single vascular disease or no ASCVD. However, patients with T2D and polyvascular disease may derive greater absolute benefit from semaglutide treatment owing to their higher risk.

Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction

Abstract Background Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. Objectives To investigate the association of dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). Methods We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in a prospective observational study. Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2* mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. Results Persistent infarct core iron was present in 89 (26%) patients (HBA1c &amp;lt;5.7%: 16%, 5.7-6.4: 37%, ≥6.5: 34%) and was independently associated with HbA1c levels (OR: 1.64 [95% CI: 1.11-2.42]; p=0.01), but not glucose levels on admission. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n=42). Infarct core iron resolution was observed in 34 (14%) patients and was independently associated with HbA1c levels at 4 months (OR: 0.51 [95% CI: 0.28-0.93]; p=0.03). Conclusions In STEMI patients treated with primary PCI, dysglycaemia is independently associated with persistent infarct core iron and impaired iron resolution at 4 months. Persistent infarct core iron might represent a mechanistic driver for adverse outcome and a potential therapeutic target in patients with altered glycemic status suffering acute STEMI.

Impact of heart failure severity and major bleeding events after percutaneous coronary intervention on subsequent major adverse cardiac events

Abstract Background Heart failure (HF) is one of high bleeding risk after percutaneous coronary intervention (PCI). Furthermore, major bleeding events increase the risk of subsequent cardiovascular events. However, it is unknown whether HF severity and bleeding events are associated with major adverse cardiac events (MACE). Purpose The aim of this study was investigating the impact of HF severity or bleeding events on subsequent MACE. Methods Clinical Deep Data Accumulation System (CLIDAS), a multicenter database with 7 tertiary medical hospitals, was developed to collect data directly for patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment in electronic medical records. This retrospective analysis included 7,160 patients with PCI between April 2014 and March 2020 and have completed 3-year follow-up. The patients were divided into two groups: HF with high BNP (HF-hBNP) (&amp;gt;100 pg/ml) (n=384) and non-HF-hBNP (HF with low BNP and non-HF) (n=6,776). Furthermore, both groups were re-classified into two groups according to presence of major bleeding events in 30 days: HF-hBNP with 30-day bleeding (n=14), without 30-day bleeding (n=370), non-HF-hBNP with 30-day bleeding (n=74) and without 30-day bleeding (n=6,702). Primary endpoint was defined as MACE. Results HF with high BNP was an independent risk factor of MACE (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.64-2.98) compared with non-HF. Among the HF-hBNP patients, MACE incidence tended to be increased by 30-day bleeding (p=0.075). In addition, among the non-HF-hBNP patients, the bleeding events increased the risk of MACE (p=0.003). The multivariable Cox regression model revealed that other three groups were associated with a high risk compared with non-HF-hBNP without 30-day bleeding group: non-HF-hBNP with 30-day bleeding (HR, 3.90; 95% CI, 1.59-9.54), HF-hBNP without 30-day bleeding (HR, 2.19; 95% CI, 1.56-3.07) and HF-hBNP with 30-day bleeding (HR, 8.33; 95% CI, 2.57-27.0). Conclusion The real-world database CLIDAS revealed that HF with high BNP and major bleeding events in 30 days might be associated with MACE. Those results suggest that management of HF and prevention of bleeding complication in early days after PCI could be important to prevent MACE.

Abstract 16697: Chronic Venous Insufficiency is Associated With Increased Risk of Limb Events in Patients Undergoing Lower Extremity Revascularization

Introduction: Chronic venous disease is associated with an increased risk of cardiovascular (CV) events, possibly due to systemic inflammation and increased oxidative stress. Hypothesis: To evaluate the impact of chronic venous insufficiency (CVI) on the risk of subsequent CV and limb events in patients undergoing lower extremity revascularization (LER). Methods: Real-world data from the University of Colorado health system, which serves a diverse population of rural and urban patients, were extracted from TriNetX (Cambridge, MA, USA) for patients undergoing LER from 2015 to 2022. The cohort was divided into those with vs without concomitant CVI and assessed for subsequent limb events (defined as major amputation or re-intervention) and CV events (defined as stroke, myocardial infarction or death). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated between propensity score (PS)-matched patients with and without CVI. Results: Among 5090 patients with LER, the 1370 (27%) with concurrent CVI were older (67±14 vs. 66±14, p &lt;0.01) and had more comorbidities such as hypertension (72 vs. 58%, p &lt;0.01), diabetes (40 vs. 30%, p &lt;0.01), chronic kidney disease (32 vs. 18%, p &lt;0.01), and obesity (28 vs. 15%, p &lt;0.01). During the 2-years following LER, occurrence of CV (37.2% vs. 31.9%) and limb events (27.0% vs. 18.0%) was higher among patients with CVI (upper panel). After PS matching, limb events remained significantly more frequent (HR 1.53, 95% CI 1.273-1.829) in the group with CVI (lower panel). Conclusion: Among patients undergoing LER, the presence of concurrent CVI identifies a population at significantly increased risk for subsequent limb events.

Abstract 12307: Machine Learning Model Predicting Bleeding Risk in Patients With Coronary Artery Disease

Background: Bleeding complication during antiplatelet therapy for coronary artery disease (CAD) is an adverse issue due to high risk of subsequent death and cardiovascular events. Although many bleeding risk scores have been proposed, simple and personalized risk assessment in routine clinical practice is challenging because of the heterogeneous and multifactorial pathophysiological condition. We aimed to develop a machine learning-based risk prediction for bleeding events in CAD patients treated with antiplatelet therapy. Methods: This study was a retrospective, observational cohort study using the Japanese nationwide electronic medical record database. Data from 49,324 CAD patients who underwent revascularization and received antiplatelet therapy between July 2008 through July 2022 were randomly assigned to the model derivation and validation sets. Data balancing technique: synthetic minority over-sampling technique was used to process the imbalanced data. Risk prediction model was developed using random forest (RF) after feature selection by the Boruta algorithm. Outcome was defined as bleeding events requiring hospitalization. Results: Of all, 1,684 (3.4%) bleeding events were observed during study period. The area under the curves of receiver operator characteristics of RF (95% confidence intervals) for bleeding were 0.977 (0.976-0.978) in derivation and 0.975 (0.972-0.977) in validation set. The performance metrics of the model were well acceptable (accuracy, 0.939; precision, 0.990; recall, 0.887; F1-score 0.936, respectively) in validation set. The sigmoid calibrated RF models resulted in well approximating observed bleeding events in the calibration plot and the Brier score of 0.042. Conclusions: This machine learning model could predict bleeding risk for CAD patients treated with antiplatelet therapy in real-world setting.

Abstract 16718: Association of Elevated Lipoprotein A With Adverse Cardiovascular Events Following Percutaneous Coronary Intervention

Background: Patients who undergo percutaneous coronary intervention (PCI) are at increased risk for subsequent cardiovascular (CV) events. Elevated lipoprotein A [Lp(a)] is associated with atherothrombotic disease; however, its role in risk stratification for patients with prior PCI is unknown. Methods: Patients with prior PCI were identified in the Mass General Brigham Lp(a) Registry, a retrospective cohort that included patients who had Lp(a) measured as part of routine care from 2000-2019 and excluded those with severe renal dysfunction (eGFR &lt; 15 mL/min/m 2 , dialysis, or renal transplant) or a malignant neoplasm diagnosis (excepting non-melanoma skin cancers). Lp(a) percentile groups were derived as follows: 1st-50th (ref), 51st-70th, 71st-90th, 91st-100th. The primary outcome was a composite of CV death or myocardial infarction (MI). Results: A total of 2,389 patients with prior PCI were included with a median follow-up period of 12.8 years. Median age was 60 and 583 (24.4%) were women. Higher Lp(a) percentile group was associated with increased incidence of the primary outcome with patients in the 71 st -90 th percentile (112-215 nmol/L) having a HR of 1.39 (95% CI: 1.15-1.69, p = 0.001) and patients in the 91 st -100 th percentile (≥ 216 nmol/L) having a HR: 1.61 (95% CI: 1.26-2.06, p &lt; 0.001). Findings remained significant after adjustment for age, sex, smoking, diabetes, chronic kidney disease, and insulin use with adjusted HR of 1.25 (95% CI: 1.03-1.53, p = 0.024) and adjusted HR of 1.63 (95% CI: 1.27-2.10, p &lt; 0.001) for the 71 st -90 th and 91 st -100 th percentiles, respectively. A similar magnitude of association was observed in evaluating Lp(a) and CV death alone (Figure). Conclusions: Elevated Lp(a) is strongly and independently associated with increased risk of CV death or MI among patients with prior PCI in a stepwise manner that persists over time. Findings support the use of Lp(a) screening in patients with prior PCI to enhance risk stratification.

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.

Role of Cardiac Biomarkers in the Evaluation of Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can cause permanent joint damage and premature death. Cardiovascular disease (CVD) has recently been known to have become a significant cause of death in rheumatoid arthritis patients, and cardiovascular (CV) deaths have risen by 20-50% in rheumatoid arthritis patients. Early detection methods are necessary to improve the outcome for such patients. Cardiac biomarkers have been proven to be an effective tool for evaluating the heart's activity. In this study, we have used a systematic literature review approach in order to establish an overview of the current literature, highlight the advantages of using cardiac biomarkers in early detection and diagnosis, and improve the prognosis of patients with rheumatoid arthritis. We reviewed 269 articles from January 1, 2012, to August 6, 2023, from reputed journals, out of which we focused on seven papers for in-depth analysis. This analysis considered certain factors, including the age factor, sex factor, clinical risk score, and comparison of the benefits of using this method amongst clinicians for diagnosis purposes. The systematic review has revealed that cardiac biomarkers have a good ability to act as predictors of subsequent cardiovascular events. Cardiac biomarkers include high-sensitivity troponin T (hsTropT) and B-type natriuretic peptide (BNP). We learned that the cardiac biomarkers indicate inflammation, extracellular matrix remodeling, congestion, and myocardial injury, which are linked with elementary changes in cardiac structure and function. Biomarkers could be used for the purpose of screening cardiac variations in patients with rheumatoid arthritis. However, this method tends to have its own challenges to implement, considering other factors such as age and NSAID use. Nonetheless, further research and intervention about the use of cardiac biomarkers are important in order to earn the potential to make this method available to be used worldwide to improve outcomes for patients with rheumatoid arthritis.

Association Between Obstructive Sleep Apnea and Cardiovascular Events in Acute Coronary Syndrome Patients With or Without Revascularization - A Prospective Cohort Study.

The effects of obstructive sleep apnea (OSA) on the prognosis of acute coronary syndrome (ACS) without revascularization remain unclear, so the aim of the present study was to elucidate the association of OSA with subsequent cardiovascular events in ACS patients with and without revascularization. We prospectively recruited hospitalized ACS patients undergoing sleep monitoring between June 2015 and January 2020. OSA was defined as an apnea-hypopnea index ≥15 events/h. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Among 1,927 patients, 52.6% had OSA and 69.4% underwent revascularization. During a 2.9-year follow-up (1.5-3.6 years), the risk of MACCE was similar in patients with or without revascularization. OSA was an independent predictor of MACCE in the non-revascularization group (22.6% vs. 14.6%; hazard ratio (HR) 1.861; 95% confidence interval (CI) 1.239-2.796; P=0.003) but not in revascularization group (22.3% vs. 19.3%; HR 1.135; 95% CI 0.882-1.460; P=0.324). The incremental risk in the non-revascularization group was attributable to more hospitalizations for unstable angina (14.2% vs. 8.6%; HR 1.896; 95% CI 1.124-3.199; P=0.016). For patients with ACS, OSA was independently associated with higher risk of recurrent cardiovascular events among patients without revascularization but not among patients undergoing revascularization. The benefits of suitable OSA treatment for patients without revascularization need further investigation.

Lipoprotein(a): A Residual Cardiovascular Risk Factor in Statin-Treated Stroke Survivors: Insights From the SPARCL Trial

BackgroundIn the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol levels) trial, atorvastatin (80 mg/d) was compared to placebo in patients with recent stroke or transient ischemic attack (TIA) and no known coronary artery disease. ObjectivesThis study aimed to assess the contribution of lipoprotein(a) [Lp(a)] to subsequent cerebrovascular and cardiovascular events in stroke/TIA survivors. MethodsLp(a) levels and apolipoprotein(a) [apo(a)] isoform size were determined by liquid-chromatography mass spectrometry in samples collected at baseline from 2,814 SPARCL participants (1,418 randomized to atorvastatin and 1,396 to placebo). Within each treatment arm, patients in the highest quartile (≥84.0 nmol/L) were compared with those in the lowest quartiles of Lp(a) concentrations. Patients in the lowest quartile (≤25.9 Kringle IV domains) of apo(a) isoform sizes were compared with those in the highest quartiles. Multivariable-adjusted HRs were calculated using Cox proportional regression models. ResultsThere was no significant association between Lp(a) concentrations or apo(a) isoform sizes and the risk of recurrent stroke, the primary outcome of SPARCL, or cerebrovascular events in patients randomized to atorvastatin or placebo. In contrast, in patients randomized to atorvastatin, elevated Lp(a) concentrations and short apo(a) isoforms were positively and independently associated with an increased risk of coronary events (HR: 1.607 [95% CI: 1.007-2.563] and HR: 2.052 [95% CI: 1.303-3.232]). No such association was found in patients randomized to placebo (HR: 1.025 [95% CI: 0.675-1.555] and HR: 1.097 [95% CI: 0.735-1.637]). ConclusionsLp(a) contributes to the residual coronary artery disease risk of statin-treated stroke/TIA survivors, paving the way for use of therapies targeting Lp(a) in this population with stroke. (Lipitor In The Prevention Of Stroke, For Patients Who Have Had A Previous Stroke [SPARCL]; NCT00147602)

Myocardial injury after non-cardiac surgery and per operative fibrin metabolism in patients undergoing hip-fracture surgery: an observational study

Myocardial injury after non-cardiac surgery (MINS) is associated with a 2-3-fold increased risk of subsequent major cardiovascular events and postoperative mortality. The pathological mechanism behind MINS is not fully uncovered. We hypothesized that patients with MINS following hip fracture surgery would have an altered haemostatic balance pre- and postoperative compared with patients without MINS. This was investigated in a prospective single-centre observational study including patients consecutively. The outcomes were changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements in patients developing MINS and patients who did not. Outcomes were measured preoperatively and two hours postoperatively. Seventy-two patients were included whereof 26 (36%) patients developed MINS. D-dimer delta values were significantly higher in patients developing MINS than in patients who did not (p = 0.01). After adjusting for age, sex, smoking, alcohol abuse, atrial fibrillation, anticoagulant medication preoperative CRP, preoperative creatinine and duration of surgery, the association remained significant (p = 0.04). There were no significant changes in thrombin generation, in markers of fibrinogen/fibrin turnover besides D-dimer, or in fibrin structure measurements pre- and postoperatively between patients with and without MINS. As such, a relationship between the coagulative and fibrinolytic activity and MINS cannot be ruled out in patients with MINS after hip fracture surgery. Registration: The study was an observational sub-study to a multicentre randomised clinical trial registered at ClinicalTrials.gov (NCT02344797)

Statin Treatment on Cardiovascular Risk After Retinal Artery Occlusion: A Historical Cohort Study

IntroductionRetinal artery occlusion (RAO) is a major cause of acute visual loss and patients with RAO have an increased risk for subsequent cardiovascular events. However, there is little evidence of whether the use of statins is associated with the prevention of cardiovascular events in patients with RAO. We investigated whether statin treatment in patients with RAO is associated with a lower risk of cardiovascular events.MethodsThis study was a historical cohort study with nested case–control analysis. Using the nationwide health insurance claims database in Korea, we retrospectively established a cohort of newly diagnosed RAO patients without prior cardiovascular events between January 2008 and March 2020. We defined the case group as those who had cardiovascular events (stroke or myocardial infarction) and the control group as RAO patients without primary outcome matched by sex, age, comorbidities, and duration of follow-up (1:2 incidence density sampling). Conditional logistic regression was performed.ResultsAmong 13,843 patients newly diagnosed with RAO, 1030 patients had cardiovascular events (mean follow-up period of 6.4 ± 3.7 years). A total of 957 cases were matched to 1914 controls. Throughout the study period, the proportion of patients taking statin was less than half. Statin treatment after RAO was associated with a low risk of cardiovascular events (adjusted OR, 0.637; 95% CI 0.520–0.780; P < 0.001). A longer duration of statin exposure was associated with a lower cardiovascular risk.ConclusionsIn patients with newly diagnosed RAO, treatment with statins, particularly long-term use, was associated with a low risk of future cardiovascular events.

Implications of bleeding on subsequent cardiovascular events in patients with atrial fibrillation after acute coronary syndrome or PCI

IntroductionThe association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains poorly characterized. We aimed to evaluate the impact of hemorrhagic events in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Materials and methodsA total of 1877 consecutive patients with AF and ACS or undergoing PCI were prospectively recruited. The primary endpoint was MACCE, including all-cause death, myocardial infarction, ischemic stroke, systemic embolism or ischemia-driven revascularization during follow-up. Post-discharge bleeding was graded according to TIMI criteria. Associations between bleeding and subsequent MACCE were examined using time-dependent multivariate Cox regression after adjusting for baseline covariates and the time from bleeding. ResultsDuring a median follow-up of 34.2 months, 341 (18.2 %) had TIMI major or minor bleeding events, of whom 86 (25.2 %) also experienced MACCE. The risk of MACCE was significantly higher in patients with bleeding than those without (8.85 % versus 6.99 % per patient-year; HR, 1.568, 95 % CI, 1.232–1.994). In patients who had both bleeding and MACCE, 65.1 % (56 of 86) bleeding events occurred first. Temporal gradients in MACCE risk after major bleeding was highest within 30 days (HRadj, 23.877; 95 % CI, 12.810–44.506) and remained significant beyond 1 year (HRadj, 3.640; 95 % CI, 1.278–10.366). Minor bleeding was associated with increased risk of MACCE within 1 year. ConclusionsIn patients with AF and ACS or PCI, major and minor bleeding were associated with subsequent MACCE with time-dependency. Our findings may aid in better defining net clinical benefit of optimal antithrombotic therapy.