Risk Of Recurrent Cardiovascular Events Research Articles

Association of life's essential 8 with risk of recurrent cardiovascular events among patients with coronary heart disease

AimsTo examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD. MethodsThis prospective cohort study included 11,997 patients with CHD from the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval). ResultsDuring a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%–87.7% of the associations between the lifestyle factors and recurrent cardiovascular events. ConclusionsBetter cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events.

Risk-stratified analysis of long-term clinical outcomes and cumulative costs in Finnish patients with recent acute coronary syndrome or coronary revascularization: a 5-year real-world study using electronic health records.

Risk assessment is essential in the prevention of cardiovascular disease. In patients with recent acute coronary syndrome (ACS) or coronary revascularization, risk prediction tools, like the European Society of Cardiology guideline recommended SMART-REACH risk score, are increasingly used to predict the risk of recurrent cardiovascular events enabling risk-based personalized prevention. However, little is known about the association between risk stratification and the social and healthcare costs at a population level. This study evaluated the associations between baseline SMART-REACH risk scores, long-term recurrent clinical events, cumulative costs, and post-index event LDL-C goal attainment in patients with recent ACS and/or revascularization. This retrospective study used electronic health records and was conducted in the North Karelia region of Finland. The study cohort included all patients aged 45-85 admitted to a hospital for ACS or who underwent percutaneous coronary intervention or coronary artery bypass surgery between 1 January 2017 and 31 December 2021. Patients were divided into quintiles based on their baseline SMART-REACH risk scores to examine the associations between predicted 5-year scores and selected clinical and economic outcomes. In addition, simple age-based stratification was conducted as a sensitivity analysis. The observed 5-year cumulative incidence of recurrent events ranged from 20% in the lowest to 41% in the highest risk quintile, whereas the corresponding predicted risks ranged from 13% to 51%, and cumulative 5-year mean total costs per patient ranged from 15 827 to 46 182€, respectively. Both monitoring and attainment of low LDL-C values were suboptimal. The use of the SMART-REACH quintiles as a population-level risk stratification tool successfully stratified patients into subgroups with different cumulative numbers of recurrent events and cumulative total costs. However, more research is needed to define clinically and economically optimal threshold values for a population-level stratification.

Dietary habits and compliance with dietary guidelines in patients with established cardiovascular disease.

Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk. 2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction). Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 [IQR: 1536-2351] kcal/day. The median DHD-15 index was 81.7 [IQR 71.2-92.0], with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction. Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.

#2551 Treatment and prognosis for myocardial infarction in patients with chronic kidney disease 2010-2022: a nationwide cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is present in >30% of patients with acute coronary syndrome. Although prognosis following myocardial infarction (MI) has improved throughout the last decades, patients with CKD remain at considerably increased risk of recurrent cardiovascular events. We investigate use of guideline-directed cardiovascular interventions and cardioprotective medical therapy and associated cardiovascular outcomes in patients with and without CKD. Method From 2010 to 2022, all adult patients hospitalized with first-time MI (ICD10: DI21) were identified in nationwide Danish health care registers. CKD was defined by an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Study outcomes were evaluated in multiple logistic and cause-specific Cox regression models with computation of standardized risks/probabilities of outcomes. The probability of referral for interventional work-up was evaluated based on 30-days probability of cardiovascular interventions, i.e. coronary angiography (CAG) and/or revascularization. Guideline-directed cardioprotective medical therapy, i.e. lipid-lowering treatment, dual antiplatelet therapy, renin-angiotensin-system inhibitors, aldosterone antagonists, beta blockers, calcium channel blockers, and nitrates, was evaluated as 90-days probability of treatment in 90-days survivors. Lastly, one-year standardized risk of mortality was evaluated. All models were adjusted for age, sex, kidney transplant, congestive heart failure, hypertension, diabetes, cancer, thromboembolism, and any arrhythmia. Results In total, 21 009 patients were included; median age 72 years (IQR 63; 81), 60.8% males, median eGFR 82 ml/min/1.73 m2, 20.9% CKD. Patients with CKD were older, less likely to be male, had a longer admission time, had more comorbidities, and received more medical treatment compared with patients without CKD. The 30-days probability of CAG was 77.8% (95% CI 77.2%-78.5%) and 65.8% (95% CI 64.1%-67.3%), p < 0.001, and of revascularization 58.2% (95% CI 57.3%-59.0%) and 48.8% (95% CI46.9%-50.5%), p < 0.001, in patients without and with CKD, respectively. Development in probability of cardiovascular interventions and risk of 1-year mortality during the study period is depicted in Fig. 1. Probability of cardioprotective medical therapy in 90-days survivors is presented in Fig. 2. The 1-year risk of mortality was 16.4% (95% CI 15.7%-17.0%) and 20.9% (95% CI 19.9%-22.0%) in patients without and with CKD. Conclusion Although prognosis following first-time myocardial infarction has been improved for all patients, CKD continues to be associated with lower rates of guideline-directed cardiovascular interventions and cardioprotective medical therapy and increased 1-year mortality compared with patients without CKD.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction

BackgroundCardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux — a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein — has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.MethodsWe conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up.ResultsA total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P=0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group.ConclusionsAmong patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.)

Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. To investigateany difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.

Peripheral vascular function in stroke: systematic review and meta-analysis.

Peripheral vascular dysfunction, measured as flow-mediated dilation (FMD), is present across all phases of stroke recovery and elevates the risk for recurrent cardiovascular events. The objective of this systematic review and meta-analysis was to characterize baseline FMD in individuals' poststroke, with consideration for each phase of stroke recovery. Three databases (PubMed, CINAHL, and Embase) were searched between January 1, 2000 and October 12, 2023 for studies that examined baseline FMD in stroke. Three reviewers conducted abstract and full-text screening, data extraction, and quality assessment. A random effects model was used to estimate FMD across studies. Meta-regression was used to examine the impact of age and time since stroke (acute, subacute, chronic) on FMD. Twenty-eight studies with ischemic and hemorrhagic stroke were included. Descriptive statistics for the demographics and FMD values of each study are presented. For the meta-analysis, average estimate FMD was 3.9% (95% CI: 2.5-5.3%). We report a large amount of heterogeneity (Cochrane's Q P value <0.001, and I2 = 99.6%). Differences in average age and the time poststroke between studies were not significantly associated with differences in FMD values. Despite the large heterogeneity for FMD values across studies, our primary finding suggests that FMD remains impaired across all phases of stroke.NEW & NOTEWORTHY This systematic review and meta-analysis offers invaluable insight into poststroke vascular function. Despite the inherent heterogeneity among the 28 studies analyzed, we report that peripheral vascular dysfunction, as quantified by flow-mediated dilation, exists across all stages of stroke recovery. This finding underscores the importance for interventions that focus on improving vascular health and secondary stroke prevention.

Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.

Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study.

The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.

The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing.

In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI). This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784. Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively). NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

Factors associated with progression of arterial stiffness in ischemic stroke survivors: the Norwegian Stroke in the Young Study

Background Progressive arterial stiffening may increase the risk of recurrent cardiovascular events in ischemic stroke survivors. Information about factors associated with progressive arterial stiffening during the follow-up of young patients with ischemic stroke is lacking. Methods Arterial stiffness by carotid-femoral pulse wave velocity (cf-PWV) and ambulatory 24-hour blood pressure (24hBP) were assessed in 81 women and 190 men ≤60 years of age included in the Norwegian Stroke in the Young (NOR-SYS) study 3 months and 5.5 years after the incident ischemic stroke, representing baseline and follow-up. Covariables of change in cf-PWV were identified using linear regression analysis. Results At baseline, women had less prevalent hypertension (53% vs. 69%, p < 0.05), and lower clinic and 24hBP than men, whereas age, obesity, and prevalence of smoking and antihypertensive drug treatment did not differ. During follow-up, systolic 24hBP remained unchanged, while diastolic 24hBP fell significantly (p < 0.01). Cf-PWV was lower in women both at baseline (7.3 m/s vs. 8.1 m/s) and at follow-up (7.3 m/s vs. 8.0 m/s, both p < 0.001), but the average change during follow-up did not differ between genders. In linear regression analysis, an increase in cf-PWV at the 5-year follow-up was associated with the presence of hypertension and lower cf-PWV at baseline, and higher systolic 24hBP and lack of use of antihypertensive treatment at follow-up (all p < 0.05). Conclusion In ischemic stroke survivors participating in the NOR-SYS study, the 5-year increase in cf-PWV did not differ between genders and was associated with higher systolic 24hBP and lack of antihypertensive treatment.

Continuous Positive Airway Pressure Therapy and Long-Term Outcomes in Patients with Coronary Artery Disease and Obstructive Sleep Apnea: A Meta-Analysis of Randomized Trials

Background: Obstructive sleep apnea (OSA) is highly common in patients with coronary artery disease (CAD) and it is a strong predictor of subsequent cardiovascular events. However, whether treatment with continuous positive airway pressure (CPAP) can decrease this risk remains controversial. Methods: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify randomized clinical trials reporting cardiovascular events from database inception to February 12, 2022. Results: Four trials with 3043 participants were included. The median follow-up duration ranged from 3 to 4.75 years. Compared with usual care alone, CPAP was not associated with decreased MACCE risk (RR 0.96, 95% CI 0.77–1.21, P = 0.75), and the results were consistent regardless of CPAP adherence (≥4 hours/night vs. &lt;4 hours/night, RR 0.48, 95% CI 0.20–1.16). Similarly, no significant differences were observed between groups in the risks of all-cause death (RR 0.81, 95% CI 0.52–1.26), cardiovascular death (RR 0.70, 95% CI 0.36–1.33), myocardial infarction (RR 1.08, 95% CI 0.73–1.60), revascularization (RR 1.03, 95% CI 0.77–1.38), and cerebrovascular events (RR 0.77, 95% CI 0.23–2.61). Conclusion: Existing evidence does not support an association between CPAP treatment and decreased risk of recurrent cardiovascular events in patients with CAD and OSA, regardless of adherence to CPAP.

Association of Cardiovascular Diseases With Post-Traumatic Stress Disorder: An Updated Review

The intricate relationship between post-traumatic stress disorder (PTSD) and cardiovascular disease (CVD) has garnered increasing attention due to its bidirectional impact and potential for significant health consequences. Epidemiological evidence suggests that PTSD may serve as a risk factor for incident CVD, while acute CVD events can trigger PTSD, subsequently increasing the risk of recurrent cardiovascular events. This dynamic interplay is characterized by the human stress response, disrupted behavioral and lifestyle factors, and potential physiological mechanisms. Notably, the immediate aftermath of a cardiovascular event presents a critical window for intervention, offering the possibility of preventing the development of PTSD and its associated physiological and behavioral sequelae. However, while candidate mechanisms linking PTSD and CVD have been identified, determining which mechanisms are most amenable to intervention remains a challenge. This article emphasizes the urgency of addressing key unanswered questions in this domain. Despite an evolving understanding of the association between PTSD and CVD, causal relationships remain to be firmly established. Comprehensive investigations into the intricate interplay of behavioral and biological mechanisms are essential for identifying precise targets for intervention. Innovations in research methodologies, including the exploration of PTSD symptom dynamics and their impact on cardiovascular function, hold the potential for identifying crucial intervention points. Drawing parallels from prior challenges in translating identified risk factors into effective interventions, the field must prioritize systematic investigations and early-phase intervention trials. By doing so, researchers and clinicians can potentially develop strategies to mitigate CVD risk in the context of PTSD and improve both cardiovascular and mental health outcomes.

CSL112 (apolipoprotein A-I [human]) reduces the elevation in neutrophil-lymphocyte ratio (NLR) induced by acute myocardial infarction

Abstract Background CSL112 (apolipoprotein A-I [human]) is a novel therapy designed to reduce the risk of recurrent cardiovascular events following acute myocardial infarction (AMI). Preclinical data suggest that apolipoprotein A-I has anti-inflammatory properties which might contribute to atherosclerotic plaque stabilization (1). The neutrophil-lymphocyte ratio (NLR) is a clinically accessible measure of inflammatory status and predicts incident cardiovascular events in large outcome trials (2). It is unknown whether CSL112 can reduce inflammation as measured by the NLR. Purpose To evaluate whether infusion of CSL112 inhibits post-AMI inflammation as measured by NLR. Methods In a Phase 2 multicenter, double-blind study, 83 AMI patients with stage 3 chronic kidney disease were randomized 2:1 to receive 4 infusions of either 6 g CSL112 (n=55) or saline placebo (n=28) each separated by one week. The first infusion delivered on protocol Day 1 occurred 12h to 7d after presentation (mean 83 h). Blood samples were drawn prior to each infusion on Days 1, 8, 15 and 22 as well as at both Day 29 and 60 post the first infusion. Leukocyte data were available for up to 75 participants across the 6 sampling timepoints and neutrophil and lymphocyte counts were measured at the central laboratory. NLR was calculated and found to be non-normal in distribution and so analyses were performed on Loge transformed data. A mixed model repeated measures (MMRM) analysis was used to compare change from baseline (Day 1) in LogeNLR, neutrophil count and lymphocyte count between treatment groups (CSL112 6g versus Placebo) at the other 5 timepoints. An analysis of covariance (ANCOVA) was used to assess the effect of time from index MI to first infusion on change from baseline (Day 1) in LogeNLR at Day 8. Results The LogeNLR increased after AMI (between Day 1 and Day 8) with placebo treatment, whereas CSL112 infusion given after the Day 1 blood sample resulted in a decline (p=0.012; Fig 1, left panel, mean±SD). This effect of CSL112 was driven by reduction in neutrophil count (p=0.002; Fig 1, right panel) with lymphocyte levels remaining stable (p=0.537). Importantly, the magnitude of the effect of CSL112 to reduce NLR was greater if the timing of administration was closer to the index MI (treatment X time interaction and treatment effect both p=0.008). Conclusion CSL112 inhibits post-AMI elevation in NLR and this effect is maximized when infusion occurs early after presentation. It remains to be determined whether these anti-inflammatory effects of CSL112, in conjunction with previously demonstrated enhancement in cholesterol efflux capacity, will improve cardiovascular outcomes (3).Fig 1: Change in LogeNLR from baseline

Lower income is associated with non-persistence to statin treatment after a first myocardial infarction

Abstract Introduction Low socioeconomic status (SES), characterized by low education level and/or income, is associated with increased incidence and mortality in cardiovascular diseases (CVD) and recurrent atherosclerotic cardiovascular diseases (rASCVD) even in countries with universal healthcare. Treatment with statins is a cornerstone in the secondary prevention after myocardial infarction (MI) that reduces the risk for rASCVD and mortality. Mechanisms for how SES affects outcome post-MI are largely unknown. Aim The aim of this study was to investigate the association between low SES and non-persistence to statin treatment in the stable phase after a MI as a potential mediator for poorer outcome in those with low SES. Methods Nationwide Swedeheart registry-based cohort study on 63,900, 18–80-year-old survivors of a first MI (15,792 women) between 2006-2020 that participated in the follow-up after MI and claimed a statin-prescription (ATC-code C10AA) ≤120 days after the one-year revisit. Patients with previous history of CVD including stroke were excluded. Primary exposure was disposable income the year before MI divided into quintiles, stratified by income year and sex. Education level in three categories was investigated as a secondary exposure. The outcome was defined as time to first non-persistence to statin therapy where non-persistence was defined as a period over 180 days without expediting a new prescription. Hazard ratios (HR) with 95% CI were calculated for associations between income-quintile and non-persistence using Cox-regression adjusted for confounders (sex, age, inclusion-year, region of birth). Results During a median (IQR) follow-up on 7.47 years (3.7-11.2), 29,922 (46.8%) patients became non-persistent to statin treatment. An association between lower income and non-persistence was observed with a gradually increased risk for non-persistence in the lower income quintiles (table 1 and figure 1). The hazard ratio for non-persistence in the lowest compared to the highest income quintile was 1.29 (95% CI 1.24-1.34). The risk for non-persistence associated with low income remained significant after adjusting for confounders, including region of birth, where the risk for non-persistence in the lowest compared to the highest quintile was 1.17 (95% 1.13-1.22). Education was not associated with non-persistence. Conclusions In a nationwide post-MI population with access to universal healthcare, a strong association between income and non-persistence to statins was observed. Non-persistence to statins may be an important mediator for the increased risk for recurrent cardiovascular events after MI in patients with lower income.

Abstract 13300: Recovery From Acute Cardiac Events in Lower-Socioeconomic Status Patients: Physical and Psychological Outcomes Over Time

Introduction: Participation in cardiac rehabilitation (CR) reduces morbidity, and mortality, while improving quality of life following major cardiovascular events. Patients with lower-socioeconomic status (SES), such as those enrolled in Medicaid, are much less likely to attend and complete CR, despite being at increased risk for recurrent cardiovascular events. Methods: A secondary analysis was performed on a randomized controlled trial in which 130 individuals enrolled in Medicaid, with a CR-qualifying cardiac event, were randomized 1:1 to receive financial incentives for completing CR sessions or to usual care. Participants were assessed on clinical and cognitive outcomes soon after discharge as well as at 4 months, and 1 year following entry. The current analyses focused on how outcomes changed over the three timepoints. Outcomes included changes in psychological measurements (depressive/anxious symptoms, quality of life), body composition (waist circumference, body mass index), and fitness (peak VO2/METS). Mixed model repeated measures analyses of variance were used to test for main effects while controlling for sex, smoking status, age, and qualifying diagnosis. Results: Lower-SES patients entering CR had remarkably low levels of fitness and high rates of psychological issues. Fitness improved between intake and 4-months, and gains were maintained through one year (p&lt;0.001) (Table 1) however gains were less in females and those who completed fewer sessions of CR. Body composition measurements significantly worsened between 4-months and 1-year (p&lt;0.03). Psychological measures did not improve in the year following the event. Conclusion: While fitness improved in lower-SES patients, especially among those who completed more sessions of CR, psychological symptoms were elevated and did not improve. Future research should seek to understand how we can better serve this population, especially in the area of psych symptoms.

Abstract 12463: Awareness and Perceptions Towards Inflammatory Risk in Atherosclerotic Cardiovascular Disease: A Multinational Survey Amongst Cardiologists

Background: In patients (pts.) with atherosclerotic cardiovascular disease and chronic kidney disease (ASCVD+CKD), systemic inflammation (SI) contributes to high cardiovascular (CV) risk. Awareness and perception of SI and use of high sensitivity C-reactive protein (hsCRP) amongst cardiologists is less understood. Aims FLAME-ASCVD survey assessed the level of awareness and perceptions of cardiologists towards the role of SI (primary objective) and hsCRP as a biomarker in pts. with ASCVD+CKD. Methods: This was a non-interventional, cross-sectional, global online survey-based study that collected data from interventional (IC) and/or general cardiologists (GC), treating ≥15 ASCVD+CKD pts./month and practiced for ≥3 years. Survey used an online questionnaire, across 10 countries (Australia, Brazil, China, France, Germany, India, Italy, Japan, Saudi Arabia, UK) during Mar-May 2023. Data were analysed using descriptive statistics. Results: Of the 1755 who responded to the survey invitation, 602 eligible cardiologists (IC=247, GC=355) completed the questionnaire (~60/country). Overall, CV risk factors discussed with pts. were hypertension (88%), hyperlipidaemia (82%), hyperglycaemia (78%), and SI ranked tenth at 43%. Overall, 72% agreed that SI was a risk factor for ASCVD, 64% as one of the drivers for CV events and 73% agreed that SI contributed to risk of recurrent CV events. Overall, 64% (n=386) acknowledged intent to test for SI in management, and 41% of these, stated that results influenced decision to initiate anti-inflammatory treatment. 49% of those not measuring for SI (n=216), stated lack of medication for SI as a reason. Overall, 47% used hsCRP as a test for SI and 45% stated the need for guidelines as one of the factors to establish testing in practice. Conclusion: In this survey, SI was perceived as a CV risk factor, but not to the same level as traditional CV risk factors. There is a need for better understanding of SI and hsCRP testing in patients with ASCVD+CKD.

Hemostasis Biomarkers and Long-Term Risk of Recurrent Cardiovascular Events and Bleeding Complications in Young Patients with an Ischemic Stroke

Background: Patients with ischemic stroke at a young age (18-50 years) have a persistent increased risk of recurrent ischemic cardiovascular events, despite antithrombotic treatment. Additionally, antithrombotic agents result in a higher risk of bleeding complications. Balancing hemostasis to prevent thrombotic events and minimizing the risk of hemorrhagic events is challenging. Previous research observed a hypercoagulable state and a significant degree of inflammation years after an acute ischemic stroke in young adults. It is known that an increased clotting tendency is a risk factor for a first ischemic stroke, especially in young adults. However, the risk profile of a recurrent event in these individuals can be different. To this end, our study aims to investigate the role of plasma pro- and anticoagulation biomarkers, platelet activation markers and thrombin generation parameters in the risk of recurrent ischemic arterial events and bleeding complications after a first ischemic stroke or transient ischemic attack (TIA) at a young age. Method: Patients from a single-center cohort study (the FUTURE cohort) with a first-ever TIA or ischemic stroke event between 1980 and 2010 were included. Blood was collected in 2010 and patients were followed on recurrent ischemic events or bleeding complications between 2010 and 2023. The following coagulation parameters were measured: blood cell count, Von Willebrand factor, active Von Willebrand factor, factor VIII, prothrombin, fragment 1.2, d-dimer, fibrinogen, fibrin degradation products, antithrombin, alpha-2-macroglobulin, serum CXCL-4 and CXCL-7. In addition, thrombin generation (TG) was determined using 1pM and 5pM tissue factor, and thrombomodulin in platelet-poor plasma to assess the functional capacity of plasma to form thrombin. The primary outcome was a composite of recurrent ischemic stroke, TIA, acute coronary syndrome or peripheral artery disease. The secondary outcome was the occurrence of a bleeding complication using the Bleeding Academic Research Consortium (BARC) criteria. We applied Cox proportional hazard models to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results : Among 378 patients (median age 42.1 years, 56% women), 74 experienced a recurrent ischemic event during a mean follow-up of 6.5 years. An increased platelet and leukocyte count, along with elevated levels of fragment 1.2, fibrinogen and D-dimer were associated with a higher risk of ischemic events (table 1). Patients with low plasma antithrombin activity had a higher risk of recurrent ischemic events, especially in women (HR 0.67 [0.47-0.96]). After adjustment for age, sex and traditional risk factors, the association between leukocytes numbers, fragment 1.2 and fibrinogen levels and antithrombin activity and the risk of recurrent ischemic events remained: HR 1.14 [1.05-1.25], 1.07 [1.01-1.14], 0.80 [0.65-0.98], and 1.09 [1.00-1.17], respectively. In patients without vitamin K antagonist treatment, the association between antithrombin activity (HR 0.78 [0.62-0.98]) and leukocytes numbers (HR 1.15 [1.05-1.25]) with recurrent ischemic events were stronger. Thrombin generation parameters were not related to recurrence. Bleeding complications were observed in 16% of patients, mainly among women and predominantly attributable to gynecological bleedings. Hemoglobin, platelets, CXCL-4 and -7, prothrombin, fragment 1.2 and alpha-2-macroglobulin were associated with a bleeding complication (table 2). The association for platelets (HR 0.93 [0.89-0.97]), CXCL-4 (HR 0.90 [0.82-0.99]) and alpha-2-macroglobulin (HR 1.15 [1.03-1.29]) remained after adjustment. Conclusion: Lower antithrombin activity and, higher fragment 1.2, fibrinogen levels, and leukocytes counts were linked to an increased risk of recurrent ischemic events. Bleeding was associated with platelets, CXCL4, and alpha-2-macroglobulin. Overall, especially platelets appear to be significantly involved in the risk of both recurrent arterial thrombosis and bleeding, whereas the observed association with risk of recurrent ischemic events implies a more dominant role of the coagulation system.

HbA1c control in type 2 diabetes mellitus patients with coronary artery disease: a retrospective study in a tertiary hospital in South Africa.

Type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD) have an increased risk of recurrent cardiovascular events. These patients require optimal glucose control to prevent the progression of atherosclerotic cardiovascular disease (ASCVD). Contemporary guidelines recommend an HbA1c ≤7% to mitigate this risk. The aim of this study was to evaluate HbA1c control in T2DM patients with angiographically proven ASCVD. We conducted a cross-sectional, retrospective study on consecutive T2DM patients with acute and chronic coronary syndromes managed in a tertiary academic hospital in South Africa. Glycaemic control was assessed by evaluating the glycated haemoglobin (HbA1c) level measured at index presentation with acute and chronic coronary syndromes and during the most recent follow-up visit. The study population comprised 262 T2DM patients with a mean age of 61.3 ± 10.4 years. At index presentation, 110 (42.0%) T2DM patients presented with ST-segment elevation myocardial infarction, 69 (26.3%) had non-ST-segment elevation myocardial infarction, 43 (16.4%) had unstable angina, and 40 (15.3%) had stable angina. After a median duration of 16.5 months (IQR: 7-29), 28.7% of the study participants had an HbA1c ≤7%. On multivariable logistic regression analysis, females were less likely to have poor glycaemic control (HbA1c above 7%) [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.95, p=0.038]. Also, T2DM patients prescribed metformin monotherapy (OR: 0.34, 95% CI: 0.14-0.82, p=0.017) and patients with ST-segment depression on the electrocardiogram (OR: 0.39, 95% CI: 0.16-0.96, p=0.041) were less likely to have poor glycaemic control. After a median duration of 16.5 months, only 28.7% of T2DM patients with CAD had an HbA1c ≤7%. This finding underscores the substantial unmet need for optimal diabetes control in this very high-risk group.

Modern strategy of combined antihyperlipidemic therapy in the post-infarction period: focus on phytosteroid saponins

Patients who have suffered a myocardial infarction have a high risk of recurrent cardiovascular events – almost every fifth patient develops new episodes of acute myocardial ischemia during the first year [5]. One of the most important tasks of the therapy of these patients is the most effective and early reduction of atherogenic lipoprotein fractions to target values. The initiating basic therapy is statins, which have proven to be highly effective. However, in a number of patients, the necessary high-dose statin treatment cannot be implemented due to developing side effects or intolerance. The article discusses the issues of combined antihyperlipidemic therapy with a discussion of the role of all available groups of drugs. A possible clinical and pharmacological niche of phyto-steroid saponins is being considered.