Risk Of Recurrent Cardiovascular Events Research Articles

Factors influencing low-density-lipoprotein cholesterol after acute coronary syndrome and effectiveness of intensive teleconsultation monitoring, the teleobjectif cohort study

Abstract Context: Low-density lipoprotein cholesterol (LDL-c) plays a key role in the development and progression of atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective lipid-lowering treatments, patients who have experienced an acute coronary syndrome (ACS) continue to face a high risk of recurrent cardiovascular events and mortality. Achieving the recommended LDL-c target of <0.55 g/L in secondary cardiovascular prevention remains a significant challenge, with fewer than 30% of patients reaching this goal. Aim To investigate the factors influencing LDL-c control after ACS and the effectiveness of intensive teleconsultation monitoring to control LDL-c, even in sub-groups where control is poorest. Methods This bi-centric prospective cohort study conducted between december 2019 and december 2021 compared a group that received standard follow-up after an ACS with an interventional group that received regular follow-up by teleconsultation in addition of usual care to optimize lipid-lowering treatment. A subgroup analysis was carried out to examine the effect of teleconsultation in subpopulations known to be significantly associated with better or worse LDL-c control in the usual care group or described in the literature. Results 1602 patients met the inclusion criteria for our study (814 in the usual care group and 788 in the teleconsultation group). Baseline characteristics were similar between groups. In the usual care group, factors influencing lipid control included gender, diabetes, cardiology consultation, distance to the nearest cardiologist, social deprivation and initial LDL-C levels. Teleconsultation significantly improved LDL-C target attainment compared to usual care (74.7% vs. 26.6%, p<0.001 with multivariate analysis OR 5.06 [4.21 ; 6.07]), particularly benefiting geographically and socially disadvantaged patients. Conclusion Teleconsultation significantly improves lipid control in acute coronary syndrome patients compared to usual care. This universal intervention, particularly beneficial for geographically and socially disadvantaged patients, highlights the potential of telemedicine in enhancing cardiovascular management.analysis in usual care groupTeleconsultation effect in sub-groups

Delirium and risk of incident cardiovascular events in elderly: data from a global health research network

Abstract Introduction Delirium is a common complication of acute medical disorders. A strong association between cardiovascular events and the occurrence of delirium has been recorded. Thus far, no data are available regarding the risk of incident cardiovascular events after delirium onset in older adults. Methods Using data from TriNetX, a global health federated research network, we performed a propensity score matched (PSM) analysis of older adults (age ≥65 years) admitted to the emergency department (ED) reporting delirium within two weeks, who were compared with those without delirium. We evaluated the occurrence of a composite outcome of cardiovascular events (myocardial infarction, ischemic stroke, heart failure, intracranial haemorrhage, ventricular arrhythmias, takotsubo syndrome, and atrial fibrillation) at 30 days and 1 and 3 years of follow-up. Results 4,480,229 patients were retrieved for the analysis, and 82,693 (1.8%) reported delirium. Before PSM, patients reporting delirium were older, with more prevalent comorbidities. After PSM, a total of 165,386 patients were included in the analysis (mean (SD) age 76.6 (9.0) years, 51.1% females). Throughout the entire follow-up period, the cumulative composite cardiovascular events outcome was significantly higher in patients which reported delirium [Red Line, Figure 1]. Delirium was associated with cardiovascular events at 30 days (HR 1.96, 95% CI 1.92-2.00) ,1 year (HR 1.75, 95% CI 1.72-1.78) and 3 years (HR 1.67, 95% CI 1.64-1.69) of follow-up, as well as for each of its components (Table 1). The presence of delirium was also associated with a higher risk of all-cause death and hospital access (Table 1), evaluated as secondary outcomes. In patients with delirium associated with the occurrence of incident cardiovascular events, there was a higher risk of recurrent cardiovascular events at 1 year (HR 3.11, 95% CI 2.92-3.31) and 3 years (HR 2.84, 95% CI 2.67-3.01) of follow-up. Conclusions In a large, unselected cohort of older adults admitted to ED, occurrence of delirium was associated with a higher risk of cardiovascular events, both in the short and long-term follow-up.Figure 1:Delirium and CV EventsTable 1:Cox Regression Analysis

Differences in non-flow limiting non-culprit plaque characteristics after myocardial infarction in patients with versus without chronic kidney disease

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk for recurrent cardiovascular events after myocardial infarction compared to patients with preserved renal function. This disparity may be related to differences in plaque morphology. Purpose To compare non-flow limiting non-culprit (NC) plaque characteristics as assessed by optical coherence tomography in patients with versus without chronic kidney disease presenting with myocardial infarction. Methods 438 patients presenting with myocardial infarction with additional non-flow limiting (defined as a fractional flow reserve >0.80) NC lesions were included in the prospective observational PECTUS-obs study after treatment of the infarct related artery. An independent core laboratory performed all quantitative and qualitative OCT analyses. For the present subgroup analysis, patients were grouped according to the presence or absence of CKD, which was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². Baseline characteristics were compared between groups on a patient-level and OCT characteristics were compared on a lesion-level while accounting for within-patient clustering. Results Out of 420 patients with at least one analyzable OCT, baseline renal function was known in 416. Among them, there were 55 patients with and 361 patients without CKD (mean eGFR 47.4 ± 9.2 vs 84.7 ± 15.0 ml/min/1.73 m², p<0.001). Patients with CKD were older (mean age 73 ± 9 vs 62 ± 10 years, p<0.001), more frequently were female (29.1% vs 17.2%, p=0.035) and predominantly presented with a non-ST-segment elevation myocardial infarction (72.2% vs 44.9%, p<0.001). Comorbid disease was more prevalent among patients with CKD, including a higher prevalence of hypertension (p=0.010), hypercholesterolemia (p=0.020), diabetes (p<0.001), history of myocardial infarction (p<0.001), carotid artery disease (p=0.019) and peripheral artery disease (p=0.002). Coronary lesions in patients with CKD on average had a larger maximal calcium arc (188 ± 114 vs 137 ± 87º, p=0.003) and length (11.9 ± 10.3 vs 8.4 ± 7.4 mm, p=0.021). Lipid plaques were less prevalent among lesions in patients with CKD (63.6% vs 78.0%, p=0.016) and less frequently had a lipid arc ≥90º (60.6% vs 76.1%, p=0.018). Although the mean minimal fibrous cap thickness was lower in patients with CKD (p=0.025), no difference was observed in the prevalence of thin-cap fibroatheromas (p=0.984) or high-risk plaques according to the PECTUS-obs criteria (p=0.665). Conclusion Non-flow limiting NC lesions in patients with CKD differ from those in patients without CKD in a cohort of patients presenting with myocardial infarction. Overall, plaques in patients with CKD show more extensive calcification, whereas lesions in patients without CKD more often consist of lipid plaques, but the prevalence of high-risk plaques was comparable.

Prediction of 10-year risk for recurrent atherosclerotic cardiovascular events in a secondary prevention population: Insights from CHART-2 and Suita studies in the Japanese population

Abstract Background Despite the European Society of Cardiology (ESC) guidelines advocating risk prediction models for secondary prevention in established atherosclerotic cardiovascular disease (ASCVD) patients, such models for Japanese individuals remain limited, owing to their comparatively lower ASCVD risk than Western populations. Given this gap, there is a need to develop tailored risk assessment tools for Japanese ASCVD patients to optimize secondary prevention strategies. Purpose Leveraging data from two large-scale, long-term cardiovascular cohorts in Japan, our aim was to develop and externally validate a 10-year risk model predicting recurrent cardiovascular events among patients with established ASCVD. Methods The CHART-2 and Suita studies, large-scale prospective observational multicenter cohort studies in Japan, served as the primary data sources for this investigation. From the CHART-2 study, which comprised 3,560 patients with a history of coronary artery disease or ischemic stroke, we derived our risk model. External validation was conducted using data from the Suita study, which included 445 patients with similar ASCVD backgrounds. The primary outcome of interest was a composite endpoint encompassing cardiovascular death, myocardial infarction, or stroke. Variable selection was performed based on clinically relevant factors previously employed in established risk scores (SMART, REACH, and TRS 2°P risk scores). Logistic regression was utilized for model development, and the predictive performance was assessed using the C-index. Results Over a median follow-up of 10.1 years, the derivation cohort experienced 756 cardiovascular events. Patients in the derivation cohort had an average age of 68.9 ± 10.6 years, with 91% and 24% having a history of coronary artery disease and ischemic stroke, respectively. Using logistic regression, the multivariate model revealed a higher recurrent risk associated with several factors including age, smoking status, systolic blood pressure, diabetes, renal function, number of ASCVD events, atrial fibrillation, lipid levels, left ventricular systolic dysfunction, and statin use. A simple risk score based on these predictors demonstrated a >5-fold gradient of 10-year recurrent risk with a C-index of 0.65 (95% CI 0.63-0.68, Figure). The prediction model was externally validated in the Suita study wit 245 cardiovascular events and a median follow-up of 10.4 years, showing good discriminative ability with a C-index of 0.64 (95% CI 0.60–0.68). Conclusion Our newly developed prediction model offers a valuable tool for identifying individuals at heightened risk of recurrent cardiovascular events over a 10-year period, thereby facilitating more targeted and effective secondary prevention strategies tailored to the unique characteristics of Japanese ASCVD patients.

Rationale for Early Administration of PCSK9 Inhibitors in Acute Coronary Syndrome.

Acute coronary syndromes (ACSs) represent a significant global health challenge arising from atherosclerotic cardiovascular disease (ASCVD), with elevated low-density lipoprotein cholesterol (LDL-C) levels being a primary contributor. Despite standard statin therapy, individuals with ACS remain at high risk for recurrent cardiovascular events, particularly in the initial post-ACS period. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), such as evolocumab and alirocumab, offer a potential strategy to reduce LDL-C levels further and mitigate this residual risk. This review delves into the molecular mechanisms, effects on cholesterol metabolism, inflammatory modulation, and clinical outcomes associated with early administration of PCSK9 inhibitors following ACS.

Incidence rate of recurrent cardiovascular events in patients with radiographic axial spondyloarthritis and the effect of tumor necrosis factor inhibitors

BackgroundPatients with radiographic axial spondyloarthritis (r-axSpA) are at increased risk of incident cardiovascular events. Tumor necrosis factor inhibitors (TNFi) have shown a protective effect against incident cardiovacular events. However, the incidence of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events, and the effect of TNFi on recurrent cardiovascular events remain unclear. We aimed to assess the incidence rate of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events and evaluate the effect of TNFi on the risk of recurrent cardiovascular events.MethodsThis nationwide cohort study used data from the Korean National Claims Database. Data of patients with r-axSpA who had a history of cardiovascular events after being diagnosed with r-axSpA were extracted from the database. The outcome of interest was the recurrence of cardiovascular events (myocardial infarction or stroke). Patients were followed from the index date (date of the first cardiovascular event) to the date of cardiovascular event recurrence, the last date with claims data, or December 31, 2021, whichever occured first. The incidence rate of recurrent cardiovascular events was calculated. An inverse probability weighted Cox model was used to assess the effect of TNFi exposure on the risk of recurrent cardiovascular events.ResultsThis study included 413 patients (TNFi non-exposure, n = 338; TNFi exposure, n = 75). The incidence rate of recurrent cardiovascular events was 32 (95% confidence interval [CI] 22–42) per 1,000 person-years (TNFi non-exposure, 36 [95% CI 24–48] per 1,000 person-years; TNFi exposure, 19 [95% CI 2–35] per 1,000 person-years). In the inverse probability weighted Cox model, TNFi exposure was significantly associated with a lower risk of recurrent cardiovascular events (hazard ratio 0.33, 95% CI 0.12–0.94).ConclusionsThe incidence rate of recurrent cardiovascular events in patients with r-axSpA is substantial. TNFi exposure was associated with a lower risk of recurrent cardiovascular events.

Apolipoprotein A-I Infusions and Cardiovascular Outcomes in Acute Myocardial Infarction According to Baseline LDL-Cholesterol Levels: The AEGIS-II Trial.

In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days versus placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C. Overall, 18,219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n=15,731). As baseline LDL-C increased, risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days (hazard ratio 0.69 [0.53-0.90], 0.71 [0.57-0.88], and 0.78 [0.65-0.93]). In contrast, there was no difference between treatment groups among those with LDL-C <100 mg/dL at baseline. In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.

Five-year trend in secondary prevention medication prescription and risk factor control among patients with diabetes mellitus and cardiovascular diseases in Perak health clinics.

Prescription of secondary prevention medications (SPMs) and effective control of cardiovascular risk factors (RFs) are crucial to reduce the risk of recurrent cardiovascular events, particularly in high-risk individuals including those with diabetes mellitus (DM). This study aimed to analyse the trends in SPM prescription and identify the factors associated with RF control among patients with DM and cardiovascular diseases in Perak health clinics. Data of patients with ischaemic heart disease (IHD) and cerebrovascular diseases (CeVDs) audited from 2018 to 2022, excluding those lost to follow-up, were extracted from the National Diabetes Registry. Descriptive and trend analyses were conducted. Multivariable logistic regression was utilised to identify the factors associated with RF control. Most patients (76.7%) were aged ≥60 years and were Malays (62.3%). The majority had IHD (60.8%) and CeVDs (54.7%) for ≥5 years. SPM prescription increased significantly over the past 5 years. However, blood pressure (BP) and lipid control remained static. Good BP control was associated with a DM duration of ≥10 years and poor control with Malay ethnicity and prescription of two or three antihypertensives. Good DM control was associated with an age of ≥60 years and age at DM diagnosis of ≥60 years and poor control with Malay and Indian ethnicities, DM duration of ≥10 years and prescription of two or three and more glucose-lowering drugs. Poor lipid control was associated only with Malay and Indian ethnicities. SPM prescription has increased over time, but the achievement of treatment targets, particularly for lipid control, has remained poor and unchanged. Statin use is not associated with lipid control. The accessibility and availability of alternative lipid-lowering drugs must be improved to enhance overall RF control, especially lipid control, in patients with DM and cardiovascular diseases.

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.

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

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 &amp;gt;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) &amp;lt;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 &amp;lt; 0.001, and of revascularization 58.2% (95% CI 57.3%-59.0%) and 48.8% (95% CI46.9%-50.5%), p &amp;lt; 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.

Mobile phone text messaging for medication adherence in secondary prevention of cardiovascular disease.

Mobile phone text messaging for medication adherence in secondary prevention of cardiovascular disease.

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.