Secondary Cardiovascular Events Research Articles

The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population

BackgroundClopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel.MethodsOur study examined clopidogrel-related genes (CYP2C19, ABCB1, PON1, and P2Y12R) in a cohort of 298 healthy Emiratis individuals. The study used whole exome sequencing (WES) data to comprehensively analyze pertinent variations of these genes, including their minor allele frequencies, haplotype distribution, and their resulting phenotypes.ResultsOur data shows that approximately 37% (n = 119) of the cohort are likely to benefit from the use of alternative anti-platelet drugs due to their classification as intermediate or poor CYP2C19 metabolizers. Additionally, more than 50% of the studied cohort exhibited variants in ABCB1, PON1, and P2YR12 genes, potentially influencing clopidogrel’s transport, enzymatic clearance, and receptor performance.ConclusionsRecognizing these alleles and genotype frequencies may explain the clinical differences in medication response across different ethnicities and predict adverse events. Our findings underscore the need to consider genetic variations in prescribing clopidogrel, with potential implications for implementing personalized anti-platelet therapy among Emiratis based on their genetic profiles.

NLRP3 inflammasome in the pathogenesis of acute myocardial infarction: a cardiologist's view

Within five years after myocardial infarction (MI), a third of patients have secondary major adverse cardiovascular events (MACEs). The first randomized clinical trials to show the effectiveness of anti-inflammatory strategies in the prevention of MACEs are CANTOS, COLCOT and LoDoCo2. These studies have identified an effective therapeutic target — the NLRP3 inflammasome. The results of COLCOT and LoDoCo2 led to colchicine becoming the first anti-inflammatory drug to be included in clinical guidelines for the treatment of patients with coronary artery disease (CAD). However, considering colchicine in routine clinical practice requires the cardiologist to have knowledge of the basic molecular mechanisms of inflammation in cardiovascular diseases. The review discusses current data on inflammation and the NLRP3 inflammasome in the pathogenesis of CAD and MI, results and issues of their application in clinical cardiology.

Risk factors of secondary cardiovascular events in a multi-ethnic Asian population with acute myocardial infarction

Risk factors of secondary cardiovascular events in a multi-ethnic Asian population with acute myocardial infarction

A narrative analysis of patients’ experiences of taking medication for secondary prevention of acute myocardial infarction

Abstract Introduction Following an acute myocardial infarction, patients are given a daily regime of five medications to prevent secondary cardiovascular events. However, adherence to these medications has been measured to be 66%1. Sub-optimal adherence leads to increased mortality, morbidity and associated healthcare system costs. There is a lack of qualitative research of this experience for these patients, and current interventions, such as Dossett trays and New Medicines Service interviews are based upon presumed difficulties, such as memory and physical medication issues. Aim The aim of this study was to better understand patient’s experience of taking medication to prevent a further AMI, using a narrative analysis framework to describe their relationship with their medication and healthcare professionals. Methods Following ethical approval (UREC 18/36), participants were recruited with inclusion criteria of adults taking medication following at least one previous episode of AMI. Following signed informed consent, semi-structured interviews were conducted with fifteen people from central and southern England. Interviews were conducted in person, online, or on the telephone and audio recorded. The recordings were transcribed verbatim and organised using NVivo software. A narrative analysis framework was used to organise themes within the whole of each participant’s story and then separated into narrative arcs and organised by theme2. Results The whole story analysis showed the differences between each participant’s story, and that each participant’s story contained varying complicating factors that were personal and specifically important to their lives. The presence of side effects was a complicating factor for most participants. The narrative arc analysis showed that initially, participants felt they began taking medication with little control, feeling compelled to follow their prescriber’s directions and ‘do what they were told’. They understood the benefit to their health, and quickly built routine into their lives. At the next stage, participants worked in collaboration with their prescriber. They had acquired knowledge and social support of non-prescribing professionals, which enabled them to recognise side effects, which they tolerated. Missed doses were viewed as insignificant, happening infrequently and balanced by a history of medication continuity. A crisis point was reached when side effects became unmanageable, where they sought help from their prescriber to change their medication. The desired stage to reach was stability, where participants continued to take medication, and found it simple, unnoticed, fitted into their life and monitored using biometric results. Discussion/Conclusion These participants were non-intentional non-adherers, and described how they successfully added a medication regime into their lives, the details of which could assist patients who find this process more difficult. They described personal and detailed stories, indicating that interventions to assist medication-taking are suited to individual patient work. Themes across all their narratives included the presence of side effects, for which they deferred to their prescriber as decision-maker for their treatment. Non-prescribing healthcare professionals were described as providing social support at later stages, but there is a potential for pharmacists to offer more support at the initial stage where participants felt they lacked control, using services such as the New Medicines Service.

Improving risk stratification of recurrent myocardial infarction in a large real-world dataset using machine learning

Abstract Background Patient (pt) risk stratification for cardiovascular (CV) events is key to determine the appropriate approach to secondary prevention. Several risk scores have been developed (SCORE2, EUROASPIRE, Thrombolysis in Myocardial Infarction [TIMI] risk score for secondary prevention [TRS 2°P]); these are based on few predictors and have low discriminatory power. Machine learning methods using real-word data (RWD) from electronic health records (EHR) databases and capable of handling a multitude of commonly available variables can serve as powerful tools to improve the discriminatory power and generate efficient and clinically relevant risk scores. Purpose This study used a non-linear machine learning model to build an improved risk score for secondary CV events from a large Israeli EHR database. Methods Records of pts with a first record of atherosclerotic CV disease (ASCVD) admission or coronary procedure and available follow-up data (mean: 1052 days) from the period of 01/2005–11/2020 were considered (n=77432 [67% coronary artery disease, 21% carotid artery disease, 12% peripheral artery disease], a stratified 1:1 randomization by cause of admission yielding in training set [n=38716] and test set [n=38716]). The model’s performance was assessed by comparison with TRS 2°P score on the test set independent of the training set. Twenty-six covariates commonly used in clinical routine and widely available in EHR have been selected and a gradient boosting trees algorithm was applied to the pt data at baseline after the original event to predict recurrent myocardial infarction (MI). The ability of the model to discriminate pts was evaluated using the concordance index (c-index), which expresses how well a predicted risk score describes the observed events (1 implies perfect concordance, 0.5 implies random concordance). Results Prediction accuracy of our model showed a c-index for a future MI of 0.74 (95% confidence interval [CI]: 0.72, 0.76) which is significantly higher than 0.57 (95% CI: 0.56, 0.58) obtained with TRS 2°P. Our 2-tier risk score has successfully discriminated a low-risk group (74% of cohort) with a 3-year MI prevalence of 5% from a high-risk group (26% of cohort) that had a 5-fold higher prevalence (26.6%) (Figure 1). In comparison, the 3-tier TRS 2°P yielded an unbalanced distribution of group sizes with a disproportionate intermediate risk group (22% low, 67% intermediate, 11% of high-risk) with a limited clinical discriminatory power (7.1%, 10,2% and 15.6% of observed events, respectively) (Figure 2). Conclusions Our machine learning based risk score model created on a large set of RWD with a long follow-up seems to offer substantial gain of performance compared to the TRS 2°P. The present 2-tier model shows significant gain of accuracy and clinical discriminatory power paving the way for more individualized prevention strategies.Figure 1Figure 2

Six month incidence of major adverse cardiovascular events among adults with HIV in northern Tanzania: a prospective observational study

ObjectivesWe aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and...

Wildfire, evacuation, and cardiovascular events: A spatial exposure approach

Increasingly, adverse health effects from wildfire exposure are not limited to select populations in the wildland-urban interface. As wildfires continue to grow in frequency and intensity, they are also continuing to encroach on urban areas, putting larger and larger populations at risk. In this study we develop an innovative research design in the wildfire and health literature, and report results for a small scale implementation on California's central coast. Instead of focusing on smoke exposure and PM 2.5 or PM 10 as the primary physiological pathway linking wildfire and adverse cardiovascular health outcomes, we draw on a stress pathway as a potential link between stress and heart health. We use a novel spatiotemporal definition of wildfire exposure that is directly measurable at the individual level and acutely stressful: evacuation orders. Combining longitudinal health data from the dominant local hospital system in southern Santa Barbara County, California, we directly determine exposure to an evacuation order and smoke plumes from three large fires in the 2017–2019 wildfire period. Controlling for additional known risk factors, such as diabetes status and smoking status, we model the risk of secondary cardiovascular events (CVE) for 2411 patients with existing cardiovascular disease. Roughly 16.2% of patients (n = 391) were exposed to an evacuation order. We found evacuation order exposure was not significantly associated with an increased risk of cardiac events for the CVD population, but estimates hovered between 12.5 and 16.3% over un-evacuated cohorts. Smoke exposures were not significantly associated with CVE risk in models adjusted for evacuation orders nor unadjusted models, and estimates of effects varied widely. Both the method and the findings have implications for public health departments, clinicians and wildfire researchers.

Predictive value of combining leucocyte and platelet counts for mortality in ST-segment elevation myocardial infarction patients after percutaneous coronary intervention treatment in Chinese population: a retrospective cohort study

ObjectiveRisk stratification is challenging in patients with acute ST segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). We investigated the prognostic value of a novel score system...

Prognostic impact of Achilles tendon thickness in elderly patients after percutaneous coronary intervention: A 5-year follow-up

BackgroundEvaluating the Achilles tendon thickness (ATT) may be beneficial for risk stratification of long-term secondary cardiovascular events among patients who underwent percutaneous coronary intervention (PCI). MethodsThis observational study evaluated major adverse cardiac and cerebrovascular events (MACCEs), including cardiovascular death/death from unknown causes, at 5 years after PCI according to the baseline ATT (≥9 mm vs. <9 mm). ResultsOverall, 355 patients aged ≥75 years were enrolled; 47 (13.2 %) and 308 patients (86.8 %) had an ATT ≥9 mm and <9 mm, respectively. The incidence of MACCEs at 5 years was numerically higher but not significantly different for the ATT ≥9 mm group compared with the ATT <9 mm group (Gray's p-value = 0.10). However, the incidence of cardiovascular death/death from unknown causes at 5 years was significantly higher in the ATT ≥9 mm group than in the ATT <9 mm group (Gray's p-value = 0.034). Multivariable Fine and Gray competing risk analysis showed that an ATT ≥9 mm was associated with both MACCEs [hazard ratio (HR), 1.95; 95 % confidence interval (CI), 1.12–3.41; p-value = 0.019] and cardiovascular death/death from unknown causes (HR, 2.81; 95 % CI, 1.31–6.03; p-value = 0.008) at 5 years in patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. ConclusionsA significantly thick Achilles tendon could be a marker for MACCEs, including cardiovascular death/death from unknown causes, at 5 years among elderly patients with an eGFR ≥30 mL/min/1.73 m2 after PCI.

Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.

This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 <pmol/L, hazard ratio in Q4: 1.74, [95% CI, 1.04-2.93]). Monitoring ANGPTL8 levels over time might be useful to assess residual risk of cardiovascular secondary events in patients with cardiovascular disease undergoing statin therapy.

LATE EFFECTS AFTER TREATMENT OF HODGKIN LYMPHOMA, A SINGLE CENTRE EXPERIENCE

Introduction: Classical Hodgkin Lymphoma (cHL) has an incredibly high survival rate, exceeding 80% at 10 years. Continuous improvement in treatment strategies led to an increased number of survivors in the community. Most common complications encountered are secondary malignant neoplasms (SMN) and cardiovascular (CV) toxicity. Methods: We conducted a single-centre retrospective study including 157 patients diagnosed and treated for cHL between 1974 and 2016. Results: Median age at diagnosis in our cohort is 30 years old. Ninety-six patients (61%) had a stage 1 or 2 disease. Front line treatment consisted of radiotherapy alone for 3 patients (2%), chemotherapy alone for 74 patients (47%) and combined modalities for 80 patients (51%). Our median follow-up time is 11 years. We reported 96 cardiovascular events in 75 patients (48%). Median time to CV event was 10 years. Most of the events were graded 1 or 2 (71%) and were related to valvular heart disease. Grade 3 and 4 CV events (n = 21) were mainly due to coronary heart disease (43%) while most of the deaths related to CV toxicity were consequent to heart failure (57%). Twenty-seven patients (17%) were diagnosed with SMN, with a median time to SMN of 10 years. Most of them were solid malignancies (71%), including 6 lung cancers and 2 breast cancers (both BRCA2+). We encountered 2 secondary leukaemia, 3 myelodysplastic syndromes and 2 Non-Hodgkin Lymphoma. Overall survival rate in our cohort is 76% at 10 years. We observed 38 deaths, at a median age of 60 years old. Six patients (16%) died from cHL, and main causes of non-lymphoma deaths were secondary malignant neoplasms (10 pts, 28%) and cardiovascular events (7 pts, 18%). Discussion: Long-term complications in Hodgkin Lymphoma survivors are well-known and focus on how to decrease treatment related toxicity is constantly growing. Special attention is brought to the use of anthracyclines and mediastinal radiotherapy. Regarding CV toxicity, we tend to review our patients annually and to offer periodic screening with heart imaging. Our study showed that we detected CV events in almost half of our patients. Those events were mostly low-grade valvular disease not requiring treatment. However, more than 1 out of 4 CV event was graded 3 or more. The impact of the doses of anthracycline and/or radiotherapy received in our population still need to be determined. With a median time to CV event and to SMN of 10 years, we can confirm that long-term surveillance is recommended for the survivors. Conclusion: Cure is no longer enough when managing cHL. Our past and previous treatments led to an increasing number of survivors who are at higher risk of long-term complications. Recommendations for long-term surveillance programmes are emerging and are mostly experts-based opinions. More data are needed to identify high-risk patients and to provide them with an adequate monitoring. Keywords: Hodgkin lymphoma, late effects in lymphoma survivors, prevention and cancer interception No conflicts of interests pertinent to the abstract.

Abstract 463: Convocals: A Convolutional Neural Network To Predict Symptoms And Major Secondary Cardiovascular Events Based On High-resolution Scanned Histological Slides

Background: Atherosclerosis is a primary risk factor underlying myocardial infarction and stroke, and there remains an unmet need to identify atherosclerotic plaque subtypes to improve clinical outcomes. Histological examination is used to manually characterize the extent and type of atherosclerosis, and histological traits are associated with major adverse cardiovascular events (MACE). Recent applications of automated machine learning approaches may improve scalability and precision in predicting symptoms and cardiovascular events, however this has yet to be fully evaluated in the setting of atherosclerosis. Methods: CONVOCALS uses a convolutional neural network (CNN), feature embedding and attention-based pooling model to develop an internal representation of whole slide images (WSI) and learn position and scale invariant structures in the data. We evaluated this model on human arterial H&amp;E histology WSI from the Genotype Tissue Expression Project (GTEx), consisting of 688 WSI of normal and atherosclerotic coronary, tibial and aortic artery tissues. Results and Conclusions: We evaluated the performance of a base model of CONVOCALS on the GTEx artery H&amp;E WSI dataset, which achieved a mean AUC of 0.86 and accuracy of 0.72 on a test dataset of 68 WSI images. Principal component analysis demonstrated clear separation of the 4 distinct atherosclerosis stages. We also visualized different pathological hallmarks (e.g., calcification) using attention scores overlaying the WSI. We further evaluate CONVOCALS performance on more granular feature extraction and demonstrate improved WSI segmentation. Next we plan to evaluate the performance on a large-scale AtheroExpress dataset to predict symptoms and MACE.

Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.

Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear. Gene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe-/- mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque. We have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe-/- mice. These results point toward a promising treatment to combat atherosclerosis.

Abstract P435: Proton Pump Inhibitor Use and Risk of Incident Primary Cardiovascular Disease: A Systematic Review and Meta-Analysis

Background: The risk of secondary cardiovascular events associated with proton pump inhibitor (PPI) use and their interaction with thienopyridine antiplatelets such as clopidogrel is well established. Recent evidence from in-vitro and animal studies suggests PPIs may impact cardiovascular disease (CVD) irrespective of antiplatelet use. However, whether PPI use is associated with primary cardiovascular events in humans remains uncertain. Methods: Systematic searches were conducted in the MEDLINE and EMBASE databases from their inception to September 2022. Inclusion criteria included studies that examined participants free from cardiovascular disease at baseline who were followed over time to assess any of the following outcomes according to PPI use: incident myocardial infarction (MI), incident ischemic stroke (IS), or CVD mortality. Hazard ratios (HR) and their 95% confidence intervals (CI) were abstracted, combined estimates and heterogeneity (I 2 ) were calculated using the random-effects model in RevMan 5.4 software. Results: A total of 15 observational studies met the inclusion criteria, 2,272,479 participants were studied for MI, 2,689,943 for IS, and 1,591,428 for CVD mortality. The mean age of participants ranged from 49.3 to 82.2 years. Compared to non-use, PPI use was associated with 30% higher risk of incident MI (HR: 1.30, 95%CI: 1.10-1.53, I 2 =91%) and 15% higher risk of CVD mortality (HR: 1.15, 95%CI: 1.05-1.26, I 2 =56%). However, there was no statistically significant association with incident IS (HR: 1.05, 95%CI: 0.91-1.22, I 2 =96%). Conclusion: The meta-analysis results from published studies suggests PPI use is associated with higher risk of incident MI and CVD mortality. However, these findings should be interpreted with caution given the considerable heterogeneity among published studies and the possibility of residual confounding. More studies are needed to address these limitations and determine the validity of these associations.

Impact of Vitamin D Supplementation on the Clinical Outcomes and Epigenetic Markers in Patients with Acute Coronary Syndrome.

Vitamin D has recently been found to influence the renin-angiotensin system (RAS); it can reduce the effects of renin-angiotensin system inhibitors (RASI) by decreasing plasma renin. This study examines the effect of vitamin D supplements on cardiac fibrosis markers, echocardiographic parameters, and epigenetic markers in patients with established acute coronary syndrome (ACS). It also looks at the incidence of vitamin D receptor (VDR) gene polymorphisms Apa I (rs7975232), Bsm I (rs1544410), Taq I (rs731236), and Fok I (rs2228570) and its association with the development of secondary major acute cardiovascular events (MACE) and heart failure (HF). A randomized controlled trial in which patients were divided into two groups was performed. Group 1 comprised of 125 ACS patients who received ACS standard therapy alone, while Group 2 consisted of 125 ACS patients who received ACS standard therapy plus vitamin D according to their vitamin D levels. Patients were monitored for 24 months to find subsequent MACE and HF. Vitamin D therapy for ACS patients resulted in a substantial decline in end systolic and end diastolic volumes (p = 0.0075 and 0.002, respectively), procollagen type III N-terminal peptide (PIIINP) and soluble ST2 levels (p = 0.007 and 0.001, respectively), as well as in ejection fraction and vitamin D level (p = 0.0001 and 0.008, respectively). In addition, vitamin D treatment was linked to a significant decline in the levels of noncoding RNA, such as mir361, lncRNA MEG3, and lncRNA Chaer (p = 2.9 × 10-4, 2.2 × 10-6, and 1.2 × 10-5, respectively). Furthermore, patients who suffered MACE had significantly higher levels of the Bsm I CC and Fok I GG genotypes (p = 4.8 × 10-4 and 0.003, respectively), while patients with HF had significantly higher levels of the Taq I AA genotype (p = 4.2 × 10-7). Supplementing ACS patients with vitamin D has been demonstrated to limit cardiac fibrosis and echocardiographic parameters, as well as epigenetic markers. Additionally, MACE and HF among ACS patients may be related to genetic variations among VDR gene polymorphisms.

Small Intestinal Perforation Caused by Enteric-coated Low-dose Aspirin: A Case Report.

A 77-year-old man presented with abdominal pain for 1 week. He was taking enteric-coated low-dose aspirin (LDA) to prevent secondary cardiovascular events and a proton pump inhibitor (PPI). Computed tomography indicated a small intestinal perforation; thus, small intestine resection was performed. Two months after surgery, he experienced a recurrence of the perforation. Since his repeated perforation was suspected to be due to LDA, LDA was discontinued. He has experienced no further recurrence since then. This is the first case of small intestinal perforation caused by enteric-coated LDA. Enteric-coated LDA may cause small intestinal perforation in patients with severe atherosclerosis under PPI administration.

Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model.

Kawasaki disease (KD) is an acute inflammatory syndrome of unknown etiology that is complicated by cardiovascular sequelae. Chronic inflammation (vasculitis) due to KD might cause vascular cellular senescence and vascular endothelial cell damage, and is a potential cause of atherosclerosis in young adults. This study examined the effect of KD and HMG-CoA inhibitors (statins) on vascular cellular senescence and vascular endothelial cells. Candida albicans water-soluble fraction (CAWS) was administered intraperitoneally to 5-week-old male apolipoprotein E-deficient (ApoE-) mice to induce KD-like vasculitis. The mice were then divided into three groups: control, CAWS, and CAWS+statin groups. Ten weeks after injection, the mice were sacrificed and whole aortic tissue specimens were collected. Endothelial nitric oxide synthase (eNOS) expression in the ascending aortic intima epithelium was evaluated using immunostaining. In addition, eNOS expression and levels of cellular senescence markers were measured in RNA and proteins extracted from whole aortic tissue. KD-like vasculitis impaired vascular endothelial cells that produce eNOS, which maintains vascular homeostasis, and promoted macrophage infiltration into the tissue. Statins also restored vascular endothelial cell function by promoting eNOS expression. Statins may be used to prevent secondary cardiovascular events during the chronic phase of KD.

Assessment of Depression and Adherence to Guideline-Directed Medical Therapies Following Percutaneous Coronary Intervention

Depression is associated with increased risk of primary and secondary cardiovascular events. Medication adherence may play an essential role. To evaluate the association of depression and 12-month adherence to guideline-directed medical therapies (eg, antiplatelet agents, β-blockers, renin-angiotensin-aldosterone system inhibitors [ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers], and statins) following percutaneous coronary intervention. This retrospective cohort study included individuals who underwent percutaneous coronary intervention from January 1, 2014, to December 31, 2019. Data were collected from a large US health claims database and analyzed between February and August 2022. Proportion of days covered (PDC) for classes of guideline-directed medical therapies, with 12-month adherence categorized as adequate (PDC ≥80% to <90%) or optimal (PDC ≥90%). Multivariable-adjusted regression models were used to evaluate the association of depression with adherence; models incorporated demographic characteristics, comorbid medical and psychiatric conditions, depression treatment, and guideline-directed medical therapy treatment adjustment. The hypothesis was that those with depression would have lower odds of either adequate or optimal adherence to agents essential for guideline-directed medical therapy. Of 124 443 individuals (mean [SD] age, 69.3 [10.6] years; 41 430 [33.3%] female sex; 3694 [3.0%] Asian, 12 611 [10.1%] Black, and 12 337 [9.9%] Hispanic individuals) who received percutaneous coronary interventions, 20 711 (16.6%) had a diagnosis of depression. Those with depression were significantly less likely to obtain adequate 12-month adherence to antiplatelets (odds ratio [OR], 0.80; 95% CI, 0.77-0.85), β-blockers (OR, 0.84; 95% CI, 0.80-0.88), and statins (OR, 0.88; 95% CI, 0.85-0.93) than those without depression; there was no association between depression and adherence to renin-angiotensin-aldosterone system inhibitors (OR, 0.93; 95% CI, 0.85-1.00). Those with depression had similarly decreased likelihood of optimal 12-month adherence to antiplatelets, β-blockers, and statins as well as renin-angiotensin-aldosterone system inhibitors (OR, 0.87; 95% CI, 0.82-0.94). In this cohort study, patients with depression were less likely to achieve adequate or optimal adherence to medications essential to guideline-directed medical therapies following percutaneous coronary intervention compared with those without depression. Recognition of depression may facilitate targeted interventions to address medication adherence and thereby improve secondary cardiovascular disease prevention.

“Nobody wants to rock the boat”: a grounded theory study of taking medication to prevent a further heart attack

Abstract Introduction Following an acute myocardial infarction (AMI), patients are prescribed a daily regime of five medications to prevent secondary cardiovascular events, however medication adherence in this patient group has been measured at only 66%.1 Sub-optimal adherence leads to increased mortality, morbidity and healthcare system costs. Current interventions such as monitored dosage systems, phone message reminders and pharmacist consultations have made some improvements but are largely based on presumptions about adherence than formal evidence. Studying the experience of medication-taking following an AMI, and the personal requirement and adjustment that is required to enable adherence could arguably generate the evidence needed to support future interventions in this field. Aim The aim of this study was to use grounded theory methodology to create a model explaining the process of medication-taking in patients prescribed medication following an AMI. Methods Following ethical approval (UREC 18/36), semi-structured interviews were conducted with thirteen people (based in South-East England) taking medication following at least one AMI episode in the past. The interviews were conducted in person, online or via the telephone and audio-recorded. These recordings were transcribed verbatim and analysed according to constructed grounded theory.2 NVivo software was used to organise and display the coded data and produce a model of the medication-taking process. Results Patients took medication because they wanted to continue living their lives. They saw medication as offering them protection, alongside diet and exercise. Following hospital discharge, patients incorporated medication into their daily routines at home. They used mealtimes and bedtime as a prompt, and kept medication located close to these activities. Patients described rarely missing doses but recognised being away from routines was a cause of medication omission. In this stable stage, patients considered medication-taking unproblematic; they ‘just got on with it’. The professional trust established with the medical team was the basis for following medication directions, and patients conferred the authority to make decisions about their treatment, not wanting to initiate changes themselves; to not ‘rock the boat’. The main cause of change to medication-taking was experiencing adverse bodily effects, ascribed by patients to medication and described as side effects. Patients used small noticeable bodily changes as a prompt for further investigation and information- seeking, after which they presented evidence to the medical team, who instigated medication changes. There was a background dislike of taking medication, which was eased by knowledge of medication action and personal biomedical results. These patients were intentionally adherent to medication but were drawn to question their treatment when ‘side effects’ or misunderstanding arose. Discussion/Conclusion Medication-taking in this group is driven by a desire to live, so they accommodate medication routine to fit their lives, but ‘side effects’ can disturb their intention to continue the routine. This action is reinforced by trust relationships with medical professionals. Resistance to taking medication is alleviated by knowledge of medication action and biomedical results. Practitioners can use patient education, test results and shared decision-making as points to further the patient relationship and strengthen adherence behaviours.