Coronary Atherosclerosis Disease Research Articles

Absence of platelet overactivation and thrombosis formation among patients with coronary atherosclerosis disease after vaccination against SARS-CoV-2

BackgroundAssociation of Coronavirus disease 2019 vaccines with thrombosis has raised concerns among patients with coronary atherosclerosis disease (CAD). ObjectivesAfter vaccination against SARS-CoV-2, to detect thrombosis formation in atherosclerosis ApoE−/− mice, and platelet activation, coagulation, the profile of prothrombotic antibodies, and the production of platelet factor 4 (PF4) antibodies in patients with CAD. MethodsAtherosclerotic ApoE−/− mice were immunized with saline or inactivated SARS-CoV vaccines. We investigated FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. Inpatients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and defined according to vaccination status. We evaluated coagulation by thrombelastograph (TEG), platelet activation makers by flow cytometry, PF4 antibody and antiphospholipid antibodies by ELISA, and SARS-CoV-2 neutralizing antibody. ResultsIn atherosclerotic ApoE−/− mice, FeCl3-induced thrombus formation and thrombus formation under flow conditions were similar between saline-treated and inactivated SARS-CoV-2 vaccines-treated groups. A total of 182 patients undergoing PCI were included in the final analysis, of whom 92 had been vaccinated. Baseline characteristics were well balanced between unvaccinated and vaccinated groups. The expression of PAC-1 and P-selectin, the prevalence of positivity for PF4 antibodies and antiphospholipid antibodies were similar between these two groups. ConclusionsInactivated SARS-CoV-2 vaccines did not potentiate thrombosis formation in atherosclerotic mice. Inactivated SARS-CoV-2 vaccines did not enhance platelet activation, or trigger the production of PF4 and antiphospholipid antibodies in patients with CAD. In light of the observed thrombotic risks associated with adenovirus-based COVID-19 vaccines, inactivated vaccines may offer a potentially safer option for individuals with CAD.

A clinical randomized controlled study on the psycho-cardiological therapy for patients with coronary atherosclerosis disease

Objective: To explore the prognosis efficacy of psycho-cardiological therapy and management on patients with coronary atherosclerosis disease (CAD). Methods: This was a clinical randomized controlled study. This study included inpatients with CAD at the cardiology department in Beijing Anzhen Hospital, Capital Medical University from August 2021 to January 2024. The patients enrolled in this study were asked for basic information, and received measurements for depression, anxiety, sleep quality and living quality by the scales of Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder scale-7 (GAD-7), Athens Insomnia Scale (AIS), EuroQol 5-dimension 5-level (EQ-5D-5L) respectively. The patients were randomly grouped into a regular treatment group and a psycho-cardiological treatment group which included WeChat management or antidepressant/antianxiety medical therapy according to the situation. After the patients discharging from hospital for 2, 4, 12, 24, 48, 72, and 96 weeks, professional cardiovascular doctors would follow up by telephone, WeChat, and outpatient department, including scales (2-48 weeks), and cardiac events (2-96 weeks). Kaplan-Meier survival curve and multivariate Cox proportional hazards model were used for analyzing the association between psycho-cardiological treatment and cardiac events. Results: This study recruited a total of 552 patients with CAD, aged 61.0(54.0, 67.0) years, and 379 (68.7%) were male. There were 279(50.5%) in the regular treatment group and 273(49.5%) in the psycho-cardiological treatment group. After treatment for 4, 12 and 48 weeks, the PHQ-9 score in psycho-cardiological was significantly lower than the regular treatment group; After treatment for 12 weeks, the EQ-5D-5L effective value in psycho-cardiological group was higher than the regular treatment group; After treatment for 2, 4, 12, 24 and 48 weeks, the EQ-5D-5L VAS score in psycho-cardiological group was higher than the regular therapy group (all P<0.05). The Kaplan-Meier survival curve showed that, during the different follow-up periods, the rate of cardiac events in psycho-cardiological treatment group was lower than regular treatment group (log-rank P<0.001). The multivariate Cox proportional hazards model adjusted the factor of age, the psycho-cardiological treatment contributed to reducing the cardiac events rate by 80.3% (HR=0.197, 95%CI: 0.067-0.582, P=0.003). Conclusion: Psycho-cardiological treatment is beneficial for improving psychological stress, living quality, and reducing cardiac events, and helps to improve prognosis and psycho-cardiological rehabilitation in CAD patients.

Lymphocyte subsets in epicardial, thymic and subcutaneous adipose tissue during advanced coronary atherosclerosis in patients with coronary artery disease

The important role of epicardial (EAT) and thymic (TAT) adipose tissue in the development of atherosclerosis in patients with coronary artery disease (CAD) is widely discussed. The purpose of the study was to investigate the lymphocyte subsets and FoxP3+Treg lymphocytes in epicardial, thymic and subcutaneous adipose tissue depending on the severity of coronary atherosclerosis in patients with chronic CAD. We examined 24 patients with CAD (21 men; mean age 65.0 (58.0-68.0) years) scheduled for open-heart surgery. In samples of EAT, TAT and subcutaneous adipose tissue (SAT), the content of CD4+, CD8+, B lymphocytes, NK and NKT cells, CD4+CD25hiFoxP3+ and CD4+CD25lowFoxP3+T regulatory lymphocytes (Treg) and a proportion of Tregs with FoxP3 nuclear translocation was determined by imaging flow cytometry. Depending on the severity of atherosclerosis, assessed according to Gensini Score, patients were divided into groups: group 1 – patients with Gensini Score 65; group 2 – patients with Gensini Score ≥ 65. Patients in group 2 had higher frequency of EAT CD4+CD25lowTreg with FoxP3nuclear translocation, TAT CD8+T lymphocytes and NK cells, a lower content of TAT double positive CD4+CD8+T lymphocytes, and a tendency towards a decrease of frequency of TAT CD4+CD25hiTreg with FoxP3 nuclear translocation compared to patients in group 1. The level of nuclear translocation of FoxP3 in CD4+CD25hiTreg cells in TAT was inversely related to the proportion of CD8+T lymphocytes (rs = -0.653; p = 0.012) and NK cells (rs = -0.723; p = 0.003) in TAT, and directly – to the proportion of double positive CD4+CD8+T lymphocytes in TAT (rs = 0.567; p = 0.034) and the value of the waist-to-hip ratio (rs = -0.474; p = 0.041). Further research is required to study the molecular mechanisms of these relationships in patients with coronary atherosclerosis and chronic coronary artery disease.

Systemic aging fuels heart failure: Molecular mechanisms and therapeutic avenues.

Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional strain on the heart. Dysregulated mechanosignalling and impaired nitric oxide signalling play critical roles in the age-related vascular dysfunction associated with HF. Metabolic aging drives intricate shifts in glucose and lipid metabolism, leading to insulin resistance, mitochondrial dysfunction and lipid accumulation within cardiomyocytes. These alterations contribute to cardiac hypertrophy, fibrosis and impaired contractility, ultimately propelling HF. Systemic low-grade chronic inflammation, in conjunction with the senescence-associated secretory phenotype, aggravates cardiac dysfunction with age by promoting immune cell infiltration into the myocardium, fostering HF. This is further exacerbated by age-related comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes and chronic kidney disease (CKD). CAD and atherosclerosis induce myocardial ischaemia and adverse remodelling, while hypertension contributes to cardiac hypertrophy and fibrosis. Obesity-associated insulin resistance, inflammation and dyslipidaemia create a profibrotic cardiac environment, whereas diabetes-related metabolic disturbances further impair cardiac function. CKD-related fluid overload, electrolyte imbalances and uraemic toxins exacerbate HF through systemic inflammation and neurohormonal renin-angiotensin-aldosterone system (RAAS) activation. Recognizing aging as a modifiable process has opened avenues to target systemic aging in HF through both lifestyle interventions and therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological cardiac remodelling in the elderly by countering processes linked to age-related chronic HF, such as mitochondrial dysfunction, inflammation, senescence and declining cardiomyocyte regeneration. Dietary interventions such as plant-based and ketogenic diets, caloric restriction and macronutrient supplementation are instrumental in maintaining energy balance, reducing adiposity and addressing micronutrient and macronutrient imbalances associated with age-related HF. Therapeutic advancements targeting systemic aging in HF are underway. Key approaches include senomorphics and senolytics to limit senescence, antioxidants targeting mitochondrial stress, anti-inflammatory drugs like interleukin (IL)-1β inhibitors, metabolic rejuvenators such as nicotinamide riboside, resveratrol and sirtuin (SIRT) activators and autophagy enhancers like metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, all of which offer potential for preserving cardiac function and alleviating the age-related HF burden.

Effects of ankylosing spondylitis on cardiovascular disease: aMendelian randomization study.

Accumulating evidence suggests that patients with ankylosing spondylitis (AS) have an elevated risk for cardiovascular disease (CVD) and cardiovascular death, however, whether AS has causal effects on the risk of CVD is unclear.Two-sample Mendelian randomization (MR) was utilizedto examine the probable causal link between them. Summary statistics from publicly released genome-wide association studies (GWAS) was used to perform MR analyses. Genetically predicted AS was selected as the exposure variable from published GWAS meta-analyses. CVD was adopted as the outcome variable. The inverse variant weighted method was employed to obtain the casual estimates. The robustness of the results was also examined by evaluating the pleiotropy and heterogeneity of single-nucleotide polymorphisms. According to MR analyses, genetic susceptibility to AS was associated with a high risk of heart failure and ischemic stroke, while negativelygenetic susceptibility was found between AS and peripheral atherosclerosis. No statistical relationship was found between AS and venous thromboembolism, atrial fibrillation, coronary atherosclerosis, and valvular heart disease. Sensitivity analysis showed no evidence of horizontal pleiotropy or heterogeneity. The present study suggests that AS exerts causal effects on the risk of CVD, including heart failure, ischemic stroke, and peripheral atherosclerosis.

Mendelian randomization evidence for the causal effect of mental well-being on healthy aging.

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (β [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (β [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

LDL-C and TC mediate the risk of PNPLA3 inhibition on cardiovascular diseases.

PNPLA3 is a promising target for the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. ARO-PNPLA3 is a drug that efficiently lowers PNPLA3 expression in hepatocytes at the mRNA level, resulting in a significant reduction in liver fat in Phase I clinical trials. However, the long-term effects and potential side effects of ARO-PNPLA3 are not well understood. We conducted a two-sample, two-step Mendelian randomization (MR) analysis to investigate the association between PNPLA3 inhibition and 10 cardiovascular diseases (CVDs), as well as the role of lipid traits as mediators. We identified genetic variants near the PNPLA3 gene, which are linked to liver fat percentage, as instrumental variables for inhibiting PNPLA3. Additionally, positive control analyses on liver diseases were conducted to validate the selection of the genetic instruments. Genetically predicted PNPLA3 inhibition significantly increased the risk of coronary atherosclerosis (1.14, 95% CI 1.06, 1.23), coronary heart disease (1.14, 95% CI 1.08, 1.21), and myocardial infarction (1.16, 95% CI 1.08, 1.26). Suggestive associations were observed for increased risk of heart failure (1.09, 95% CI 1.02, 1.17, P = 0.0143) and atrial fibrillation (1.17, 95% CI 1.00, 1.36, P = 0.0468). Blood low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) mediated approximately 16-25%, 16-30%, and 14-22% of the associations between PNPLA3 inhibition and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. This study suggests that PNPLA3 inhibition increases the risk of major CVDs. Moreover, blood LDL-C and TC may mediate a significant proportion of the associations between PNPLA3 inhibition and coronary atherosclerosis, coronary heart disease, or myocardial infarction.

Identification of PPARG as key gene to link coronary atherosclerosis disease and rheumatoid arthritis via microarray data analysis.

Inflammation is the common pathogenesis of coronary atherosclerosis disease (CAD) and rheumatoid arthritis (RA). Although it is established that RA increases the risk of CAD, the underlining mechanism remained indefinite. This study seeks to explore the molecular mechanisms of RA linked CAD and identify potential target gene for early prediction of CAD in RA patients. The study utilized five raw datasets: GSE55235, GSE55457, GSE12021 for RA patients, and GSE42148 and GSE20680 for CAD patients. Gene Set Enrichment Analysis (GSEA) was used to investigate common signaling pathways associated with RA and CAD. Then, weighted gene co-expression network analysis (WGCNA) was performed on RA and CAD training datasets to identify gene modules related to single-sample GSEA (ssGSEA) scores. Overlapping module genes and differentially expressed genes (DEGs) were considered as co-susceptible genes for both diseases. Three hub genes were screened using a protein-protein interaction (PPI) network analysis via Cytoscape plug-ins. The signaling pathways, immune infiltration, and transcription factors associated with these hub genes were analyzed to explore the underlying mechanism connecting both diseases. Immunohistochemistry and qRT-PCR were conducted to validate the expression of the key candidate gene, PPARG, in macrophages of synovial tissue and arterial walls from RA and CAD patients. The study found that Fc-gamma receptor-mediated endocytosis is a common signaling pathway for both RA and CAD. A total of 25 genes were screened by WGCNA and DEGs, which are involved in inflammation-related ligand-receptor interactions, cytoskeleton, and endocytosis signaling pathways. The principal component analysis(PCA) and support vector machine (SVM) and receiver-operator characteristic (ROC) analysis demonstrate that 25 DEGs can effectively distinguish RA and CAD groups from normal groups. Three hub genes TUBB2A, FKBP5, and PPARG were further identified by the Cytoscape software. Both FKBP5 and PPARG were downregulated in synovial tissue of RA and upregulated in the peripheral blood of CAD patients and differential mRNAexpreesion between normal and disease groups in both diseases were validated by qRT-PCR.Association of PPARG with monocyte was demonstrated across both training and validation datasets in CAD. PPARG expression is observed in control synovial epithelial cells and foamy macrophages of arterial walls, but was decreased in synovial epithelium of RA patients. Its expression in foamy macrophages of atherosclerotic vascular walls exhibits a positive correlation (r = 0.6276, p = 0.0002) with CD68. Our findings suggest that PPARG may serve as a potentially predictive marker for CAD in RA patients, which provides new insights into the molecular mechanism underling RA linked CAD.

Variability in Plasma Lipids Between Intensive Statin Therapy and Conventional-Dose Statins Combined with Ezetimibe Therapy in Patients with Coronary Atherosclerosis Disease.

Dyslipidemia has been widely recognized as a significant risk factor for coronary atherosclerosis disease (CAD). In fact, lipid variability has emerged as a more reliable predictor of cardiovascular events. In this study, we aimed to examine the variability in plasma lipids under two different lipid-lowering regimens (intensive statin therapy versus the combination of conventional-dose statins with ezetimibe). In total, we have retrospectively examined 1275 patients with CAD from January 2009 to April 2019 and divided them into two groups: intensive statin group and conventional-dose statins combined with ezetimibe group. All patients were followed up for at least 1 year. Lipid variability was verified by standard deviation (SD), coefficient of variation (CV), and variability independent of mean (VIM) triple methods. Multiple linear regression and subgroup analyses were performed. In the overall participants, the mean age was 62.3 ± 10.4 years old, and 72.8% were male. Multivariate linear regression analysis indicated that the intensive statin group had lower variability in terms of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) in all SD, CV, and VIM triple methods than statins combined with ezetimibe group (P for all <0.05). Similar results were established in the subgroup analyses based on atorvastatin or rosuvastatin, diabetes mellitus or not, and hypertension or not (P for all < 0.05). Thus, we can conclude that intensive statin therapy could contribute in lowering lipid variability than conventional-dose statins combined with ezetimibe therapy among patients with CAD.

Blood phytosterols in relation to cardiovascular diseases and mediating effects of blood lipids and hematological traits: a Mendelian randomization analysis.

Short-term clinical trials have shown the cholesterol-lowering potentials of phytosterols, but their impacts on cardiovascular disease (CVD) remain controversial. This study used the Mendelian randomization (MR) to investigate the relationships between genetic predisposition to blood sitosterol concentration and 11 CVD endpoints, along with the potential mediating effects of blood lipids and hematological traits. Random-effect inverse-variance weighted method was used as the main analysis of MR. Genetic instruments of sitosterol (seven SNPs, F=253, and R2=15.4%) were derived from an Icelandic cohort. Summary-level data of the 11 CVDs were obtained from UK Biobank, FinnGen, and publicly available genome-wide association study results. Genetically predicted one unit increment in log-transformed blood total sitosterol was significantly associated with a higher risk of coronary atherosclerosis (OR: 1.52; 95% CI: 1.41, 1.65; n=667,551), myocardial infarction (OR: 1.40; 95% CI: 1.25, 1.56; n=596,436), all coronary heart disease (OR: 1.33; 95% CI: 1.22, 1.46; n=766,053), intracerebral hemorrhage (OR: 1.68; 95% CI: 1.24, 2.27; n=659,181), heart failure (OR: 1.16; 95% CI: 1.08, 1.25; n=1,195,531), and aortic aneurysm (OR: 1.74; 95% CI: 1.42, 2.13; n=665,714). Suggestive associations were observed for an increased risk of ischemic stroke (OR: 1.06; 95% CI: 1.01, 1.12; n=2,021,995) and peripheral artery disease (OR: 1.20; 95% CI: 1.05, 1.37; n=660,791). Notably, blood non-high-density lipoprotein cholesterol (nonHDL-C) and apolipoprotein B mediated about 38-47%, 46-60%, and 43-58% of the associations between sitosterol and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. However, the associations between sitosterol and CVDs were less likely to depend on hematological traits. The study suggests that genetic predisposition to higher blood total sitosterol is linked to a greater risk of major CVDs. Moreover, blood nonHDL-C and apolipoprotein B might mediate a significant proportion of the associations between sitosterol and coronary diseases.

Ancestral diversity in lipoprotein(a) studies helps address evidence gaps

IntroductionThe independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.MethodsHere, we examined how ancestrally diverse studies could...

СРАВНИТЕЛЬНЫЙ АНАЛИЗ 9-ЛЕТНЕЙ ДИНАМИКИ ПАРАМЕТРОВ СЕРДЕЧНО-СОСУДИСТОГО СТАТУСА ЖИТЕЛЕЙ АРКТИЧЕСКИХ И ЮЖНЫХ ТЕРРИТОРИЙ ТЮМЕНСКОЙ ОБЛАСТИ

Introduction. Studies show that coronary atherosclerosis and coronary artery disease in the Arctic and Subarctic regions have their own characteristics and need to be further studied. Aim. To conduct a comparative prospective analysis of clinical, laboratory, echocardiographic and coronary angiography data in middle-aged residents of the Arctic regions compared with residents of the south of Tyumen region. Material and methods. From the Coronary Angiography Registry we selected 229 patients of mean age 45-59 years who underwent coronary angiography more than once between 2000 and 2021. The average interval between the 1st and 2nd survey points was 9.0±3.4 years. Patients who underwent coronary angiography to verify the diagnosis, patients with stable coronary artery disease and old myocardial infarction were included. Individuals with acute coronary syndrome were not included. Patients were divided into 2 groups: 85 residents of Tyumen and the south of Tyumen region and 144 residents of the Yamal-Nenets Autonomous Okrug. Differences between groups and dynamics of the studied parameters were assessed using the application package IBM SPSS Statistics 21. Results and discussion. The groups were comparable in demographic characteristics. Initially, cardiovascular status was more severe in Yamal-Nenets Autonomous Okrug group of patients: more severe (II and III) functional classes of exertional angina and a history of myocardial infarction, hemodynamically significant coronary lesions, including coronary artery occlusion, were more common. In Yamal-Nenets Autonomous Okrug group, the level of high-density lipoprotein cholesterol was initially lower. During the follow-up period, obesity and echo-signs of post-infarction changes were detected in patients of Yamal-Nenets Autonomous Okrug more often, higher asynergy index and triglyceride levels were recorded. Intergroup differences in the incidence of myocardial infarction and occlusive lesions and high-density lipoprotein cholesterol levels persisted. Conclusion. During 9-year follow-up, middle-aged patients who underwent elective coronary angiography and lived in the Arctic zone had more severe baseline indicators of cardiovascular status, as well as their more significant negative dynamics compared to patients lived in the south of Tyumen region.

P135 A CASE OF RIGHT CORONARY ARTERY ANEURYSM COMPLICATED BY ENDOVASCULAR THROMBOSIS

Abstract Coronary artery aneurysm is a rare disorder with prevalence in male population. The most commonly involved vessel is the right coronary artery followed by the anterior descending artery. The most frequent etiologies are coronary atherosclerosis and Kawasaki disease. The treatment of coronary aneurysms with significant stenosis is often surgical, with implantation of covered stents in case of saccular aneurysms. In coronary artery aneurysms without significant stenosis, medical therapy is often the most suitable choice. Case report We present a case of a 68–year–old man with history of hypertension and dyslipidemia, who arrived to our ED with inferior STEMI. Left coronary angiography showed a 75% stenosis of the distal anterior descending artery and subocclusion of the first left marginal artery. Right coronary angiography revealed a severely ectatic vessel (7–8 mm diameter) with intraluminal thrombosis and markedly slowed flow (TIMI 1). Considering the regression of symptoms and ECG alterations, intracoronary bolus of Tirofiban was performed followed by i.v. infusion of 24 hours in association with DAPT. Blood tests did not detect any relevant alterations of coagulation profile but only an heterozygous mutation for MTHFR with slightly altered homocysteine values. Six days later, a second coronary angiography was performed which confirmed the persistence of thrombotic formation into the right coronary artery that was treated with rheolytic thromboaspiration and TIMI 2 final flow. In consideration of the angiographic findings, it was decided not to implant coronary stents. After multidisciplinary team discussion it was decided to associate DAPT with oral anticoagulant therapy (Warfarin 5 mg, INR 2–3) The patient was discharged with indication to continue the triple antithrombotic therapy for 6 months followed by double antithrombotic therapy with ASA and Warfarin. Conclusions Coronary aneurysms in the context of ACS are rare findings, often caused by endovascular thrombosis. Thrombolytic therapy, rheolytic thromboaspiration and anticoagulation therapy are valid tools for the successful treatment of such cases.

Inactivated whole-virion SARS-CoV-2 vaccines and long-term clinical outcomes in patients with coronary atherosclerosis disease in China: a prospective cohort study.

Publicized adverse events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised concern among patients with coronary atherosclerosis disease (CAD). We sought to study the association between SARS-CoV-2 vaccines and long-term clinical outcomes including ischaemic and bleeding events among patients with CAD. Inpatients diagnosed with CAD by coronary angiography, without a history of SARS-CoV-2 infection and vaccination, were included between 1 January and 30 April 2021, and underwent follow-up until 31 January 2022. Two doses of inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, BBIBPCorV, or WIBP-CorV) were available after discharge, and the group was stratified by vaccination. The primary composite outcomes were cardiovascular death, non-fatal myocardial infarction, stent thrombosis, unplanned revascularization, ischaemic stroke, venous thrombo-embolism, or peripheral arterial thrombosis. The bleeding outcomes were Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Cox regression models with vaccination status as a time-dependent covariate were used to calculate the hazard ratio (HR) for the outcomes. A propensity score matching method was used to reduce confounding biases. This prospective cohort study included 2078 individuals with CAD, 1021 (49.1%) were vaccinated. During a median follow-up of 9.1 months, 45 (4.3%) primary composite outcomes occurred in the unvaccinated group, and 33 (3.2%) in the vaccinated group. In Cox regression, the adjusted HR was 1.13 [95% confidence interval (CI) 0.65-1.93]. The adjusted HR for the bleeding outcomes associated with vaccination was 0.81 [95% CI 0.35-1.19]. After matching, the adjusted HR for the primary composite outcomes associated with vaccination was 1.06 [95% CI 0.57-1.99] and for the bleeding outcomes was 0.91 [95% CI 0.35-2.38]. Similar results were found in the seven prespecified subgroups. No grade 3 adverse reactions after vaccination were recorded. Our results indicated no evidence of an increased ischaemic or bleeding risk after vaccination with inactivated SARS-CoV-2 vaccine among Chinese patients with CAD, with limited statistical power.

The prevalence of coronary atherosclerosis in patients with refractory gastroesophageal reflux disease ready for antireflux surgery.

Coronary atherosclerosis (CAS) and gastroesophageal reflux disease (GERD) share common risk factors. The existing CAS may not only increase the possibility of GERD to be refractory GERD (RGERD), but also increase the risk of antireflux surgery for these patients. The aim of this study was to estimate the prevalence of CAS and its potential risk factors in patients with RGERD ready for antireflux surgery. The retrospective analysis was performed in the digestive disease center of Suining Central Hospital, a teritary hospital in Sichuan, China. Records of patients with RGERD admitted to the hospital for antireflux surgery between July 2018, and June 2021 were included. The included patients were divided into the RGERD group and RGERD-CAS group based on the coronary computed tomography angiography (CCTA) results, which were defined as no CAS and CAS (<50% mild stenosis or ≥50% significant stenosis). In total, 448 patients with RGERD qualified for the study. The prevalence of CAS in these patients was 45.1%. Specifically, 246 patients (54.9%) were in the RGERD group, and 202 patients (45.1%) were in the RGERD-CAS group. Among these 202 patients with CAS, 120 patients (59.4%) had mild CAS (<50% stenosis), 82 patients (40.6%) had significant CAS (≥50% stenosis). Five independent risk factors, including male sex, high blood pressure (HBP), diabetes mellitus (DM), Barrett's esophagus (BE) and family history of coronary artery disease were identified for the occurrence of CAS in patients with RGERD ready for antireflux surgery after adjusting for other factors. CAS is prevalent in patients with RGERD ready for antireflux surgery. Routing CTTA was suggested to exclude potential coronary artery disease in RGERD patients ready for antireflux surgery with independent risk factors.

Risk of premature coronary atherosclerosis in patients with nonalcoholic fatty liver disease.

In the current literature, there are few studies investigating the relationship between premature coronary atherosclerosis and nonalcoholic fatty liver disease. We aimed to evaluate the relationship between nonalcoholic fatty liver disease and premature coronary atherosclerosis. In this cross-sectional study, female patients aged <55 years and male patients aged <50 years were enrolled. Both male and female patients underwent coronary angiography and abdomen ultrasonography between 2014 and 2019. A stepwise binary logistic regression analysis was carried out to evaluate the independent variables related to premature coronary atherosclerosis and nonalcoholic fatty liver disease. A p-value<0.05 was considered statistically significant. nonalcoholic fatty liver disease was present in 44% of patients (n=377). Notably, 62% of the patients were female and the mean age was 44.5 (39-49) years. In a multivariate analysis, nonalcoholic fatty liver disease was shown to be an independent risk factor of premature coronary atherosclerosis (OR 1.438; 95%CI, 1.050-1.969; p=0.024). The presence of nonalcoholic fatty liver disease is an important independent risk factor for the development of premature coronary atherosclerosis.

Serum Carboxylated and Undercarboxylated Osteocalcin association with Coronary Atherosclerosis Disease and Cardiovascular Risk Markers in: Analysis of a Syrian Male Cohort

Background: New assumption concerning association of osteocalcin and Vascular calcification has emerged in reaction to observations that the mechanism of vascular calcification resembles that of bone mineralization, thus linking bone and the vasculature. However, studies reported contrasting results about the association between osteocalcin and atherosclerosis. This study was designed to evaluate capacity relationships among different forms of circulating osteocalcin and cardiovascular risk markers in male with coronary atherosclerosis. Methods: A cross-sectional study was conducted on 58 male patients, divided into two groups according to the severity of coronary artery disease (CAD), as determined by coronary angiography assessment: Early coronary atherosclerosis (ECA), n=20, patients with mild CAD (&lt;50% stenosis in any major epicardial arteries), and late coronary atherosclerosis (LCA), n=38, patients with severe, multivessel CAD (&gt;50% stenosis in at least one or more major epicardial arteries). The healthy control (HC) group included 26 healthy male subjects. Carboxylated (cOC) and ucOC were measured using ELISA technique. Results: We observed significantly lower ucOC levels in both stages of cardiovascular disease (CVD) (ECA and LCA) compared to the HC group (2.34±2.23 and 2.48±1.60 vs 6.65±1.78ng/mL, P&lt;0.01). ucOC was inversely correlated with an increasing number of cardiovascular risk factors (CVRFs). Moreover, ucOC levels were markedly reduced in high-fasting plasma glucose (FPG) groups (IFG and T2DM-threshold level), compared to the normal FPG group (NG). cOC levels were higher in the IFG group, compared to the normal FPG group (8.50±4.76 vs 7.13±3.13ng/mL, p=0.008) possibly predicting such condition. Conclusions: In the present study, patients with coronary atherosclerosis, regardless of the onset of stenosis, showed lower ucOC levels which were inversely correlated with an increasing number of CVRFs. Moreover, ucOC levels were markedly reduced in high-FPG groups. Serum ucOC may be considered as a potential biomarker for coronary atherosclerosis disease and therefore its measurement may help to establish preventive and therapeutic approaches. Moreover, cOC may be associated with a high alert for diabetes at the IFG stage, but not when the disease progresses to diabetes.

Pathophysiology of Coronary Microvascular Dysfunction.

Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD ("primary" microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.

Spasm, inflammation, coronary microcirculation and metabolism: how big is the iceberg under the stenosis

Ischemic heart disease (IHD) is a leading global cause of death and coronary artery disease has long been considered the main determinant of inducible ischemia and symptoms. However, after the performance of hundreds of thousands of percutaneous coronary revascularizations (PCI) worldwide, outcome analysis suggests that the direct relationship between chronic obstructive coronary atherosclerosis and ischemic heart disease (IHD) may represent a too simplified view of IHD; growing evidence has demonstrated the importance of a number of other underlying mechanisms. The purpose of this review is to highlight the multiple mechanisms responsible of myocardial ischemia.

Apolipoprotein B Displays Superior Predictive Value Than Other Lipids for Long-Term Prognosis in Coronary Atherosclerosis Patients and Particular Subpopulations: A Retrospective Study

Accumulating evidence that apolipoprotein B (apoB) plays a critical role in predicting coronary heart disease (CHD) and future outcomes. The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines suggest that apoB can be an alternative to non-HDL-C or LDL-C in patients with high triglyceride levels, diabetes, obesity, metabolic syndrome, or very low LDL-C levels. This study explores whether apoB can also serve as predictive value for long-term major adverse cardiovascular events (MACEs) in normal people and specific coronary atherosclerosis patients. A total of 826 patients were followed up over 10 years, and the risk factors for MACEs were retrospectively analyzed in patients with CHD and particular subpopulations. All statistical analyses were performed in R software. Cox regressions were performed to assess independent risk factors of long-term MACEs in the atherosclerosis group and CHD subgroups. Kaplan-Meier survival curves were used to evaluate the survival rate for patients in different apoB quartiles, and receiver-operating characteristic curves were used to compare apoB and other lipids in predicting the presence of long-term MACE. apoB could be a "risk-enhancing factor" in patients with coronary atherosclerosis disease, whereas in the Normal population, LDL-C still acted as a major risk factor for predicting MACEs. apoB was a good risk predictor for long-term cardiovascular events in coronary atherosclerosis (AS) patients, including the AS group and CHD subpopulations (including CHD+triglyceride ≥2.3 mmol/L, CHD+diabetes mellitus, CHD+body mass index ≥25 kg/m2, or CHD+metabolic syndrome). In patients with CHD whose condition was complicated with diabetes, obesity, and metabolic syndrome, apoB performed better than other lipids in predicting the presence of myocardial infarction, hospitalization due to angina, and cardiac death. Despite achieving optimal LDL-C or non-HDL-C levels, patients with CHD are still at risk of worse survival if they are unable to reach a low apoB level (lower cut points such as 65 mg/dL). More attention should be paid to special populations with residual elevations of atherogenic particle numbers, and greater focus should be placed on lowering baseline apoB to achieve long-term benefits. However, given that this was an observational study, the association of baseline apoB level and long-term MACEs only was evaluated; it is unclear whether the emergence of MACEs would be influenced by the dynamic changes of apoB. Because this was a retrospective and observational analysis, bias in data analysis was unavoidable; thus, the results cannot be used to generalize implications to broader patient populations, and more large-scale clinical trials are required to verify these findings. (Clin Ther. 2022;44:1071-1092) © 2022 Elsevier HS Journals, Inc.