Atherosclerotic Coronary Artery Disease Research Articles

Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.

Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.

Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions

Atherosclerotic coronary artery disease is a significant global health threat, impacting millions annually. Over time, plaque buildup narrows the coronary arteries, reducing blood flow to the heart muscle and resulting in myocardial ischemia. Timely diagnosis and intervention are crucial for restoring the blood flow to the heart muscle and preventing myocardial infarction. Given the limited availability of screening and diagnostic tests, the early diagnosis of myocardial ischemia remains challenging. While cardiac troponin is considered the gold standard for detecting myocardial injury, its effectiveness in identifying myocardial ischemia is limited. Ischemia-modified albumin (IMA) is a modified albumin variant that serves as a sensitive and early marker for ischemia. Despite extensive research on diagnostic applications of IMA as a biomarker for ischemia, significant gaps remain in understanding its formation, sensitive and specific detection, and precise clinical utility. This review aims to address these gaps by compiling literature on IMA discussing the latest findings on structure and formation, and detection methods. Further research is required to enhance understanding of the structure and formation of IMA, aiming to develop novel detection techniques or improve existing ones. However, currently, available sophisticated methods are associated with higher expenses and require specialized equipment and qualified personnel.

Jingzhi Guanxin Oral Liquids Attenuate Atherosclerotic Coronary Heart Disease via Modulating Lipid Metabolism and PPAR-Related Targets.

Jingzhi Guanxin Oral Liquids (JZGX), a traditional Chinese medicine formulation prepared from the decoction of five herbs, has been utilized to relieve chest pain with coronary artery disease (CAD). However, the chemical composition and therapeutic mechanisms of JZGX remain obscured. In this research, the potential targets and pathways of JZGX against CAD were anticipated through network pharmacology based on analyzing its chemical constituents using UPLC-Q-TOF-MS/MS. One hundred seven ingredients in JZGX were identified. The 39 active chemicals and 37 key targets were screened, and CAD-related signaling pathways were clustered, mainly associated with lipid metabolism. Subsequently, the atherosclerotic CAD animal model employing 24 weeks of high-fat diet (HFD) ApoE-/- mice was constructed to investigate the JZGX efficacy and underlying mechanisms validating network forecasts. The histological staining examination and cardiovascular biomarker tests confirmed that JZGX reduced plaque formation in the aorta and decreased blood lipids in vivo. It featured anti-inflammatory, anti-thrombotic, and myocardial protective effects. JZGX prevented excessive lipid deposits and inflammation within the liver and exhibited hepatoprotective properties. Serum untargeted metabolomics analysis indicated that JZGX ameliorated metabolic abnormalities in atherosclerotic CAD mice and prompted lipid metabolism, especially linoleic acid. The PPARs and attached critical targets (SREBP1, FASN, PTGS2, and CYP3A), filtered from the networks and connected with lipid metabolism, were dramatically modulated through JZGX administration, as revealed by western blotting. The molecular docking outcomes showed that all 39 active ingredients in JZGX had good binding activity with PPARα and PPARγ. These findings illustrate that JZGX alleviates atherosclerotic CAD progression by remodeling the lipid metabolism and regulating PPAR-related proteins.

A Rare Symptomatic Case of Heterozygous Cerebro-Tendinous Xanthomatosis (CTX) Treated with Urso-Deoxycholic Acid (UDCA): With Mini Review

Cerebrotendinous Xanthamatosis (CTX) is a rare autosomal recessive disorder caused by a mutation in the CYP27A1 gene leading to impaired metabolism of cholesterol and accumulation of cholestenol and the cholesterol in various tissues such as the brain, eyes, lungs and bones and reduced formation of cheno-deoxycholic acid (CDCA). The clinical presentation is diverse, starting in the early neonatal period and progressing till adulthood unless treated early. A common neurological manifestation is a spino-cerebellar ataxia followed by spastic paraparesis. Tendon xanthoma is a classical finding that usually helps in clinching the diagnosis but may not be present in all cases. Brain MRI also reveals characteristic abnormalities with cerebellar atrophy and hyper-intensities in the dentate nucleus and surrounding cerebellar white matter on T1weighted images. It is a rare cause of treatable ataxia in young individuals. Treatment is by replacement by CDCA or Urso-deoxycholic acid (UDCA). Supplemented with statins these individuals also have premature atherosclerosis causing death due to athero-sclerotic coronary artery disease. Here a rare case of symptomatic heterologous CYP27A1 mutation is reported with syndrome of spino-cerebellar ataxia treated with UDCA.

Defining the cardiovascular phenotype of adults with Alström syndrome

Background>40% of infants with Alström Syndrome (AS) present with a transient, severe cardiomyopathy in the first months of life, with apparent recovery in survivors. One in five individuals then develop a later-onset cardiomyopathy but wide clinical variability is observed, even within the same family. The rationale for this study is to provide a comprehensive evaluation of the cardiovascular phenotype in adults with AS. MethodsAdults attending the National Centre for AS in England were studied. All patients underwent biochemical, 12- lead electrocardiography, echocardiography, and cardiovascular magnetic resonance imaging. Results47 adults with AS (64% male; mean age 33 years; 66% white British) were studied. Seven (15%) survived infantile cardiomyopathy and 23 (49%) developed adult-onset cardiomyopathy. Conventional risk factors for cardiovascular disease were present in 39 (83%). Abnormalities were present on biomarkers in 16 (34%), ECG 30 (64%), echocardiography 19 (40%) and CMR 31 (66%). Coronary artery imaging was performed in six (13%), with abnormalities in two. Cardiac, renal, and liver markers were more often impaired in older patients, with impaired left ventricular ejection fraction, reduced global longitudinal strain and late enhancement. 6 (13%) had severe pulmonary hypertension (mean pulmonary artery pressure 46 mmHg) due to left heart disease on invasive testing. ConclusionCardiomyopathy is common in adults with AS, complicated in a significant proportion by atherosclerotic coronary artery disease and restrictive cardiomyopathy, confirmed on CMR and invasive testing. With advancing age, cardiovascular complications are compounded by contemporaneous renal and liver disease.

From Atherosclerosis to Spontaneous Coronary Artery Dissection: Defining a Clinical and Genetic Risk Spectrum for Myocardial Infarction.

Spontaneous coronary artery dissection (SCAD) has been increasingly recognized as a significant cause of acute myocardial infarction (AMI) in young and middle-aged women and arises through mechanisms independent of atherosclerosis. SCAD has a multifactorial etiology that includes environmental, individual, and genetic factors distinct from those typically associated with coronary artery disease. Here, we summarize the current understanding of the genetic factors contributing to the development of SCAD and highlight those factors which differentiate SCAD from atherosclerotic coronary artery disease. Recent studies have revealed several associated variants with varying effect sizes for SCAD, giving rise to a complex genetic architecture. Associated genes highlight an important role for arterial cells and their extracellular matrix in the pathogenesis of SCAD, as well as notable genetic overlap between SCAD and other systemic arteriopathies such as fibromuscular dysplasia and vascular connective tissue diseases. Further investigation of individual variants (including in the associated gene PHACTR1) along with polygenic score analysis have demonstrated an inverse genetic relationship between SCAD and atherosclerosis as distinct causes of AMI. SCAD represents an increasingly recognized cause of AMI with opposing clinical and genetic risk factors from that of AMI due to atherosclerosis, and it is often associated with complex underlying genetic conditions. Genetic study of SCAD on a larger scale and with more diverse cohorts will not only further our evolving understanding of a newly defined genetic spectrum for AMI, but it will also inform the clinical utility of integrating genetic testing in AMI prevention and management moving forward.

Two case reports of spontaneous coronary dissection

Spontaneous coronary artery dissection (SCAD) has nowadays been described as a non-negligible etiology of acute coronary syndromes (ACS). Its prevalence approximates 3% in most cohorts. It mainly affects women in the young to middle-aged range. Individuals with SCAD typically exhibit fewer conventional cardiovascular risk factors associated with ischemic heart disease compared to those with atherosclerotic coronary artery disease. Nevertheless, some SCAD patients may present with risk factors such as hypertension, smoking, and dyslipidemia, although their direct contribution to SCAD risk remains uncertain. We present two cases of spontaneous coronary dissection to explore its pathogenesis, diagnosis, and treatment options. Learning objectives · Recognize spontaneous coronary artery dissection as the possible cause of ACS in females even with cardiovascular risk factors. Learn the importance of angiographic control after a conservative therapy that may lead to a more invasive approach.

Ethnicity and Sudden Cardiac Death in Athletes: Insights from a Large United Kingdom Registry.

The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood. To investigate etiology of SCD among different ethnicities in a large cohort of athletes. Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. Most of athletes were white (n = 758; 89%). Black and Asian athletes were 51 (6%) and 39 (5%) respectively. A structurally normal heart, indicative of sudden arrhythmic death syndrome (SADS) was the most common autopsy finding (n = 385, 45%), followed by myocardial diseases (n = 275; 32%) cases, atherosclerotic coronary artery disease (CAD) (n = 58, 7%) and coronary artery anomalies (n = 29, 3%). In most of cases, death occurred during exercise (n = 737; 87%) . Arrhythmogenic cardiomyopathy (ACM) was more common in black (n = 13; 25%) than in white (n = 109; 14%) and Asian (n = 3; 8%) athletes (p = 0.03 between black and white athletes; p = 0.04 between black and Asian athletes); in contrast, CAD was more common in Asians (n = 6; 15% vs n = 51; 7% in whites vs 2% n = 1; in blacks, p = 0.02 between Asian and black athletes). Among white athletes, ACM was more common in individuals who died during exercise than in the ones who died at rest (p = 0.005). Such a difference was not observed in Asian and black athletes. In Asian athletes, CAD was the diagnosis at autopsy in 18% of individuals who died during exercise and in none of individuals who died at rest. A structurally normal heart at autopsy and myocardial diseases are the most common findings in athletes who died suddenly. While ACM is more common in black athletes, atherosclerotic CAD is more common in Asian athletes, with a strong association with exercise-induced SCD. ACM appears to be a driver of exercise-induced SCD in white athletes, however this is not the case in black and Asian athletes.

Endothelin-converting Enzyme-1b Genetic Variants Increase the Risk of Coronary Artery Ectasia.

Coronary artery ectasia (CAE), defined as a 1.5-fold or greater enlargement of a coronary artery segment compared to the adjacent normal coronary artery, is frequently associated with atherosclerotic coronary artery disease (CAD). Membrane-bound endothelin converting enzyme-1 (ECE-1) is involved in the maturation process of the most potent vasoconstrictor ET-1. Polymorphisms in the endothelin (ET) gene family have been shown associated with the development of atherosclerosis. This study aims to investigate the effects of rs213045 and rs2038089 polymorphisms in the ECE-1 gene which have been previously shown to be associated with atherosclerosis and hypertension (HT), in CAE patients. Ninety-six CAE and 175 patients with normal coronary arteries were included in the study. ECE-1b gene variations rs213045 and rs2038089 were determined by real-time PCR. The frequencies of rs213045 C > A (C338A) CC genotype (60.4% vs. 35.4%, p < 0.001) and rs2038089 T > C T allele (64.58% vs. 35.42%, p = 0.017) were higher in the CAE group compared to the control group. The multivariate regression analysis showed that the ECE-1b rs213045 CC genotype (p = 0.001), rs2038089 T allele (p = 0.017), and hypercholesterolemia (HC) (p = 0.001) are risk factors for CAE. Moreover, in nondiabetic individuals of the CAE and control groups, it was observed that the rs213045 CC genotype (p < 0.001), and rs2038089 T allele (p = 0.003) were a risk factor for CAE, but this relationship was not found in the diabetic subgroups of the study groups (p > 0.05). These results show that ECE-1b polymorphisms may be associated with the risk of CAE and this relationship may change according to the presence of type II diabetes.

Multidistrict atherosclerotic disease: epidemiological and clinical framework

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

The Prevalence and Predictors of Atherosclerotic Coronary Artery Disease in Rheumatic and Non-rheumatic Valvular Heart Disease Patients.

The paradox of concurrent coronary artery disease (CAD) among patients with rheumatic and non-rheumatic valvular heart disease (RVHD; non-RVHD) is unclear. We aimed to evaluate the impact of the RVHD and non-RVHD on the prevalence of CAD and various risk factors, assess the number of diseased coronaries, clinical profile and the possible predictors of CAD in these patients, which may clarify the paradox and provide an insight for the prevention of CAD. The records of 106 valvular heart disease patients who had undergone valve replacement surgery at the King Faisal Cardiac Centrefrom January 2014 to October 2019 were evaluated. The clinical data and established risk factors were compared andlogistic regression analyses were performed to identify plausible predictors of CAD. Transthoracic echocardiographic diagnosis of 106 patients confirmed, 43 had RVHD (56.4 ± 8 years), of whom six (13.9%) had CAD with the highest mitral valve regurgitation (p < 0.01), and 63 had non-RVHD (60.0 ± 12 years). Of these, 31 patients showed the highest CAD (49.2%). Single- and triple-vessel disease was most common in RVHD and non-RVHD patients with concurrent CAD (33.3%; 41.9%, respectively), while non-RVHD patients also had quadruple vessel disease. The mean age of the RVHD and non-RVHD patients with coexisting CAD was significantly higher (66.7 ± 5; 66.7 ± 8 years) than those without CAD (46.1± 12.0; 54.7± 20, respectively). RVHD patients showed a significantly lower prevalence of diabetes, dyslipidaemia, hypertension, inflammatory cells, hepatorenal function markers, ejection fraction, and regional wall motion abnormality compared to RVHD patients with coexisting CAD (p < 0.01). Bivariate analysis indicated white blood cells, monocytes, neutrophils, gamma-glutamyl-transferase (GGT), bilirubin and blood urea nitrogen (BUN) to be significantly lower in RVHD patients. Predictors of high risk of CAD were BUN and hyperlipidaemia for RVHD and BUN, creatinine and GGT for non-RVHD patients. The prevalence of CAD in Saudi RVHD patients was significantly lower than in the Western countries, whereas non-RVHD was higher. The low prevalence may partly be attributed to age, reduced mitral regurgitation, and low frequency of risk and inflammatory factors.

Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy.

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes.

Novel indel variation of LTBP4 gene associates with risk of sudden cardiac death in Chinese populations with coronary artery disease

The objective of this study is to investigate whether common genetic variants of the LTBP4 gene are linked to the susceptibility of sudden cardiac death in individuals who have atherosclerotic coronary artery disease (SCD-CAD) in Chinese populations. A total of 208 SCD-CAD cases and 638 controls were included in the analysis, and logistic regression was employed to assess the association between a 4-bp insertion/deletion polymorphism (rs34005443) within LTBP4 and the susceptibility to SCD-CAD among Chinese individuals. Logistic regression analysis demonstrated a notable association between the insertion allele of rs34005443 and an escalated susceptibility to SCD-CAD [odds ratio (OR) = 1.434; 95 % confidence interval:1.14–1.80; P = 1.79 × 10−3]. Genotype-phenotype correlation analysis was performed using Genotype-Tissue expression (GTEx) database and further validated by human myocardium using qPCR. Correlation analysis revealed that LTBP4 expression level was lower in samples with the insertion allele. Furthermore, the dual-luciferase activity assays indicated that rs34005443 may play a regulatory role. Additionally, we predicted 30 transcription factors that are likely to bind to rs34005443 and its highly linked genetic variants via 3DSNP database. Subsequent GO and KEGG analysis indicated that these transcription factors have a significant function in regulating gene expression. Finally, PPI network analysis suggested a tight connection between LTBP4 proteins and TGFβs, highlighting these genes as potential hub genes in the context of SCD-CAD. In summary, our study revealed that rs34005443 might contribute to SCD-CAD susceptibility by regulating LTBP4 expression. These findings revealed that this indel could be a potentially functional marker for molecular diagnosis and risk stratification of SCD-CAD.

CT pericoronary adipose tissue density predicts coronary allograft vasculopathy and adverse clinical outcomes after cardiac transplantation.

To assess pericoronary adipose tissue (PCAT) density on Coronary Computed Tomography Angiography (CCTA) as a marker of inflammatory disease activity in coronary allograft vasculopathy (CAV). PCAT density, lesion volumes, and total vessel volume-to-myocardial mass ratio (V/M) were retrospectively measured in 126 CCTAs from 94 heart transplant patients (mean age 49 [SD 14.5] years, 40% female) who underwent imaging between 2010 to 2021; age and sex-matched controls; and patients with atherosclerosis. PCAT density was higher in transplant patients with CAV (n = 40; -73.0 HU [SD 9.3]) than without CAV (n = 86; -77.9 HU [SD 8.2]), and controls (n = 12; -86.2 HU [SD 5.4]), p < 0.01 for both. Unlike patients with atherosclerotic coronary artery disease (n = 32), CAV lesions were predominantly non-calcified, comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without (32.4 mm3/g [SD 9.7] vs. 41.4 mm3/g [SD 12.3], p < 0.0001). PCAT density and V/M improved the ability to predict CAV from AUC 0.75 to 0.85 when added to donor age and donor hypertension status (p < 0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality (OR 18.0 [95%CI 3.25-99.6], p < 0.01) and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularization (OR 7.47 [95%CI 1.8-31.6], p = 0.01) over 5.3 (SD 2.1) years. Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Increased PCAT density is associated with adverse clinical outcomes. These CCTA metrics could be useful for diagnosis and monitoring of CAV severity.

Acute Coronary Syndrome in Women: An Update.

The goal of this manuscript is to provide a concise summary of recent developments in the approach to and treatment of women with acute coronary syndrome (ACS). This review covers terminology updates relating to ACS and myocardial injury and infarction. Updates on disparities in recognition, treatments, and outcomes of women with ACS due to atherosclerotic coronary artery disease are covered. Other causes of ACS, including spontaneous coronary artery dissection and myocardial infarction with non-obstructive coronary artery disease are discussed, given the increased frequency in women compared with men. The review summarizes the latest on the unique circumstance of ACS in women who are pregnant or post-partum, including etiologies, diagnostic approaches, medication safety, and revascularization considerations. Compared with men, women with ACS have unique risk factors, presentations, and pathophysiology. Treatments known to be effective for men with atherosclerosis-related ACS are also effective for women; further work remains on reducing the disparities in diagnosis and treatment. Implementation of multimodality imaging will improve diagnostic accuracy and allow for targeted medical therapy in the setting of myocardial infarction with non-obstructive coronary artery disease.

Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Aortic aneurysms in patients with atherosclerotic coronary artery disease in the southwestern region of Romania - clinical and histopathological study.

An aneurysm is defined as a dilation of the arterial wall with a diameter exceeding 1.5 times the normal diameter of the vessel concerned. Aortic aneurysms (AAs) can develop at any level but are mostly found at the abdominal and infrarenal levels and extend to the iliac arteries. AAs are usually asymptomatic and are most often discovered incidentally during various imaging investigations for other conditions. Rupture of an AA is usually dramatic, being one of the causes of sudden cardiac death. Surgical treatment and, more recently, endovascular treatment are the only effective methods of AA repair. In this study, we screened for the diagnosis of AAs in patients with stable exertional angina who had indications for coronary angiography. The study was carried out in the period 2021-2023 in the Institute of Cardiovascular Diseases Timişoara, Romania. Of the 2458 patients with exertional angina who required coronary angiography, a number of 1844 (75%) patients had at least one stenotic atheromatous plaque, and of these 312 patients had AAs, of which 173 at the level of the abdominal aorta.

Correlation of circulatory VEGF and miRNA 126 in angiographically proven coronary artery disease and its clinical importance

Background: Atherosclerotic ischemic coronary artery disease (CAD) is a major cause of morbidity and mortality in both developed and developing countries, indicating the need for the discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Vascular endothelial growth factor (VEGF) may have some role, in the progression of human coronary atherosclerosis. Circulating microRNAs (miR) have a potential as a diagnostic as well as a prognostic biomarker of cardiovascular disease and dysfunctions. Aims and Objectives: The aim of the study was to correlate the levels of miRNA-126 and VEGF in the serum of CAD patients. Materials and Methods: The study was conducted on 100 cases of freshly diagnosed CAD patients (angiographically proven) and 80 normal healthy patients. Various serum biomarkers were estimated. The level of serum VEGF and Mi-RNA was correlated for CAD patients. Results: Highly significantly difference was found in levels of hemoglobin A1C, low density lipoprotein, total cholesterol, and total homocysteine while high-density lipoproteins and triglycerides were less significantly different for controls and cases. VEGF levels of CAD cases were found to be very significantly higher as compared to controls. The miRNA-126 expression was found to be lower in the CAD subjects compared to non-CAD subjects. Conclusion: The study was suggested the role of VEGF in atherogenesis and plaque instability. No significant correlation was found among between miR-126 levels and VEGF levels among CAD cases. The study is limited by a smaller sample size and was single-centered; therefore, multicentric study with a larger patient cohort needs to be done and to validate our findings.

Takotsubo Syndrome and Coronary Artery Disease: Which Came First-The Chicken or the Egg?

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.