Atherosclerotic Coronary Artery 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.

Vitamin-K antagonist versus dual antiplatelet therapy in management of isolated and non-obstructive atherosclerotic coronary artery ectasia

BackgroundTreatment of isolated and non-obstructive atherosclerotic coronary artery ectasia (CAE) is still controversial. AimTo assess the efficacy and safety of vitamin-K antagonist (VKA) versus dual antiplatelet (DAPT) therapy in management of patients with isolated and non-obstructive atherosclerotic CAE. MethodsWe prospectively enrolled 79 patients diagnosed on elective coronary angiography to have either isolated CAE or non-obstructive atherosclerotic CAE. Patients were assigned in 1:1 pattern to receive either VKA (warfarin) or DAPT (aspirin plus clopidogrel). Patients were followed-up for nine-months. The primary endpoint was the cumulative events rate including acute coronary event, target vessel intervention, or cardiac death. Analysis of cumulative events at different time intervals, its individual components, and bleeding were considered secondary endpoints. ResultsCumulative events rate was 33%, with mortality rate of 2.5%. Both treatment groups showed comparable cumulative events during the nine-months follow-up duration. Nevertheless, Kaplan-Meier analysis beyond the first 3-months of follow-up showed significantly higher event-free survival among the VKA-group. Recurrent events (≥2) were significantly higher among the DAPT-group. Both groups showed no major bleeding events. Multivariable cox-regression analysis showed that presence of significant coronary tortuosity, use of DAPT in reference to VKA, and lower percent time in therapeutic range (%TTR) among those receiving VKA were significant independent predictors of clinical adverse events beyond the first 3-months of follow-up. ConclusionCumulative adverse events were comparable among both treatment groups for isolated non-obstructive CAE. However, adverse events were significantly more frequent in the DAPT-group beyond the first three months.

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.

Integrating Computational and Biological Hemodynamic Approaches to Improve Modeling of Atherosclerotic Arteries.

Atherosclerosis is the primary cause of cardiovascular disease, resulting in mortality, elevated healthcare costs, diminished productivity, and reduced quality of life for individuals and their communities. This is exacerbated by the limited understanding of its underlying causes and limitations in current therapeutic interventions, highlighting the need for sophisticated models of atherosclerosis. This review critically evaluates the computational and biological models of atherosclerosis, focusing on the study of hemodynamics in atherosclerotic coronary arteries. Computational models account for the geometrical complexities and hemodynamics of the blood vessels and stenoses, but they fail to capture the complex biological processes involved in atherosclerosis. Different in vitro and in vivo biological models can capture aspects of the biological complexity of healthy and stenosed vessels, but rarely mimic the human anatomy and physiological hemodynamics, and require significantly more time, cost, and resources. Therefore, emerging strategies are examined that integrate computational and biological models, and the potential of advances in imaging, biofabrication, and machine learning is explored in developing more effective models of atherosclerosis.

Coronary Plaque in People With HIV vs Non-HIV Asymptomatic Community and Symptomatic Higher-Risk Populations

BackgroundPeople with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification. ObjectivesThe purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH. MethodsNonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence. ResultsCompared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 years vs 57.3 ± 4.3 years and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001). ConclusionsAsymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.

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.

The Role of Fatty Acid Synthase in the Vascular Smooth Muscle Cell to Foam Cell Transition.

Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells-lipid-laden, macrophage-like cells pivotal in atherosclerotic plaque formation. CHO uptake by VSMCs leads to two primary pathways: ABCA1-mediated efflux or storage in lipid droplets as cholesterol esters (CEs). CE formation, involving the condensation of free CHO and fatty acids, is catalyzed by sterol O-acyltransferase 1 (SOAT1). The necessary fatty acids are synthesized by the lipogenic enzyme fatty acid synthase (FASN), which we found to be upregulated in atherosclerotic human coronary arteries. This observation led us to hypothesize that FASN-mediated fatty acid biosynthesis is crucial in the transformation of VSMCs into foam cells. Our study reveals that CHO treatment upregulates FASN in human aortic SMCs, concurrent with increased expression of CD68 and upregulation of KLF4, markers associated with the foam cell transition. Crucially, downregulation of FASN inhibits the CHO-induced upregulation of CD68 and KLF4 in VSMCs. Additionally, FASN-deficient VSMCs exhibit hindered lipid accumulation and an impaired transition to the foam cell phenotype following CHO exposure, while the addition of the fatty acid palmitate, the main FASN product, exacerbates this transition. FASN-deficient cells also show decreased SOAT1 expression and elevated ABCA1. Notably, similar effects are observed in KLF4-deficient cells. Our findings demonstrate that FASN plays an essential role in the CHO-induced upregulation of KLF4 and the VSMC to foam cell transition and suggest that targeting FASN could be a novel therapeutic strategy to regulate VSMC phenotypic modulation.

Internal Mammary Artery Graft Flow Steal by a Large Dialysis Arteriovenous Fistula Characterized by Electrical Storm

Background: Steal syndrome describes a condition in which a dilated vessel distal to a smaller artery attempts to compensate for decreased blood flow by “stealing” from the smaller artery. Steal syndrome is not uncommon and can be seen in certain physiologic and pathologic states. The classic example is an occluded atherosclerotic coronary artery resulting in a misdirection of blood flow into the open channels that have developed over time resulting in downstream ischemia. Case Report: A 66-year-old male fourteen years post 4-vessel coronary artery bypass grafting using his left internal mammary artery to bypass a stenotic segment of the left anterior descending artery, along with three saphenous venous conduits to the right coronary artery. He also had a stent placement by PCI. He was on dual antiplatelet therapy with aspirin and clopidogrel. An electrophysiology study revealed inducible VF and he underwent implantation of a dual chamber ICD 9 months prior to presentation. He experienced an unprovoked fall at home and a workup revealed the flow volume through the patient’s fistula increased to such a degree that the patient developed a steal syndrome from his left internal mammary artery graft. In addition, went into a state of electrical storm caused by ischemic damage to cardiac tissue distal to the graft. By ligating the fistula, the patient’s steal syndrome resolved and he did not suffer further ventricular arrhythmias. Conclusion: Both coronary bypass grafting and fistula formation are common and necessary interventions and providers should take care to monitor for interactions between these proposed interventions to best serve their patients without causing additional harm. Increased vascular flow through any portion of the body can induce a steal syndrome from an upstream region. Patients who undergo arteriovenous (AV) fistula placement may develop a steal syndrome from ipsilateral bypass grafts.

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.