Atherosclerotic Plaques In Coronary Arteries Research Articles

Coronary atherosclerosis among symptomatic patients with zero coronary artery calcium score in computed tomography coronary angiography

BackgroundComputed tomographic coronary angiography has been recognized as a reliable imaging modality with excellent negative predictive value and a good negative likelihood ratio to exclude coronary artery disease in stable, symptomatic patients with intermediate or high risk. 1) Coronary calcium scoring has been extensively shown to be an invaluable tool to exclude the presence of coronary artery disease in low-risk patients. 2) Our aim was to identify the presence and extent of coronary atherosclerosis in computed tomographic coronary angiography in stable symptomatic patients with a zero Coronary Calcium score. ResultsThree hundred and eighty-three (383) consecutive patients aged ≥ 18 years fulfilling the criteria were enrolled as of January 1, 2021; 165 (43.1%) were male and 218 (56.9%) were female, with a mean age of 57.8 ± 4.9 years and a zero coronary artery calcium score. Two hundred and twenty-six (226) (59.0%) were hypertensive, followed by 125 (32.6%) who were smokers, and 117 (30.5%) who were diabetic. The frequency of atherosclerotic plaque in coronary arteries was 34 (8.9%), with 16 (47.1%) being male and 18 (52.9%) being female. The mean age of patients with atherosclerosis was 54.9 ± 3.3 years; among them, 13 (38.2%) were between the ages of 45 and 54, and 10 (29.4%) were between the ages of 55 and 64. Nineteen (19) (55.9%) were hypertensive, followed by 10 (29.4%) with dyslipidemia. Twenty-three (23) (67.6%) had non-obstructive plaque, and 11 (32.3%) had obstructive plaque. In the subgroup of patients with non-obstructive plaque, 13 (56.5%) were hypertensive, 8 (34.8%) were diabetic, and 16 (69.6%) had single vessel disease, while among patients with obstructive plaque, 6 (54.5%) were hypertensive, 5 (45.5%) were smokers, and all of them had single vessel disease. The most affected artery was the left anterior descending artery. ConclusionAs the frequency of atherosclerotic plaque in patients with a zero coronary calcium score is relatively high, computed tomographic coronary angiography is indicated in stable, symptomatic patients with a lower likelihood of coronary artery disease.

Predictors of coronary artery calcium burden in asymptomatic patients with newly diagnosed type 2 diabetes mellitus.

Long-standing diabetes mellitus is often associated with cardiovascular complications. We aimed to evaluate the presence, extent and composition of subclinical atherosclerotic plaques in coronary arteries by Computed Tomography in patients with newly diagnosed type 2 diabetes mellitus (NDT2DM), and to identify the predictors. In this study 101 consecutive patients with NDT2DM were included. Patients were categorized into five groups based on their Coronary Artery Calcium Score (CACS) ranging from 0, 0-10, 11-100, 101-400 to >400. All parameters were compared across these groups. The average patient age was 54.4 ± 11.6years and 48 (47.5%) were females. Eight (7.9%) patients had CACS 0, 6.9% CACS 1-10, 42.6% CACS 11-100, 22.8% CACS 101-400 and 19.8% had CACS >400. Multiple regression analysis for the general data identified weight (p = .04) and systolic blood pressure (p = .033) as independent predictors for CACS. Asymptomatic patients with NDT2DM in more than 90% of cases may present with calcified atherosclerotic plaques and this may be predicted by: patient weight and the level of systolic arterial pressure. Our study emphasizes the need for comprehensive care and early prevention of cardiovascular complications in individuals with NDT2DM.

A Race Against Time: Coronary Computed Tomography Angiography Discovers a Highly Inflamed Plaque in 49-Year-Old Right Before STEMI

Abstract In the modern management of coronary artery disease (CAD), cardiac computed tomography angiography (CCTA) has emerged as a pivotal diagnostic tool, offering detailed visualization of coronary artery lumens and atherosclerotic plaques. We present the case of a 49-year-old woman, with no prior cardiovascular history but with several risk factors, in whom CCTA identified a highly inflamed atherosclerotic plaque, which led immediately to an acute myocardial infarction. Significantly, this case spotlights the vital role of perivascular inflammation mapping in CCTA, crucial for identifying high-risk plaques. The case emphasizes the necessity for a comprehensive, multifaceted diagnostic approach in the evaluation and management of CAD, incorporating advanced techniques like perivascular inflammation mapping for a more accurate and predictive assessment.

Abstract 18964: Long-Term Prognostication of Atherosclerotic Cardiovascular Disease Risk Based on the Discordance Between Coronary Artery Calcium Area and Density

Introduction and Hypothesis: Coronary artery calcium scoring is used to quantify the burden of atherosclerotic plaque in coronary arteries in patients with coronary artery disease. It is measured as a product of two variables: plaque area and density. Our study sought to evaluate the long-term prognosis of atherosclerotic cardiovascular disease (CVD) based on the discordance between these two variables. Methods: 1750 patients with a CAC score greater than 0 were enrolled in this retrospective, multicenter study. Agatston CAC score was used to quantify a lesion as the product of plaque area and a 4-level categorical peak calcium density factor. COX proportional hazards were performed for atherosclerotic CVD mortality over a median period of 5.2 years while adjusting the Agatston CAC score and other classic risk factors. Results: The mean age was 61.2 years, and 19% were female. The prevalence of plaque discordance was 23% (12% high calcium area/low calcium density, 11% low calcium area/high calcium density). Compared to those with low calcium area/low calcium density, patients with low calcium area/high calcium density had a 65% lower risk of ASCVD death (HR: 0.27 [95% CI: 0.08-0.95]). Female sex ([95% CI: 1.25-1.76]) and body mass index ([95% CI: 1.16-1.32], per 5 kg/m2 higher) were significantly associated with high calcium density discordance. Conclusions: Our study concluded that high calcium density relative to plaque area confers lower long-term ASCVD risk, likely as an imaging marker for lesion severity. Additional studies are needed to define a robust definition of calcium area/density discordance for real-life clinical risk prediction.

Association between visceral adiposity index and coronary artery calcification score and atherosclerotic plaque morphology.

The relationship between the visceral adipose index (VAI), a surrogate marker of visceral adipose tissue dysfunction, and coronary atherosclerotic plaque (CAP) morphology remains unclear. This study aimed to investigate the relationships between the VAI and the coronary artery calcification (CAC) score and CAP morphology in asymptomatic patients. We retrospectively assessed 782 patients between January 2012 and January 2020. CAC scores were determined at the threshold of 130 Hounsfield units according to the Agatston technique using 64-slice computed tomography. Patients were assigned to groups with no plaque (NP), fatty plaque (FP), calcified plaque (CP), and mixed plaque (MP). The median VAI levels were significantly different in each group (NP: 1.2 vs. FP: 1.7 vs. CP: 2.3 vs. MP: 2.8; P <0.001). An increased VAI level was an independent predictor of the CAC score. The threshold value of the VAI exhibited a gradual increase in predicting CAP morphology. VAI threshold values were >1.6 for the FP group (vs. the NP group), >2.1 for the CP group (vs. the FP group), and >2.6 for the MP group (vs. the CP group). High VAI levels independently predict an increased CAC score and CAP morphology. The VAI exhibits superior diagnostic performance in distinguishing the presence and morphology of CAP in asymptomatic patients and offers gradual cut-off values. Therefore, the VAI may be a potential screening tool for risk stratification and diagnosing CAP morphology in patients with suspected coronary artery disease.

Influenza Vaccination Decreases The Risk Of Cardiovascular Disease In End Stage Renal Disease Patients.

Madam, Influenza is a viral respiratory tract infection that causes symptoms such as fever, sore throat, cough and runny nose with a mostly self-limiting prognosis. However, it can cause an increased risk of hospitalization and mortality in high-risk groups such as those suffering from end-stage renal disease (ESRD) [1]. CVD is present in &gt;50% of cases of ESRD and is associated with a 20 times greater relative risk of death than in the general population, particularly with patients infected with influenza [2] [3]. This is due to the dysfunctional immunity in those affected by chronic kidney disease. The pathophysiology behind the influenza infection leading to CVD in ESRD patients is due to the rise of acute phase reactants in response to viral infection markers triggering a systemic inflammatory reaction. This reaction comprises damage to the endothelial cell lining of vessels, impaired vasodilation, dysfunctional platelet activation, and elevated pro-coagulation. In addition, the increased metabolic demand and altered coronary vascular tone can bring about disruption and instability of atherosclerotic plaques in coronary arteries, thus inducing an acute coronary syndrome. [1] Using influenza vaccine can significantly lower the risk of CVD in ESRD patients. Currently, available influenza vaccines include inactivated, recombinant, and live-attenuated (LAIVs).[4] Inactivated vaccines contain either surface glycoproteins such as hemagglutinin (HA) and neuraminidase (NA) or whole viral protein without the lipid envelope or chemically inactivated virus, whereas recombinant vaccines are composed of genetically synthesized HA subunits and LAIVs have the whole virus with weakened pathogenicity. These vaccines are produced as either trivalent (with both, influenza A subtypes H1N1 andH3N2 and dominant influenza B of either Yamagata or Victoria lineage) or quadrivalent (having both influenza B lineages) vaccines.[4] According to a population-based case-cohort study, annual influenza vaccinations have been seen to greatly reduce the hospitalisation rates for CVD in elderly patients with chronic kidney disease regardless of gender and influenza seasonality [5]. Moreover, it reduces the risk of CVD in patients with a hazard ratio of 0.74 for hospitalisation due to CVD among the vaccinated group compared to the non-vaccinated group, indicating a 26% lower risk and 35% reduction in overall mortality. [3] Therefore, the protective mechanism of influenza vaccination may be beneficial in reducing the risk of hospitalisations and morbidity in ESRD patients by reducing the likelihood of cardiovascular-associated complications. Thus, it should be incorporated as an integral part of the management of ESRD.

Roadmap on the use of artificial intelligence for imaging of vulnerable atherosclerotic plaque in coronary arteries.

Artificial intelligence (AI) is likely to revolutionize the way medical images are analysed and has the potential to improve the identification andanalysis of vulnerable or high-risk atherosclerotic plaques in coronary arteries, leading to advances in the treatment of coronary artery disease. However, coronary plaque analysis is challenging owing to cardiac and respiratory motion, as well as the small size of cardiovascular structures. Moreover, the analysis of coronary imaging data is time-consuming, can be performed only by clinicians with dedicated cardiovascular imaging training, and is subject to considerable interreader and intrareader variability. AI has the potential to improve the assessment of images of vulnerable plaque in coronary arteries, but requires robust development, testing and validation. Combining human expertise with AI might facilitate the reliable and valid interpretation of images obtained using CT, MRI, PET, intravascular ultrasonography and optical coherence tomography. In this Roadmap, we review existing evidence on the application of AI to the imaging of vulnerable plaque in coronary arteries and provide consensus recommendations developed by an interdisciplinary group of experts on AI and non-invasive and invasive coronary imaging. We also outline future requirements of AI technology to address bias, uncertainty, explainability and generalizability, which are all essential for the acceptance of AI and its clinical utility in handling the anticipated growing volume of coronary imaging procedures.

Predicting coronary atherosclerosis heart disease with pericoronary adipose tissue attenuation parameters based on dual-layer spectral detector computed tomography: a preliminary exploration.

Coronary atherosclerosis is a chronic inflammatory condition. Pericoronary adipose tissue (PCAT) attenuation is closely related to coronary inflammation. This study aimed to investigate the relationship between PCAT attenuation parameters and coronary atherosclerotic heart disease (CAD) using dual-layer spectral detector computed tomography (SDCT). This cross-sectional study included eligible patients who underwent coronary computed tomography angiography using SDCT at the First Affiliated Hospital of Harbin Medical University between April 2021 and September 2021. Patients were classified as CAD (with coronary artery atherosclerotic plaque) or non-CAD (without coronary artery atherosclerotic plaque). Propensity score matching was used to match the two groups. The fat attenuation index (FAI) was used to quantify PCAT attenuation. The FAI was measured on conventional images (120 kVp) and virtual monoenergetic images (VMI) by semiautomatic software. The slope of the spectral attenuation curve (λ) was calculated. Regression models were established to evaluate the predictive value of PCAT attenuation parameters for CAD. A total of 45 patients with CAD and 45 patients without CAD were enrolled. The PCAT attenuation parameters in the CAD group were significantly higher than those in the non-CAD group (all P values <0.05). The PCAT attenuation parameters of vessels with or without plaques in the CAD group were higher than those of vessels without plaques in the non-CAD group (all P values <0.05). In the CAD group, the PCAT attenuation parameters of vessels with plaques were slightly higher than those of vessels without plaques (all P values >0.05). In receiver operating characteristic curve analysis, the FAIVMI model achieved an area under the curve (AUC) of 0.8123 for discriminating between patients with and without CAD, which was higher than those of the FAI120 kVp model (AUC =0.7444) and the λ model (AUC =0.7230). However, the combined model of FAIVMI, FAI120 kVp, and λ obtained the best performance (AUC =0.8296) of all the models. PCAT attenuation parameters obtained using dual-layer SDCT can aid in distinguishing patients with and without CAD. By detecting increases in PCAT attenuation parameters, it might be possible to predict the formation of atherosclerotic plaques before they appear.

Study of associations of blood proteins with development of unstable atherosclerotic plaques in coronary arteries by quantitative proteomics

Aim. To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries in patients with coronary artery disease using the quantitative proteomic analysis.Materials and methods. The study included patients with coronary artery disease (n = 40); the average age of patients was 58 ± 7 years. Material for the study was blood serum. Protein concentrations in serum samples were determined using the PeptiQuant Plus Proteomics Kit (Cambridge Isotope Laboratories, USA). Protein fractions were identified using the liquid chromatograph and tandem mass spectrometer Q-TRAP 6500.Results. Mass spectrometry revealed an increased concentration of proteins, such as fibrinogen, fibulin-1, and complement factor H, in the serum samples of patients with unstable atherosclerotic plaques. It took place with a simultaneous decrease in the levels of α 2-antiplasmin, heparin cofactor II, coagulation factor XII, plasminogen, prothrombin, vitronectin, complement proteins (C1, C3, C7, C9), and complement factor B. The differences were considered significant at p &lt; 0.05. It was revealed that the presence of unstable atherosclerotic plaques was associated with the level of fibulin-1 (Exp(B) = 1.008; р = 0.05), plasminogen (Exp(В) = 0.995; р = 0.027), and coagulation factor X (Exp(В) = 0.973; р = 0.037).Conclusion. An increased concentration of fibulin-1 can be considered as a potential biomarker of unstable atherosclerotic plaque development in coronary artery disease. The possibility of using the studied proteins as biomarkers of unstable atherosclerotic plaques requires further studies on their potential role in the development of this disease.

Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study.

Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (β, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (β, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.

Prevalence of Microorganisms in Atherosclerotic Plaques of Coronary Arteries: A Systematic Review and Meta-Analysis.

In this systematic review and meta-analysis, the existence of pathogens in atherosclerotic plaques of coronary arteries was investigated in coronary arteries diseases (CAD) patients. This study was designed and implemented up to 31 August 2020. The findings present according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist. Two independent reviewers (I.RJ and S.H) performed a comprehensive search on four different English databases including PubMed, ISI, Scopus, and Embase. In order to assess the quality of the articles, a checklist prepared by The Joanna Briggs Institute (JBI) was used. Finally, 44 studies were selected. The prevalence of different microorganisms in coronary arteries were as follows: Aggregatibacter actinomycetemcomitans (46.2%), Campylobacter rectus (43.0%), Chlamydia pneumonia (42.8%), Cytomegalovirus (29.1%), Helicobacter pylori (18.9%), Herpes simplex virus type 1 (5.9%), Porphyromonas gingivalis (42.6%), Prevotella intermedia (47.6%), Tannerella forsythia (43.7%), and Treponema denticola (32.9%). Based on the result of this meta-analysis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans are the most common microorganisms in atherosclerotic plaques of coronary arteries and may have an important role in the development of atherosclerosis.

A Method to Study the Correlation Between Local Collagen Structure and Mechanical Properties of Atherosclerotic Plaque Fibrous Tissue.

The rupture of atherosclerotic plaques in coronary and carotid arteries is the primary cause of fatal cardiovascular events. However, the rupture mechanics of the heterogeneous, highly collagenous plaque tissue, and how this is related to the tissue's fibrous structure, are not known yet. Existing pipelines to study plaque mechanics are limited to obtaining only gross mechanical characteristics of the plaque tissue, based on the assumption of structural homogeneity of the tissue. However, fibrous plaque tissue is structurally heterogeneous, arguably mainly due to local variation in the collagen fiber architecture. The mechano-imaging pipeline described here has been developed to study the heterogeneous structural and mechanical plaque properties. In this pipeline, the tissue's local collagen architecture is characterized using multiphoton microscopy (MPM) with second-harmonic generation (SHG), and the tissue's failure behavior is characterized under uniaxial tensile testing conditions using digital image correlation (DIC) analysis. This experimental pipeline enables correlation of the local predominant angle and dispersion of collagen fiber orientation, the rupture behavior, and the strain fingerprints of the fibrous plaque tissue. The obtained knowledge is key to better understand, predict, and prevent atherosclerotic plaque rupture events.

Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy.

We report that people with human immunodeficiency virus (HIV) diagnosed with coronary artery atherosclerotic plaques display higher levels of HIV DNA compared with those without atherosclerotic plaques. In a multivariable prediction model that included 27 traditional and HIV-related risk factors, measures of HIV DNA were among the most important predictors of atherosclerotic plaque formation.

Association between triglyceride glucose index and atherosclerotic plaques and Burden: findings from a community-based study

BackgroundInsulin resistance is an important cause of cardiovascular events and cerebral infarction development. We aimed to investigate the association of the triglyceride glucose (TyG) index with atherosclerotic burden and plaques in coronary, intra- and extracranial arteries in participants with non-diabetes, and compared the results with that of the homeostasis model assessment of insulin resistance (HOMA-IR).MethodsParticipants without diabetes in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were included. We categorized participants by tertiles of the TyG index and the concordance/discordance of the TyG index and HOMA-IR. Discordance was defined as a TyG index equal to or greater than the median and HOMA-IR less than the median, or vice versa. The atherosclerosis plaques and burden in coronary, intra- and extracranial arteries were evaluated. The association of HOMA-IR and TyG index with the presence of atherosclerotic plaques and atherosclerotic burden was assessed by binary and ordinal logistic regression models, respectively.ResultsAmong 2,719 included participants, the average age was 60.9 (± 6.6) years, and 53.0% were female. Both TyG index and HOMA-IR were associated with increased odds of coronary/intra- and extracranial atherosclerotic plaques and burden after adjustment for age, sex, currenting smoking and drinking (all P < 0.05). However, the association between HOMA-IR and intracranial atherosclerosis was not statistically significant after adjustment for all potential confounders. Discordantly high TyG index with HOMA-IR had a higher odd of extracranial plaque (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.04–1.71), extracranial atherosclerotic burden (common odds ratio [cOR]: 1.35, 95% CI 1.06–1.71), coronary plaque (OR: 1.30, 95% CI 1.01–1.68) and segment stenosis score (cOR: 1.39, 95% CI 1.09–1.78) as compared with concordantly low TyG index with HOMA-IR. The TyG index had a better net reclassification improvement ability than HOMA-IR for atherosclerotic plaques when adding to baseline model.ConclusionElevated TyG index was associated with increased odds of atherosclerosis in coronary/intra- and extracranial arteries. Compared with HOMA-IR, the TyG index was more strongly associated with intracranial atherosclerosis. Moreover, discordantly high TyG index with HOMA-IR was also important for atherosclerosis identification.

THE COMPLEX RELATIONSHIP OF PARAOXONASE GENE POLYMORPHISMS WITH CORONARY ARTERY DISEASE AND LIPID METABOLISM

Cardiovascular disorder (CVD) is one of the major reasons for mortality in developing and developed countries. According to the World Health Organization (WHO), non-communicable diseases (NCDs) are responsible for 50% of the overall disease burden in Pakistan. And among the NCDs, the most prevalent disease is CVD, as approximately every 1 out of 4 adults suffered from coronary artery disease (CAD). Coronary artery disease mainly causes ischemia or hypoxia of the heart due to coronary vessels stenosis or atherosclerosis.1 The key risk factors include smoking, dyslipidemia, hypertension, obesity, family history, and type 2 diabetes mellitus. The genetic contribution to CAD is an independent factor that includes genetic polymorphisms such as single nucleotide polymorphisms (SNPs). Genome-wide association studies (GWAS) suggest many genes SNPs involved in the pathogenesis of coronary artery disease.2 Although many studies identified the genes and single nucleotide polymorphisms but still, the role of these genetic factors is not clearly understood. Paraoxonase (PON) gene cluster is one of the most widely studied genes that consist of three genes PON1, PON2, and PON3, and located on chromosome 7. The PON2 is the oldest gene among this cluster however, all the 3 genes have a high structural homology. The International Union of Biochemistry and Molecular Biology classified the paraoxonases as aryldialkyl phosphatases. The enzymes coded by these gene clusters exhibit the antiatherosclerotic properties that play an essential role in high-density lipoproteins (HDL) or antioxidant properties. The PON1 activity is highly influenced by both genetic (non-modifiable) and environmental factors (modifiable).3 It involves a complex interaction between both genetic and modifiable factors. The human PON1 is a calcium-dependent glycoprotein that is first identified by its ability to hydrolyze various organophosphates. Through lipid peroxides hydrolysis, it reduces the low-density lipoprotein (LDL). Low enzyme levels are associated with cardiac disorders, familial hypercholesterolemia, and diabetes mellitus. To date, approximately 184 SNPs reported, and some coding region SNPs i.e. rs662 and rs854560 are the most widely studied single nucleotide polymorphisms.4 The most commonly studied Q192R polymorphism is associated with poor patient outcomes. The risk allele or R allele is associated with abnormal HDL and triglycerides levels and the worst CVD outcome. Furthermore, the levels of paraoxonase levels are also decreased in CVD patients and there is a complex relationship between different variables particularly genetic markers, lipid profile, or environmental factors with PON activity.5 The PON2 and PON3 similarly play a crucial role in lipid metabolism and inhibit atherosclerosis due to their protective role against the formation of atherosclerotic plaques in coronary arteries. In PON2 rs12704796 is significantly associated with coronary heart disease risk.6 Robertson et al. first reported single nucleotide polymorphism in PON3 at positions number 107 and 99 but the exact mechanism of these SNPs in the pathophysiology of CAD remains to be understood.7 The multi-locus model also revealed a gene to gene interaction between PON2 and PON3 and gene-environment in the Pakistani cardiac patients.8 The single nucleotide polymorphisms in this gene cluster are significantly important in CAD patients. These SNPs may exert their effect by modulating the lipid metabolism and enzyme concentrations in CAD patients, which can be varied according to certain environmental factors and ethnic groups. Thus, in the future, it is suggested to perform a study with more sample size in different populations that can help us in better understanding disease pathophysiology and prevention.

Growth differentiation factor-15 as a biomarker of atherosclerotic coronary plaque: Value in people living with and without HIV.

BackgroundIncreased rates of cardiovascular diseases (CVD) and larger subclinical high-risk coronary plaques in coronary CT angiography have been observed in people living with HIV (PLWH) treated with antiretroviral therapy (ART) compared to HIV-uninfected people. Growth differentiation factor-15 (GDF-15) is a cytokine emerging as an optimal marker for CVD in the general population.MethodsWe cross-sectionally analyzed plasma of 95 PLWH on ART and 52 controls. We measured GDF-15, fibroblast growth factor-21 (FGF-21), glucagon-like peptide-2 (GLP-2), soluble urokinase plasminogen activator receptor (suPAR), CRP, and anti-CMV and anti-EBV IgG levels. All participants had no clinical CVD and underwent coronary CT angiography with the 3D reconstruction of coronary artery atherosclerotic plaques. Total plaque volume (TPV) and low attenuation plaque volume (LAPV, defined as density <30 Hounsfield Units) were calculated (mm3).ResultsIn both PLWH and controls, GDF-15 levels were increased in participants with presence of coronary plaque vs. without (p = 0.04 and p < 0.001, respectively) and correlated with TPV (r = 0.27, p = 0.009 and r = 0.62, p < 0.001, respectively) and LAPV (r = 0.28, p = 0.008, r = 0.60, p < 0.001, respectively). However, in a multivariate model, GDF-15 was independently associated with LAPV in controls only (adjusted OR 35.1, p = 0.04) and not in PLWH, mainly due to confounding by smoking. Other markers were not independently associated with plaque volume, except for anti-EBV IgGs in controls (adjusted OR 3.51, p = 0.02).ConclusionIn PLWH, GDF-15 and smoking seemed to synergistically contribute to coronary plaque volume. Conversely, increased GDF-15 levels were associated with the presence of coronary artery plaques in people without HIV, independently of CV risk factors.

Intravascular molecular imaging: translating pathophysiology of atherosclerosis into human disease conditions.

Progression of atherosclerotic plaque in coronary arteries is characterized by complex cellular and non-cellular molecular interactions. Within recent years, atherosclerosis has been recognized as inflammation-driven disease condition, where progressive stages are characterized by morphological changes in plaque composition but also relevant molecular processes resulting in increased plaque vulnerability. While existing intravascular imaging modalities are able to resolve key morphological features during plaque progression, they lack capability to characterize the molecular profile of advanced atherosclerotic plaque. Because hybrid imaging modalities may provide incremental information related to plaque biology, they are expected to provide synergistic effects in detecting high risk patients and lesions. The aim of this article is to review existing literature on intravascular molecular imaging approaches, and to provide clinically oriented proposals of their application. In addition, we assembled an overview of future developments in this field geared towards detection of patients at risk for cardiovascular events.

Coronary Artery Embolism: a Rare Cause of ST Segment Elevation Myocardial Infarction

Acute myocardial infarction (AMI) is a fatal clinical disease, and is often caused by thrombotic occlusion, secondary to coronary artery atherosclerotic plaque erosion or rupture [1]. But about 1-14% of AMI is caused by myocardial infarction with non-obstructive coronary atherosclerosis (MINOCA [2], which is characterized by evidence of myocardial infarction, normal coronary angiography or coronary artery stenosis of &lt;50&gt;]. The causes of MINOCA vary from person to person [4], such as coronary artery spasm [5], Stress cardiomyopathy [6], Thrombophilia [7], coronary artery embolism(CE) [8,9]. CE is a rare cause of AMI in clinical practice. We had presented a female patient who had left anterior descending artery embolism, with dilated cardiomyopathy and paroxysmal atrial flutter [10]. CE, while rare, is now recognized as an important non-atherosclerotic cause of AMI. In the past, the description of clinical features about CE was little or just case reports [8-9]. A recent study involving 1776 patients evaluated the clinical features of CE-related myocardial infarction. It is pointed out that the prevalence rate is 2.9% in the initial AMI. and atrial fibrillation is the most important cause of CE (73%). Other causes include cardiomyopathy and valvular heart disease. And proposed CE diagnostic criteria [11]. In recent years, thrombus aspiration devices have been widely used in AMI patients with angiographically confirmed thrombosis and have proved to be a viable and effective strategy for the treatment of thrombotically burdened AMI, including CE-related infarction. Moreover, histological examination of aspiration thrombus provides additional information for the diagnosis of CE. Although thrombus aspiration is an effective method for treating patients with CE, Stoel et al [12] reported that the diameter of the lumen of the aspiration catheter is small and useless for aspirating large thrombi. In addition, it is challenging to access to the distal lumen through the suction device. In fact, 42% of existing patients are treated conservatively because of distal occlusion or small vessel with a criminal lesion. The treatment of CE-related risk factors is also very important. Including atrial fibrillation, cardiomyopathy, rheumatic heart valve disease, prosthetic heart valve, patent foramen ovale, atrial septal defect, history of cardiac surgery, infective endocarditis or hypercoagulable state. The patient in this case was dilated cardiomyopathy with paroxysmal atrial flutter, both of which were high risk for CE. She had chest pain, typical changes in the ECG, coronary angiography revealed coronary embolization of the LAD. that are consistent with acute myocardial infarction. Intravascular ultrasound (IVUS) or optical coherence Tomography (OCT) is an effective method to detect the atherosclerotic plaque erosion or rupture of coronary artery. This patient was proved to be CE by IVUS. It is very important to given sufficient anticoagulant therapy to prevent CE in clinical practice.

Helical Flow in Healthy and Diseased Patient-specific Coronary Bifurcations.

Helical flow (HF) exists in healthy and diseased coronary bifurcations and was found to have a protective atherosclerotic vascular effect in other vessels. However, the role of HF in patient-specific human coronary arteries still needs further study, and is therefore the objective of this study in both healthy and diseased bifurcations. Computational studies were conducted on 16 patient-specific coronary bifurcations, including eight healthy and eight identical cases with idealized narrowing to represent disease. In general, higher HF intensity may have a favorable effect as it corelated to the reduction of the percentage vessel area exposed to adverse time averaged wall shear stress (TAWSS%) in both healthy and diseased models. The HF intensity and distribution of each model varies due to the complex shape of patient-specific models. The presence of disease appears to have an important impact on the downstream HF patterns and the TAWSS distributions. Clinical Relevance- By understanding the relationship between HF and hemodynamics, HF may be used as a predictor for the formation and progression of atherosclerotic plaque in coronary arteries instead of near-wall WSS measures, which can be determined with higher accuracy in vivo.

Uncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factors

Endothelial dysfunction (ED) is a hallmark of atherosclerosis and is influenced by well-defined risk factors, including hypoxia, dyslipidemia, inflammation, and oscillatory flow. However, the individual and combined contributions to the molecular underpinnings of ED remain elusive. We used global gene expression in human coronary artery endothelial cells to identify gene pathways and cellular processes in response to chemical hypoxia, oxidized lipids, IL-1β induced inflammation, oscillatory flow, and these combined stimuli. We found that clustering of the surrogate risk factors differed from the sum of the individual insults that gave rise to emergent phenotypes such as cell proliferation. We validated these observations in samples of human coronary artery atherosclerotic plaques analyzed using single-cell RNA sequencing. Our findings suggest a hierarchical interaction between surrogates of CV risk factors and the advent of emergent phenotypes in response to combined stimulation in endothelial cells that may influence ED.