CAD Patients Research Articles

Association of ANGPTL8 gene polymorphism with the occurrence of coronary artery disease in Iraqi patients

OBJECTIVE: It has been shown that ANGPTL8 controls the metabolism of fatty acids and triglycerides (TG). Reduced adipogenesis, which was defined by decreased TG, was linked to decreased ANGPTL8. The aim of the present study was to evaluate the association of ANGPTL8 gene polymorphism with the occurrence of coronary artery disease in Iraqi population. RESEARCH DESIGN AND METHODS: two hundred coronary artery disease patients with >70 blockage coronary artery as well as to 200 apparently individuals who were diagnosed as negative findings by coronary angiography (Control group) were investigated for several biochemical parameters as well as genotyping for rs892066 and rs2278426 of ANGPTL8 gene SNPs by ARM-PCR technique. RESULTS: The examinations of rs892066 approved significant varaition after the adjustment for age and sex under the codominant model in heterozygous genotype, and under the dominant model the GG+CG genotype in patients group was be higher than of control group. The assessment of the minor allele frequency (G) approved the association of rs892066 in the occurrence of CAD. Along with the most recent outcomes, Multinominal logistic regression analysis was used to analyze the genotype and allele frequencies of the rs2278426 ANGPTL8 gene polymorphism in CAD and control individuals under the codominant, dominant, recessive, and overdominant models. The examinations failed to explore significant varaition after the adjustment for age, sex and BMI and smoking status. The assessment of the minor allel frequency (T) indicated that no association between presence minor allel frequency (T) in CAD patients and the control group. CONCLUSIONS: SNP rs892066 may play unique role in the occurrence of CAD while rs2278426 of ANGPTL8 genes are not associated with CAD in Iraqi patients.

Incidence and Outcome Predictors in the Treatment of In-Stent Restenosis with Drug-Eluting Ballons

Background and Aim: In-stent restenosis (ISR) in coronary artery disease patients can be effectively treated with drug-eluting ballons (DEB). Yet, the prevalence and binary restenosis related factors have not been assessed in the past. The present study intended to determine the incidence and outcome predictors in drug-eluting ballons treatment of in-stent restenosis. Methods: This retrospective study was carried out on 152 coronary artery disease patients in Punjab Institute of Cardiology, Lahore from January 2021 to July 2022. Prior to study conduction, the research and ethical committees approved the procedure. Patient’s demographic details, clinical characteristics, laboratory tests, and lesion features were recorded. Data analysis was done in SPSS version 26. Results: Of the total CAD patients, 110 (72.4%) were male and 42 (27.6%) were females. The overall mean age was 56.82±4.56 years. The prevalence of different risk factors for cardiovascular disease such as diabetes, hypertension, smoking, LDL >1.40 mmol/l, and family history was 82 (53.9%), 94 (61.8%), 92 (60.5%), 64 (42.1%), and 16 (10.5%) respectively. Other comorbidities such as chronic kidney disease and heart failure were present in 58 (38.2%) and 12 (7.9%) respectively. High-dose statin therapy was given to 40 (26.3%) patients. The occurrence of MACEs, myocardial infarction, targeted vessel revascularization (TVR), and target lesion revascularization (TLR) during follow-up was 56 (36.8%), 40 (26.3%), 10 (6.6%), and 33 (21.7%) respectively. The mortality rate was 13 (8.6%). Multivariate logistic regression were used to identify the independent factors such as diffuse ISR [OR=2.21: CI 95%, (1.2-1.76), stents ≥2 per lesion [OR=1.78; 95% CI (1.12-2.19)], proximal left anterior descending artery [OR=1.31; 95% CI (1.2-1.76)], and triple vessel disease [OR=2.87, 95% CI (1.1-6.3), p=0.005)]. Conclusion: The present study concluded that In-stent restenosis is a coronary angioplasty serious complication with adverse outcomes. For in-stent restenosis, drug-eluting balloons are an effective alternative to stenting. MACE was shown to be prevalent in our data. MACE is a measure of all-cause mortality in a high-risk group and demonstrates that DEB provides both short-term and long-term advantages in ISR. Keywords: In-stent restenosis, Drug-eluting ballons, Predictor outcomes.

Circulating Soluble TREM2 and Cardiovascular Outcome in Cohort Study of Coronary Atherosclerosis Patients.

Triggering Receptor Expressed in Myeloid Cells 2 (TREM2) is a membrane receptor in myeloid cells that mediates cellular phagocytosis and inflammation. TREM2 and its soluble extracellular domain are clearly implicated in neuroinflammation and neurodegeneration. sTREM2 is also expressed in atherosclerotic macrophages. We hypothesized that sTREM2 would predict cardiovascular mortality in patients with established coronary atherosclerosis (CAD). Consecutive patients undergoing coronary angiography with the establishment of the diagnosis of CAD (n = 230) and without CAD (n = 53) were tested for their baseline serum sTREM2 levels. All patients were followed up for 84 months or until death occurred. sTREM2 correlated with age; however, no association was found between sTREM2 and the number of atherosclerotic vessels involved (p = 0.642). After 84 months of follow-up, 68 out of the 230 CAD patients had died. After adjusting for age and other risk factors, the adjusted hazard ratio for the highest quartile of sTREM2 was 2.37 (95% confidence interval 1.17-4.83) for death. In patients with established CAD, serum sTREM2 appears to predict cardiovascular death as a potential surrogate for plaque rupture. TREM2 and its soluble extracellular form might be implicated in the fate of the atherosclerotic plaque, but corroboration within larger studies is needed.

Prior activation of social work team process by pre-admission one-click automatic referral system

Abstract Background Coronary artery disease (CAD) is the leading global cause of mortality. Coronary angiography (CAG) is often performed for CAD patients, and the mean length of stay (LoS) is 4 d. Requests to the social work team (SWT) are often delayed until just before discharge, causing unnecessarily prolonged LoS and reduced chances of obtaining financial support. If the SWT’s support system is activated beforehand for scheduled CAGs, the LoS would be shorter and patients would be relieved of emotional and financial burdens. Methods Collaborating with the cardiology and medical informatics departments, a one-click automatic referral system (OARS) was set up (January-May 2021). When cardiologists scheduled a CAG in the outpatient department, an OARS cue popped automatically for the medical aid recipients. The cardiologists could also activate the pre-admission OARS for other patients when necessary. Subsequently, the SWT responded on that day to discuss initiating the financial support process with the candidates. The rate of cardiologists’ pre-admission referral to SWT, decision-making time on financial support provision, and proportion of patients receiving financial support were compared before and after initiating OARS. Results After initiating pre-admission OARS, the rate of cardiologists’ pre-admission referral to SWT increased from 17.8% (18/101: mean age, 64.6±12.0 y; 32 females; January-December 2020) to 59.1% (55/93: mean age, 64.0±11.8 y; 29 females; June-December 2021) (p < 0.001). Although the decision-making time to provide financial support did not change significantly (8.4±11.1 vs. 4.7±11.6 d; p = 0.96), the proportion of patients receiving financial support increased (45.5% [46/101] vs. 60.2% [56/93]; p = 0.045). Conclusions By enhancing the cardiologists’ pre-admission referral to SWT and success rate of receiving financial support, the proactive strategy of pre-admission OARS benefits CAD patients scheduled for CAG. Key messages • By building a proactive referral strategy of pre-admission OARS, more CAD patients scheduled for CAG could obtain timely financial support and be relieved both emotionally and financially by the SWT. • This pre-admission OARS might be incorporated for more disease entities for patients in need.

Feasibility and impact of whole-body high-intensity interval training in patients with stable coronary artery disease: a randomised controlled trial

Exercise training reduces cardiovascular mortality and improves quality of life in CAD patients. We investigated the feasibility and impact of 12 weeks of low-volume high-intensity interval training (HIIT) in CAD-patients. Patients with stable CAD were randomized 1:1 to supervised HIIT or standard care. HIIT sessions were completed three times weekly for 12 weeks on a rowing ergometer. Before and after the 12-week intervention, patients completed a physiological evaluation of cardiorespiratory performance and quality of life questionnaires. Mixed model analysis was used to evaluate differences between and within groups. A total of 142 patients (67 ± 9 years, nHIIT = 64, nStandard care = 78) completed the trial. Training adherence was 97% (range 86–100%). Six patients dropped out because of non-fatal adverse events. Weekly training duration was 54 min with an average power output of 138 W. HIIT increased peak oxygen uptake by 2.5 mL/kg/min (95% CI 2.1–3.0), whereas no change was observed in standard care (0.2 mL/kg/min, 95% CI − 0.2–0.6, P < 0.001). In addition, HIIT improved markers of quality of life, including physical functioning, limitations due to physical illness, general health and vitality (P < 0.05). Twelve weeks of low-volume whole-body HIIT increased cardiorespiratory capacity and improved quality of life in patients with stable CAD compared to standard care. In addition, our study demonstrates that the applied vigorous training regime is feasible for this patient group.Clinical trial registration:www.clinicaltrials.gov. Identification number: NCT04268992.

Role of miRNA-27a and miRNA-224 in posttranscriptional regulation of PCSK9 gene in Iraqi patient with coronary artery disease

AimThe aim of this study was to assess miRNA-27a and miRNA-224 expression levels in the blood samples from CAD patients and their role in the regulation of Proprotein Convertase Subtilisin/Kexin Type 9 Gene (PCSK9) expression. MethodsThis case-control study included (150) participants ranged in age from 30 to 65 years old, both male and female. Patients with atherosclerosis (n = 100) were chosen based on the clinical appearance of atherosclerotic coronary artery disease (ASCAD), as well as a medical and physical examination and documentation via coronary angiography, while the healthy group (n = 50) were chosen at random, and the health questionnaire and clinical examination revealed no signs of cardiovascular disease (CVD). For estimation of the expression levels of PCSK9, MiRNA-27a, and MiRNA-224 genes utilize reverse transcription-quantitative polymerase chain reaction (qRT-PCR) method was used. ResultsA current study found miRNA-27a gene expression level was 5.01 ± 0.75 in the ASCAD patients group based on 2-∆∆Ct and 1.00 ± 0.58 in the healthy control group, while miRNA-224 gene expression level of two study groups was 0.31 ± 0.15 vs 1.00 ± 0.58. In addition, analysis of PCSK9 expression level indicated that was 6.06 ± 1.84 in patient group and 1.00 ± 0.19 in healthy control group. ConclusionsThe fact that miRNA-27a and PCSK9 gene expression levels increased while miRNA-224 gene expression levels decreased indicated they have opposite activity in the development of CAD.

Lipoprotein(a) and cardiovascular outcomes in patients with coronary artery disease and impaired glucose metabolism

Abstract Introduction Lipoprotein(a) [Lp(a)] is an LDL-like molecule composed of a part of apolipoprotein(a) bounding covalently to apolipoprotein B-100. High plasma Lp(a) levels were associated with MACE in stable CAD patients. Recent research shows contradictory results in stable CAD patients with high Lp(a) plasmatic levels and impaired glucose metabolism in MACE occurrence. Purpose Investigate whether high Lp(a) levels were associated with MACE in CAD patients with impaired glucose metabolism, at an extended follow-up. Methods A prospective cohort of 1,127 CAD patients with impaired glucose metabolism (pre-diabetes and diabetes) was observed during 4.9±3.4 years. Pre-diabetes was considered when fasting plasma glucose ranged from 5.6 to 6.9 mmol/L, or hemoglobin A1c levels ranging from 5.7 to 6.4%. Lp(a) levels ≥30 mg/dL were considered high. Bivariate and multivariate Cox regression analysis evaluated the risk of Lp(a) ≥30 mg/dL for MACE occurrence. Kaplan-Meier curves estimated the survival probability for high and low Lp(a) levels. Results Of the patients with Lp(a) levels ≥30, 44.4% presented MACE and 32.0% had no MACE (p&amp;lt;0.0001). Cox regression analysis with smoking, hypertension, dyslipidemia, physical inactivity and kidney failure (creatinine clearance &amp;lt;60 mL/min) showed that high Lp(a) remained in the equation as an independent risk factor for MACE (HR=1.24; p=0.031). The Kaplan-Meier showed, at 10-year' follow-up, a better survival in the group with lower Lp(a) levels (p=0.023). Conclusion Our study demonstrated that high Lp(a) levels were an independent predictor of MACE and cardiovascular mortality in a CAD population with impaired glucose metabolism. Lp(a) measurement may help further risk stratification for diabetes and pre-diabetes patients suffering CAD. With the recent development of drugs that selectively lower Lp(a) levels, this marker can become a clinical target for reducing CVD risk. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM

Defining patients needs and expectations for eHealth-based cardiac rehabilitation in Germany and Spain: living lab data from the TIMELY study

Abstract Background eHealth innovations have set the stage to optimize personalized care and provide assistance for disease control to patients with CAD. TIMELY is the first artificial intelligence (AI)-driven eHealth approach that employs internet of things devices and is based on cardiac rehabilitation (CR) components. To guarantee acceptance and usability of eHealth solutions, patients are actively participating in development through a Living Lab approach. Purpose To define patients' needs for an eHealth-based lifestyle intervention and self-care support. Methods The Living Lab approach included a guided survey conducted among CAD patients at CR centers in Germany and Spain during inpatient or outpatient CR, respectively. Questions referred to current use of technology and patients' opinion on the usefulness of suggested features of a future eHealth application. Ratings for usefulness/importance were recorded on a 5-point Likert scale reported as median score. Results 79 patients (20% female) were interviewed (DE, n=49; ES, n=30). Patients' mean age was 57 years (range 37–79), educational level was 87% ≤ high school and 13% &amp;gt; high school. All patients owned a smartphone that they also used for information (76%) and documentation (43%). Patients rated the importance of all CR components (regular exercise, healthy diet, stress management, smoking cessation, risk factor reduction) along the continuum of care as “very high” (5/5). Individual need for regular exercise support after structured CR was rated “high” (4/5). Exercise reminders, suggestions on activities, update of recommended training heart rate, evaluation of training progress, and achieved goals were rated “useful” (4/5) to “very useful” (5/5). The importance of support for diet, stress management, overall risk factor management, and medication was rated 3/5. Usefulness of a learning/education tool was rated 4/5, while motivational messages scored 3/5 and individual feedback of a person or virtual agent scored 4/5 and 3/5, respectively. The availability of electronic health records was evaluated as “very useful” (5/5) remote ECG monitoring and blood pressure management were rated as “useful” (4/5). The range of all items accessed was 1–5, indicating large interindividual differences. No significant differences existed between female and male patients or German and Spanish patients, though the importance of sharing training progress with family/ friends was rated higher by men (3/5) compared to women (1/5) and higher by Spanish (4/5) compared to German patients (2/5). Conclusions CR patients expressed a strong need for individual support of regular physical exercise and updated training recommendations. The observed inter-individual differences regarding usefulness and acceptance indicate the need for a highly adaptive system to prevent exclusion from eHealth access. CR patients from Germany and Spain showed equally high acceptance of eHealth components for the management of CAD. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission Horizon 2020

ZNF259 rs964184 variant is associated with dyslipidemia and coronary artery disease in the young population

Abstract Introduction Coronary artery disease (CAD) is a dynamic inflammatory disease caused by atherosclerosis. GWAS showed that ZNF259 rs964184 encoding zinc finger protein (ZPR1) was associated with dyslipidemia and CAD. Recent research found that ZPR1 transcription is up-regulated in the brain of mice fed a high-fat diet, influencing the cell cycle, apoptosis, and RNA metabolism in neurons. This process at the heart vessels may increase oxidative stress and CAD. Purpose Study the association between the ZNF259 rs964184 C&amp;gt;G polymorphism with dyslipidemia and CAD susceptibility in a Portuguese population. Methods A case-control study was performed with 3,160 individuals, namely 1,723 CAD patients (mean age 53.3±7.9; 78.7% male) and 1,437 controls (mean age 52.8±7.8; 76.3% male). Participants were stratified into two age groups (&amp;lt;45 and &amp;gt;55 years). ZNF259 rs964184 C&amp;gt;G was genotyped and analysed using the dominant model (CG+GG vs CC). Multivariate logistic regression was performed in both age groups to investigate whether rs964184 polymorphism was associated with dyslipidemia and CAD susceptibility. Results The dominant model of ZNF259 was associated with dyslipidemia (OR=1.85; 95% CI: 1.22–2.79; p=0.003) and CAD (OR=1.46; 95% CI: 1.02–2.09; p=0.036) in the younger population under 45 years. In the &amp;gt;55 years group, this model was associated with dyslipidemia (OR 1.46; 95% CI: 1.06–2.01; p=0.020) but not with CAD. After multivariate logistic regression, the CG+GG remained an independent risk factor for CAD susceptibility only in the population &amp;lt;45 years (OR=1.60; 95% CI: 1.03–2.50; p=0.037). Conclusion ZNF259 rs964184 is a risk factor for dyslipidemia in the whole population. Dyslipidemia may up-regulate ZPR1 transcription, enhancing the vulnerability of coronary endothelial cells to both oxidative stress and inflammatory response, increasing CAD susceptibility. This mechanism seems more relevant at the cellular level in young patients representing a possible prophylactic and therapeutic target, especially in this age group. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM

RNA-sequencing reveals significant differences in the inflammatory response of iPSC-derived endothelial cells from ACS patients and healthy controls

Abstract Background Coronary artery disease (CAD) and cardiovascular diseases (CVD) in general still represent the leading cause of death worldwide. As a multifactorial disease entity, genetic predisposition and lifestyle strongly impact disease development and progression. Here, induced pluripotent stem cells (iPSC) are an ideal tool to differentiate (epi-)genetic from lifestyle disease risk modulation and identify the underlying molecular mechanisms. Aim This study aims to determine differences in iPSC-derived endothelial cell (iPSC-EC) characteristics and functionality between healthy donors and high-risk CAD patients. Methods IPSC from participants with similar lifestyle but different disease status (healthy &amp;gt;65 y/o, n=5, acute coronary syndrome (ACS) &amp;lt;65y/o, n=6) were differentiated into iPSC-EC. Cells were exposed to inflammatory stimulation with tumour necrosis factor alpha (TNF-a) followed by bulk RNA-seq. Monocyte (THP-1) recruitment was assessed under protective and atherogenic flow conditions. Mitotic age was calculated based on DNA-methylation via Hannum estimate (1) for each donor at the iPSC and iPSC-EC (passage 4) stage. Results ACS-iPSC-EC had significantly higher upregulation of E-selectin upon TNF-a stimulation on mRNA level (ACS: 532.1-fold±48.7 vs healthy: 322.3-fold±55.7 with p=0.02). Similarly, ICAM1 protein upregulation was higher in ACS-iPSC-EC compared to healthy iPSC-EC as determined by flow cytometry (ACS: 1.4-fold±0.01 vs healthy: 1.1-fold±0.0007; p&amp;lt;0.001). ACS-iPSC-EC recruited significantly more THP-1 per view field under protective (high shear stress, laminar) flow conditions (ACS: 78.4±20.7 vs healthy: 33.25±12.3 with p=0.04) compared to healthy iPSC-EC. While both groups recruited significantly more THP-1 under atherogenic than protective conditions (ACS: 302±38.9 with p=0.0055 vs healthy: 340±70.4 with p=0.0005), there was no difference between the donor groups (p=0.43). Analysis of bulk RNA-seq data showed significant differences in TNF-a-induced transcriptome changes. Gene set enrichment analysis identified differences in signalling pathways related to leukocyte and lymphocyte-mediated immunity, adaptive immune response, cytokine activity, and many more as shown in Figure 1 (p.adj ≤1e-10). IPSC of both groups had a negative calculated mitotic age (in years) which significantly increased after endothelial differentiation and four population doublings (ACS-iPSC: −14.1±0.7 vs ACS-EC: −0.1±1.1, p&amp;lt;0.0001 and healthy-iPSC: −13.7±0.8 vs healthy-EC: 2.5±1.5, p=0.0001). Conclusion The higher rate of basal THP-1 recruitment and upregulation of adhesion molecules on mRNA and protein level and the distinct transcriptome changes suggest intrinsic differences between patient and healthy iPSC-EC both in the basal state and in inflammatory response. Furthermore, this demonstrates iPSC as a viable in vitro model also for polygenetic diseases such as CAD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Cardiac Society, Research Scholarship

Characterization of lipidic plaque materials at calcified atheroma: its association with calcification thickness evaluated by optical coherence tomography and near-infrared spectroscopy imaging

Abstract Introduction The degree of calcification and its thickness have been considered to affect stent expansion, leading to an increases risk of repeat revascularization in patients receiving PCI. Pathophysiologically, accumulation of lipidic materials within vessel wall could trigger the formation of plaque calcification. Elucidating characteristics of lipidic plaque components at calcified atheroma may enable to identify phenotypes with thick calcification which less likely responds to PCI. Purpose This study investigated the relationship of calcification thickness with lipidic plaque materials at calcified atheroma by using OCT and near-infrared spectroscopy (NIRS) imaging. Methods We analyzed 52 calcified lesions (culprit/non culprit lesions=44/8) in 47 CAD patients (stable CAD/ACS=36/11) from the REASSURE-NIRS registry (NCT04864171). OCT and NIRS imaging evaluated 4-mm segment exhibiting maximum superficial calcification arc. Calcification thickness on OCT imaging, its arc on IVUS imaging, and NIRS-derived lipid arc were analyzed at every 1-mm interval cross-sectional images. In addition, yellow-calcification ratio (YCR = lipid arc/calcification arc) was calculated (Figure 1). Results 53% of study subjects exhibited chronic kidney disease and 70% of them received a statin (averaged on-treatment LDL-C =89mg/dL). Throughout OCT and NIRS/IVUS imaging analysis of 260 cross-sectional images, the averaged calcification arc, its maximum thickness, lipid arc and YCR were 210° (167–285°), 0.78mm (0.62–0.95mm), 95° (31–169°) and 0.33 (0.09–0.59), respectively. As expected, thicker calcification more likely exhibited a greater calcification arc (r=0.30, p&amp;lt;0.001). Furthermore, a greater thickness of calcification was associated with smaller lipidic plaque burden, reflected by yellow arc (r=−0.36, p&amp;lt;0.001) and YCR (r=−0.36, p&amp;lt;0.001) (Figure 2). After adjusting age, gender and ACS, calcification arc (p&amp;lt;0.001) and YCR (p&amp;lt;0.001) continued to predict thicker calcification. Conclusion Thickening of calcification was associated with severer calcification arc, which was accompanied by the shrinkage of lipidic plaques. Our findings suggest the evaluation of lipidic plaque component as a potential tool to identify calcified atheroma harbouring thick calcification, which may cause a greater risk of stent underexpansion. Funding Acknowledgement Type of funding sources: None.

Arterial and venous thromboembolism risk associated with blood eosinophils: A systematic review and meta-analysis.

The association between blood eosinophil (EOS) counts and arterial/venous thrombosis is unclear. We aim to explore whether EOS count is a risk factor for thrombosis. We searched several databases and preprint platforms using core terms ‘eosinophil’, ‘myocardial infarction’, ‘ischemic stroke’, and ‘venous thromboembolism’ (VTE), among others. Studies comparing the odds ratios (ORs) or risk ratios (RRs) of EOSs with the abovementioned diseases were eligible. Overall, 22 studies were included. A high EOS count was associated with acute coronary artery thrombosis events (OR: 1.23, 95% CI: 1.15–1.32), short‐term cerebral infarction and mortality (RR: 2.87, 95% CI: 1.49–5.51). The short‐term risk of VTE was more common in patients with EOS‐related diseases (RR: 6.52, 95% CI: 2.42–17.54). For coronary artery disease, a high EOS count was a protective factor against 6‐month to 1‐year mortality (RR: 0.56, 95% CI: 0.45–0.69) but was associated with long‐term mortality (RR: 1.64, 95% CI: 1.25–2.14). Therefore, we conclude that for coronary artery thrombosis, EOS count is not associated with AMI events in general population. It may be associated with NSTEMI and STEMI in CAD patients, but more studies are needed to confirm this. In addition, EOS count is associated with an increased risk of both short‐ and long‐term mortality but is not predictive of the composite endpoints. For cerebral artery thrombosis, EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short‐term prognosis. For VTEs, EOS count was a risk factor for some patients, especially those with acute‐phase EOS‐related diseases.

Impacto clínico de la extensión del miocardio en riesgo en pacientes sometidos a intervención percutánea de la válvula aórtica

Introduction and objectivesCoronary artery disease (CAD) is found in 30%-50% of patients with severe aortic stenosis (AS) undergoing treatment. The best management of CAD in AS patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear. We investigated the clinical impact of the extent of jeopardized myocardium in patients with concomitant CAD and severe AS treated by TAVI. MethodsConsecutive patients who underwent TAVI procedures at our hospital were identified. In the presence of CAD, the myocardium jeopardized before TAVI was graded using the British Cardiovascular Intervention Society (BCIS) jeopardy score (JS). The study population was divided in 3 groups: patients without concomitant CAD (no-CAD), patients with CAD and BCIS-JS ≤ 4 (CAD BCIS-JS ≤ 4) and patients with concomitant CAD and BCIS-JS> 4 (CAD BCIS-JS> 4). The primary study endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). ResultsA total of 403 patients entered the study: 223 no-CAD, 94 CAD BCIS-JS ≤ 4 and 86 CAD BCIS-JS> 4. At> 3 months of follow-up [range 104–3296 days], patients without CAD and CAD patients with BCIS-JS ≤ 4 had better survival free from MACCE compared with those with less extensive revascularization (BCIS-JS> 4) (P=.049). This result was driven by a significant reduction in death (P=.031). On multivariate analysis, residual BCIS-JS ≤ 4 and NYHA class III-IV independently predicted MACCE. ConclusionsIn patients with concomitant CAD and severe AS, the extent of jeopardized myocardium before TAVI impacts on clinical outcomes.

Platelet SR-PSOX/CXCL16-CXCR6 Axis Influences Thrombotic Propensity and Prognosis in Coronary Artery Disease.

Platelets express the transmembrane chemokine SR-PSOX/CXCL16, proteolytic cleavage of which generates the sCXCL16 soluble-(s) chemokine. The sCXCL16 engages CXCR6 on platelets to synergistically propagate degranulation, aggregation and thrombotic response. Currently, we have investigated the pro-thrombotic and prognostic association of platelet CXCL16–CXCR6 axis in CAD-(n = 240; CCS n = 62; ACS n = 178) patients. Platelet surface-associated-CXCL16 and CXCR6 surface expression ascertained by flow cytometry correlated significantly with platelet activation markers (CD62P denoting degranulation and PAC-1 binding denoting α2bβ3-integrin activation). Higher platelet CXCL16 surface association (1st quartile vs. 2nd–4th quartiles) corresponded to significantly elevated collagen-induced platelet aggregation assessed by whole blood impedance aggregometry. Platelet-CXCL16 and CXCR6 expression did not alter with dyslipidemia, triglyceride, total cholesterol, or LDL levels, but higher (>median) plasma HDL levels corresponded with decreased platelet-CXCL16 and CXCR6. Although platelet-CXCL16 and CXCR6 expression did not change significantly with or correlate with troponin I levels, they corresponded with higher Creatine Kinase-(CK) activity and progressively deteriorating left ventricular ejection fraction (LVEF) at admission. Elevated-(4th quartile) platelet-CXCL16 (p = 0.023) and CXCR6 (p = 0.030) measured at admission were significantly associated with a worse prognosis. However, after Cox-PH regression analysis, only platelet-CXCL16 was ascertained as an independent predictor for all-cause of mortality. Therefore, the platelet CXCL16–CXCR6 axis may influence thrombotic propensity and prognosis in CAD patients.

An Evaluation of Psychometric Properties of Needs Assessment Instruments in Patients with Coronary Artery Disease Undergoing Cardiac Rehabilitation Programs: A Systematic Review

Background: Coronary Artery Disease is the foremost reason of illnesses and death in the world. Assessment of the needs is a priority in these patients. However, there is a paucity of tools for the evaluation of needs, with the controversy surrounding their validity.Purpose: This review aimed to evaluate the psychometric properties of tools used to assess needs of patients with CAD undergoing cardiac rehabilitation (CR) plans.Methods: An online literature search combined with manual search was carried out on 11 databases to identify relevant articles. The terms used in the search were: cardiac rehabilitation AND coronary artery disease, cardiac rehabilitation AND acute coronary syndrome, and questionnaires OR need assessment OR tool OR scale. Articles from 1989 to 2021 were selected using some inclusion criteria and no validation studies were excluded. The quality of the questionnaires was evaluated by researchers using consensus-based standards for the selection of health status measurement instruments (COSMIN) list. Data analysis had been done by calculating overall methodological quality scores per study on a measurement property using COSMIN checklist. A methodological quality score per box was obtained by taking the lowest rating of any item in a box (‘worse score counts’).Results: Of 653 articles, 15 papers were involved in the study. Six studies reported cross-cultural validity, nine studies for criterion validity, and none reported measurement error, hypothesis testing, and responsiveness. There is no vigorous and valid single scale for the measurement of needs in CAD patients Overall, the CADEQ questionnaire was good and a patient self-assessment tool for cardiac rehabilitation was poor based on psychometric properties.Conclusions: The findings of this study disclosed that even though it has been more than 32 years, from 1989 to 2021, of the development in need assessment instruments; each instrument has as a minimum of one “poor” psychometric property according to the COSMIN checklist. So, it is recommended for the next studies to design and develop instruments with better psychometric validities for clinical environment.

Hyperglycemia newly detected by glycated hemoglobin affects all-cause mortality in coronary artery disease patients: a retrospective cohort study

AimsWe aim to assess the relationship between hyperglycemia and long-term prognosis in CAD patients without known diabetes. MethodsIn this retrospective observational study, we enrolled 11,384 CAD patients without known diabetes. Newly detected diabetes was defined as HbA1c ≥ 6.5 %, and prediabetes was defined as HbA1c ranging from 5.7 to 6.4 %.The association between hyperglycemia and long-term all-cause mortality was examined using Cox proportional hazards regression analysis. ResultsAccording to HbA1c level, 8207 (72.1 %) patients had hyperglycemia, including 13.0 % with diabetes and 59.1 % with prediabetes. During a median follow-up of 4.9 years, 1157(10.2 %) patients died. Compared with normoglycemia, hyperglycemia was associated with increased risk for long-term mortality (adjusted hazard ratio for diabetes and prediabetes: 1.23 [95 % confidence interval (CI): 1.00 to 1.51] and 1.17 [95 % CI: 1.01 to 1.36], respectively). ConclusionsHyperglycemia detected by HbA1c was common in CAD patients without known diabetes and was associated with increased long-term mortality. It is necessary to routinely use HbA1c to assess glucose metabolic status in CAD patients and treat hyperglycemia as early as possible to reduce the risk of adverse outcomes.

Effectiveness of an Instructional program on patients’ knowledge about exercises to prevent coronary artery disease progression after percutaneous coronary intervention (PCI)

Pre-experimental design (one group pretest-posttest) A non-probability (purposive) sample of 35patients who have coronary artery disease and are being treated with percutaneous coronary intervention to manage coronary artery occlusions. The study started from November 2021 to May 2022.The data was collected using sociodemographic, the clinical characteristics of the client, and the Coronary Artery Disease Education Questionnaire Short Version (CADE-SV), and lifestyle compliance items after PCI: Physical activity. The collected data were statistically analyzed using SPSS software version 26. The study result revealed that the majority of CAD patients are males with age 48 and above, married, secondary school graduates, and housewives. More than half of the study sample had risk factors for coronary artery disease, except for the patient's own smoking. Patients with coronary artery disease had a low degree of knowledge about healthy lifestyles before beginning the program, and significant improvement in patients’ knowledge regarding healthy lifestyles after giving the program also presented a significant difference in all items about physical activity for patients with percutaneous coronary intervention. The finding presented that there were significant differences in post-test knowledge of all items about physical activity for patients with percutaneous coronary intervention after completing the program. There is a need to instruct patients following PCI by offeringpamphlets, books, and brochures about healthy lifestyle aspects (especially exercise). Conducting a relatively large nursing health education program for patients after PCI to see how the program affects patients' understanding of healthy lifestyles. Also, suggest that all CHD patients have a full understanding and practice of exercise.

Association of health insurance status with coronary risk factors, coronary artery disease, interventions and outcomes in India

ObjectiveCoronary artery disease (CAD) related hospitalization and interventions are associated with catastrophic out-of-pocket health expenditure in India. To evaluate differences in risk factors, disease severity, management and outcomes in uninsured vs insured CAD patients we performed a study. MethodsSuccessive CAD patients who underwent percutaneous intervention (PCI) at our centre were enrolled from January 2018 to June 2021. Clinical, angiographic and intervention data were periodically uploaded in the American College of Cardiology CathPCI platform. Descriptive statistics are reported. Results4672 CAD patients (men 3736, women 936) were included; uninsured were 2166 (46%), government insurance was in 1635 (36%) and private insurance in 871 (18%). Mean age was 60.1 ± 11 years, uninsured <50y were 21.6% vs 14.0% and 20.3% with government and private insurance. Among the uninsured prevalence of raised total and non-HDL cholesterol, any tobacco use, ST-elevation myocardial infarction (STEMI) and ejection fraction <30% were more (p < 0.01). In the STEMI group (n = 1985), rates of primary PCI were the highest in those with private insurance (38.7%) compared to others. Multivessel stenting (≥2 stents) was more among the insured patients. Median length of hospital stay was similar in the three groups. In-hospital mortality was slightly more in the uninsured (1.43%), compared to government (0.88) and privately insured (0.82) (p = 0.242). The cost of hospitalization and procedures was the highest among uninsured (US$ 2240, IQR 1877–2783) compared to government (US$ 1977, IQR 1653–2437) and privately insured (US$ 2013, IQR 1668–2633) (p < 0.001). ConclusionsUninsured CAD patients in India are younger with more risk factors, acute coronary syndrome, STEMI, multivessel disease and coronary stenting compared to those with government or private insurance. The uninsured bear significantly greater direct costs with slightly greater mortality.

Abstract P2093: Immunodominant Human Leukocyte Antigen-ii-restricted Epitopes In Human Apolipoprotein B

Introduction: CD4 + T cell responses to apolipoprotein B are well characterized in atherosclerotic mice and also detectable in humans. CD4 + T cells recognize peptides displayed on highly polymorphic Human Leukocyte Antigen-II molecules. Immunogenicity of individual APOB peptides is largely unknown in humans. Only one HLA-II-restricted epitope was validated using a DRB1*07:01-APOB 3036-3050 tetramer. We reasoned that the T cell epitope repertoire of APOB is broader and may contain dominant antigenic regions. Hypothesis: Human APOB harbors discrete immunodominant sequences that are targeted by autoreactive CD4 + T cells in majority of donors. These trigger atherosclerosis-related autoimmune responses in humans. Objective: To optimize a restimulation-based workflow to examine antigenicity of multiple candidate peptides in HLA-typed donors, to chart TCR specificities and phenotypes of APOB-reactive cells and to profile T helper cytokine responses to APOB epitopes. Methods and Results: We selected twenty APOB peptides (APOB 20 ) from an in silico screen and validated peptide binding to the most commonly occurring HLA-II alleles. Using stringent controls, we confirmed specificity of expansion-based protocols to detect CD4 + T cytokine responses to APOB 20 pool. Ex vivo assessment of activation-induced markers revealed statistically significant autoimmune response to APOB 20 , but not to a ubiquitously-expressed negative control protein, actin. CD4 + T responses to the APOB 20 pool were resolved to the level of individual peptides using an IFNγ enzyme-linked immune-absorbent spot (ELISpot) assay. This led to the discovery of six immunodominant epitopes (APOB 6 ) that triggered robust T cell responses in most donors. High-throughput sequencing identified unique APOB 6 -specific expanded TCR clonotypes. Responding CD4 + T cells were enriched in antigen-experienced memory phenotypes. APOB 6 induced secretion of both pro-inflammatory and regulatory cytokines. In matched clinical samples, APOB 6 stimulation detected heightened expression of activation and memory markers and augmented secretion of proinflammatory cytokines in patients with more severe coronary artery disease. Conclusions: Using &gt;60 donors expressing diverse HLA-II alleles and distributed over a screening and a validation cohort of healthy subjects and a clinical cohort of CAD patients, we discovered six immunodominant APOB epitopes that allowed interrogation of dynamic antigen-specific CD4 + T responses associated with human atherosclerosis.

IL-21R blockade reduces atherosclerosis development in LDLR-/- mice

Background and Aims : Many pro-inflammatory cytokines increase during atherosclerosis and contribute to disease progression. Elevated IL-21 serum levels have been found in CAD patients, but its exact role in atherosclerosis remains unknown. IL-21 is primarily secreted by T-cells and binds to the IL-21 receptor (IL-21R), which is expressed on most lymphoid and myeloid cells. Consequently, IL-21/IL-21R signaling has pleiotropic effects and can cause activation of immune cells but can also inhibit anti-inflammatory Tregs. In this study, we aim to provide further insight into the role of IL-21 in atherosclerosis by blocking the IL-21/IL-21R axis.Methods: First, we confirmed IL-21R expression on many immune cells within the atherosclerotic plaque of Ldlr-/- mice and carotid endarterectomy patients using flow cytometry and scRNAseq. Next, Ldlr-/- mice were fed a Western-type diet for five weeks, during which mice were treated with an IL-21R blocking antibody or an isotype control.Results: IL-21R blockade significantly reduced atherosclerosis development by 38%. This coincided with increased atheroprotective Foxp3 expression within aortic CD4+ T-cells and elevated percentages of CD4+Foxp3+ cells in lymphoid organs (spleen: αIL-21R: 14.02±0.48% vs. ctr: 12.18±0.32%, P <0.01, HLN: αIL-21R: 21.97±1.05% vs. ctr: 18.77±1.06%, P<0.05). Similarly, significantly increased anti-inflammatory IL-10 was observed in serum (αIL-21R: 617.63±156.93 vs ctr: 36.01±29.93 pg/mL, P <0.001) and culture supernatant from splenocytes (αIL-21R: 64.86±10.24 vs ctr: 38.48±5.41 pg/mL, P <0.05) of αIL-21R-treated mice.Conclusions: Collectively, we show that IL-21R blockade reduces atherosclerosis by promoting atheroprotective regulatory T-cell immunity and elevating anti-inflammatory IL-10 production, representing a promising novel therapeutic strategy to extend health span and to combat CVD. Background and Aims : Many pro-inflammatory cytokines increase during atherosclerosis and contribute to disease progression. Elevated IL-21 serum levels have been found in CAD patients, but its exact role in atherosclerosis remains unknown. IL-21 is primarily secreted by T-cells and binds to the IL-21 receptor (IL-21R), which is expressed on most lymphoid and myeloid cells. Consequently, IL-21/IL-21R signaling has pleiotropic effects and can cause activation of immune cells but can also inhibit anti-inflammatory Tregs. In this study, we aim to provide further insight into the role of IL-21 in atherosclerosis by blocking the IL-21/IL-21R axis. Methods: First, we confirmed IL-21R expression on many immune cells within the atherosclerotic plaque of Ldlr-/- mice and carotid endarterectomy patients using flow cytometry and scRNAseq. Next, Ldlr-/- mice were fed a Western-type diet for five weeks, during which mice were treated with an IL-21R blocking antibody or an isotype control. Results: IL-21R blockade significantly reduced atherosclerosis development by 38%. This coincided with increased atheroprotective Foxp3 expression within aortic CD4+ T-cells and elevated percentages of CD4+Foxp3+ cells in lymphoid organs (spleen: αIL-21R: 14.02±0.48% vs. ctr: 12.18±0.32%, P <0.01, HLN: αIL-21R: 21.97±1.05% vs. ctr: 18.77±1.06%, P<0.05). Similarly, significantly increased anti-inflammatory IL-10 was observed in serum (αIL-21R: 617.63±156.93 vs ctr: 36.01±29.93 pg/mL, P <0.001) and culture supernatant from splenocytes (αIL-21R: 64.86±10.24 vs ctr: 38.48±5.41 pg/mL, P <0.05) of αIL-21R-treated mice. Conclusions: Collectively, we show that IL-21R blockade reduces atherosclerosis by promoting atheroprotective regulatory T-cell immunity and elevating anti-inflammatory IL-10 production, representing a promising novel therapeutic strategy to extend health span and to combat CVD.