Gensini Score Research Articles

Association of PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study

Abstract Background An increasing proportion of younger patients are currently hospitalized for acute myocardial infarction. Exploring the factors affecting coronary artery lesions and prognosis in patients with premature myocardial infarction (PMI) from a genetic perspective is of great significance to clinical management. Proprotein convertase subtilisins/kexins 6(PCSK6), a member of the PCSK family, functions in protein hydrolytic cleavage. It has been shown that PCSK6 polymorphisms are associated with carotid atherosclerosis. Purpose This research intended to evaluate the relationship between the PCSK6 rs1531817 polymorphism and the prognosis of PMI patients and their coronary stenosis. Methods This study was a prospective cohort study, which consecutively included 605 patients with PMI who underwent emergency PCI from January 2017 to August 2022 at X Hospital. Using the Massarray technique, the single nucleotide polymorphisms(SNPs) of PCSK6 rs1531817 were identified, and the patients underwent follow-up for 12 to 72 months, with major adverse cardiovascular events (MACEs) as the outcome. Analyze the relationship between patients' SNPs, Gensini score(GS), Triple vessel diseases(TVD), and MACEs. Results In PMI patients with PCSK6 rs1531817 CA+AA genotypes, ApoA1/ApoB levels were higher than in patients with CC genotype, and TC/HDL levels were lower (p < 0.05). Logistic regression analysis showed that the PCSK6 rs1531817 polymorphism (Dominant model: CA+AA vs.CC) was significantly correlated with the GS (high vs. low GS, adjOR=0.297, 95%CI:0.139-0.632, p=0.002; high vs. medium GS, adjOR=0.449, 95%CI:0.211-0.956, p=0.038), and it was correlated with the number of coronary artery lesions (TVD vs. SVD, adjOR=0.420, 95%CI:0.226-0.782, p=0.006; TVD vs. DVD, adjOR=0.406, 95%CI:0.214-0.773, p=0.006). According to multivariate Cox regression analysis, the PCSK6 rs1531817 dominant model was associated with the MACEs in PMI patients (adjHR=0.454, 95%CI:0.269-0.766, p=0.003). The mediation effect results showed that ApoA1/ApoB played a partially mediating role in the association between PCSK6 rs1531817 polymorphism and the severity of coronary stenosis (the effect leading to high GS and TVD accounted for 14.6% and 8.3% respectively), TC/HDL and TVD partially parallel mediated the association between PCSK6 rs1531817 polymorphism and MACEs (effect proportions were 8.1% and 17.1%, respectively). Conclusion Carrying the PCSK6 rs1531817 mutant A allele is an independent protective predictor of severe coronary stenosis and long-term prognosis in patients with PMI. Patients with the PCSK6 CA+AA genotypes have milder coronary stenosis partially because they have higher levels of ApoA1/ApoB; in addition, these patients have a better long-term prognosis partially because they have lower TC/HDL levels and fewer TVD patients.Figure 1.ApoA1/ApoB and TC/HDL were compareFigure 2.Correlation of PCSK6 rs1531817 pol

Prognostic impact of the extent of coronary artery disease in patients with acute transmural myocardial infarction undergoing complete percutaneous revascularization

Abstract Background The management of acute myocardial infarction has been revolutionised by the introduction of early coronary angiography and the reperfusion strategies. Recent studies support the standard of care of complete myocardial revascularization in all patients with ST-elevation myocardial infarction (STEMI) without assessing the prognostic role of the extent of coronary artery disease (CAD). Purpose To evaluate whether the extent of CAD in patients with STEMI has a prognostic impact independent of complete myocardial revascularization. Methods Observational cohort study of 365 patients with STEMI who underwent complete revascularization. For each patient the extent of CAD has been quantified using Gensini Score (GS), which takes into account both the severity and location of the lesions. The primary endpoint of the study was all-cause mortality, while cardiovascular mortality and a composite of major adverse cardiovascular events (MACE: cardiovascular mortality, recurrent acute myocardial infarction or myocardial revascularization and stroke) were defined as secondary endpoints. To assess the prognostic role of GS in predicting all-cause mortality, the area under the curve (AUC) was calculated. The best cut-off was determined as the one that maximized Youden's index (sensitivity + specificity - 1). Results Patients with a GS >80, indicating extensive coronary disease, had significantly higher rates of both cardiovascular [4 (16.7%) vs. 12 (3.5%); p = 0.002] and all-cause mortality [5 (20.8%) vs. 24 (7%); p = 0.016], than those with a GS ≤80. A GS >80 was demonstrated to be an independent predictor of all-cause mortality [hazard ratio = 5; 95% confidence interval: 1.5-16.8; p = 0.01] Conclusions The Gensini Score can identify high-risk patients with STEMI who may benefit from more intensive therapies to improve prognosis, although current guidelines do not specify treatment based on the extent of coronary disease.Long-term outcomes according to GSPrognostic value of GS

Coronary artery disease polygenic risk score in patients undergoing coronary angiography and risk of future revascularization

Abstract Background Coronary artery disease (CAD) polygenic risk score (PRS) is a strong predictor of incident CAD. The role of CAD PRS in patients with known or suspected CAD already presenting for invasive coronary angiography remains poorly understood. Purpose We aimed to (i) study the association between CAD PRS and coronary angiography traits, and (ii) determine whether CAD PRS can predict risk of future revascularization after an initial coronary angiogram. Methods Patients who underwent coronary angiography at a single hospital and were part of its biobank were included in the study. Participants were classified into 3 risk groups based on CAD PRS distribution–low (0-20%), intermediate (21-80%), and high (81-100%)–computed from a recently reported PRS comprised of 1,296,172 variants (GPSMult, PGS003725). Revascularization was defined as a composite of coronary artery bypass graft and percutaneous coronary intervention with a 3-month blocking window after the initial angiogram. Associations between coronary stenosis severity and burden, and CAD PRS were assessed using multinomial logistic regression adjusted for age, sex, and genetic ancestry. The cumulative incidence of revascularization was tested using Fine-Gray regression accounting for competing risk of all-cause mortality and compared across CAD PRS strata by log-rank test. Results Among 3,518 participants (29.90% female, mean age 63.29±12.14 years), 2,568 (73%) had angiographic evidence of CAD – 340 (13.24%) mild, 346 (13.47%) moderate, and 1,882 (73.29%) severe. Out of those with CAD, 844 (32.87%) presented with acute coronary syndromes (ACS) and 1,724 (67.13%) with stable CAD. CAD PRS was strongly associated with angiographic presence of CAD (OR 2.62, 95%CI 2.08-3.29) and this did not differ among patients presenting with ACS vs. stable CAD (Fig1A). The association was weakest for mild CAD (OR 1.14, 95%CI 0.77-1.68) and strongest for severe CAD (OR 3.04, 95%CI 2.40-3.84). Besides severity, CAD PRS was also strongly associated with angiographic burden of CAD with the strongest association observed for presence of left main coronary stenosis (OR 2.63, 95%CI 1.86-3.73). Each standard deviation increase in CAD PRS was associated with a 10-point increase in the Gensini score, a continuous measure of angiographic burden of CAD (p<2e-16) (Fig1B). Over a mean follow-up period of 9.26±5.81 years, 659 (18.73%) patients required revascularization at a mean period of 5.31±4.69 years. Risk of revascularization varied dramatically by CAD PRS; HR was 1.64 (95%CI 1.28-2.10, p=8.7e-5) for high vs. low CAD PRS (Fig2). CAD PRS remained predictive of future revascularization even after adjusting for the angiographic burden of CAD at baseline (HR 1.41, 95%CI 1.09-1.82, p=7.9e-3). Conclusion CAD PRS is strongly associated with severity and burden of CAD assessed on coronary angiography and is predictive of future risk of revascularization even after accounting for baseline disease burden.Figure 1.CAD PRS and angiographic traitsFigure 2.CAD PRS and revascularization

Early coronary artery atherosclerosis in humans is associated with attenuated coronary retention of klotho

Abstract Background Vascular aging is a key feature of cardiovascular disease. α-klotho (klotho) is a protein inversely associated with aging and may contribute to vascular repair. Lower levels of systemic klotho have been identified in humans with features of early and advanced coronary atherosclerosis. It remains unknown if circulating klotho is present within human coronary circulation and whether cardiovascular klotho retention correlates with atherosclerosis. Purpose The current study aimed to assess the presence of klotho within coronary circulation compared to systemic circulation and hypothesized that net coronary klotho retention is attenuated in patients with early age-related features of coronary artery disease (CAD). Methods A total of 42 patients that underwent clinically indicated coronary angiogram for chest pain that had no obstructive CAD underwent intravascular ultrasound (IVUS) assessment were retrospectively examined. Virtual histology assessed coronary plaque characteristics. Blood samples simultaneously collected from the proximal aorta and coronary sinus were used for klotho detection using enzyme-linked immunosorbent assay. The net gradient of klotho across cardiovascular circulation was calculated by multiplying the arteriovenous klotho gradient by basal coronary blood flow. A net positive gradient indicated less cardiovascular klotho retention; a net negative gradient indicated greater cardiovascular klotho retention. Results Overall, participants were age 54±10 years old and 76% were female. There were overall higher levels of klotho within the coronary sinus (median 0.49 ng/mL [0.15; 1.69]) compared to systemic circulation (median 0.30 ng/mL [0.16; 1.14]). Participant groups were determined by those with positive (n = 20) or negative (n = 22) cardiovascular retention of klotho. Both groups were similar in age (56 ±2 vs. 51 ±2 years old, p = 0.080), gender (72% vs. 80% female, p = 0.580), and had similar occurrences of traditional cardiovascular comorbidities. Those with less cardiovascular klotho retention in the coronary vascular bed had significantly greater degree of non-obstructive coronary artery plaque (Gensini score 3.5 vs. 0, p < 0.001) and had higher percent plaque burden (46% [35; 53] vs. 34% [28; 46], p = 0.044) than those with greater cardiovascular klotho retention. Conclusions Patients with early coronary atherosclerosis may be characterized by attenuated retention of klotho within coronary circulation. Moreover, humans appear to have higher circulating klotho in coronary circulation than in systemic circulation. The current study may support a role for mechanism or potential therapeutic target for klotho in coronary atherosclerosis in humans.

Sex-differences in the clinical features, managements and outcomes of early-onset atherosclerotic coronary artery disease in China

Abstract Background/Introduction There is an alarming rise in the incidence of atherosclerotic coronary artery disease (CAD) among young adults, particularly in young women. Sex disparities of early-onset CAD in the context of contemporary cardiovascular practice are not well understood. Purpose We aimed to delineate the differences in clinical profiles and prognosis between young men and women with established early-onset CAD. Methods This is a nationwide, hospital-based, longitudinal prospective cohort study. Young patients (aged ≥18 years and ≤ 45 years) with angiographically confirmed severe atherosclerotic obstructive coronary arteries (luminal narrowing ≥ 70%) were included from 38 hospitals across China between May 2017 and May 2020. Coronary risk factors, clinical features and treatments were compared between men and women at baseline. Participants were followed for 3 years. The outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), unplanned revascularization, and ischemic stroke. The Cox regression analyses were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for outcome. Results There were 1524 patients (female: 4.4%) included in this study. The female patients were older than the male patients (41.1±4.0 years for females vs. 39.6±4.4 years for males, p=0.006). They showed a lower prevalence of hypertension, lipid disorders, and smoking or drinking (all p<0.01). The female patients were less likely to have at least 1 modifiable risk factors (female: n=45 (67.2%) vs. male: n=1382 [94.6 %], p<0.001); they showed more favorable laboratory results at baseline, including lipids, serum creatinine and uric acid (all p<0.05) as compared to male patients. Besides, young females presented more often with stable angina on admission, whereas young males tended to present with acute MI (p<0.001). There was no significant sex difference in Gensini Score (p=0.15). Female patients were less likely to undergo revascularization procedures than male patients (73.1% vs. 85.3%, p=0.01). During the 3 years of follow-up, female patients were at a significantly higher risk of MACE compared to their male counterparts (13.4% vs. 5.8%, adjusted HR: 3.07, 95% CI:1.36–6.94, p=0.007) after adjusting for age, smoking, drinking, body mass index, hypertension, diabetes, dyslipidemia, diagnosis and revascularization. Conclusions Distinct sex disparities, unfavorable to young females, were documented among patients with early-onset CAD, with the largest gaps noted in the treatment and prognosis. Despite more favorable baseline profiles, young female patients had insufficient care and 3-fold greater risk for MACE compared to young males. These results highlight the need for strengthening the treatment strategies for this vulnerable disease entity.Figure 1

Serum Level of Cadherin-P (CDH3) Is a Novel Predictor of Cardiovascular Events Related to Atherosclerosis in a 3-Year Follow-Up Study

Background: Placental cadherin (CDH3) is an adhesion molecule expressed in many malignant tumors. The role of serum CDH3 in atherosclerosis is unclear. Methods: This 3-year follow-up study measured atherosclerosis and serum CDH3 in 218 angiography inpatients. Coronary stenosis was assessed as the Gensini score. The brachiocephalic and femoral plaques were quantified by ultrasound. Microarray serum profiling was conducted in selected samples. CDH3 in the serum was measured using an indirect ELISA. The odds ratio (OR), ROC analysis, and logistic regressions were used to evaluate the associations between CDH3 content, atherosclerotic lesions, and various serum biomarkers. Results: Serum CDH3 was associated with the severity of atherosclerosis and diastolic blood pressure. The levels of CDH3 were able to discriminate patients with total subclinical and hemodynamically significant atherosclerotic lesions in all circulation pools (coronary, brachiocephalic, and femoral). Elevated serum CDH3 appeared to be a risk factor for cardiovascular outcomes after 3-year follow up with OR = 1.81 (95% CI: 1.07–3.72; p = 0.022). Endothelin-1 and NOx were associated with the content of CDH3 in the serum, suggesting the involvement of certain signal transduction pathways that may participate in plaque formation. Conclusions: CDH3 was associated with cardiovascular outcomes adjusted for coronary plaque presence, indicating a role of CDH3 in plaque biology.

Independent role of atherosclerotic plaque composition and extension in predicting the risk of cardiac events: a CLIMA substudy.

To investigate two different approaches to determine patient risk to develop cardiac events: the burden of coronary atherosclerosis, as assessed by the Gensini score, and plaque morphology, as assessed by intracoronary optical coherence tomography (OCT). We assessed the Gensini score and OCT features of plaque vulnerability in 847 patients from the CLIMA registry. Patients were divided into four Gensini quartiles. The main study endpoint was the 1-year composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). A total of 56 patients (6.6%) experienced the one-year main composite endpoint. The composite endpoint was significantly affected by the Gensini score (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.81, p = 0.005), with a low incidence in the first Gensini quartile (Q1 1.3%) and a higher incidence in the remaining groups (Q2 8.3%, Q3 8.9% and Q4 8.3%). At the multivariable analysis, the combined four OCT criteria (HR 6.4, 95%CI 3.0-13.7, p < 0.001), thin fibrous cap (HR 2.9, 95%CI 1.7-5.0, p < 0.001), lipid arc > 180° (HR 2.1, 95%CI 1.2-3.6, p = 0.010), minimum lumen area < 3.5 mm2 (HR 1.7, 95%CI 1.01-3.0, p = 0.047) and the Gensini score (HR 1.4, 95%CI 1.1-1.8, p = 0.017) were independent predictors of the main composite endpoint. In this post-hoc analysis of the CLIMA study, the burden of coronary atherosclerosis as assessed by the Gensini score and OCT plaque characteristics were independent predictors of cardiac events. Patients with the largest atherosclerosis burden and with plaque vulnerability by OCT were at the highest risk of poor outcome. Clinicaltrials.gov identifier: NCT02883088.

Relationship between the AGT M235T genetic variant and the characteristics and prognosis of coronary atherosclerosis in patients with acute myocardial infarction.

Along with environmental components, genetic factors play an essential role in the pathophysiology and progression of acute myocardial infarction (AMI). There is limited and conflicting data on the influence of the AGT M235T genetic variant on coronary atherosclerosis and death in AMI patients. We carried out a prospective cohort study among 504 Vietnamese AMI patients selected between January 2020 and May 2021. All patients underwent invasive coronary angiography, had AGT M235T genetic variant genotyped using the polymerase chain reaction method, and were followed up for 12-month all-cause mortality. The proportions of the MM, MT, and TT genotypes were 0.4%, 20.8%, and 78.8%, respectively. There was no significant difference between the TT genotype and the MM + MT genotype groups regarding the position and number of stenosed coronary artery branches and the Gensini score. The AGT M235T genetic variant did not affect 12-month mortality (hazard ratio of TT vs. MM + MT: 1.185; 95% confidence interval: 0.596-2.354; P = 0.629). Subgroup analyses by age, sex, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy also did not reveal an association between the AGT M235T variant and all-cause mortality. In summary, the AGT M235T genetic variant was not found to be associated with coronary atherosclerosis characteristics and 12-month mortality in Vietnamese patients with AMI. Further multicenter studies with larger sample sizes and extended follow-up periods are needed to investigate this issue.

A retrospective study on the relationship between plasma β-hydroxybutyric acid levels and short-term prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure

Abstract Background Ketone body metabolism can improve cardiomyocytes metabolism and reduce myocardial oxygen consumption; however, its role in the short-term prognosis of patients with acute myocardial infarction combined with heart failure has not been clearly elucidated. The aim of this study was to investigate the effect of β-hydroxybutyric acid, the main component of ketone bodies, on the short-term prognosis of patients with acute myocardial infarction combined with heart failure. Methods This was a retrospective observational study that enrolled patients admitted to the Qilu Hospital of Shandong University for acute myocardial infarction combined with heart failure between January 1, 2019, and December 31, 2022. According to whether β-hydroxybutyric acid was elevated or not, subjects were divided into a β-hydroxybutyric acid elevated and nonelevated groups, to observe the difference in cardiac function improvement between the two groups. Results This study included a total of 260 patients, of which 170 exhibited elevated levels of β-hydroxybutyric acid. Compared to the patients in the nonelevated group, patients in the elevated β-hydroxybutyric acid group had higher plasma levels of creatine kinase myocardial band and greater Gensini scores. Multivariate logistic regression analysis indicated that an increase in β-hydroxybutyric acid levels (odds ratio: 2.517; 95% confidence intervals: 1.394–4.597; P = 0.002) is an independent protective factor affecting the prognosis of cardiac function in patients with acute myocardial infarction combined with heart failure. Conclusion In patients with acute myocardial infarction combined with heart failure, plasma β-hydroxybutyric acid serves as an independent protective factor for short-term improvement in cardiac function.

Severity Stratification of Coronary Artery Disease Using Novel Inner Ellipse-Based Foveal Avascular Zone Biomarkers.

Given the similarities between the retinal and coronary microvasculature, the retina holds promising potential to serve as a non-invasive screening tool for coronary artery disease (CAD). We aimed to develop novel inner ellipse-based metrics and discern whether foveal avascular zone (FAZ) alterations can serve as indicators for CAD presence and severity. Patients admitted to the Department of Cardiology who underwent coronary angiography were included. This resulted in an inclusion of 212 patients, of which 73 had no CAD. During the same visit, 6 × 6-mm (nominal size) fovea-centered optical coherence tomography angiography images of both eyes were acquired. The Gensini score (GS) was utilized to quantify CAD severity. Six known FAZ shape metrics were assessed and three novel biomarkers based on the inner ellipse were defined: absolute inner ellipse difference, Hausdorff distance, and Chamfer distance. Eight out of nine metrics showed significant associations with the GS in the left eye. However, significant differences across three CAD severity groups were only demonstrated by the novel metrics. Utilizing the Chamfer distance, age, and sex, patients with and without CAD could be distinguished with an average area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.84-0.95). Moreover, three CAD severity groups could be discerned with a macro average AUC of 0.77 (95% CI, 0.72-0.84). A comprehensive assessment of FAZ shape descriptors was performed, and a strong association with CAD was found. The inner ellipse-based biomarkers especially demonstrated high predictive abilities for CAD presence and severity.

Quantitative analysis of three-dimensional choroidal changes in coronary artery disease patients with swept-source optical coherence tomography angiography

PurposeTo quantitatively analyze three-dimensional (3D) choroidal changes in coronary artery disease (CAD) patients with swept-source optical coherence tomography angiography (SS-OCTA) based on a scan area of 12×12mm. Methods236 CAD patients and 78 controls were included after coronary angiography (CAG) evaluation in this prospective cross-sectional study. Choroidal and foveal avascular zone (FAZ) parameters were compared between the two groups. Choroidal morphological characteristics were also evaluated based on ETDRS quadrants. Receiver operating characteristics (ROC) curves were generated to determine the discriminative power of choroidal and FAZ parameters. Linear regression analysis was used to determine the relationships between Gensini score and choroidal parameters. ResultsChoroidal thickness (CT), choroidal vascular volume/ area (CVV/a), and choroidal stromal volume/ area (CSV/a) were significantly reduced in CAD patients, while 2D vascular density decreased only in 1-6mm, and no statistical difference in choroidal vascularity index (CVI) values was detected. The AUC values of choroidal parameters were greater in the inner-6mm area than the outer-6mm area, and good performance was found with a combination with FAZ parameters (AUC=0.77, P<0.001). For morphological analysis, both groups showed the greatest values in superior quadrant and the lowest in nasal quadrant. After controlling for confounding factors, Gensini score was negatively associated with CT (β=-0.35, P=0.003), CVV/a (β=-0.17, P=0.004), and CSV/a (β=-0.18, P=0.005). ConclusionThe SS-OCTA provided excellent visualization and quantification of the choroid and showed decreased choroidal thickness and volume in CAD patients, but the morphological features were unchanged. The severity of coronary artery stenosis was independently associated with choroidal changes.

Neutrophil-to-HDL-C Ratio as an inflammatory biomarker in patients with anxiety and obstructive coronary artery disease: A retrospective study

BackgroundAnxiety is a common comorbidity with coronary artery disease (CAD). The neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-high-density lipoprotein cholesterol (HDL-C) ratio (NHR), lymphocyte-to-HDL-C ratio (LHR), and monocytes-to-lymphocyte ratio (MLR) can predict the severity of CAD. This retrospective study aimed to explore the relationship between NLR, NHR, LHR, and MLR and the presence of obstructive or severe CAD (OCAD, SCAD) in patients with comorbid anxiety and chest pain. MethodsA total of 1063 patients with anxiety and chest pain were divided into an NOCAD group and OCAD group according to computed topography angiography (CCTA). The 455 patients in the OCAD group were further divided into the NSCAD group (n = 216) and SCAD group (n = 239) according to coronary angiography (CAG) results, and the Gensini score (GS) was calculated. Demographic and laboratory data were collected. ResultsMultiple regression analysis showed that higher NLR, NHR, and LHR served as independent risk factors for OCAD in patients with anxiety and chest pain (OR 1.37, 95%CI: 1.13–1.65, p = 0.001; OR 2.24, 95%CI: 1.89–2.65, p < 0.001; OR 2.47, 95%CI: 1.87–3.62, p < 0.001), and both were significantly associated with SCAD (OR 1.93, 95%CI: 1.44–2.59, p < 0.001; OR 4.45, 95%CI: 3.28–6.31, p < 0.001; OR 2.86, 95%CI: 1.93–4.25, p < 0.001). Area under the receiver operating characteristic curve analysis showed that NHR had the highest predictive value for OCAD and SCAD compared with NLR and LHR (AUC 0.71, sensitivity 57.14 %, specificity 68.20 %; AUC 0.86, sensitivity 83.68 %, specificity 74.54 %, respectively). When NHR and GS were combined, the predictive value for SCAD further increased compared to other parameters (AUC 0.94, sensitivity 92.05 %, specificity 87.05 %). ConclusionNLR, NHR, and LHR were associated with severity of coronary stenosis in patients with comorbid anxiety and chest pain. Among these systemic inflammatory markers, NHR served as a more effective independent predictor of OCAD and SCAD in these patients.

JNK Pathway-Associated Phosphatase Deficiency Facilitates Atherosclerotic Progression by Inducing T-Helper 1 and 17 Polarization and Inflammation in an ERK- and NF-κB Pathway-Dependent Manner.

JNK pathway-associated phosphatase (JKAP) regulates T cell-mediated immunity and inflammation, which are involved in atherosclerosis pathogenesis. This study investigated the effects of JKAP on T-helper (Th) cell polarization, inflammation, and atherosclerotic progression. Serum JKAP levels were measured in 30 patients with coronary heart disease (CHD) and 30 controls. CHD blood naïve CD4＋ T cells were acquired, followed by JKAP overexpression and knockdown with or without treatment with PD98059 (ERK inhibitor) or BAY-11-7082 (NF-κB inhibitor) in vitro. CD4＋ T-cell conditional JKAP ablation mice were established in vivo, followed by the construction of an atherosclerosis model. JKAP was reduced and negatively correlated with the Gensini score, CRP, Th1 cells, Th17 cells, and proinflammatory cytokines in patients with CHD. In vitro, JKAP overexpression suppressed Th1 and Th17 cell differentiation and proinflammatory cytokines, whereas JKAP knockdown exerted the opposite effect; however, JKAP modification did not affect Th2 cell differentiation. Interestingly, JKAP negatively regulated the ERK and NF-κB pathways; meanwhile, the PD98059 and BAY-11-7082 treatments repressed Th1 and Th17 cell differentiation, and attenuated the effect of JKAP knockdown on these indices. In vivo, conditional CD4＋ T-cell JKAP ablation increased Th1 and Th17 cell polarization in the spleen, lymph node, blood, and/or aortic root. Furthermore, CD4＋ T-cell conditional JKAP ablation exaggerated atherosclerotic lesions in the aorta, elevated CD4+ cell infiltration and proinflammatory cytokines in the aortic root, and activated the ERK and NF-κB pathways in the aortic root. JKAP ablation facilitates atherosclerosis progression by promoting Th1 and 17 polarization and inflammation through regulation of the ERK and NF-κB pathways.

Incorporating Inflammation Biomarker-Driven Multivariate Predictive Model for Coronary Microcirculatory Dysfunction in Acute Myocardial Infarction Following Emergency Percutaneous Coronary Intervention.

Despite patients with successful revascularization as evidenced by angiographic findings, inadequate clinical management of coronary microcirculatory dysfunction (CMD) may result in preventable adverse outcomes. Therefore, it is imperative to use a multimodal data‑driven predictive model for the occurrence of CMD in patients with acute myocardial infarction (AMI) following emergency percutaneous coronary intervention (PCI). A prospective case-control analysis was conducted on a cohort of 77 patients with AMI who underwent PCI. The most informative predictors were selected for the predictive model through the application of LASSO analysis and multi-factor logistic regression. The diagnosis of CMD is based on findings from cardiac magnetic resonance (CMR). Based on the findings from LASSO analysis and multi-factor logistic regression, variables including sex, neutrophil-to-lymphocyte ratio (NLR), Gensini score, and diabetes mellitus were identified as independent predictors for the development of CMD in AMI patients who underwent emergency PCI. The predictive model was evaluated using bootstrap self-sampling 500 times. The resulting predictive model demonstrated an AUC value of 0.897 (95% CI: 0.827-0.958). The calibration curves exhibited good concordance between the predictions generated by the model and the CMR analysis. Furthermore, decision curve analysis revealed that the predictive model provided valuable clinical benefit in predicting CMD. The multivariate predictive model, constructed using readily available clinical variables in patients with AMI who underwent PCI, demonstrates satisfactory predictability for identifying comorbid CMD, thereby facilitating the identification of high-risk patients.

Association Between Pericoronary Fat Attenuation Index as Evaluated by Coronary Artery CT Angiography and Clinical Interventions in Lipid Management Among Patients with Coronary Artery Disease.

This study aims to evaluate the relationship between the pericoronary fat attenuation index (FAI), derived from coronary artery computed tomography angiography, and post-lipid management levels of low-density lipoprotein cholesterol in patients with coronary artery disease (CAD). Additionally, the study investigates coronary inflammation across different lipid management strategies. We selected a cohort comprising 521 CAD patients who met the inclusion criteria. Patients were categorized into well-managed (LDL-C<2.6mmol/L) and poorly managed (LDL-C≥2.6mmol/L) groups based on lipid management efficacy. We collected anthropometric measures (height, weight, body mass index, and body surface area) and clinical indicators, including Gensini score, and FAI-related parameters for coronary atherosclerotic lesions. We analyzed the interrelations along these parameters and lipid management using statistical methods and assessed diagnostic value via receiver operating characteristic (ROC) curve analysis of these parameters was assessed through. The poorly managed group exhibited significantly higher levels of total cholesterol, triglycerides, and lower levels of high-density lipoprotein compared to the well-managed group (P < 0.05). Significant differences were observed between the groups in terms of lesion length in the proximal segment of the left anterior descending artery, FAI value in the proximal segment of lesions in the right coronary artery (RCA), volume thickness in the middle segment of RCA lesions, and lesion length in the distal segment of RCA (P < 0.05). ROC curve analysis revealed areas under the curve ranging from 0.484 to 0.660 for the parameters, indicating limited diagnostic efficacy. The FAI in the RCA varies with lipid management strategies, suggesting it as a valuable metric for monitoring both perivascular inflammation and lipid status in CAD patients. However, its current diagnostic efficacy is limited, indicating the need for further research to improve its clinical utility.

Prevalence of genetically diagnosed familial hypercholesterolemia in Vietnamese patients with premature acute myocardial infarction.

Familial hypercholesterolemia (FH) is a genetic disorder that results in elevated low-density lipoprotein cholesterol (LDL-C) levels, which manifest early in the first decades of life. It is a major cause of premature coronary artery disease worldwide, leading to significant public health challenges. The prevalence of genetically determined FH in patients with premature coronary artery disease remains underestimated, particularly in developing countries. This study aimed to assess the prevalence of genetically defined FH in Vietnamese patients with premature acute myocardial infarction (AMI) in the Vietnamese population. This cross-sectional study enrolled 218 consecutive patients diagnosed with premature AMI who underwent coronary angiography. The low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 genes were analyzed by next-generation sequencing. FH was diagnosed according to Dutch Lipid Clinic Network criteria. Among the patients with premature AMI who underwent coronary angiography, the mean age was 46.9 ± 6.1 years, with a predominance of males (83.9%). The prevalence of potential FH diagnosed using Dutch Lipid Clinic Network criteria was 14.7% (definite FH, 6.0%; probable FH, 8.7%). Pathogenic or likely pathogenic variants in LDLR, apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 were found in 9 of 218 patients (4.1%), all of which were causative mutations in LDLR. Patients with premature AMI and FH had significantly greater LDL-C levels (217.6 vs 125.7 mg/dL) and more severe coronary artery lesions, as assessed by the Gensini score (100.3 vs 60.5), than did those in the No FH group. The prevalence of genetically determined FH among Vietnamese patients with premature AMI is relatively high. Screening and diagnosis of hereditary conditions in patients with premature AMI are essential to improve early detection and management and reduce the burden of coronary artery disease in this population.

Investigation of TLR4, TLR6, TLR7, and CD36 expression on T lymphocytes in coronary artery disease

Background: Coronary artery disease (CAD) is among the significant causes of death globally, caused by fatty deposits in blood vessel walls. Increasing evidence indicates that toll-like receptors (TLRs) are pivotal to atherosclerosis progression. The function of CD36 as a glycoprotein in atherosclerosis was also suggested. This study aimed to investigate the levels of TLR4, TLR6, and TLR7, as well as CD36 cell surface markers in CAD. Methods: This study included 64 patients undergoing angiography to determine whether atherosclerosis was present. The patients were categorized into two groups. The three main coronary arteries are all stenosed at over 50% in patients with CAD+ (n=22) as cases and CAD− (n=42) with smooth angiography as controls. Each patient's syntax score (SS) and Gensini (vessel score) were calculated. The TLR-4, TLR-6, TLR-7, and CD36 expression were measured using Flow cytometry. Results: TLR4 and TLR6 showed a significant link with the Gensini score in the subject group. In addition, TLR7 had an association with Syntax scoring in this study. Conclusion: The findings illustrated the association between TLR4, TLR6, and TLR7 cell surface markers with Gensini and Syntax scoring in individuals with coronary artery disease.

Correlation analysis between the expression of serum microRNA-665 and the degree of coronary artery stenosis and major adverse cardiovascular events in patients with acute myocardial infarction

BackgroundThe purpose of this study was to explore the expression of miR-665 in acute myocardial infarction (AMI) and evaluate its significance in the diagnosis and prognosis of AMI.Methods100 patients with AMI were selected as the study group and 80 healthy subjects were chosen as the control group. The levels of miR-665 were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the two groups. The diagnostic value of miR-665 expression level in AMI was analyzed by the receiver operator characteristic (ROC) curve. Kaplan-Meier curve and Cox regression were used to evaluate the predictive value of miR-665 for major adverse cardiovascular events (MACEs) in patients with AMI within 30 days after percutaneous coronary intervention (PCI).ResultsThe serum miR-665 level of the study group was significantly lower than that of the control group. The level of miR-665 was significantly correlated with clinical indicators of patients with AMI. ROC curve showed that miR-665 has a high diagnostic value for AMI. Survival analysis showed that Gensini score and miR-665 were independent risk factors for the occurrence of MACEs within 30 days after PCI in patients with AMI.ConclusionsAbnormal decrease of serum miR-665 expression level in patients with AMI may increase the risk of MACEs occurrence after PCI.

Risk Factors Associated with Angiographic Severity of Coronary Artery Disease Based on Serum Uric Acid: A Study in a Tertiary Care Hospital, Chattogram, Bangladesh

Background: Coronary Artery Disease (CAD) is a leading cause of death worldwide, identifying risk factors and severity is crucial for management and prevention. Serum Uric Acid (SUA) has been proposed as a potential marker for the severity of CAD. Elevated SUA levels are associated with endothelial dysfunction, oxidative stress, and inflammation, all of which contribute to the development and progression of atherosclerosis. This study aims to determine the association of risk factors with the severity of CAD using SUA levels. Materials and methods: This was a cross-sectional observational study conducted in the Department of Cardiology at CMCH in Chattogram over one year from October 2020 to September 2021. After case selection demographic data were collected and transthoracic echocardiography was performed on study patients. Results: The study analyzed the association between SUA level and CAD severity in 130 patients undergoing coronary angiography. The mean SUA level was 5.06 mg/dl and was significantly associated with the presence of CAD, number of vessel involvement and severity of CAD assessed by the Gensini score. The mean SUA level in cases with CAD was significantly higher (5.26 ± 1.32 mg/dl) than in cases without CAD (4.22 ± 1.03 mg/dl). Conclusion: This study concluded that demographic variables and risk factors are associated with the severity of CAD. The severity of CAD was higher in elderly and male patients. The study suggests that when assessing the risk in a CAD patient, hyperuricemia should be considered. IAHS Medical Journal Volume 6(2) December 2023; 48-52

Coronary Artery Disease among Type-II Diabetic Patient in Bangladesh

This study aimed to evaluate the relationship between microalbuminuria and the angiographic severity of CAD patients with type 2 diabetes by SYNTAX I, SYNTAX II, and Gensini scores. Diabetes mellitus is one of the strongest risk factors for coronary artery disease, so it is imperative to identify CAD in diabetic patients as soon as feasible. In this study, 82 patients with type II diabetes who had a suspected case of coronary artery disease (CAD) had elective coronary angiography. The urine albumin-creatinine ratio (UACR) was measured for each patient, and the severity of each patient's CAD was assessed using the Gensini, SYNTAX, and SYNTAX II scores. In the studied population, there were 26 (31.7%) females and 56 (68.3%) males. On average, they were 56.29 + 9.18 years old. Patients were categorized into two groups based on their UACR level: group 1 consisted of 41 patients whose UACR was less than 30 mg/g, and group 2 consisted of 41 patients whose UACR was greater than or equal to 30 mg/g. The study found that patients in group 2 had significantly higher SYNTAX scores (P=0.001) and significantly higher Gensini scores (P=0.001) than patients in group 1. Age and the length of UACR and DM showed a positive correlation (p=0.003), as did hypertension (HTN) and the length of UACR and DM (p=0.049). Microalbuminuria can be used to predict the severity and presence of CAD in type II diabetes. Keywords: Gensini score, SYNTAX score, microalbuminuria, diabetes, and coronary artery disease.