Angiography-derived physiological patterns of coronary artery disease: implications with post-stenting physiology and long-term clinical outcomes.

BACKGROUND: Physiological patterns of coronary artery disease (CAD) have emerged as potential determinants of functional results of percutaneous coronary interventions (PCI) and of vessel-oriented clinical outcomes (VOCE). OBJECTIVES: In this study, we evaluated the impact of angiography-derived physiological patterns of CAD on post-PCI functional results and long-term clinical outcomes. METHODS: Pre-PCI angiography-derived fractional flow reserve (FFR) virtual pullbacks were quantitatively interpreted and used to determine the physiological patterns of CAD. Suboptimal post-PCI physiology was defined as an angiography-derived FFR value ≤ 0.91. The primary endpoint was the occurrence of VOCE at the longest available follow-up. RESULTS: Six hundred fifteen lesions from 516 patients were stratified into predominantly focal (n = 322, 52.3%) and predominantly diffuse (n = 293, 47.7%). Diffuse pattern of CAD was associated with lower post-PCI angiography-derived FFR values (0.91 ± 0.05 vs. 0.94 ± 0.05; p = 0.001) and larger rate of suboptimal post-PCI physiology (43.0 vs. 22.7%; p = 0.001), as compared to focal CAD. At the median follow-up time of 37 months (33-58), post-PCI suboptimal physiology was related to a higher risk of VOCE (16.2% vs. 7.6%; HR: 2.311; 95% CI 1.410-3.794; p = 0.0009), while no significant difference was noted according to baseline physiological pattern. In diffuse disease, the use of intracoronary imaging was associated with a lower incidence of long-term VOCE (5.1% vs 14.8%; HR: 0.313, 95% CI 0.167-0.614, p = 0.030). CONCLUSIONS: Suboptimal post-PCI physiology is observed more often in diffusely diseased arteries and it is associated with higher risk of VOCE at follow-up. The use of intravascular imaging might improve clinical outcomes in the setting of diffuse CAD.

Soluble receptor for advanced glycation end-products positively correlated to kidney injury with coronary heart disease.

AIMS: Coronary heart disease (CHD) patients with changed serum soluble receptor for advanced glycation end products (sRAGE) will experience microalbuminuria and even kidney dysfunction. However, the role of sRAGE for microalbuminuria in CHD is still not established. This study aimed to evaluate the association between sRAGE and early kidney dysfunction in CHD patients. MATERIALS AND METHODS: In this cross-sectional study, sRAGE and urinary albumin-to-creatinine ratio (uACR) were measured in hospitalized CHD patients who have undergone coronary arteriography to evaluate the distinction and correlation between sRAGE and uACR. RESULTS: There were 127 CHD patients (mean age: 63.06 ±â€¯10.93 years, 93 males) in the study, whose sRAGE were 1.83 ±â€¯0.64 µg/L. The sRAGE level was higher in kidney injury group (uACR ≥ 30 mg/g) compared with no kidney injury group (uACR < 30 mg/g) [(2.08 ±â€¯0.70 vs. 1.75 ±â€¯0.61) µg/L, P < 0.05]. Moreover, the positive correlation between serum sRAGE and uACR was significant in CHD patients (r = 0.196, P < 0.05). Binary logistic regression suggests sRAGE as a predictor for microalbuminuria in CHD patients [Odd Ratio = 2.62 (1.12-6.15), P < 0.05)]. The area under the receiver operating characteristic curve (AUC) of sRAGE is higher than that of the traditional indicators of renal function such as creatinine and estimated glomerular filtration rate, indicating sRAGE might have a good performance in evaluating early kidney injury in CHD patients [AUC is 0.660 (0.543-0.778), P < 0.01)]. CONCLUSIONS: Serum sRAGE was positively correlated to uACR and might serve as a potential marker to predict early kidney injury in CHD patients.

An overview of the application and potential mechanism on the triglyceride glucose index with multi-vessel coronary disease.

Multi-vessel coronary disease (MVCD) is a severe form of coronary artery disease (CAD) that significantly increases the risk of acute coronary syndrome (ACS) and heart attacks. The triglyceride glucose (TyG) index is a reliable and convenient marker for insulin resistance (IR). Recent studies have demonstrated its predictive value for CAD in patients with MVCD. This review aims to explore the application of the TyG index in managing MVCD and its underlying pathogenesis to enhance risk stratification and improve therapeutic decision-making.

Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.

BACKGROUND: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations. METHODS: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples. After quality control, 896 case-control pairs remained and were randomly divided into discovery (70%) and validation (30%) sets within each race. In the discovery set, conditional logistic regression and least absolute shrinkage and selection operator over 100 subsamples were applied to identify metabolites robustly associated with CHD risk and construct the MRS. The MRS-CHD association was evaluated using conditional logistic regression and the C-index. Mediation analysis was performed to examine if MRS mediated associations between conventional risk factors and incident CHD. The results from the validation set were presented as the main findings. RESULTS: Twenty-four metabolites selected in ≥90% of subsamples comprised the MRS, which was significantly associated with incident CHD (odds ratio per 1 SD, 2.21 [95% CI, 1.62-3.00] after adjusting for sociodemographics, lifestyles, family history, and metabolic health status). MRS could distinguish incident CHD cases from matched controls (C-index, 0.69 [95% CI, 0.63-0.74]) and improve CHD risk prediction when adding to conventional risk factors (C-index, 0.71 [95% CI, 0.65-0.76] versus 0.67 [95% CI, 0.61-0.73]; P<0.001). The odds ratios and C-index were similar across subgroups defined by race, sex, socioeconomic status, lifestyles, metabolic health, family history, and follow-up duration. The MRS mediated large portions (46.0%-74.2%) of the associations for body mass index, smoking, diabetes, hypertension, and dyslipidemia with incident CHD. CONCLUSIONS: In a diverse study sample, we identified 24 circulating metabolites that, when combined into an MRS, were robustly associated with incident CHD and modestly improved CHD risk prediction beyond conventional risk factors.

Aortic Dissection Complicated by Coronary Malperfusion and Tamponade: A Case Report.

Aortic dissection is rare and often presents with atypical symptoms. We describe a case of a patient with acute aortic dissection involving the coronary arteries, complicated by pericardial tamponade, and discuss findings using point-of-care ultrasound, diagnostics, and treatment of this condition.

Number of comorbidities and the risk of delay in seeking treatment for coronary heart disease: a longitudinal study in Bogor City, Indonesia.

BACKGROUND: The aim of this study was to investigate the relationship between the number of patient comorbidities and the delays in seeking treatment for coronary heart disease (CHD). METHODS: This longitudinal study utilized secondary data from the Non-Communicable Disease Risk Factor (NCDRF) cohort study conducted in Bogor City. Individuals who participated in the NCDRF cohort study and were diagnosed with CHD within the 6-year study period met the inclusion criteria. Respondents who were not continuously monitored up to the 6th year were excluded. The final sample included data from respondents with CHD who participated in the NCDRF cohort study and were monitored for the full 6-year duration. The final logistic regression analysis was conducted on data collected from 812 participants. RESULTS: Among the participants with CHD, 702 out of 812 exhibited a delay in seeking treatment. The risk of a delay in seeking treatment was significantly higher among individuals without comorbidities, with an odds ratio (OR) of 3.5 (95% confidence interval [CI], 1.735-7.036; p<0.001). Among those with a single comorbidity, the risk of delay in seeking treatment was still notable (OR, 2.6; 95% CI, 1.259-5.418; p=0.010) when compared to those with 2 or more comorbidities. These odds were adjusted for age, sex, education level, and health insurance status. CONCLUSION: The proportion of patients with CHD who delayed seeking treatment was high, particularly among individuals with no comorbidities. Low levels of comorbidity also appeared to correlate with a greater tendency to delay in seeking treatment.

Coronary heart disease and tuberculosis: an unnoticed syndemia. Review of literature and management proposal.

Tuberculosis is an increasing disease that affects about one-third of the global population. In line with the rise of tuberculosis, cardiovascular disease has shown a similar trend, with ischemic coronary heart disease becoming the leading cause of death worldwide. Based on the literature, a relationship can be drawn between tuberculosis and ischemic coronary heart disease through their shared multiple risk factors and a possible pathophysiological substrate linking them. The presentation of these two conditions reported so far is varied: it has been found as the onset of acute coronary syndrome in patients with active tuberculosis, the progressive development of coronary atherosclerosis in patients with latent tuberculosis, among others. Given this possible link and the progressive increase in their incidence rates, we can assert that we are facing an unnoticed syndemic, with their concurrent management posing a challenge due to significant pharmacological interactions. The purpose of this review is to clarify this possible link, propose an approach for diagnosis, and provide a treatment algorithm for the entire spectrum of coronary disease coexisting with tuberculosis according to the current available literature.

La tuberculosis es una enfermedad que viene en aumento y que afecta cerca de un tercio de la población mundial. En consonancia con el aumento de la tuberculosis, la enfermedad cardiovascular ha tenido un comportamiento similar, de este grupo, la cardiopatía coronaria isquémica se ha convertido en la principal causa de muerte en todo el mundo. Se podría extraer, en base a la literatura, una relación entre la tuberculosis y la cardiopatía coronaria isquémica a través de que comparten múltiples factores de riesgo en común y desde un posible sustrato fisiopatológico que las vincula. La forma conjunta de presentación de estas dos entidades reportada hasta el momento es variada: se ha encontrado como debut de un síndrome coronario agudo en pacientes con tuberculosis activa, el desarrollo progresivo de aterosclerosis coronaria en pacientes con tuberculosis latente, entre otras. Dado este posible vínculo y el aumento progresivo de sus tasas de incidencia podemos afirmar que estamos ante una sindemia inadvertida, siendo su manejo conjunto un desafío por las grandes interacciones farmacológicas. El propósito de esta revisión es esclarecer este posible vínculo, plantear un enfoque para el diagnóstico, así como suministrar un algoritmo de tratamiento de todo el espectro de la enfermedad coronaria que coexiste con la tuberculosis de acuerdo con la literatura actual disponible.

Exploring Cardiovascular Risk Factors and Atherosclerosis in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the peripheral diarthrodial joints symmetrically and also presenting many extra-articular manifestations. Morbidity and mortality in RA patients are higher compared to the general population. Cardiovascular (CV) disease is one of the most common causes of death in these patients. Classical or traditional risk factors for atherosclerosis development occur more frequently in RA patients compared to those without this condition. Studies have showed that RA patients often present comorbidities such as hypertension, dyslipidemia, diabetes mellitus and obesity. However, the high incidence of CV events occurring in RA patients is not explained by the presence of traditional risk factors. Systemic inflammation, as it is expressed with the presence of proinflammatory cytokines and increased acute phase reactants, may contribute to the development of premature atherosclerosis in these patients. In this review, we explore the risk factors for CV disease, the generation of dyslipidemia, the lipid paradox and the role of systemic inflammation in the atherosclerotic process in RA. We discuss also the role of early therapeutic intervention that suppresses inflammation which may have beneficial effects on CV disease in RA patients.

Network analysis of the effects of long non-coding RNAs in artemisinin treatment of atherosclerosis in APOE-/- mice.

Introduction: Atherosclerosis has become a worldwide medical burden. Our previous studies have shown that artemisinin (ART) had the capability to reduce atherosclerosis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are involved in the development of atherosclerosis. However, whether lncRNAs might participate in the mechanism through which artemisinin mitigates atherosclerosis has not been reported. Material and methods: Eight-week-old apolipoprotein E deficient (APOE-/-) mice were divided into two groups, one of which was treated with artemisinin. Red oil O staining was used to measure the sizes of the atherosclerotic lesions. We conducted deep sequencing to investigate lncRNA profiles in the aorta tissue in high-fat diet fed APOE knockdown mice with and without artemisinin treatment. CeRNA network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed through bioinformatics analysis. RT-PCR was used to validate the differentially expressed lncRNAs. Results: A total of 102 lncRNAs and 4,630 mRNAs were differentially expressed (p < 0.05) between the artemisinin treatment group and atherosclerosis model group. KEGG and GO analyses indicated that the categories metabolic process, specific amino acid degradation and PI3K-Akt signaling pathway are involved in the effects of artemisinin treatment in atherosclerosis (q < 0.05). LncRNA ENSMUST00000099676.4, ENSMUST00000143673.1, ENSMUST00000070085.5 and ENSMUST00000224554 might be engaged in the treatment mechanism through which artemisinin alleviates atherosclerosis. Conclusions: These findings indicated the possible mechanism and therapeutic role of lncRNAs in artemisinin treatment of atherosclerosis and provided a theoretical basis for the future application of artemisinin in patients with atherosclerosis.

Impact of Chronic Kidney Disease on the Coronary Revascularization Guided by Intracoronary Physiology: Results of the First Registry with Long-Term Follow-Up in a Latin American Population.

The use of invasive physiology methods in patients with renal dysfunction is not well elucidated. Our objective was to evaluate the in-hospital and long-term results of using intracoronary physiology to guide revascularization in patients with chronic kidney disease. In this retrospective study, we evaluated 151 patients from January 2018 to January 2022, divided into 2 groups: CKD (81 patients [114 lesions]) and non-CKD (70 patients [117 lesions]). The mean age was higher (p < 0.001), body mass index was lower (p = 0.007), contrast volume used was lower (p = 0.02) and the number of ischemic lesions/patients was higher (p = 0.005) in the CKD group. The primary outcomes (rate of major adverse cardiac events during follow-up, defined as death, infarction, and need for new revascularization) in the CKD and non-CKD groups were 22.07% and 14.92%, respectively (p = 0.363). There was a significant difference in the target lesion revascularization (TLR) rate (11.68%, CKD group vs. 1.49%, non-CKD group, p = 0.02), this initial statistical difference was not significant after adjusting for variables in the logistic regression model. There was no difference between the rates of death from all causes (6.49%, CKD group vs. 1.49%, non-CKD group, p = 0.15), reinfarction (3.89%, CKD group vs. 1.49%, non-CKD group, p = 0.394), and need for new revascularization (11.68%, CKD group vs. 5.97%, non-CKD group, p = 0.297). As there was no difference in the endpoints between groups with long-term follow-up, this study demonstrated the safety of using intracoronary physiology to guide revascularization in patients with CKD.

Transgender Women With Suppressed Testosterone Display Lower Burden of Coronary Disease Than Matched Cisgender Men.

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Long-Term Outcomes of Sex Differences in Three-Vessel Coronary Disease with Different Treatment Strategies: A Large Cohort Study.

Aim: The information assessing sex differences in outcomes of patients with three-vessel coronary disease (TVD) after different treatment strategies is sparse. This study aimed to investigate long-term outcomes of TVD among women compared with men after medical therapy (MT) alone, percutaneous coronary intervention (PCI), or coronary artery bypass grafting surgery (CABG). Methods: Consecutive 8943 patients with TVD were enrolled. Associations between sex and all-cause death and major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, myocardial infarction, or stroke) were assessed. Results: Of the 8943 patients, 1821 (20.4%) were women. During a median follow-up of 6.6 years, women had comparable incidences of all-cause death (16.6% vs. 14.9%, P = 0.079) and MACCE (27.2% vs. 26.1%, P = 0.320) to men. After multivariable analysis, women showed lower adjusted risks of all-cause death (HR: 0.777; P = 0.001) and MACCE (HR: 0.870; P = 0.016) than men in the entire cohort. Subgroup analysis revealed that the less all-cause death risk of women relative to men was significant in PCI (HR: 0.702; P = 0.009), and CABG groups (HR: 0.708; P = 0.047), but not in MT alone group. Lower MACCE risk for women vs. men was significant only in PCI group (HR: 0.821; P = 0.037). However, no significant interaction between sex and three strategies was observed for all-cause death (P for interaction = 0.312) or MACCE (P for interaction = 0.228). Conclusions: The cardiovascular prognosis of TVD female patients is better than that of men, which has no interaction with the treatment strategies received (MT alone, PCI, or CABG).

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

BACKGROUND: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. METHODS AND RESULTS: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). CONCLUSIONS: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

Addition of Social Determinants of Health to Coronary Heart Disease Risk Prediction: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Social determinants of health (SDoH) are associated with cardiovascular risk factors and outcomes; however, they are absent from risk prediction models. We aimed to assess if the addition of SDoH improves the predictive ability of the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score. METHODS AND RESULTS: This was a community-based prospective population cohort study that enrolled 6286 men and women, ages 45-84 years, who were free of clinical coronary heart disease (CHD) at baseline. Data from 10-year follow-up were examined for CHD events, defined as myocardial infarction, fatal CHD, resuscitated cardiac arrest, and revascularization in cases of anginal symptoms. Participants included 53% women with average age of 62 years. When adjusting for traditional cardiovascular risk factors, SDoH, and coronary artery calcium, economic strain, specifically low family income, was associated with a greater risk of CHD events (hazard ratio [HR], 1.42 [95% CI, 1.17-1.71], P value<0.001). Area under the curve of risk prediction with SDoH was 0.822, compared with 0.816 without SDoH. The calibration slope was 0.860 with SDoH and 0.878 in the original model. CONCLUSIONS: Significant associations were found between economic/financial SDoH and CHD risk factors and outcomes. Incorporation of SDoH into the MESA Risk Score did not improve predictive ability of the model. Our findings do not support the incorporation of SDoH into current risk prediction algorithms.

Percutaneous Coronary Intervention of Left Main Disease: Outcome After 1-year Follow-up at a Tertiary Hospital in Vietnam.

Background: Left main (LM) coronary artery disease (CAD) is a severe condition that can lead to severe outcomes. Treatment options include medication, coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI). Recent advancements in PCI techniques position it as a viable alternative to CABG for LM revascularisation. Methods: This prospective observational study evaluated outcomes after PCI for LM CAD, encompassing in-hospital and post-discharge mortality, in a single-centre registry in Vietnam. Results: Our research involved 59 patients who underwent PCI for LM lesions, with an average age of 66.7 ±1.5 years, who were divided into two groups based on presentation diagnosis - acute coronary syndrome or chronic coronary syndrome. After PCI, one individual was diagnosed with contrast-induced nephropathy and one with cardiac shock. There were two cases of in-hospital mortality in the acute coronary syndrome group and one in the chronic coronary syndrome group giving a rate of major adverse cardiac and cerebrovascular events (MACCE) of 5.1%. After a 12-month follow-up, the MACCE rate increased to 18.6%. Triple vessel coronary artery disease and troponin I elevation exhibited significant associations with adverse in-hospital outcomes (p<0.05). Conclusion: PCI for LM coronary artery disease is considered a safe treatment option, demonstrating relatively favourable in-hospital and mid-term outcomes. It presents a viable alternative for patients in need of revascularisation, particularly in cases where CABG is not the preferred choice. Clinical indicators, such as triple vessel coronary artery disease and elevated troponin I levels, may serve as predictors of adverse outcomes during hospitalisation.

Novel Mouse Model of Myocardial Infarction, Plaque Rupture, and Stroke Shows Improved Survival With Myeloperoxidase Inhibition.

BACKGROUND: Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke. METHODS: We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with Ldlr knockout (designated SR-BI∆CT/∆CT/Ldlr-/-). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI∆CT/∆CT/Ldlr-/- mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions. RESULTS: SR-BI∆CT/∆CT/Ldlr-/- mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions. CONCLUSIONS: WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.

The association between glycated hemoglobin levels and long-term prognosis in patients with diabetes and triple-vessel coronary disease across different age groups: A cohort study.

AIM: Our study aimed to investigate the correlation between glycated hemoglobin (HbA1c) and adverse prognostic events in patients with diabetes and triple-vessel coronary disease (TVD). METHODS: This study ultimately included 2051 patients with TVD and diabetes. Patients were categorized into five groups based on their HbA1c levels: < 6.0 %, 6.0-6.4 %, 6.5-6.9 %, 7.0-7.9 %, and ≥ 8.0 %. The primary endpoint was all-cause death, and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: The median follow-up time was 5.88 years. During this period, a total of 323 (15.7 %) all-cause deaths and 537 (26.2 %) MACCEs were recorded. The relationship between HbA1c and the risk of endpoint events showed a J-shaped pattern, with the lowest risk observed between 6.0 % and 6.4 %. Further analysis revealed a significant interaction between HbA1c and age. In the subgroup with age < 70 years, as HbA1c increased, the risk of endpoint events gradually rose. While in the subgroup with age ≥70 years, there was an L-shaped relationship between HbA1c and endpoint events, with the highest risk observed in patients with HbA1c < 6.0 %. CONCLUSION: Our study revealed variations in the relationship between HbA1c levels and endpoint events among patients with TVD and diabetes of different ages. In younger patients, elevated HbA1c levels were associated with a higher risk of death and MACCE, while in older patients, excessively low HbA1c levels (HbA1c < 6 %) were linked to a higher risk of death and MACCE.

CPHEN-017: Comprehensive phenotyping of neutrophil extracellular traps (NETs) on peripheral human neutrophils.

With the recent discovery of their ability to produce neutrophil extracellular traps (NETs), neutrophils are increasingly appreciated as active participants in infection and inflammation. NETs are characterized as large, web-like networks of DNA and proteins extruded from neutrophils, and there is considerable interest in how these structures drive disease in humans. Advancing research in this field is contingent on developing novel tools for quantifying NETosis. To this end, we have developed a 7-marker flow cytometry panel for analyzing NETosis on human peripheral neutrophils following in vitro stimulation, and in fresh circulating neutrophils under inflammatory conditions. This panel was optimized on neutrophils isolated from whole blood and analyzed fresh or in vitro stimulated with phorbol 12-myristate 13-acetate (PMA) or ionomycin, two known NET-inducing agonists. Neutrophils were identified as SSChighFSChighCD15+CD66b+. Neutrophils positive for amine residues and 7-Aminoactinomycin D (7-AAD), our DNA dye of choice, were deemed necrotic (Zombie-NIR+7-AAD+) and were removed from downstream analysis. Exclusion of Zombie-NIR and positivity for 7-AAD (Zombie-NIRdim7-AAD+) was used here as a marker of neutrophil-appendant DNA, a key feature of NETs. The presence of two NET-associated proteins - myeloperoxidase (MPO) and neutrophil elastase (NE) - were utilized to identify neutrophil-appendant NET events (SSChighFSChighCD15+CD66b+Zombie NIRdim7-AAD+MPO+NE+). We also demonstrate that NETotic neutrophils express citrullinated histone H3 (H3cit), are concentration-dependently induced by in vitro PMA and ionomycin stimulation but are disassembled with DNase treatment, and are present in both chronic and acute inflammation. This 7-color flow cytometry panel provides a novel tool for examining NETosis in humans.