High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study.

BACKGROUND: Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. METHODS: 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)-2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). RESULTS: During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58-2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08-2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42-2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination. CONCLUSIONS: SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.

Triglyceride-glucose index is associated with myocardial ischemia and poor prognosis in patients with ischemia and no obstructive coronary artery disease.

BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. METHODS: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). RESULTS: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008). CONCLUSION: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.

Analysis of correlative factors of female coronary slow-flow phenomenon: A retrospective study.

The coronary slow-flow phenomenon (CSFP) is a manifestation of coronary artery disease wherein coronary angiography reveals no apparent stenosis; however, there is a delay in blood flow perfusion. Given its increased occurrence in male patients, with the majority of subjects in previous studies being male, this study aimed to explore whether distinct risk factors are present in female patients with CSFP. This single-center retrospective study focused on female patients diagnosed with CSFP by using coronary angiography. Eligible patients meeting the predefined inclusion and exclusion criteria were divided into the study group (presenting with CSFP) and control group (displaying normal epicardial coronary arteries). Comparative analyses of clinical and diagnostic data were performed. Ninety-two patients with CSFP and an equal number of controls were enrolled in this study. Patients with CSFP exhibited a higher prevalence of smokers (P = .017) and a heightened incidence of diabetes mellitus (DM) (P = .007). Significantly elevated levels of total cholesterol (TC) (P = .034) and free fatty acids (FFA) (P = .016) were observed in the CSFP group compared to those in the control group. Additionally, patients with CSFP displayed lower levels of apolipoprotein E (ApoE) (P = .092), free thyroxine (FT4) (P = .001), and total thyroxine (TT4) (P = .025). Logistic regression analysis indicated that smoking (P = .019), FFA (P < .001), ApoE (P = .015), and FT4 (P < .001) were independent risk factors for CSFP, accounting for confounding factors. Additionally, the area under the ROC curve (AUC) of the combined effect of smoking, ApoE, FT4, and FFA on CSFP was 0.793 (95% CI: 0.729-0.857, P < .01). In addition to the established risk factors for smoking, diabetes, and hyperlipidemia, female patients with CSFP exhibited significant differences in apoE, FFA, FT4, and TT4 levels compared to the control group. Smoking, FFA, and FT4 levels emerged as independent risk factors for CSFP.

Myocardial ischemia-reperfusion injury released cellular fibronectin containing domain A (CFN-EDA): A destructive positive loop amplifying arterial thrombosis formation and exacerbating myocardial reperfusion injury.

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored. This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG). Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide. The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.

The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

Whole exome sequencing and proteomics-based investigation of the pathogenesis of coronary artery disease with diffuse long lesion.

OBJECTIVES: The long-term prognosis of patients with coronary artery disease (CAD) with diffuse long lesion underwent coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) remains worse. Here, we aimed to identify distinctive genes involved and offer novel insights into the pathogenesis of diffuse long lesion. MATERIALS AND METHODS: Whole exome sequencing was performed on peripheral blood samples from 20 CAD patients with diffuse long lesion (CAD-DLL) and from 10 controls with focal lesion (CAD-FL) through a uniform pipeline. Proteomics analysis was conducted on the serum samples from 10 CAD-DLL patients and from 10 controls with CAD-FL by mass spectrometry. Bioinformatics analysis was performed to elucidate the involved genes, including functional annotation and protein-protein interaction analysis. RESULTS: A total of 742 shared variant genes were found in CAD-DLL patients but not in controls. Of these, 46 genes were identified as high-frequency variant genes (≥ 4/20) distinctive genes. According to the consensus variant site, 148 shared variant sites were found in the CAD-DLL group. The lysosome and cellular senescence-related pathway may be the most significant pathway in diffuse long lesion. Following the DNA-protein combined analysis, eight genes were screened whose expression levels were altered at both DNA and protein levels. Among these genes, the MAN2A2 gene, the only one that was highly expressed at the protein level, was associated with metabolic and immune-inflammatory dysregulation. CONCLUSIONS: Compared to individuals with CAD-FL, patients with CAD-DLL show additional variants. These findings contribute to the understanding of the mechanism of CAD-DLL and provide potential targets for the diagnosis and treatment of CAD-DLL.

Association of inflammatory markers based on routine blood with prognosis in patients underwent percutaneous coronary intervention.

Inflammation contributes to the pathophysiological processes of coronary artery disease. We evaluated the association between inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), systemic inflammatory index, platelet-lymphocyte ratio, and 1-year all-cause mortality in patients underwent percutaneous coronary intervention (PCI). In this retrospective cohort, we consecutively enrolled 4651 patients who underwent PCI. Baseline demographic details, clinical data, and laboratory parameters on admission were analyzed. The primary outcome was 1-year all-cause mortality after PCI. We performed Cox regression and restricted cubic spline analysis to assessed the association between the inflammatory biomarkers and the clinical outcome. The area under the curve from receiver operating characteristic analysis was determined for the ability to classify mortality outcomes. A total of 4651 patients were included. Of these, 198 (4.26%) died on follow-up. Univariate Cox regression showed that NLR (heart rate [HR]: 1.070, 95% confidence interval [CI]: 1.060-1.082, P < .001), RDW (HR: 1.441, 95% CI 1.368-1.518, P < .001), systemic inflammatory index (HR: 1.000, 95% CI 1.000-3.180, P < .001), platelet-lymphocyte ratio (HR: 3.812, 95% CI 1.901-3.364, P < .001) were significant predictors of 1-year all-cause mortality. After adjusting for other confounders in multivariate analysis, NLR (HR: 01.038, 95% CI 1.022-1.054, P < .001) and RDW (HR: 1.437, 95% CI 1.346-1.535, P < .001) remained significant predictors. Restricted cubic spline analysis showed the relationship between RDW, NLR, and 1-year all-cause mortality was linear after adjusting for the covariables (P for non-linearity < 0.001). The multivariable adjusted model led to improvement in the area under the curve to 0.83 (P < .05). Nomogram was created to predict the probability of 1 year mortality. Among the laboratory indices, RDW and NLR showed the best performance for mortality risk prediction. Multivariate predictive models significantly improved risk stratification.

Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease in Indians: a pilot study.

Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.

Circulating trimethylamine N-oxide is correlated with high coronary artery atherosclerotic burden in individuals with newly diagnosed coronary heart disease.

BACKGROUND: Trimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota and has been reported to be correlated with cardiovascular diseases. Although TMAO is associated with the severity of coronary artery disease in subjects with coronary heart disease (CHD) history. However, the correlation between TMAO and the atherosclerotic burden in newly diagnosed cases of CHD is unknown. METHODS: In this hospital-based study, we enrolled 429 individuals newly diagnosed with CHD undergoing coronary angiography. Plasma TMAO was assessed before coronary angiography. SYNTAX score was computed during coronary angiography to estimate the coronary artery atherosclerotic burden. Both linear and logistic regression analyses were conducted to explore the correlation between plasma TMAO levels and SYNTAX score in newly diagnosed CHD population. RESULTS: The TMAO in patients with SYNTAX ≥ 33 and subjects with SYNTAX < 23 were 6.10 (interquartile range [IQR]: 3.53 to 9.15) µmol/L and 4.90 [IQR: 3.25 to 7.68] µmol/L, respectively. Linear regression adjusting for traditional risk factors showed TMAO level was positively correlated with SYNTAX score (ß = 0.179; p = 0.006) in CHD population. When TMAO was added to models with traditional risk factors, the predictive value improved significantly, with the receiver operating characteristic curve (AUC) increased from 0.7312 to 0.7502 (p = 0.003). Stratified analysis showed that the correlations did not hold true for subjects who were non-smoker or with histories of diabetes. None of the stratifying factors significantly altered the correlation (all p for interaction < 0.05). CONCLUSIONS: We found a positive linear correlation between plasma TMAO and SYNTAX score among newly diagnosed CHD individuals in Chinese population.

The clinical role of combined circulating complement C1q and AIP for CAD with LDL-C level below 1.8mmol/L.

BACKGROUND: In the past few years, circulating complement C1q involvement in atherosclerosis has garnered growing research interest in addition to the emerging recognition of the novel lipid marker named atherogenic index of plasma (AIP). Nevertheless, among patients experiencing low-density lipoprotein cholesterol (LDL-C) levels less than 1.8mmol/L, the interplay between C1q combined with the AIP for coronary artery disease (CAD) is ambiguous. METHODS: Patients were stratified into a non-CAD and CAD group according to their coronary angiography. The association between C1q in conjunction with the AIP and CAD was explored using restricted cubic spline analyses and logistic regression models. To assess how it predicted, a receiver operating characteristic analysis was undertaken. RESULTS: A total of 7270 patients comprised 1476 non-CAD patients and 5794 patients diagnosed with CAD were analyzed. A comparison of the two groups showed that the C1q levels were notably higher compared to the CAD group, while AIP exhibited an inverse trend. Across quartiles of C1q, the AIP demonstrated a decline with increasing C1q levels, and significant differences were observed between the groups. A correlation analysis underscored a notable negative correlation between the two variables. Univariate and multivariate logistic regression analyses revealed significant associations between CAD and the C1q quartile groups/AIP. Furthermore, compared with the Q4 group, a decrease in the C1q levels corresponded to an escalation in CAD risk, with the odds ratio rising from 1.661 to 2.314. CONCLUSIONS: In conclusion, there appears to be a notable positive correlation between the combination of C1q with the AIP and CAD.

Confounding Factors Responsible for Elevated Lp(a) Levels in Patients with Coronary Artery Disease.

BACKGROUND: Cardiovascular diseases (CVDs) are a leading cause of global mortality, motivating research into novel approaches for their management. Lipoprotein(a) (Lp(a)), a unique lipoprotein particle, has been implicated in atherosclerosis and thrombosis, suggesting its potential as a therapeutic target for CVDs. AIM: This study aimed to investigate the association of Lp(a) levels with various cardiovascular parameters and events among patients with confirmed cardiovascular disease. METHODOLOGY: A prospective study was conducted, enrolling 600 participants, predominantly comprising males (79%), with a mean age of 52.78 ± 0.412 years diagnosed with cardiovascular disease. The follow-up was done for 18 months. Patient demographics, blood investigations, and occurrence of major adverse cardiac events (MACE) were collected. SPSS version 21 was used to statistically analyze the relationships between elevated Lp(a) levels and factors such as age, glycated hemoglobin, mortality, MACE, cardiac death, target vessel revascularization, and stroke. RESULTS: The study revealed significant (P < 0.05) associations between elevated Lp(a) levels and advanced age, increased glycated hemoglobin levels, as well as occurrences of all-cause mortality, MACE, cardiac death, target vessel revascularization, and stroke. Notably, a significant (P < 0.05), association between high Lp(a) levels and acute coronary syndrome (ACS) emerged, suggesting Lp(a)'s role in advanced cardiac events. CONCLUSION: The findings highlight the potential significance of Lp(a) as a notable risk factor in cardiovascular health. The observed associations between elevated Lp(a) and adverse cardiovascular events, including ACS, underscore its pathogenic role. Consequently, this study supports the rationale for further research into Lp(a)-specific therapeutic interventions, offering substantial promise in refining the management strategies for cardiovascular diseases.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BACKGROUND: Insulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes. METHODS: The baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status. RESULTS: In 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status. CONCLUSIONS: In type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Association between NT-proBNP level and the number of stents with major advanced cardiovascular events (MACE) in patients with multivessel coronary artery disease treated with percutaneous coronary intervention: A prospective cohort study.

Complex revascularization strategies, particularly complete revascularization, are controversial in coronary artery disease (CAD), and data supporting routine revascularization in stable CAD is lacking. The importance of percutaneous coronary intervention (PCI) in CAD and N-terminal pro-brain natriuretic peptide (NT-proBNP), which has been studied as a predictor of major advanced cardiovascular events (MACE) in CAD patients, still requires further research. The aim of this study was to determine the association between NT-proBNP levels and the number of stents with MACE incidence in CAD cases. A prospective cohort study was conducted in both types of CAD (acute coronary syndrome (ACS) and chronic coronary syndrome (CCS)). The NT-proBNP levels were measured pre- and post-PCI using fluorescence immunoassay, while MACE was assessed three months post-PCI. The Student t-test was used to compare the levels of NT-proBNP between pre- and post-PCI and between those who had MACE and did not; both in patients treated with single or multiple stenting groups. A total of 32 CAD patients were recruited, consisting of 20 ACS cases and 12 CCS cases. NT-proBNP levels post-PCI increased significantly in both ACS and CCS patients compared to pre-PCI either among those treated with single and multiple stentings. MACE occurred in 4 (12.5%) out of a total of 32 patients, all of which occurred in ACS patients treated with multiple stentings. Those who had MACE had higher post-PCI NT-proBNP levels compared to those who did not have MACE (23,703.50 vs 11,600.17 pg/mL, p=0.013). This study highlights the association between elevated NT-proBNP levels and multiple stenting with the presence of MACE in CAD patients, particularly in ACS cases.

The relationship between workload and exercise-induced cardiac troponin elevations is influenced by non-obstructive coronary atherosclerosis.

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

BACKGROUND AND AIMS: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. METHODS: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. RESULTS: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (ß = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. CONCLUSIONS: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

[Predictive indicators and risk model construction for coronary artery lesions in Kawasaki disease children over 5 years old]. / 5å²ä»¥ä¸Šå·å´Žç— å„¿ç«¥åˆå¹¶å† çŠ¶åŠ¨è„‰ç— å˜çš„é¢„æµ‹æŒ‡æ ‡ä¸Žé£Žé™©æ¨¡åž‹æž„å»º.

OBJECTIVES: To study predictive indicators for coronary artery lesions (CAL) and construct a risk prediction model for CAL in Kawasaki disease (KD) children over 5 years old. METHODS: A retrospective analysis of KD children over 5 years old at Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2018 to January 2023 was conducted. Among them, 47 cases were complicated with CAL, and 178 cases were not. Multivariate logistic regression analysis was used to explore predictive indicators for CAL in KD children over 5 years old and construct a risk prediction model. The receiver operating characteristic curve was used to evaluate the effectiveness of the prediction model. Finally, the Framingham risk scoring method was used to quantify the predictive indicators, calculate the contribution of each indicator to the prediction of CAL in KD children over 5 years old, and construct a risk prediction scoring model. RESULTS: The multivariate logistic regression analysis showed that the duration of fever before the initial intravenous immunoglobulin (IVIG) treatment (OR=1.374, 95%CI: 1.117-1.689), levels of hypersensitive C-reactive protein (hs-CRP; OR=1.008, 95%CI: 1.001-1.015), and serum ferritin levels (OR=1.002, 95%CI: 1.001-1.003) were predictive indicators for CAL in KD children over 5 years old. The optimal cutoff values for predicting CAL were: duration of fever before initial IVIG treatment of 6.5 days (AUC=0.654, 95%CI: 0.565-0.744), hs-CRP of 110.50 mg/L (AUC=0.686, 95%CI: 0.597-0.774), and ferritin of 313.62 mg/L (AUC=0.724, 95%CI: 0.642-0.805). According to the Framingham risk scoring method, the low, medium, and high-risk states of CAL occurrence were defined as probabilities of <10%, 10%-20%, and >20%, respectively, with corresponding scores of 0-4 points, 5-6 points, and ≥7 points. CONCLUSIONS: In KD children over 5 years old, those with a longer duration of fever before initial IVIG treatment, higher levels of hs-CRP, or elevated serum ferritin levels are more likely to develop CAL.