Association between plasma metal exposure and health span in very elderly adults: a prospective cohort study with mixture statistical approach.

BACKGROUND: Metals have been linked to a diverse spectrum of age-related diseases; however, the effects of metal exposure on health span remains largely unknown. This cohort study aims to determine the association between plasma metal and health span in elder adults aged ≥ 90 years. METHODS: The plasma concentrations of seven metals were measured at baseline in 300 elder adults. The end of the health span (EHS) was identified as the occurrence of one of eight major morbidities or mortality events. We used Cox regression to assess hazard ratios (HR). The combined effects of multiple metal mixtures were estimated using grouped-weighted quantile sum (GWQS), quantile g-computation (Q-gcomp), and Bayesian kernel machine regression (BKMR) methods. RESULTS: The estimated HR for EHS with an inter-quartile range (IQR) increment for selenium (Se) was 0.826 (95% confidence interval [CI]: 0.737-0.926); magnesium (Mg), 0.806 (95% CI: 0.691-0.941); iron (Fe), 0.756 (95% CI: 0.623-0.917), and copper (Cu), 0.856 (95% CI: 0.750-0.976). The P for trend of Se, Mg, and Fe were all < 0.05. In the mixture analyses, Q-gcomp showed a negative correlation with EHS (P = 0.904), with the sum of the negative coefficients being -0.211. CONCLUSION: Higher plasma Se, Mg, and Fe reduced the risk of premature end of health span, suggesting that essential metal elements played a role in health maintenance in elder adults.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Predictive value of free triiodothyronine to free thyroxine ratio on contrast-associated acute kidney injury and poor prognosis in euthyroid patients after percutaneous coronary intervention.

PURPOSE: The purpose of the study was to explore the predictive value of free triiodothyronine to free thyroxine ratio (FT3/FT4) on contrast-associated acute kidney injury (CA-AKI) and poor prognosis in euthyroid patients after percutaneous coronary intervention (PCI). METHODS: The present study included 3,116 euthyroid patients who underwent elective PCI. The main outcome was CA-AKI, and the secondary outcome was long-term mortality. All patients were divided into three groups according to the tertiles of FT3/FT4 levels. RESULTS: During hospitalization, a total of 160 cases (5.1%) of CA-AKI occurred. Restricted cubic spline (RCS) analysis indicated a linear and negative relationship between FT3/FT4 and CA-AKI risk (P for nonlinearity = 0.2621). Besides, the fully-adjusted logistic regression model revealed that patients in tertile 3 (low FT3/FT4 group) had 1.82 times [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.13-3.02, P = 0.016] as high as the risk of CA-AKI than those in tertile 1 (high FT3/FT4 group). Similarly, patients in tertile 3 were observed to have a higher incidence of long-term mortality [fully-adjusted hazard ratio (HR): 1.58, 95% CI: 1.07-2.32, P = 0.021]. Similarly, the Kaplan-Meier curves displayed significant differences in long-term mortality among the three groups (log-rank test, P < 0.001). CONCLUSION: In euthyroid patients undergoing elective PCI, low levels of FT3/FT4 were independently associated with an increased risk of CA-AKI and long-term mortality. Routine evaluation of FT3/FT4 may aid in risk stratification and guide treatment decisions within this particular patient group.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.

BACKGROUND AND AIMS: The Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene is closely associated with myocardial ischaemia/reperfusion injury (I/RI). The effects of ALDH2 on neutrophil extracellular trap (NET) formation (i.e. NETosis) during I/RI remain unknown. This study aimed to investigate the role of ALDH2 in NETosis in the pathogenesis of myocardial I/RI. METHODS: The mouse model of myocardial I/RI was constructed on wild-type, ALDH2 knockout, peptidylarginine deiminase 4 (Pad4) knockout, and ALDH2/PAD4 double knockout mice. Overall, 308 ST-elevation myocardial infarction patients after primary percutaneous coronary intervention were enrolled in the study. RESULTS: Enhanced NETosis was observed in human neutrophils carrying the ALDH2 genetic mutation and ischaemic myocardium of ALDH2 knockout mice compared with controls. PAD4 knockout or treatment with NETosis-targeting drugs (GSK484, DNase1) substantially attenuated the extent of myocardial damage, particularly in ALDH2 knockout. Mechanistically, ALDH2 deficiency increased damage-associated molecular pattern release and susceptibility to NET-induced damage during myocardial I/RI. ALDH2 deficiency induced NOX2-dependent NETosis via upregulating the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/leukotriene C4 (LTC4) pathway. The Food and Drug Administration-approved LTC4 receptor antagonist pranlukast ameliorated I/RI by inhibiting NETosis in both wild-type and ALDH2 knockout mice. Serum myeloperoxidase-DNA complex and LTC4 levels exhibited the predictive effect on adverse left ventricular remodelling at 6 months after primary percutaneous coronary intervention in ST-elevation myocardial infarction patients. CONCLUSIONS: ALDH2 deficiency exacerbates myocardial I/RI by promoting NETosis via the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/LTC4/NOX2 pathway. This study hints at the role of NETosis in the pathogenesis of myocardial I/RI, and pranlukast might be a potential therapeutic option for attenuating I/RI, particularly in individuals with the ALDH2 mutation.

The Association of Intraindividual Difference Between Cystatin- and Creatinine-Based Estimated GFR and Contrast-Associated Acute Kidney Injury.

Purpose: The estimated glomerular filtration rate (eGFR) based on creatinine is crucial for the risk assessment of contrast-associated acute kidney injury (CA-AKI). In recent, the difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been widely documented. We aimed to explore whether intraindividual differences between eGFRcys and eGFRcr had potential value for CA-AKI risk assessment in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: From January 2012 to December 2018, we retrospectively observed 5049 patients receiving elective PCI. To determine eGFR, serum creatinine and cystatin C levels were measured. CA-AKI was defined as serum creatinine being increased ≥ 50% or 0.3 mg/dL within 48 h after contrast agents exposure. Chronic kidney disease (CKD) was defined as the eGFR < 60 mL/min/1.73 m2. Results: Approximately half of the participants (2479, 49.1%) had a baseline eGFRdiff (eGFRcys-eGFRcr) between -15 and 15 mL/min/1.73 m2. Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and CA-AKI. Multivariable logistic regression analysis indicated that compared with the reference group (-15 to 15 mL/min/1.73 m2), the negative-eGFRdiff group (less than -15 mL/min/1.73 m2) had a higher risk of CA-AKI (OR, 3.44; 95% CI, 2.57-4.64). Furthermore, patients were divided into four groups based on CKD identified by eGFRcys or eGFRcr. Multivariable logistic analysis revealed that patients with either CKDcys (OR, 2.94; 95% CI, 2.19-3.95, P < 0.001) or CKDcr (OR, 2.44; 95% CI, 1.19-4.63, P < 0.001) had an elevated risk of CA-AKI compared to those without CKDcys and CKDcr. Conclusion: There are frequent intraindividual differences between eGFRcys and eGFRcr, and these differences can be used to forecast the risk of CA-AKI.

Safety and efficacy of the DragonFly system for transcatheter valve repair of degenerative mitral regurgitation: one-year results of the DRAGONFLY-DMR trial.

BACKGROUND: Severe degenerative mitral regurgitation (DMR) can cause a poor prognosis if left untreated. For patients considered at prohibitive surgical risk, transcatheter edge-to-edge repair (TEER) has become an accepted alternative therapy. The DragonFly transcatheter valve repair system is an innovative evolution of the mitral TEER device family to treat DMR. AIMS: Herein we report on the DRAGONFLY-DMR trial (ClinicalTrials.gov: NCT04734756), which was a prospective, single-arm, multicentre study on the safety and effectiveness of the DragonFly system. METHODS: A total of 120 eligible patients with prohibitive surgical risk and DMR ≥3+ were screened by a central eligibility committee for enrolment. The study utilised an independent echocardiography core laboratory and clinical event committee. The primary endpoint was the clinical success rate, which measured freedom from all-cause mortality, mitral valve reintervention, and mitral regurgitation (MR) >2+ at 1-year follow-up. RESULTS: At 1 year, the trial successfully achieved its prespecified primary efficacy endpoint, with a clinical success rate of 87.5% (95% confidence interval: 80.1-92.3%). The rates of major adverse events, all-cause mortality, mitral valve reintervention, and heart failure hospitalisation were 9.0%, 5.0%, 0.8%, and 3.4%, respectively. MR ≤2+ was 90.4% at 1 month and 92.0% at 1 year. Over time, left ventricular reverse remodelling was observed (p<0.05), along with significant improvements in the patients' functional and quality-of-life outcomes, shown by an increase in the New York Heart Association Class I/II from 32.4% at baseline to 93.6% at 12 months (p<0.001) and increased Kansas City Cardiomyopathy Questionnaire (KCCQ) score of 31.1±18.2 from baseline to 12 months (p<0.001). CONCLUSIONS: The DRAGONFLY-DMR trial contributes to increasing evidence supporting the safety and efficacy of TEER therapy, specifically the DragonFly system, for treating patients with chronic symptomatic DMR 3+ to 4+ at prohibitive surgical risk.

Lactate dehydrogenase-to-albumin ratio: A superior inflammatory marker for predicting contrast-associated acute kidney injury after percutaneous coronary intervention.

PURPOSE: Inflammation is commonly considered a mechanism underlying contrast-associated acute kidney injury (CA-AKI). This study aimed to explore the predictive capability of the novel inflammatory marker lactate dehydrogenase-to-albumin ratio (LAR) for CA-AKI following percutaneous coronary intervention (PCI), and further compare it with other common inflammatory biomarkers. METHODS: This study enrolled 5,435 patients undergoing elective PCI. The primary outcome was CA-AKI, and the secondary outcome was all-cause mortality. All patients were grouped into three groups based on the LAR tertiles. RESULTS: Three hundred fifteen patients (5.8%) experienced CA-AKI during hospitalization. The fully adjusted logistic regression suggested a significant increase in the risk of CA-AKI in LAR Tertile 3 (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.68-3.83, p < .001) and Tertile 2 (OR: 2.11, 95% CI: 1.42-3.20, p < .001) compared to Tertile 1. Additionally, receiver operating characteristic (ROC) analysis demonstrated that LAR exhibited significantly superior predictive capability for CA-AKI compared to other inflammatory biomarkers. Regarding the secondary outcome, multivariate COX regression analysis showed a positive correlation between elevated LAR levels and all-cause mortality. CONCLUSION: In patients undergoing elective PCI, LAR was significantly independently associated with CA-AKI, and it stood out as the optimal inflammatory biomarker for predicting CA-AKI.

The Association Between the Albumin-Bilirubin Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). We retrospectively observed 5629 patients undergoing elective PCI. Contrast-associated acute kidney injury is defined as a 50% or 0.3 mg/dl increase in baseline serum creatinine levels within 48 h of contrast exposure. The incidence of CA-AKI was 6.2% (n = 350). After adjusting for potential confounding factors, multivariate analysis showed that the ALBI score was an independent predictor of CA-AKI (P = .002). A restricted cubic spline analysis confirmed approximately linear relationships between the ALBI score and risks of CA-AKI. Furthermore, at a median follow-up of 2.8 years, multivariate Cox regression analysis indicated that the ALBI score was an independent risk factor for long-term mortality (P < .001). The ALBI score was closely related to the occurrence of CA-AKI and long-term mortality in patients who underwent elective PCI. This score might be useful for risk stratification in high-risk patient groups to predict CA-AKI.

A V-shaped association between high-density lipoprotein cholesterol levels and poor outcomes in patients after percutaneous coronary intervention.

BACKGROUND: High density lipoprotein cholesterol (HDL-C) is considered as "good cholesterol". Recent evidence suggests that a high HDL-C level may increase the risk of poor outcomes in some populations. PURPOSE: To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI during January 2012 and December 2018 were consecutively recruited and divided into three groups with different HDL-C levels: HDL-C ≤ 25 mg/dL, 25 < HDL-C ≤ 60 mg/dL, HDL-C > 60 mg/dL by the restricted cubic spline (RCS) analysis and assessed for all-cause mortality (ACM). The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis. RESULTS: The patients were followed with a median duration of 4 years. Of the 7284 participants, 727 all-cause deaths and 334 cardiovascular deaths occurred. A V-shaped association of HDL-C with the prognosis was observed, patients with either excessively low or high HDL-C levels reporting a higher risk than those with midrange values. After adjustment for confounding factors, the former exhibited a higher cumulative rate of ACM and cardiovascular mortality (CM) than the latter [low HDL-C: for ACM, hazard ratio (HR), 1.96; 95%CI, 1.41, 2.73, P < 0.001; for CM, HR, 1.66; 95%CI, 1.03, 2.67; P = 0.037; high HDL-C: for ACM, HR, 1.73; 95%CI, 1.29, 2.32, P < 0.001; for CM, HR, 1.73; 95%CI, 1.16, 2.58; P = 0.007]. CONCLUSION: HDL-C levels display a V-shaped association with poor outcomes in patients after PCI, with excessively high or low HDL-C suggesting a higher mortality risk. An optimal HDL-C level may fall in the range of 25-60 mg/dL.

Impact of post-dilatation on post-procedural physiology, microcirculatory resistance, and target vessel failure in STEMI patients undergoing PPCI: A single-center experience.

BACKGROUND: Suboptimal stent deployment is frequently observed in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). This study sought to investigate whether these patients could benefit from post-dilatation with respect to post-procedural physiology, microcirculatory resistance, and long-term clinical outcomes. METHODS: This was a retrospective study of consecutive STEMI patients who underwent successful stent implantation during PPCI from February 2016 to November 2021. Post-procedural physiology and microcirculatory resistance were assessed by Murray law-based quantitative flow ratio (µQFR) and angiographic microcirculatory resistance (AMR), respectively. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel-oriented myocardial infarction, and clinically driven target vessel revascularization. RESULTS: A total of 671 patients (671 culprit vessels) were included. Post-dilatation was selectively performed in 430 (64.1%) culprit vessels, resulting in a 0.02 (interquartile range: 0.00-0.05, p < 0.001) increase in post-procedural µQFR but no significant impact on AMR. During a median follow-up of 2.8 years (interquartile range: 1.4-3.0 years), TVF occurred in 47 (7.0%) patients. Post-dilatation demonstrated a trend toward a reduction in TVF (5.3% vs. 10.0%; adjusted hazard ratio: 0.60, 95% confidence interval: 0.33-1.09, p = 0.094), mainly driven by a lower incidence of clinically driven target vessel revascularization (1.6% vs. 4.1%; adjusted hazard ratio: 0.32, 95% confidence interval: 0.11-0.90, p = 0.030). CONCLUSIONS: In STEMI patients undergoing PPCI, selective post-dilatation was associated with improved post-procedural physiological results and a trend toward less TVF events without aggravating microcirculatory resistance.

A Pilot Study About the Role of PANoptosis-Based Genes in Atherosclerosis Development.

Background: As a chronic inflammatory disease, atherosclerosis (AS) and ischemia events are primarily affected by inflammation in AS. PANoptosis has been implicated in many human systemic disorders, including infection, cancer, neurodegeneration, and inflammation. On the other hand, little is understood about PANoptosis's function in AS. Methods: We used consensus clustering to divide the GSE100927 dataset into two panoptosis-related subgroups. PANoptosis-associated genes were screened by differential analysis and weighted gene co-expression network analysis (WGCNA) and enriched by ClueGO software. Investigating LASSO regression and MCODE to identify AS Diagnostic Markers. Immunoinfiltration analysis and single-cell analysis were used to search for cell types associated with the diagnostic genes. Final validation was performed by polymerase chain reaction (PCR). Results: We classified the GSE100927 dataset into two PANoptosis-related subtypes based on the expression of PANoptosis-related genes (PRGs) using consensus clustering. A total of 36 PANoptosis-associated genes were screened in the differentially expressed genes and WGCNA-related module. 4 hub genes were identified by MCODE and LASSO regression, and 3 AS diagnostic markers (ACP5, CCL3, HMOX1) were screened by external validation set. Immunoinfiltration analysis and single-cell analysis showed that the three diagnostic markers were associated with macrophages, and PCR results demonstrated that ACP5 and HMOX1 could be used as AS diagnostic markers. Conclusion: Our study identified ACP5 and HMOX1 as diagnostic genes for AS that may be associated with PANoptosis. ACP5 and HMOX1 may be involved in the pathogenesis of AS by regulating macrophage PANoptosis.

The predictive value of the neutrophil/platelet ratio on in-hospital adverse events and long-term prognosis in patients with coronary artery disease after percutaneous coronary intervention and its possible internal mechanism.

The neutrophil-to-platelet ratio (NPR) is considered to be an indicator of inflammatory status. The value of the NPR in predicting in-hospital adverse events (AEs) and long-term prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients has not yet been reported. Meanwhile, the mechanisms behind its predictive value for long-term prognosis remain unreported as well. The study retrospectively enrolled 7284 consecutive patients with CAD undergoing PCI from January 2012 to December 2018. Multivariable logistic regression analysis, multivariable Cox regression analysis, Kaplan‒Meier (KM) curve analysis, restricted cubic spline (RCS) curve analysis, and sensitivity analysis were used in the study. All-cause death was the endpoint of the study. According to the median value of the NPR, the patients were divided into two groups: the high group (NPR ≥ 0.02, n = 3736) and the low group (NPR < 0.02, n = 3548). Multivariate logistic regression analysis demonstrated that a high NPR was a risk factor for in-hospital AEs [odds ratio (OR) = 1.602, 95% CI 1.347-1.909, p = 0.001]. During a mean follow-up period of 3.01 ± 1.49 years, the multivariate Cox regression analysis showed that a high NPR affected the long-term prognosis of patients (HR 1.22, 95% CI 1.03-1.45, p = 0.025) and cardiac death (HR 1.49, 95% CI 1.14-1.95, p = 0.003). The subgroup analysis showed that the NPR was affected by age and sex. The mediation analysis identified that the effect of the NPR on long-term outcomes is partially mediated by serum creatinine (Scr) and triglycerides. The NPR may be a convenient indicator of in-hospital AEs and poor long-term and cardiac outcomes in CAD patients. It might have impacted prognosis through effects on kidney function and lipid metabolism.

Assessing the Predictive Value of Different Nutritional Indexes for Contrast-Associated Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The link between malnutrition and poor prognosis in cardiovascular disease has been established but the association between malnutrition and contrast-associated acute kidney injury (CA-AKI), a common complication of coronary procedures, remains poorly understood. In this study we investigated the predictive value of 3 nutritional indexes for CA-AKI in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: The study included a total of 6,049 consecutive patients undergoing PCI between May 2012 and September 2020, among whom 352 (5.8%) developed CA-AKI. We used the Controlling Nutritional Status (CONUT) score, the Geriatric Nutritional Risk Index (GNRI), and the Prognostic Nutritional Index (PNI) to assess the association between malnutrition risk and CA-AKI after PCI. Multivariate logistic regression analysis revealed that malnutrition, as identified by GNRI and PNI, was significantly associated with a higher risk of CA-AKI (moderate-severe malnutrition in GNRI: odds ratio [OR]=1.92, [95% confidence interval (CI), 1.27-2.85]; malnutrition in PNI: OR=1.87, [95% CI, 1.39-2.50]), whereas the CONUT score did not demonstrate a significant difference (P>0.05). Furthermore, GNRI (∆AUC=0.115, P<0.001) and PNI (∆AUC=0.101, P<0.001) exhibited superior predictive ability than the CONUT score for CA-AKI and significantly improved reclassification and discrimination in the fully adjusted model. CONCLUSIONS: Malnutrition, especially identified by the GNRI and PNI, was associated with a higher risk of CA-AKI after PCI. GNRI and PNI performed better than the CONUT score in predicting CA-AKI.

Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk.

BACKGROUND: Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. METHODS: This study enrolled 35,455 participants aged 35-75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. RESULTS: In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37-2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47-3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. CONCLUSIONS: The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. TRIAL REGISTRATION: retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.

Association of ambient PM10 and PM2.5 with coronary stenosis measured using selective coronary angiography.

BACKGROUND: Long-term ambient particulate matter (PM) exposure exerts detrimental effects on cardiovascular health. Evidence on the relation of chronically exposed ambient PM10 and PM2.5 with coronary stenosis remains lacking. Our aim was to investigate the association of PM10 and PM2.5 with coronary stenosis in patients undergoing coronary angiography. METHODS: We performed a retrospective cohort study consisting of 7513 individuals who underwent coronary angiography in Fujian Province, China, from January 2019 to December 2021. We calculated a modified Gensini score (GS) to represent the degree of stenosis in coronary arteries by selective coronary angiography. We fitted linear regressions and logistic models to assess the association of PM10 and PM2.5 with coronary stenosis. We employed restricted cubic splines to describe the exposure-response curves. We performed mediation analyses to assess the potential mediators. RESULTS: Long-term ambient PM10 and PM2.5 (prior three years average) exposure was significantly associated with the GS, with a breakpoint concentration of 47.5 µg/m3 and 25.8 µg/m3 for PM10 and PM2.5, respectively, above which we found a linear positive exposure-response relationship of ambient PM with GS. Each 10 µg /m3 increase in PM10 exposure (ß: 4.81, 95 % CI: 0.44-9.19) and PM2.5 exposure [ß: 10.50, 95 % CI: 3.14-17.86] were positively related to the GS. The adjusted odds ratio (OR) for each 10 µg/m3 increment in PM10 exposure on severe coronary stenosis was 1.33 (95 % CI: 1.04-1.76). Correspondingly, the adjusted OR for PM2.5 was 1.87 (95 % CI: 1.24-2.99). The mediation analysis indicated that the effect of PM10 on coronary stenosis may be partially mediated through total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum creatinine and blood urea nitrogen, and the effect of PM2.5 may be mediated in part by hemoglobin A1c. CONCLUSION: Our study provides the first evidence that chronic ambient PM10 and PM2.5 exposure was associated with coronary stenosis assessed by GS in patients with suspected coronary artery disease and reveals its potential mediators.

The optimal definition and prediction nomogram for left ventricular remodelling after acute myocardial infarction.

AIMS: Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. METHODS AND RESULTS: This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model. CONCLUSIONS: LV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Purpose: Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. Results: During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). Conclusion: The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

Inhibition of PI3K/Akt/mTOR signaling by NDRG2 contributes to neuronal apoptosis and autophagy in ischemic stroke.

BACKGROUND: Astrocytic N-myc downstream-regulated gene 2 (NDRG2), a differentiation- and stress-associated molecule, has been involved in the cause of ischemic stroke (IS). However, its downstream effector in IS remains unclear. This study aimed to characterize expression of NDRG2 in IS patients and rats and to investigate the underlying mechanism. METHODS: The protein expression of NDRG2 and mammalian target of the rapamycin (mTOR) and the extent of mTOR phosphorylation in plasma of IS patients were detected by ELISA. An oxygen-glucose deprivation model was established in mouse neuronal cells CATH.a, followed by cell counting kit-8, flow cytometry, TUNEL, and western blot assays to examine cell viability, apoptosis and autophagy. Finally, the effect of NDRG2-mediated phosphatidylinositol 3-kinase/protein kinase-B/mTOR (PI3K/AKT/mTOR) pathway on neuronal apoptosis and autophagy was verified in rats treated with middle cerebral artery occlusion. RESULTS: NDRG2 was highly expressed in the plasma of IS patients, while the extent of mTOR phosphorylation was reduced in IS patients. NDRG2 blocked the PI3K/Akt/mTOR signaling through dephosphorylation. Depletion of NDRG2 suppressed apoptosis and autophagy in CATH.a cells, which was reversed by a dual inhibitor of PI3K and mTOR, BEZ235. In vivo experiments confirmed that NDRG2 promoted neuronal apoptosis and autophagy by dephosphorylating and blocking the PI3K/Akt/mTOR signaling. CONCLUSION: The present study has shown that NDRG2 impairs the PI3K/Akt/mTOR pathway via dephosphorylation to promote neuronal apoptosis and autophagy in IS. These findings provide potential targets for future clinical therapies for IS.