Sirolimus-eluting iron bioresorbable scaffold versus cobalt-chromium everolimus-eluting stents in patients with coronary artery disease: Rationale and design of the IRONMAN-II trial.

BACKGROUND: The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). METHODS: A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). CONCLUSION: This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds.

The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999-2018.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) index in general type 2 diabetes mellitus (T2DM) patients is still unclear. Therefore, we aimed to determine the associations between TyG and all-cause/cause-specific death in a T2DM cohort and explore whether such associations would be modified by age. METHODS: A total of 3,376 patients with T2DM from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were selected and divided into the younger group (< 65 yrs) and the older group (≥ 65 yrs). Baseline TyG was calculated and cause-specific mortality status [cardiovascular (CV), cancer, and non-CV] was determined by the NHANES Public-Use Linked Mortality Files through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were used to evaluate the association between TyG and all-cause/cause-specific mortality. Interaction between TyG and age to mortality was also evaluated. Sensitivity analyses were performed in patients without cardiovascular disease, chronic kidney disease, or insulin treatment. RESULTS: During a median follow-up of 107 months, 805 all-cause deaths occurred, of which 250 and 144 were attributed to CV and cancer deaths. There was a significant age interaction to the association between TyG and all-cause/non-CV mortality. After fully adjusting for potential confounding factors, higher TyG was associated with an increased risk of all-cause [TyG per unit increase Hazard Ratio (HR) 1.33, 95% Confidence Interval (CI) 1.06-1.66, p = 0.014] and non-CV mortality (TyG per unit increase HR 1.54, 95% CI 1.18-2.01, p = 0.002) only in the younger group, but not in the older group. There was no significant association between TyG and CV/cancer death in the total cohort and two age subgroups. Similar results were found in RCS and sensitivity analyses. CONCLUSION: In a national sample of patients with T2DM in the United States, we found that the association between TyG and all-cause/non-CV death was modified by age. Higher TyG was only associated with an increased risk of all-cause/non-CV only in T2DM patients younger than 65 years old, but not in older patients.

Exendin-4 alleviates myocardial ischemia reperfusion injury by enhancing autophagy through promoting nuclear translocation of TFEB.

Ischemia-reperfusion (I/R) injury (IRI) is a common clinical consequence of myocardial infarction. Exendin-4 is a glucagon-like peptide-1 (GLP-1) analog that has been demonstrated to alleviate myocardial IRI. Autophagy, a lysosomal pathway balancing cell survival and cell death, is engaged in myocardial IRI. However, whether exendin-4 exerts a protective effect on myocardial IRI by modulating autophagy remains elusive. Herein, we investigated the effect of exendin-4 on autophagic flux and explored the underlying molecular mechanisms. Our data revealed that the autophagic flux was blocked in the human ventricular cardiomyocyte cell lines (AC16) subjected to oxygen glucose deprivation/reoxygenation (OGD/R) in vitro. Exendin-4 pre-treatment markedly restored the blocked autophagic flux induced by OGD/R through promoting nuclear translocation of TFEB and transcription of genes involving autophagy initiation, the effect of which was reversed by TFEB knockdown. The restoration of autophagic flux contributed to multiple beneficial effects of exendin-4 in cardiomyocytes, including reduction of oxidative stress, preservation of mitochondrial network as well as inhibition of cytochrome c leakage from mitochondrial permeability transition pore (MPTP) and the resulting apoptosis. Moreover, the administration of exendin-4 reduced infarct size and preserved cardiac function through its anti-apoptosis and antioxidative effects in vivo. These results shed some light on understanding the novel mechanism of exendin-4 as a protective agent against myocardial IRI.

Fibrinogen to HDL-Cholesterol ratio as a predictor of mortality risk in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI. METHODS: A retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death. RESULTS: Over a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99-3.65) and 1.48 (1.26-1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05). CONCLUSION: AMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients. TRIAL REGISTRATION: The Cardiorenal ImprovemeNt II registry NCT05050877.

Hourly Air Pollutants and Acute Coronary Syndrome Onset in 1.29 Million Patients.

BACKGROUND: Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality from acute coronary syndrome (ACS); however, the associations of subdaily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated. METHODS: We conducted a time-stratified case-crossover study among 1 292 880 patients with ACS from 2239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM2.5), coarse particulate matter (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) were collected. Hourly onset data of ACS and its subtypes, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, were also obtained. Conditional logistic regressions combined with polynomial distributed lag models were applied. RESULTS: Acute exposures to PM2.5, NO2, SO2, and CO were each associated with the onset of ACS and its subtypes. These associations were strongest in the concurrent hour of exposure and were attenuated thereafter, with the weakest effects observed after 15 to 29 hours. There were no apparent thresholds in the concentration-response curves. An interquartile range increase in concentrations of PM2.5 (36.0 µg/m3), NO2 (29.0 µg/m3), SO2 (9.0 µg/m3), and CO (0.6 mg/m3) over the 0 to 24 hours before onset was significantly associated with 1.32%, 3.89%, 0.67%, and 1.55% higher risks of ACS onset, respectively. For a given pollutant, the associations were comparable in magnitude across different subtypes of ACS. NO2 showed the strongest associations with all 3 subtypes, followed by PM2.5, CO, and SO2. Greater magnitude of associations was observed among patients older than 65 years and in the cold season. Null associations of exposure to either PM2.5-10 or O3 with ACS onset were observed. CONCLUSIONS: The results suggest that transient exposure to the air pollutants PM2.5, NO2, SO2, or CO, but not PM2.5-10 or O3, may trigger the onset of ACS, even at concentrations below the World Health Organization air quality guidelines.

Prediabetes and all-cause mortality in young patients undergoing coronary artery angiography: a multicenter cohort study in China.

BACKGROUND: The prevalence of prediabetes is increasing in young adults and patients undergoing coronary angiography. However, whether prediabetes is a considerable risk factor for all-cause mortality remains undetermined in young patients undergoing coronary angiography. METHODS: In this study, we retrospectively included 8868 young patients (men aged < 45 years, women aged < 55 years) who underwent coronary angiography (CAG). Patients were categorized as normoglycemic, prediabetes and diabetes according to the HbA1c level or documented history of diabetes. The association of all-cause mortality with diabetes and prediabetes was detected by Cox proportional hazards regression analysis. RESULTS: A total of 3240 (36.5%) among 8868 young patients receiving CAG were prediabetes and 2218 (25.0%) were diabetes. 728 patients died during a median follow-up of 4.92 years. Compared to the normoglycemic group, prediabetes increased the risk of all-cause mortality in young CAG patients by 24%(adjusted HR: 1.24, 95% CI: 1.04-1.49, p = 0.019) and diabetes increased the risk of all-cause mortality by 46%(adjusted HR:1.46, 95% CI:1.2-1.79, p < 0.001). Subgroup analysis showed that diabetes and prediabetes increased the risk of death mainly in patients without comorbidities. CONCLUSION: Prediabetes accounts for more than one-third of the young adults undergoing CAG and was associated with an increased risk of all-cause mortality, active prevention strategy should be considered for these patients.

Hourly air pollution exposure and the onset of symptomatic arrhythmia: an individual-level case-crossover study in 322 Chinese cities.

BACKGROUND: Few studies have explored the relationship between air pollution and arrhythmia onset at the hourly level. We aimed to examine the association of exposure to air pollution with the onset of acute symptomatic arrhythmia at an hourly level. METHODS: We conducted a nationwide, time-stratified, case-crossover study in China between 2015 and 2021. We obtained hourly information on the onset of symptomatic arrhythmia (including atrial fibrillation, atrial flutter, atrial and ventricular premature beats and supraventricular tachycardia) from the Chinese Cardiovascular Association Database - Chest Pain Center (including 2025 certified hospitals in 322 cities). We obtained data on hourly concentrations of 6 air pollutants from the nearest monitors, including fine particles (PM2.5), coarse particles (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone. For each patient, we matched the case period to 3 or 4 control periods during the same hour, day of week, month and year. We used conditional logistic regression models to analyze the data. RESULTS: We included a total of 190 115 patients with acute onset of symptomatic arrhythmia. Air pollution was associated with increased risk of onset of symptomatic arrhythmia within the first few hours of exposure; this risk attenuated substantially after 24 hours. An interquartile range increase in PM2.5, NO2, SO2 and CO in the first 24 hours after exposure (i.e., lag period 0-24 h) was associated with significantly higher odds of atrial fibrillation (1.7%-3.4%), atrial flutter (8.1%-11.4%) and supraventricular tachycardia (3.4%-8.9%). Exposure to PM2.5-10 was associated with significantly higher odds of atrial flutter (8.7%) and supraventricular tachycardia (5.4%), and exposure to ozone was associated with higher odds of supraventricular tachycardia (3.4%). The exposure-response relationships were approximately linear, without discernible concentration thresholds. INTERPRETATION: Exposure to air pollution was associated with the onset of symptomatic arrhythmia shortly after exposure. This finding highlights the importance of further reducing air pollution and taking prompt protective measures for susceptible populations during periods of elevated levels of air pollutants.

Comparison of cardiac biomarkers on risk assessment of contrast-associated acute kidney injury in patients undergoing cardiac catheterization: A multicenter retrospective study.

AIM: Cardiac biomarkers' predictive value of contrast-associated acute kidney injury (CA-AKI) remains unclear. We analysed whether creatine kinase isoenzyme-MB (CKMB), cardiac troponin I (cTnI) and preoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) are tied to CA-AKI patients undergoing cardiac catheterization. METHODS: In the multi-center study, we included 3553 people underwent cardiac catheterization for analysis. CA-AKI was defined as the absolute increase of over 0.3 mg/dL or an increase of more than 50% compared with the baseline serum creatinine within 48 hours following cardiac catheterization. Logistic regression model and receiver operating characteristic (ROC) curves were used to examine the association between cardiac biomarkers and CA-AKI and the efficacy of Mehran risk score (MRS) model on CA-AKI prediction with and without cardiac biomarkers. RESULTS: Among 3553 people, 200 people eventually developed CA-AKI. The logistic regression model showed that log10 CKMB (odds ratio (OR): 1.97, 95%CI:1.51-2.57, p < .001), cTnI (OR: 1.03, 95%CI: 1.02-1.04, p < .001) and log10 NT-proBNP (OR: 3.19, 95%CI: 2.46-4.17, p < .001) were independent predictors of CA-AKI. The ROC curve demonstrated that area under the curve (AUC) of MRS was 0.733. CKMB, cTnI and NT-proBNP all significantly improved the AUC value in combination with MRS model. (NT-proBNP: 0.798, p < .001; CKMB: 0.758, p = .003; cTnI: 0.755, p = .002), among which the NT-proBNP had the best predictive efficacy improvement. CONCLUSION: Cardiac biomarkers of CKMB, cTnI and NT-proBNP are all independently associated with CA-AKI among patients undergoing cardiac catheterization while NT-proBNP remains the best indicator. Adding CKMB, cTnI and NT-proBNP to MRS improved the prognostic efficacy and may be considered effective tools to predict the risk of CA-AKI in clinical practice.

Association of serum uric acid levels with cardiovascular and all-cause mortality in hypertensive patients in China: a cohort study.

PURPOSE: The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. METHODS: In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. RESULTS: After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to <7.55 mg/dL for men, 5.63 mg/dL to <6.42 mg/dL for women) as reference, the highest quintiles of SUA were associated with an elevated risk of all cause (HR: 1.34, 95% CI 1.00 to 1.80) in the crude model, but the association was not significant after adjusting for multiple comparisons. The association between low SUA and mortality and the dose-response analysis on the non-linearity of SUA-mortality relationship were not statistically significant. CONCLUSIONS: Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Effect of kidney disease on all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

Genetic predisposition to coronary artery disease is predictive of recurrent events: a Chinese prospective cohort study.

Evidence of the effects of genetic risk score (GRS) on secondary prevention is scarce and mixed. We investigated whether coronary artery disease (CAD) susceptible loci can be used to predict the risk of major adverse cardiovascular events (MACEs) in a cohort with acute coronary syndromes (ACSs). A total of 1667 patients hospitalized with ACS were enrolled and prospectively followed for a median of 2 years. We constructed a weighted GRS comprising 79 CAD risk variants and investigated the association between GRS and MACE using a multivariable cox proportional hazard regression model. The incremental value of adding GRS into the prediction model was assessed by integrated discrimination improvement (IDI) and decision curve analysis (DCA). In the age- and sex-adjusted model, each increase in standard deviation in the GRS was associated with a 33% increased risk of MACE (hazard ratio: 1.33; 95% confidence interval: 1.10-1.61; P = 0.003), with this association not attenuating after further adjustment for traditional cardiovascular risk factors. The addition of GRS to a prediction model of seven clinical risk factors and EPICOR prognostic model slightly improved risk stratification for MACE as calculated by IDI (+1.7%, P = 0.006; +0.3%, P = 0.024, respectively). DCA demonstrated positive net benefits by adding GRS to other models. GRS was associated with MACE after multivariable adjustment in a cohort comprising Chinese ACS patients. Future studies are needed to validate our results and further evaluate the predictive value of GRS in secondary prevention.

Association between triglyceride glucose index and worsening heart failure in significant secondary mitral regurgitation following percutaneous coronary intervention.

BACKGROUND: The triglyceride glucose (TyG) index is an alternative to insulin resistance (IR) as an early indicator of worsening heart failure (HF). Patients with secondary mitral regurgitation (sMR) often experience progressive deterioration of cardiac function. This study aimed to investigate the relationship between the TyG index and worsening of HF in significant sMR (grade ≥ 2) following percutaneous coronary intervention (PCI). METHODS: This study enrolled participants with significant sMR following PCI from a multicenter cohort study. The patients were divided into the following 3 groups according to tertiles of TyG index: T1, TyG ≤ 8.51; T2, TyG > 8.51 to ≤ 8.98; and T3, TyG > 8.98. The main clinical outcome was worsening HF including unplanned rehospitalization or unscheduled physician office/emergency department visit due to HF and unplanned mitral valve surgery. RESULTS: A total of 922 patients (mean ± SD age, 64.1 ± 11.0 years; 79.6% male) were enrolled. The incidence of worsening HF was 15.5% in T1, 15.7% in T2, and 26.4% in T3. In the multivariable model, the highest TyG tertile (T3 group) was more strongly correlated with worsening HF than the lowest tertile (T1 group) after adjusting for confounders (adjusted hazard ratio, 2.44; 95% confidence interval, 1.59-3.72; P < 0.001). The addition of TyG to risk factors such as N-terminal pro brain natriuretic peptide and clinical models improved the predictive ability of TyG for worsening HF. CONCLUSIONS: Elevated preprocedural TyG index is a significant and independent risk factor for worsening HF in sMR following PCI that can be used for risk stratification.

A Bioinformatics Investigation into the Pharmacological Mechanisms of Sodium-Glucose Co-transporter 2 Inhibitors in Diabetes Mellitus and Heart Failure Based on Network Pharmacology.

PURPOSE: Diabetes mellitus (DM) is a major risk factor for the development of heart failure (HF). Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated consistent benefits in the reduction of hospitalization for HF in patients with DM. However, the pharmacological mechanism is not clear. To investigate the mechanisms of SGLT2 inhibitors in DM with HF, we performed target prediction and network analysis by a network pharmacology method. METHODS: We selected targets of SGLT2 inhibitors and DM status with HF from databases and studies. The "Drug-Target" and "Drug-Target-Disease" networks were constructed using Cytoscape. Then the protein-protein interaction (PPI) was analyzed using the STRING database. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to investigate using the Bioconductor tool for analysis. RESULTS: There were 125 effective targets between SGLT2 inhibitors and DM status with HF. Through further screening, 33 core targets were obtained, including SRC, MAPK1, NARS, MAPK3 and EGFR. It was predicted that the Rap1 signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications and other signaling pathways were involved in the treatment of DM with HF by SGLT2 inhibitors. CONCLUSION: Our study elucidated the possible mechanisms of SGLT2 inhibitors from a systemic and holistic perspective based on pharmacological networks. The key targets and pathways will provide new insights for further research on the pharmacological mechanism of SGLT2 inhibitors in the treatment of DM with HF.

The effect of preoperative statin treatment on acute kidney injury in elderly patients undergoing valve replacement surgery.

PURPOSES: The effects of preoperative statin treatment on acute kidney injury (AKI) remain controversial, and current clinical evidence regarding statin use in the elderly undergoing valve replacement surgery (VRS) is insufficient. The present study aimed to investigate the association between preoperative statin treatment and AKI after VRS in the elderly. METHODS: Three thousand seven hundred ninety-one elderly patients (≥ 60 years) undergoing VRS were included in this study and divided into 2 groups, according to the receipt of statin treatment before the operation: statin users (n = 894) and non-users (n = 2897). We determined the associations between statin use, AKI, and other adverse events using a multivariate model and propensity score-matched analysis. RESULTS: After propensity score-matched analysis, there was no difference between statin users and non-users in regard to postoperative AKI (72.5% vs. 72.4%, p = 0.954), in-hospital death (5.7% vs. 5.1%, p = 0.650) and 1-year mortality (log-rank = 0, p = 0.986). The multivariate analysis showed that statin use was not an independent risk factor for postoperative AKI (OR = 0.97, 95% CI: 0.90-1.17, p = 0.733), in-hospital mortality (OR = 1.12, 95% CI: 0.75-1.68, p = 0.568), or 1-year mortality (HR = 0.95, 95% CI: 0.70-1.28, p = 0.715). CONCLUSION: Preoperative statin treatment did not significantly affect the risk of AKI among elderly patients undergoing VRS.

A risk score predicting unplanned renal replacement therapy after coronary catheterization.

BACKGROUND: Iodinated contrast medium exposure is associated with acute kidney injury (AKI). Patients with severe contrast-induced AKI (CI-AKI) may need renal replacement therapy (RRT). Prediction models exist for CI-AKI, but few need RRT. We aimed to establish a preprocedural score model to stratify patients at risk of unplanned postprocedural RRT following invasive coronary angiography (ICA) or percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between January 2010 and December 2015, a series of 3,469 patients were randomly divided into two cohorts at a 2 : 1 ratio for model development and validation, respectively. A total of 36 patients (1.0%) needed unplanned postprocedural RRT following ICA and/or PCI. Multivariable logistic regression was used to build the risk model. C-statistic and Hosmer-Lemeshow tests were used to evaluate the performance of the model. Five preprocedural variables - independently associated with unplanned postprocedural RRT - were identified as factors of the risk score model with different scores: age > 75 years (1), serum creatinine level ≥ 1.5 mg/dL (1), diabetes mellitus (1), hypotension (2), and acute myocardial infarction (2). The risk score model was demonstrated with high discrimination (C-statistic = 0.872) and goodness of fit (χ2 = 3.769, p = 0.438). Furthermore, the model allowed a hierarchical classification of low, intermediate, and high risk, within which the observed unplanned RRT rates were ~ 0.4, 3.0, and 20.0%, respectively. CONCLUSION: Using preprocedural variables, we developed and validated a risk model for unplanned postprocedural RRT following ICA and/or PCI.

Malnutrition in patients with coronary artery disease: Prevalence and mortality in a 46,485 Chinese cohort study.

BACKGROUND AND AIMS: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its long-term prognostic impact in general coronary artery disease (CAD) patients is not well known. We aim to report the prevalence and long-term mortality of malnutrition in the whole general population. METHODS AND RESULTS: In this retrospective cohort study, the controlling nutritional status (CONUT) score was applied to 46,485 consecutive patients undergoing coronary angiography (CAG) and diagnosed with CAD from January 2007 to July 2018. Patients were stratified as having no malnutrition (n = 19,780), mild (n = 21,092), moderate (n = 5286) and severe malnutrition (n = 327), based on CONUT score. Overall, mean age was 63.1 ± 10.7 years, and 75.8% of patients (n = 35,250) were male. 45.4% of patients were mildly malnourished and 12.1% were moderately or severely malnourished. During a median follow-up of 5.1 years (interquartile range: 3.0-7.7 years), 6093 (17.3%) patients died. After adjusting for confounders, malnutrition risk was associated with significantly increased risk for all-cause death (mild vs. normal, HR = 1.19,95% confidence interval [CI]: 1.12 to 1.28; moderate vs. normal, HR = 1.42,95% CI: 1.30 to 1.55; severe vs. Normal, HR = 1.95, 95% CI: 1.57 to 2.41) (p for trend<0.001). The similar result on all-cause mortality was also found in different subgroups stratified by gender, chronic kidney disease, anemia, percutaneous coronary intervention. CONCLUSIONS: Malnutrition is a common complication among patients with CAD, and is strongly associated with increased mortality. Further studies need to explore the efficacy of nutritional interventions on long-term prognosis among CAD patients. This study was registered at Clinicaltrials.gov as NCT04407936.

Prevalence and mortality of transient acute kidney injury within 48 h, as new subtype, following coronary angiography: a cohort study.

BACKGROUND: The association of transient acute kidney injury (AKI) with mortality was controversial. Our study aims to investigate the prevalence and impact of transient AKI on mortality in patients following coronary angiography (CAG). METHODS: Our study retrospectively enrolled 3970 patients with pre-operative serum creatinine (Scr) and twice measurements within 48 h after procedure. Transient AKI defined as the diagnosis of AKI (Scr > 0.3 mg/dL or > 50% from the baseline level) on day 1 when Scr failed to meet the criteria for AKI on the day 2. Maintained AKI was defined as AKI not meeting the definition for transient AKI. The primary outcome was 1-year all-cause mortality. Multivariable logistic regression was used to assess the association between transient AKI and 1-year mortality. RESULTS: Among 3,970 participants, 861 (21.7%) occurred AKI, of whom 128 (14.9%) was transient AKI and 733 (85.1%) was maintained AKI. 312 (7.9%) patients died within 1-year after admission. After multivariable analysis, transient AKI was not associated with higher 1-year mortality [adjusted odds ratio (aOR), 1.37; CI 0.68-2.51] compared without AKI. Among AKI patients, transient AKI was associated with a 52% lower 1-year mortality compared with maintained AKI. Additionally, maintained AKI was significantly associated with higher 1-year mortality (aOR, 2.67; CI 2.05-3.47). CONCLUSIONS: Our data suggested that transient AKI within 48 h was a common subtype of AKI following CAG, without increasing mortality. More attention needs to be paid to the patients suffering from maintained AKI following CAG.

CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic.

In response to the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the Chinese Society of Cardiology (CSC) issued this consensus statement after consulting with 125 medical experts in the fields of cardiovascular disease and infectious disease. The over-arching principles laid out here are the following: 1) Consider the prevention and control of COVID-19 transmission as the highest priority, including self-protection of medical staff; 2) Patient risk assessment of both infection and cardiovascular issues. Where appropriate, preferential use of conservative medical therapeutic approaches to minimize disease spread; 3) At all times, medical practices and interventional procedures should be conducted in accordance with the directives of the infection control department of local hospitals and local health commissions.

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin.

Although a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS, including MYOM2 (rs17064642), WDR24 (rs11640115), NECAB1 (rs74569896), EFR3A (rs4736529), AGAP3 (rs75750968), ZDHHC3 (rs3749187), ECHS1 (rs140410716), and KRTAP10-4 (rs201441480). Notably, the expressions of MYOM2 and ECHS1 are downregulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting 18-month MACE and achieved high predictive performance (AUC ranged between 0.92 and 0.94 for three machine-learning methods). Our findings shed light on the pathogenesis of cardiovascular outcomes and may help the clinician to make a decision on the therapeutic intervention for ACS patients.