Latexin deficiency limits foam cell formation and ameliorates atherosclerosis by promoting macrophage phenotype differentiation.

Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE-/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE-/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.

The levels of serum lipoprotein(a) on clinical outcomes in Chinese hospitalized patients with cardiovascular diseases.

OBJECTIVE: Serum lipoprotein(a) [Lp(a)] is a risk factor of cardiovascular diseases. However, the relationship between the serum Lp(a) and clinical outcomes has been seldom studied in Chinese hospitalized patients with cardiovascular diseases. METHODS: We retrospectively collected the clinical data of hospitalized patients with cardiovascular diseases in the Cardiovascular Department of Dongguan People's Hospital from 2016 to 2021 through the electronic case system. Patients were divided into 4 groups based on Lp(a) quartiles: Quartile1 (≤ 80.00 mg/L), Quartile 2 (80.01 ~ 160.90 mg/L), Quartile 3 (160.91 ~ 336.41 mg/L), Quartile 4 (> 336.41 mg/L). Cox proportional hazard regression models were constructed to examine the relationship between Lp(a) and cardiovascular events. RESULTS: A total of 8382 patients were included in this study. After an average follow-up of 619 (320 to 1061) days, 1361 (16.2%) patients developed major adverse cardiovascular events, and 125 (1.5%) all-cause death were collected. The incidence of MACEs was 7.65, 8.24, 9.73 and 10.75 per 100 person-years in each Lp(a) quartile, respectively; the all-cause mortality was 0.48, 0.69, 0.64 and 1.18 per 100 person-years in each Lp(a) quartile, respectively. The multivariate Cox regression analysis suggested that high Lp(a) level was an independent risk factor for MACEs (HR: 1.189, [95% CI: 1.045 to 1.353], P = 0.030) and all-cause death (HR: 1.573, [95% CI: 1.009 to 2.452], P = 0.046). CONCLUSION: In addition to traditional lipid indicators, higher Lp(a) exhibited higher risks of adverse cardiovascular events and death, indicated worse prognosis. Lp(a) may be a new target for the prevention of atherosclerotic diseases.

Thyroid dysfunction in nonvalvular atrial fibrillation and clinical outcomes.

BACKGROUND: Thyroid dysfunction's effects on those who have been diagnosed with atrial fibrillation have not been well investigated. We looked at how thyroid function among patients with pre-existing atrial fibrillation related to thromboembolic risk and clinical outcomes. METHODS: We gathered the medical information of patients diagnosed with nonvalvular atrial fibrillation (NVAF) between 2016 and 2020 at Dongguan People's Hospital. We then assessed the correlation between thyroid dysfunction and thrombotic risk (CHA2DS2-VASc) as well as the occurrence of clinical composite endpoint (all-cause death, heart failure, systemic embolism and hemorrhage events). RESULTS: Of 1329 patients were admitted, 82.6% were euthyroid, 7.4% had subclinical hyperthyroidism, 4.2% had subclinical hypothyroidism, and 6.7% had low triiodothyronine (T3) syndrome. Lower levels of total triiodothyronine (TT3) were linked to an increased risk of thromboembolism (P < 0.005). During a median follow-up period of 1.84 years, there were 608 clinical composite endpoint occurrences. In the adjusted model, Low T3 syndrome was linked to a higher risk of the clinical composite endpoint (HR, 1.68; 95% CI, 1.20-2.37; P < 0.05) in comparison to euthyroidism. Specifically, low T3 syndrome was linked to a higher risk of heart failure (HR, 1.52; 95%CI, 1.01-2.30; P < 0.05) and all-cause death (HR, 3.34; 95% CI, 1.76-6.36; P < 0.001). CONCLUSION: Low T3 syndrome are linked to an increased risk of heart failure and all-cause death in individuals with NVAF. And Patients with NVAF and low TT3 levels have a higher risk of thromboembolism.

Covalent organic framework-based immunosensor to detect plasma Latexin reveals novel biomarker for coronary artery diseases.

It is a great challenge to develop an efficient and rapid method to detect of biomarkers of cardiovascular disease. In this research, a differential pulse voltammetry (DPV)-based ultrasensitive immunosensor for the detection of plasma Latexin (LXN) has been established. With the aim to increase the surface area of the bare glassy carbon electrode (GCE), multi-walled carbon nanotube-graphene oxide has been developed. Covalent organic frameworks (COFs) are dropped with gold nanoparticles (AuNPs), secondary antibody and thionine (Thi-Ab2-Au-COFs) act as the signal probe with high electronic conductivity. Under the ideal conditions, the immunosensor displayed a broad linear response range from 0.01 ng mL-1 to 100 ng mL-1, with a detection limit of 50 pg mL-1 (S/N = 3). The immunosensor also demonstrates outstanding sensitivity, repeatability, and stability. Finally, we utilized the designed immunosensor to detect plasma LXN in coronary artery disease (CAD) patients, and the data showed that plasma LXN was significantly increased in CAD patients with a good performance of ROCAUC (AUC 0.871, 95 % CI 0.725-1.0, p = 0.002), indicating plasma LXN is a potential biomarker of cardiovascular disease. This immunosensor is a promising strategy for screening CAD patients in clinical practice.

Validation of plasma D-dimer in Chinese patients with acute non-ST segment elevation myocardial infarction.

Objective: To analyze the predictive values of D-dimer in Chinese patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods: We retrospectively retrieved consecutive patients hospitalized due to acute NSTEMI from January 2015 to December 2018 from the Electronic Medical Record (EMR) library. Clinical and follow-up data were collected. The primary endpoint was major adverse composite cardiovascular events (MACEs), such as all-cause death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints included all-cause death, non-fatal myocardial infarction, non-fatal stroke, heart failure, and severe arrhythmias. The Cox regression model was used to evaluate the association between risk factors and clinical outcomes in Chinese patients with NSTEMI. Results: A total of 673 patients were included; the median age was 64.0 (53.0-75.0) years old and 76.2% were men. Patients with higher D-dimer levels were more often women, older, had a higher Charlson Comorbidity Index, and had a higher incidence of MACEs (59.9 vs. control 9.0%; p < 0.001) and all-cause death (49.1 vs. control 2.2%; p < 0.001). The multivariate Cox analysis suggested that the D-dimer level was an independent predictor of MACEs (hazard ratio [HR]: 1.069, 95% CI: 1.010-1.132, p = 0.021). The receiver operating characteristic (ROC) analysis suggested that D-dimer levels were better than the Charlson Comorbidity Index in all-cause death. Conclusion: In Chinese patients with acute NSTEMI, higher D-dimer levels on admission suggest a poor long-term prognosis.

Effects of biodegradable biomedical porous MnO2 nanoparticles on blood components and functions.

In recent years, manganese dioxide (MnO2) nanoparticles with unique physicochemical properties have been widely used in many biomedical fields, such as biosensors, contrast agents, tumor therapy, and drug delivery. From these applications, MnO2 nanoparticles have great clinical translation potential. However, by contrast, the in vitro and in vivo biosafety of MnO2 nanoparticles have been deeply and thoroughly clarified for the clinical translation, which hinders their clinical applications. In this work, we deeply investigated the blood safety of MnO2 nanoparticles by conducting a series of in vitro and in vivo experiments. These included the effects of MnO2 nanoparticles on morphology of red blood cells, activation of platelets, coagulation functions, and toxicity of key organs. The obtained results show that these effects displayed a concentration-dependent manner of MnO2 nanoparticles. Different safe concentration ranges could be found in the different experimental index. This study provides important guidance for the specific biomedical applications of MnO2 nanoparticles, greatly accelerating their laboratory development and clinical translation.

Latexin deficiency attenuates adipocyte differentiation and protects mice against obesity and metabolic disorders induced by high-fat diet.

Obesity is a risk factor for many chronic diseases, and is associated with increased incidence rate of type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. Adipocyte differentiation play critical role during development of obesity. Latexin (LXN), a mammalian carboxypeptidase inhibitor, plays important role in the proliferation and differentiation of stem cells, and highlights as a differentiation-associated gene that was significantly downregulated in prostate stem cells and whose expression increases through differentiation. However, it is unclear whether LXN is involved in adipocyte differentiation. The aim of this study was to evaluate the role of LXN on adipocyte differentiation, as well as its effects on high fat-induced obesity and metabolic disorders. In this study, we determine the expression of LXN in adipose tissue of lean and fat mice by Western blot, qPCR and immunohistochemistry. We found that LXN in fat tissues was continuous increased during the development of diet-induced obesity. We fed wild-type (WT) and LXN-/-mice with high-fat diet (HFD) to study the effects of LXN on obesity and related metabolic functions. We found that mice deficient in LXN showed resistance against high-fat diet (HFD)-induced obesity, glucose tolerance, insulin tolerance and hepatic steatosis. In vitro studies indicated that LXN was highly induced during adipocyte differentiation, and positively regulated adipocyte differentiation and adipogenesis in 3T3-L1 cells and primary preadipocytes. Functional analysis revealed that the expression of LXN was positively regulated by mTOR/RXR/PPARɤ signaling pathway during the differentiation of adipocytes, while LXN deletion decreased the protein level of PPARɤ in adipocyte through enhancing FABP4 mediated ubiquitination, which led to impaired adipocyte differentiation and lipogenesis. Collectively, our data provide evidence that LXN is a key positive regulator of adipocyte differentiation, and therapeutics targeting LXN could be effective in preventing obesity and its associated disorders in clinical settings.

Prevalence and impact of fibrinolytic dysregulation in patients with acute coronary syndromes.

OBJECTIVE: Dual antiplatelet therapy can reduce coronary thrombosis and improve the prognosis in patients with acute coronary syndrome (ACS). However, there was limited prognostic information about fibrinolytic dysregulation in patients with ACS. This study is aimed to evaluated the prevalence and impact of fibrinolytic dysregulation in patients with acute coronary syndrome (ACS). METHODS: We retrospectively analyzed coagulation and fibrinolysis related indexes of ACS in hospitalized adults with rapid thrombelastography between May 2016 and December 2018. All of the follow-up visits were ended by December 2019. The primary outcome was the occurrence of major adverse cardiovascular events (MACEs), which included unstable angina pectoris, non-fatal myocardial infarction, non-fatal cerebral infarction, heart failure and all-cause death. RESULTS: Three hundred thirty-eight patients were finally included with an average age of 62.5 ± 12.8 years old, 273 (80.5%) were males, 137(40.5%) patients were with ST-elevation myocardial infraction. Fibrinolysis shutdown (LY30<0.8%) and hyperfibrinolysis (LY30 >3.0%) were observed among 163 (48.2%) and 76(22.5%) patients, respectively. During a total of 603.2 person·years of follow-up period, 77 MACEs occurred (22.8%). Multivariate Cox regression analysis indicated that LY30 [HR: 1.101, 95% CI: 1.010-1.200, P = 0.028] was independently correlated with the occurrence of MACEs. The hazard ratios pertaining to MACEs in patients with fibrinolysis shutdown and hyperfibrinolysis compared with those in the physiologic range (LY30: 0.8-3.0%) were 1.196 [HR: 1.196, 95% CI: 0.679-2.109,P = 0.535] and 2.275 [HR: 2.275, 95% CI: 1.241-4.172, P = 0.003], respectively. CONCLUSIONS: Fibrinolytic dysregulation is very common in selected patients with ACS, and hyperfibrinolysis (LY30 > 3%) is associated with poor outcomes in patients with ACS.

Whole blood dynamic platelet aggregation counting and 1-year clinical outcomes in patients with coronary heart diseases treated with clopidogrel.

In the setting of coronary heart diseases (CHDs) on treatment with clopidogrel, ADP-induced platelet aggregation has been demonstrated with ischemic events. However, there were very limited data for predicting ischemic events by platelet function test via dynamic platelet aggregation counting (DPAC). The present study aimed to evaluate the relationship between adenosine diphosphate (ADP)-induced whole blood platelet aggregation rates (PARs) and clinical outcomes in patients with CHDs on treatment with clopidogrel. We have retrospectively analyzed the clinical data of consecutive patients with CHDs based on the electronic medical records between May 2016 and December 2018. The primary endpoint was a composite endpoint events (CEEs) of ischemic cardiovascular events (including acute coronary syndrome, heart failure, transient ischemic attack, and cerebral infarction) and all-cause death. A total of 490 patients (mean age 66.6 years, 71% man) were received ADP-induced PARs via DPAC. On follow-up (mean 374 days), 107 subjects (21.8%) developed CEEs. Cox regression analysis indicated that the risk of CEEs was independently associated with ADP-induced whole blood PARs [HR: 1.023, 95% CI: 1.005-1.041, P = .011]. The distribution of CYP2C19 loss of function gene was higher in patients with on-treatment platelet hyperresponsiveness (10/12 vs 38/75, P = .042). In conclusion, ADP-induced whole blood PARs via DPAC is feasible, which can predict the incidence of 1-year CEEs in patients with CHDs on treatment with clopidogrel. CYP2C19 gene polymorphism was associated with clopidogrel on-treatment platelet hyperresponsiveness.

Impact of estimated glomerular filtration rate on long-term clinical outcomes among Chinese patients with atrial fibrillation.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is a widely accepted indicator of renal function. The aim of this study was to evaluate the relationship between eGFR and 3-year clinical outcomes among Chinese patients with atrial fibrillation (AF). METHODS: We retrospectively studied 433 consecutive Chinese patients with AF (51.0% males, mean age 65.6 ± 13.2 years) between February 2013 and December 2017. Baseline clinical data were collected according to medical records. eGFR was calculated by MDRD equation for Chinese patients according to baseline age, sex and serum creatinine. The primary clinical outcome of interest was all-cause mortality. RESULTS: During a median follow-up period of 3.1 (0.5-4.5) years, 73 deaths (16.9%) were recorded. Multivariate Cox regression analyses indicated that eGFR was independently associated with all-cause death in total population [hazard ratio (HR) 0.984; 95% confidence interval (CI) 0.972-0.995, P = 0.006] and patients free of valvular heart diseases (VHDs) (HR 0.975; 95% CI 0.959-0.992, P = 0.003), but not with VHDs. A receiver operating characteristic (ROC) analysis revealed that reduced eGFR predicted all-cause mortality with areas under the ROC curve of 0.637 (95% CI 0.539-0.735, P = 0.004) in AF patients free of VHDs. CONCLUSIONS: eGFR is an independent predictor of 3-year all-cause mortality among Chinese patients with AF, especially among those patients free of VHDs.

Clinical characteristics and outcomes of patients with myocarditis mimicking ST-segment elevation myocardial infarction: Analysis of a case series.

Acute myocarditis mimicking ST-segment elevation myocardial infarction (STEMI) is highly deceptive for an accurate diagnosis, and a systematic study is lacking with regard to the clinical features and prognosis of this distinct clinical entity.Patients with suspected STEMI and eventually diagnosed with myocarditis by cardiac magnetic resonance (CMR) from January 2012 to April 2016 at Fuwai Hospital were identified by reviewing medical records and electronic databases. Follow-up was conducted by clinical visits and phone contacts in a median duration of 17 months.A total of 18 patients were included in the study, with 17 males and 1 female. They were relatively young, and their mean age was 30.8 years. 94.4% of the patients had a high prevalence of infectious prodrome, and inflammatory biomarkers were notably elevated in all patients. Late gadolinium enhancement on CMR was detected in 13 patients. Three patients underwent fulminant course, and left ventricular ejection fraction (LVEF) <45% on admission occurred in 3 patients. The median LVEF improved from 59% on admission to 65% at discharge (P <.001), and none developed cardiac insufficiency, heart transplantation, or death during a median follow-up of 17 months.Myocarditis mimicking STEMI is featured by young age and an existence of flu-like prodrome. CMR benefits the differential diagnosis of this unique clinical entity. Notably, patients with myocarditis mimicking STEMI had a favorable prognosis, and establishing an accurate diagnosis is crucial to avoid unreasonable treatments for them.

Plasma fibrin D-dimer and the risk of left atrial thrombus: A systematic review and meta-analysis.

BACKGROUND: Plasma fibrin d-dimer has been taken as a marker for thrombus. The aim of this study was to evaluate the relationship between d-dimer (DD) levels and left atrial spontaneous echo contrast (SEC)/left atrial thrombus (LAT). METHODS: We identified clinical studies by systematic search of MEDLINE and EMBASE databases up to Feb 2016. All observational studies that considered DD as a study factor and trans-esophageal echocardiography (TEE) identified SEC/LAT as an outcome were included. Two reviewers independently selected the studies and extracted the data. RESULTS: Of the 21 included studies, 16 studies (2652 patients) have compared the mean DD differences between patients with and without an evidence of the presence of SEC/LAT, 9 studies (1667 patients) have estimated the diagnostic value of DD in the presence of LAT, and 11 studies (1856 patients) have available information to calculate a ratio of the presence of LAT among individuals in the top and the bottom third of DD levels. The pooled standardized mean difference (SMD) of DD between patients with and without left atrial SEC and/or LAT was 1.29 [95%CI: 0.51, 2.08], with SMDs of 0.42 [95% CI: 0.08, 0.77] and 2.34 [95% CI: 1.01, 3.68] in SEC/LAT and LAT subgroups, respectively. The combined risk ratio of the presence of LAT among individuals between the top of the distribution of DD levels and that in the bottom third was 3.84 [95% CI: 2.35, 6.28], associating with a mean difference of 0.78 ug/ml (1.10 vs 0.32 ug/ml). The pooled sensitivity, specificity and positive likelihood ratio of DD for LAT were 0.75 [95% CI: 0.65, 0.83], 0.81 [95% CI: 0.59, 0.93] and 4.0 [95% CI: 1.7, 9.9], respectively. CONCLUSIONS: High plasma fibrin DD was associated with left atrial SEC/LAT, particularly among patients with LAT. DD levels have moderate sensitivity and specificity for diagnosing LAT.

Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants Compared With Uninterrupted Vitamin K Antagonists in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

Anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) is of paramount importance for prevention of thromboembolic events, and recent studies favor uninterrupted vitamin K antagonists (VKAs). We aimed to compare the efficacy and safety of new oral anticoagulants (NOACs) to uninterrupted VKAs for anticoagulation in CA by performing a meta-analysis. PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov databases were searched for studies comparing NOACs with uninterrupted VKAs in patients who underwent CA for AF from January 1, 2000, to August 31, 2015. Odds ratio (OR) and Peto's OR (POR) were used to report for event rates >1% and <1%, respectively. A total of 11,686 patients with AF who underwent CA in 25 studies were included in this analysis. There was no significant difference between NOACs and uninterrupted VKAs in occurrence of stroke or transient ischemic attacks (POR 1.35, 95% CI 0.62 to 2.94) and major bleeding (POR 0.87, 95% CI 0.58 to 1.31), which were consistent in subgroup analysis of interrupted and uninterrupted NOACs. A lower risk of minor bleeding was observed with NOACs (OR 0.80, 95% CI 0.65 to 1.00), and no major differences were observed for the risk of thromboembolic events, cardiac tamponade or pericardial effusion requiring drainage, and groin hematoma. NOACs, whether interrupted preprocedure or not, were associated with equal rates of stroke or TIA and major bleeding complications and less risk of minor bleeding compared with uninterrupted VKAs in CA for AF.

An in-vitro evaluation of direct thrombin inhibitor and factor Xa inhibitor on tissue factor-induced thrombin generation and platelet aggregation: a comparison of dabigatran and rivaroxaban.

Dabigatran and rivaroxaban may simultaneously inhibit coagulation and platelet activation. This study aimed to reveal the in-vitro effects of dabigatran and rivaroxaban on thrombin generation and platelet aggregation (PAg) derived via tissue factor (TF) pathway. Citrated blood was obtained from six healthy adults (26-60 years old) and pretreated with increasing concentrations of dabigatran or rivaroxaban. Plasmatic endogenous thrombin potential (ETP) was measured by the calibrated automated thrombogram method. The whole blood PAg was evaluated via a kinetic counting method. TF produced an ETP of 1904.69 ±â€Š121.42 nmol min and a PAg of 78 ±â€Š5%. Dabigatran and rivaroxaban concentration-dependently reduced ETP with half-maximal inhibitory concentrations of 460.1 ±â€Š1.4 and 678.1 ±â€Š1.4 nmol/l, and inhibited PAg with half-maximal inhibitory concentrations of 119.5 ±â€Š1.5 and 77.5 ±â€Š1.6 nmol, respectively. Dabigatran and rivaroxaban significantly inhibit TF-induced hypercoagulation and platelet activation in vitro in a concentration-dependent manner. Rivaroxaban displays stronger inhibition on thrombin generation and PAg than dabigatran.

The relationship between elevated red cell distribution width and long-term outcomes among patients with atrial fibrillation.

OBJECTIVES: Red cell distribution width (RDW) is associated with the incidence of atrial fibrillation (AF). The aim of this study was to evaluate the relationship between elevated RDW and long-term clinical outcomes among patients with AF. DESIGN AND METHODS: We prospectively observed 300 consecutive patients with AF (50.3% males, mean age 62.6 ± 12.9 years) between February 2009 and October 2011. Baseline RDW levels and clinical data were collected. The primary clinical outcomes of interest included all-cause mortality and the incidence of major adverse events (MAEs). RESULTS: During a median follow-up period of 3.2 years, 60 deaths and 92 MAEs were recorded. From the lowest to the highest RDW quartile, an increased risk of mortality (2.76, 3.98, 8.40 and 13.77 per 100 person-years, respectively) and an incidence of MAEs (6.46, 8.18, 13.79 and 20.27 per 100 person-years, respectively) were noted. In a multivariate Cox regression analysis, RDW was independently associated with both all-cause mortality (hazard ratio (HR): 1.024; 95% confidence interval (CI): 1.012-1.036, P < 0.001) and MAEs (HR: 1.012; 95% CI: 1.002-1.023, P = 0.023). A receiver operating characteristic (ROC) analysis revealed that RDW predicted both mortality and MAEs with areas under the ROC curves (AUCs) of 0.682 (P < 0.001) and 0.617 (P = 0.001); the best cutoff points were 13.85% and 13.55%, respectively. CONCLUSIONS: Elevated RDW is an independent predictor of long-term adverse clinical outcomes, including all-cause mortality and MAEs, among patients with AF.

The prognostic effects of ventricular heart rate among patients with permanent atrial fibrillation with and without coronary artery disease: a multicenter prospective observational study.

Heart rate control is important among patients with either atrial fibrillation (AF) or coronary artery disease (CAD). However, the relationship between the ventricular heart rate and adverse outcomes among patients with AF and CAD remains unclear. This study aimed to assess the prognostic effects of ventricular heart rate in patients with permanent AF (permAF) and CAD. We performed a multicenter, prospective, observational study of patients with AF in China. Patients≥18 years old with permAF were included and divided into a CAD group and a non-CAD group. All patients underwent 1 year of follow-up. The primary outcome was total mortality. Cox proportional hazard models were used to evaluate the relationship between risk factors and the survival rate in the study population.A total of 852 patients (69.1±12.7 years old, 43.3% male, 44.7% with CAD) were included in the analysis. Patients with CAD were older, were more likely to be male and exhibited higher prevalences of hypertension, diabetes mellitus, LV dysfunction, chronic obstructive pulmonary disease (COPD) and stroke compared with patients without CAD. During the follow-up period, a higher total mortality rate was noted in the CAD group than in the non-CAD group (21.5% vs 15.5%, P = 0.023). In the patients without CAD, the lowest quartile (≤76  beats/min) exhibited the best 1-year survival rate; however, in the patients with CAD, the highest quartile (>110  beats/min) exhibited the worst survival rate. Multivariate adjusted Cox analysis indicated that age (HR 1.039, 95% CI 1.025-1.055, P < 0.001) and heart rate (P = 0.004) were each independently associated with total mortality. Patients with CAD have more risk factors, and comorbidities and higher mortality rates than patients without CAD. In the patients with permAF without CAD, a ventricular rate of ≤76  beats/minute was associated with the best survival rate; however, among the patients with CAD, no increased mortality was observed unless the heart rate was >110  beats/min.

Impact of initial 24-h urine output on short-term outcomes in patients with ST-segment elevation myocardial infarction admitted without cardiogenic shock and renal dysfunction.

OBJECTIVES: Our study aims to evaluate the prognostic value of initial 24-h urine output (UO) in patients with ST-segment elevation myocardial infarction (STEMI) admitted without cardiogenic shock and renal dysfunction, and to determine the additional risk stratification offered by adding initial 24-h UO to TIMI risk score (TRS). METHODS: Data from 7078 consecutive STEMI patients in a multi-center registry were retrospectively analyzed. Patients were divided into 4 groups according to initial 24-h UO quartiles. The primary endpoints were 7- and 30-day all-cause mortality. RESULTS: Patients in the lowest UO quartile (≤1020 mL) had significantly higher 7- and 30-day all-cause mortality rates, cardiogenic shock, and major adverse cardiovascular events (MACE) than those in other groups (all P<0.05). After multivariate adjustment, initial 24-h UO≤1020 mL was independently associated with an increased risk in 7-day all-cause mortality (HR=4.649, 95%CI 3.348-6.455) and 30-day all-cause mortality (HR=3.775, 95%CI 2.891-4.931) as well as 7-day MACE (HR=1.845, 95%CI 1.563-2.179) and 30-day MACE (HR=1.818, 95%CI 1.553-2.127). Initial 24-h UO provided additional risk stratification across all TRS groups and improved the discriminatory ability of TRS with respect to 7-day all-cause mortality (c-statistic from 0.704 to 0.764) and 30-day all-cause mortality (c-statistic from 0.706 to 0.743). CONCLUSION: Reduced initial 24-h UO (≤1020 mL) was associated with an increased risk in 7- and 30-day all-cause mortality and MACE in STEMI patients admitted without cardiogenic shock and renal dysfunction. The combination of initial 24-h UO and TRS improved short-term outcome prediction when compared to TRS alone, particularly in patients with initial 24-h UO≤1020 mL.