Evaluation of Ornidazole Tablets Bioequivalence in Chinese Healthy Participants Under Fasted and Fed Conditions Using Pharmacokinetic Parameters.

BACKGROUND AND OBJECTIVE: Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters. PATIENTS AND METHODS: Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (Cmax), time to Cmax (Tmax), the area under the curve (AUC) from t = 0 to infinity (AUC0-∞), AUC from t = 0 to the last quantifiable concentration (AUC0-t), half-life (t1/2), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure). RESULTS: For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (Cmax, AUC0-72, and AUC0-∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles. CONCLUSION: The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics. TRIAL REGISTRATION: CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Oral Formulations of Calcium Dobesilate Capsules in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5-g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268-01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7-day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography-tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half-life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%-125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P > .05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable.

Association of hemoglobin glycation index with prognosis of coronary artery disease after percutaneous coronary intervention: A retrospective cohort study.

AIMS: To analyze the association between hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). METHODS: Predicted glycated hemoglobin (HbA1c) level was calculated using an established formula and HGI represented the difference between laboratory measured HbA1c and predicted HbA1c. A total of 1780 patients were stratified into three subgroups (HGI < -0.4, -0.4 ≦ HGI < 0.12 and HGI ≧ 0.12). The primary endpoints included all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: ACM occurred in 54 patients: 22 (3.7) in the low-HGI subgroup, 8 (1.3) in the moderate-HGI subgroup and 24 (4.1) in the high-HGI subgroup (p = .012). After adjusting for the traditional clinical prognostic factors, multivariate Cox regression analysis showed that patients in both the low and high HGI subgroups had significantly increased risk of ACM as compared with patients in the moderate HGI subgroup (hazard ratio [HR] = 4.979, 95% confidence interval [CI]: 1.865-13.297, p = .001 and HR = 2.918, 95% CI: 1.075-7.922, p = .036). However, we did not find significant differences in the incidence of CM, MACEs and MACCEs. CONCLUSION: HGI can predicts risk for long-term mortality in patients undergoing PCI. This index could be helpful for the effective clinical management of the CAD population.

Prognostic Nutritional Index as a Novel Predictor of Long-Term Prognosis in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention.

BACKGROUND: The Prognostic Nutritional Index (PNI) has been reported to be correlated with long-term outcomes after gastrointestinal tumor surgery. However, to our knowledge, only a few studies have shown that the PNI is related to cardiovascular diseases. Therefore, we aimed to assess the association between the PNI and long-term outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: This was retrospective observational study. A total of 3561 patients with CAD after PCI were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3519) were divided into three groups according to PNI tertiles: the first tertile (PNI < 47.12, n = 1173), the second tertile (47.12 ≤ PNI < 51.50, n = 1185), and the third tertile (PNI ≥ 51.50, n = 1161). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM).Secondary endpoints were major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs). RESULT: In our study, the incidences of ACM in the first, second, and third tertiles were 3.8%, 1.8% and 1.4%, respectively (P < 0.001). The incidences of CM occurring in the first, second, and third tertiles were 1.7%, 3.1% and 2.1%, respectively (P < 0.001).There was statistically significant different in primary endpoints incidence. MACEs occurred in 139 patients (11.8%) in the first tertile, 121 patients(11.1%) in the second tertile and 123 patients(10.8%) in the third tertile(P = 0.691). MACCEs occurred in 183 patients (15.6%) in the first tertile, 174 patients(14.7%) in the second tertile and 160 patients(13.85%) in the third tertile(P = 0.463).There was no statistically significant different in secondary endpoints incidence. Kaplan-Meier analyses showed that elevated PNI was significantly related to long-term CM (log rank, P < 0.001) and long-term ACM (log-rank, P < 0.001). Cox regression analyses suggested that compared with the patients in the first tertile, the risk of ACM was decreased to 60.9% (HR = 0.609, 95% CI: 0.398-0.932, P = 0.029) in the second tertile and 40.3%(HR = 0.403, 95% CI: 0.279-0.766, P = 0.003) in the third tertile, while the risk of CM was decreased to 58.8%(HR = 0.588, 95% CI: 0.321-0.969, P = 0.038) in the second tertile and 46.6%(HR = 0.466, 95% CI: 0.250-0.870, P = 0.017) in the third tertile. Multivariate Cox regression analyses showed that the PNI was an independent predictor of long-term ACM and CM. CONCLUSION: Our finding shown that PNI is an independent predictor in CAD patients after PCI，the higher the PNI, the less occurring adverse event. Therefore，PNI may be an new biomarker to predict long-term outcome of CAD patients after PCI.

A retrospective study: screening failure analysis of 1,058 healthy volunteers in phase I clinical trials.

BACKGROUND: Phase I clinical trials play an important role in the follow-up clinical trials and even the drug registration and marketing. However, the screening success ratio in phase I clinical trials is low, and the screening process of the trials consumes a significant amount of human and material resources, but the results are unsatisfactory. At present, there is no large sample data analysis for screening failure in phase I clinical trials. It is therefore urgent to find the reasons for screening failure in phase I clinical trials. METHODS: A total of 1,058 healthy volunteers who failed the screening in 11 phase I clinical trials were retrospectively collected from October 2018 to June 2021 in Cangzhou Central Hospital. Data on all participants who failed screening for the study were analyzed (descriptive analysis) and reasons for their non-randomization were classified, as well as the differences of main screening failures between four years. RESULTS: A total of 1,466 healthy volunteers were enrolled in the 11 trials, and among them 1,058 subjects failed the screening. The total screening success ratio of our study was only 27.8%, the highest being 38.5% and the lowest being 18.2%. The top 3 reasons for non-randomization were abnormalities in blood biochemistry tests (23.3%), vital sign examination (19.3%), and electrocardiogram (ECG) (16.6%). Abnormal blood biochemistry was the main reason between 2019 and 2021, except for 2018 in which it was the second reason. CONCLUSIONS: Screening failure is a burdensome issue which various clinical trial sites must contend with. Investigators can still take some effective measures by strengthening the in-depth understanding of informed consent, paying attention to the quality of test samples, a correcting definition of no clinical significance (NCS). Also, low-cost and non-invasive examinations can be arranged first to better protect the volunteers and reduce the screening costs of clinical trials. To our delight, we find people's attention to the annual physical examination may help to screen healthy volunteers. Overall, this study shows that it is crucial and professional to develop a screening plan to minimize the resultant impact on timelines and budgets of phase I clinical trials enrolling healthy volunteers.

The age, NT-proBNP, and Ejection Fraction Score as a Novel Predictor of Clinical Outcomes in CAD Patients After PCI.

BACKGROUND: Previous evidences have been proved that age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and ejection fraction are tightly associated with the long-term outcomes in patients suffered from coronary artery disease (CAD). Therefore, the present study aimed to assess the prognosis value of age, NT-proBNP, and ejection fraction (ABEF) score in CAD patients who underwent percutaneous coronary intervention (PCI). METHODS: Observational cohort methodology was used in this study which enrolled totally 3561 patients. And the patients were followed up regularly for 37.59 ± 22.24 months. Patients were classed into three groups based on the tertiles of ABEF sore: first tertile (<5.06, n = 831), second tertile (5.06-6.25, n = 839), and third tertile (≥ 6.25, n = 834). The ABEF score was calculated as follows: age (years)/ejection fraction (%) + NT-proBNP (NT-proBNP<177pg/mL was 1, 177≤NT-proBNP≥524pg/mL was 2 and NT-proBNP > 524pg/mL is 3). The association between ABEF score and adverse prognosis, including all-cause death (ACD), cardiac death (CD), major adverse cardiovascular events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs), in patients who underwent PCI was analyzed. RESULTS: According to the risk category of ABEF score, the incidences of ACD (P < .001), CD (P < .001) and MACCEs (P = .021) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the respective risks of ACD and CD were increased 3.013 folds (hazard risk [HR] = 4.013 [95% confidence interval [CI]: 1.922-8.378], P < .001) and 4.922 folds ([HR] = 5.922 [95% [CI]: 2.253-15.566], P < .001) in the third tertile compared with those in the first tertile. Kaplan-Meier survival analyses showed that the cumulative risks of ACD,CD and MACCEs in patients with the high ABEF score tended to increase. CONCLUSION: The present study indicated ABEF score was a novel biomarker suitable for predicting adverse prognosis in patients after PCI, which may be used for early recognition and risk stratification.

Alkaline phosphatase-to-albumin ratio as a novel predictor of long-term adverse outcomes in coronary artery disease patients who underwent PCI.

BACKGROUND: Alkaline phosphatase (ALP) and albumin (ALB) have been shown to be associated with coronary artery disease (CAD), and it has been reported that alkaline phosphatase-to-albumin ratio (AAR) is associated with the liver damage and poorer prognosis of patients with digestive system malignancy. Moreover, several previous studies showed that there was a higher incidence of malignancy in CAD patients. However, to our knowledge, the relationship between AAR and long-term adverse outcomes in CAD patients after undergoing percutaneous coronary intervention (PCI) has not been investigated. Therefore, we aim to access the relation between AAR and long-term adverse outcomes in post-PCI patients with CAD. METHODS: A total of 3378 post-PCI patients with CAD were enrolled in the retrospective Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-ZZ) study from January 2013 to December 2017. The median duration of follow-up was 37.59 ± 22.24 months. The primary end point was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM). The secondary end points were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: Kaplan-Meier analyses showed that an increased AAR was positively correlated with incidences of long-term ACM (log-rank, P=0.014), CM (log-rank, P=0.011), MACEs (log-rank, P=0.013) and MACCEs (log-rank, P=0.006). Multivariate Cox regression analyses showed that the elevated AAR was an independent predictor of long-term ACM (adjusted HR = 1.488 [1.031-2.149], P=0.034), CM (adjusted HR = 1.837 [1.141-2.959], P=0.012), MACEs (adjusted HR = 1.257 [1.018-1.551], P=0.033) and MACCEs (adjusted HR = 1.237 [1.029-1.486], P=0.024). CONCLUSION: An elevated AAR is a novel independent predictor of long-term adverse outcomes in CAD patients following PCI.

Monocyte-to-albumin ratio as a novel predictor of long-term adverse outcomes in patients after percutaneous coronary intervention.

BACKGROUND: Monocyte count and serum albumin (Alb) have been proven to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-albumin ratio (MAR) in patients who underwent percutaneous coronary intervention (PCI). METHODS: We enrolled a total of 3561 patients in the present study from January 2013 to December 2017. They were divided into two groups according to MAR cut-off value (MAR < 0.014, n=2220; MAR ≥ 0.014, n=1119) as evaluated by receiver operating characteristic (ROC) curve. The average follow-up time was 37.59 ± 22.24 months. RESULTS: The two groups differed significantly in the incidences of all-cause mortality (ACM; P<0.001), cardiac mortality (CM; P<0.001), major adverse cardiovascular events (MACEs; P=0.038), and major adverse cardiovascular and cerebrovascular events (MACCEs; P=0.037). Multivariate Cox regression analyses revealed MAR as an independent prognostic factor for ACM and CM. The incidence of ACM increased by 56.5% (hazard ratio [HR] = 1.565; 95% confidence interval [CI], 1.086-2.256; P=0.016) and that of CM increased by 76.3% (HR = 1.763; 95% CI, 1.106-2.810; P=0.017) in patients in the higher-MAR group. Kaplan-Meier survival analysis suggested that patients with higher MAR tended to have an increased accumulated risk of ACM (Log-rank P<0.001) and CM (Log-rank P<0.001). CONCLUSION: The findings of the present study suggested that MAR was a novel independent predictor of long-term mortality in patients who underwent PCI.

Gambogic acid protects LPS-induced apoptosis and inflammation in a cell model of neonatal pneumonia through the regulation of TrkA/Akt signaling pathway.

OBJECTIVE: In this work, we investigated the effects of gambogic acid (GA) on lipopolysaccharide (LPS)-induced apoptosis and inflammation in a cell model of neonatal pneumonia. METHOD: Human WI-38 cells were maintained in vitro and incubated with various concentrations of GA to examine WI-38 survival. GA-preincubated WI-38 cells were then treated with LPS to investigate the protective effects of GA on LPS-induced death, apoptosis and inflammation. Western blot assay was utilized to analyze the effect of GA on tropomyosin receptor kinase A (TrkA) signaling pathway in LPS-treated WI-38 cells. In addition, human AKT serine/threonine kinase 1 (Akt) gene was knocked down in WI-38 cells to further investigate the associated genetic mechanisms of GA in protecting LPS-induced inflammation and apoptosis. RESULTS: Pre-incubating WI-38 cells with low and medium concentrations GA protected LPS-induced cell death, apoptosis and inflammatory protein productions of IL-6 and MCP-1. Using western blot assay, it was demonstrated that GA promoted TrkA phosphorylation and Akt activation in LPS-treated WI-38 cells. Knocking down Akt gene in WI-38 cells showed that GA-associated protections against LPS-induced apoptosis and inflammation were significantly reduced. CONCLUSIONS: GA protected LPS-induced apoptosis and inflammation, possibly through the activations of TrkA and Akt signaling pathway. This work may broaden our understanding on the molecular mechanisms of human neonatal pneumonia.

A Correlation Between Monocyte to Lymphocyte Ratio and Long-Term Prognosis in Patients With Coronary Artery Disease After PCI.

Monocyte to lymphocyte ratio (MLR) has been confirmed as a novel marker of poor prognosis in patients with coronary heart disease (CAD). However, the prognosis value of MLR for patients with CAD after percutaneous coronary intervention (PCI) needs further studies. In present study, we aimed to investigate the correlation between MLR and long-term prognosis in patients with CAD after PCI. A total of 3,461 patients with CAD after PCI at the First Affiliated Hospital of Zhengzhou University were included in the analysis. According to the cutoff value of MLR, all of the patients were divided into 2 groups: the low-MLR group (<0.34, n = 2338) and the high-MLR group (≥0.34, n = 1123). Kaplan-Meier curve was performed to compare the long-term outcome. Multivariate COX regression analysis was used to assess the independent predictors for all-cause mortality, cardiac mortality and MACCEs. Multivariate COX regression analysis showed that the high MLR group had significantly increased all-cause mortality (ACM) [hazard ratio (HR) = 1.366, 95% confidence interval (CI): 1.366-3.650, p = 0.001] and cardiac mortality (CM) (HR = 2.379, 95%CI: 1.611-3,511, p < 0.001) compared to the low MLR group. And high MLR was also found to be highly associated with major adverse cardiovascular and cerebrovascular events (MACCEs) (HR = 1.227, 95%CI: 1.003-1.500, p = 0.047) in patients with CAD undergoing PCI. MLR was an independent predictor of ACM, CM and MACCEs in CAD patients who underwent PCI.

C-reactive protein-to-serum albumin ratio as a novel predictor of long-term outcomes in coronary artery disease patients who have undergone percutaneous coronary intervention: analysis of a real-world retrospective cohort study.

BACKGROUND: C-reactive protein (CRP) has been proposed as a contributor to the pathogenesis of coronary artery disease (CAD) and inflammatory reactions, which are associated with a decrease in serum albumin, and it has been reported that the CRP-to-serum albumin ratio (CAR) can predict CAD severity in inpatient ischemic cardiomyopathy (ICM) patients. However, the relationship between the CAR and long-term adverse outcomes in CAD patients after percutaneous coronary intervention (PCI) is still unknown. METHODS: A total of 3561 CAD patients enrolled in the Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI: an investigation based on case records and follow-up (CORFCHD-ZZ), a retrospective cohort study conducted from January 2013 to December 2017, and 1630 patients meeting the study inclusion criteria were divided into two groups based on the CAR (CAR < 0.186; n = 1301 and CAR ≥ 0.186; n = 329). The primary outcome was long-term mortality, including all-cause mortality (ACM) and cardiac mortality. The average follow-up time was 37.59 months. RESULTS: We found that there were significant differences between the two groups in the incidences of ACM (P < 0.001) and cardiac mortality (P = 0.003). Cox multivariate regression analyses demonstrated that CAR was an independent predictor of ACM [hazard ratio, 2.678; (95% confidence interval (CI), 1.568-4.576); P < 0.001] and cardiac mortality (hazard ratio, 2.055; 95% CI, 1.056-3.998; P = 0.034) in CAD patients after PCI. CONCLUSION: This study revealed that the CAR is an independent and novel predictor of long-term adverse outcomes in CAD patients who have undergone PCI.

A Novel ABC Score Predicts Mortality in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Who underwent Percutaneous Coronary Intervention.

OBJECTIVE: In the present study, we aimed to establish a novel score to predict long-term mortality of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI). METHODS: A total of 2,174 NSTE-ACS patients from the CORFCHD-ZZ study were enrolled as the derivation cohort. The validation cohort including 1,808 NSTE-ACS patients were from the CORFCHD-PCI study. Receiver operating characteristic analysis and area under the curve (AUC) evaluation were used to select the candidate variables. The model performance was validated internally and externally. The primary outcome was cardiac mortality (CM). We also explored the model performance for all-cause mortality (ACM). RESULTS: Initially, 28 risk factors were selected and ranked according to their AUC values. Finally, we selected age, N-terminal pro-B-type natriuretic peptide, and creatinine to develop a novel prediction model named "ABC" model. The ABC model had a high discriminatory ability for both CM (C-index: 0.774, p < 0.001) and ACM (C-index: 0.758, p < 0.001) in the derivation cohort. In the validation cohort, the C-index of CM was 0.802 (p < 0.001) and that of ACM was 0.797 (p < 0.001), which suggested good discrimination. In addition, this model had adequate calibration in both the derivation and validation cohorts. Furthermore, the ABC score outperformed the GRACE score to predict mortality in NSTE-ACS patients who underwent PCI. CONCLUSION: In the present study, we developed and validated a novel model to predict mortality in patients with NSTE-ACS who underwent PCI. This model can be used as a credible tool for risk assessment and management of NSTE-ACS after PCI.

Fasting blood glucose to HDL-C ratio as a novel predictor of clinical outcomes in non-diabetic patients after PCI.

Background The present study was to assess the prognostic value of fasting blood glucose to high-density lipoprotein cholesterol ratio (GHR) in non-diabetic patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods and results A total of 6645 non-diabetic patients from two independent cohorts, the CORFCHD-PCI study (n=4282) and the CORFCHD-ZZ (n=2363) study, were enrolled in Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI. Patients were divided into two groups according to the GHR value. The primary outcome included all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 36.51 ± 22.50 months. We found that there were significant differences between the two groups in the incidences of ACM (P=0.013) and CM (P=0.038). Multivariate Cox regression analysis revealed GHR as an independent prognostic factor for ACM. The incidence of ACM increased 1.284-times in patients in the higher GHR group (hazard ratio [HR]: 1.284 [95% confidence interval [CI]: 1.010-1.631], P<0.05). Kaplan-Meier survival analysis suggested that patients with high GHR value tended to have an increased accumulated risk of ACM. However, we did not find significant differences in the incidence of major adverse cardiac events, main/major adverse cardiovascular and cerebrovascular events (MACCE), stroke, recurrent myocardial infarction (MI) and bleeding events. Conclusions The present study indicates that GHR index is an independent and novel predictor of ACM in non-diabetic CAD patients who underwent PCI.

D-Dimer to Fibrinogen Ratio as a Novel Prognostic Marker in Patients After Undergoing Percutaneous Coronary Intervention: A Retrospective Cohort Study.

The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan-Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD.

ALT-to-Lymphocyte Ratio as a Predictor of Long-Term Mortality in Patients with Normal Liver Function Presenting Coronary Artery Disease after Undergoing PCI: A Retrospective Cohort Study.

BACKGROUND: Alanine aminotransferase (ALT) is referred as liver transaminase and predominantly expressed by hepatocytes. Previous evidences showed that high levels of ALT were reversely associated with short- and long-term outcomes in patients with myocardial infarction. Besides, low lymphocyte has been demonstrated to be significantly correlated with adverse clinical outcomes in coronary artery disease (CAD). However, evidences about the relationship between ALT-to-lymphocyte ratio (ALR) and outcomes in CAD patients with normal liver function are limited. The aim of this study was to assess the relationship between ALR and clinical outcomes in patients with CAD. METHODS: This is a retrospective cohort study, and a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients with liver dysfunction, we finally enrolled 2714 patients. These patients were divided into two groups according to ALR value: the lower group (ALR < 14.06, n = 1804) and the higher group (ALR ≥ 14.06, n = 910). The average follow-up time was 37.59 ± 22.24 months. RESULTS: We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (P < 0.001) and cardiac mortality (CM) (P=0.010). Kaplan-Meier survival analysis suggested that CAD patients with higher ALR tended to have an increased accumulated risk of ACM and CM (log rank P < 0.001 and P=0.006, respectively). Multivariate Cox regression analysis showed that ALR was an independent predictor of ACM (hazard ratio (HR) = 2.017 (95% confidence interval (CI): 1.289-3.158), P=0.002) and CM (HR = 1.862 (95% CI: 1.047-3.313), P=0.034). We did not find significant difference in the incidence of major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs) between the two groups after adjustments of confounders. CONCLUSION: Our results indicate that ALR is an independent predictor of long-term adverse outcomes in CAD patients who underwent PCI.

Triglyceride to high-density lipoprotein cholesterol ratio as a predictor of long-term mortality in patients with coronary artery disease after undergoing percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. METHODS: A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR < 2.84, n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P < 0.001). Kaplan-Meier analyses showed that elevated THR was significantly related to long-term ACM (log-rank, P = 0.044) and the occurrence of heart failure (log-rank, P < 0.001). Multivariate Cox regression analyses showed that the THR was an independent predictor of long-term ACM (adjusted HR = 2.042 [1.264-3.300], P = 0.004) and heart failure (adjusted HR = 1.700 [1.347-2.147], P < 0.001). CONCLUSIONS: An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.