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Coronary heart disease and diabetes are highly interrelated and complex diseases. We proposed to investigate the association of genetic polymorphisms of the lipoprotein important regulatory genes Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with premature triple-vessel coronary disease (PTVD) with diabetes, blood glucose and body mass index.Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183 and rs2073547) of NPC1L1 and three SNPs (rs12916, rs2303151 and rs4629571) of HMGCR were genotyped in 872 PTVD patients.After performing logistic regression analysis adjusted for age and sex, rs2303151 of HMGCR was related to the risk of diabetes in the dominance model (odds ratio = 1.35, 95% confidence interval = 1.01-1.80, p = 0.04). However, the four SNPs of NPC1L1 were not associated with the risk of diabetes. Further analyses showed that neither the above SNPs of NPC1L1, nor the SNPs of HMGCR were related to blood glucose and body mass index (all p 0.05).We report that rs2303151 is a novel polymorphism of the HMGCR gene related to the risk of diabetes in PTVD patients, which suggests HMGCR may be a potential common targeted pathogenic pathways between coronary heart disease and diabetes.

Three-vessel disease (TVD) is a severe coronary heart disease (CHD) with poor prognosis. Niemann-Pick C1-like 1 (NPC1L1) is a transporter protein for exogenous cholesterol absorption, and 3-hydroxy...

Whether routine assessment of FT3/FT4 ratio in euthyroid patients with three-vessel disease (3VD) could help identify high-risk individuals remains unclear. This study evaluated the relationship between FT3/FT4 ratio and long-term clinical outcomes in this specific population.This study included 2106 euthyroid patients with 3VD (stenoses of ≥50% in right coronary artery, left circumflex and left anterior descending). Patients were categorized into three groups according to tertiles of FT3/FT4 ratio (Q12.58,n = 704; 2.2 ≤ Q22.58, n = 706; Q32.22, n = 696). The median follow-up time was 5.3 years, during which 206 deaths and 332 MACCEs (consisting of all-cause death, myocardial infarction, and stroke) occurred. Compared with the other two groups, patients with low level of FT3/FT4 ratio tended to be female, older, diabetic, and had significantly higher incidences of all-cause death, cardiac death and MACCE (all P 0.05). Cox regression analysis showed that patients with low level of FT3/FT4 ratio had higher risks of long-term cardiac death (adjusted HR = 1.87, 95% CI 1.06-3.28, P = 0.030) and MACCE (adjusted HR = 1.43, 95% CI 1.07-1.93, P = 0.017) than those with high level of FT3/FT4 ratio. Subgroup analysis showed there was a significant interaction between FT3/FT4 ratio and age (≥65 years vs.65 years) for MACCE (P = 0.029).Low level of FT3/FT4 ratio is independently associated with an increased risk of long-term cardiac death and MACCE in euthyroid patients with 3VD. Routine assessment of FT3/FT4 ratio might be helpful to identify high-risk individuals in this specific population.

Background Data of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD. Methods A total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, acute myocardial infarction, repeat revascularization, readmission and stroke. Patients with 1-year MACCE in this cohort were selected as MACCE group. Blood samples from MACCE group and non-CAD control groups were collected, and a deoxyribonucleic acid library was created. A total of 34 tag or hot single nucleotide polymorphisms (SNPs) in six genes including CDKN2B-AS1, ADAMTS7, ABO, ADAMTS13, IL-18, and PECAM1 were analyzed by a SNPscan™ multi-genotyping kit. Carrier frequencies of each SNP were compared between the two groups using dominant, recessive and codominant allele model, respectively. Multivariate logistic regression model was established. Results Variant allele frequencies of rs10757274, rs1333042, rs1333049, rs4977574, rs9632884, rs1063192 and rs3217986 on CDKN2B-AS1 gene showed significant differences between the two groups in at least one allele model. Variant allele frequency of rs3217986 was not statistically significant after adjusting for the false discovery rate using Benjamini-Hochberg procedure (Q > 0.05). Variant allele frequencies of rs1333049, rs10757274, rs4977574 on CDKN2B-AS1 gene were significantly higher in MACCE group in all dominant, recessive and codominant models. Rs1055432 on ADAMTS13 and rs8176694 on ABO gene showed threshold significance between the two groups. After multivariable adjustment, G mutant homozygous rs9632884 (GG vs. GC + CC) (OR: 0.24; 95% CI: 0.09–0.65; P = 0.005) on CDKN2B-AS1 gene were independent protective factor of MACCE in recessive model. Conclusions In patients with TVD in China, variant alleles on CDKN2B-AS1 gene may form part of the genetic basis of coronary atherosclerosis progression, promoting or suppressing ischemic events.

Aims In the clinical practice, the right ventricular (RV) manifestations have received less attention in hypertrophic cardiomyopathy (HCM). This paper aimed to evaluate the risk prediction value and genetic characteristics of RV involvement in HCM patients. Methods and results A total of 893 patients with HCM were recruited. RV hypertrophy, RV obstruction, and RV late gadolinium enhancement were evaluated by echocardiography and/or cardiac magnetic resonance. Patients with any of the above structural abnormalities were identified as having RV involvement. All patients were followed with a median follow-up time of 3.0 years. The primary endpoint was cardiovascular death; the secondary endpoints were all-cause death and heart failure (HF)-related death. Survival analyses were conducted to evaluate the associations between RV involvement and the endpoints. Genetic testing was performed on 669 patients. RV involvement was recognized in 114 of 893 patients (12.8%). Survival analyses demonstrated that RV involvement was an independent risk factor for cardiovascular death (P = 0.002), all-cause death (P = 0.011), and HF-related death (P = 0.004). These outcome results were then confirmed by a sensitivity analysis. Genetic testing revealed a higher frequency of genotype-positive in patients with RV involvement (57.0% vs. 31.0%, P < 0.001), and the P/LP variants of MYBPC3 were more frequently identified in patients with RV involvement (30.4% vs. 12.0%, P < 0.001). Logistic analyses indicated the independent correlation between RV involvement and these genetic factors. Conclusion RV involvement was an independent risk factor for cardiovascular death, all-cause death and HF-related death in HCM patients. Genetic factors might contribute to RV involvement in HCM.

Introduction: Risk stratification for sudden cardiac death (SCD) is a great challenge in managing hypertrophic cardiomyopathy (HCM). Hypothesis: This study attempted for the first time to build a machine learning (ML) model for SCD risk prediction. Methods: The present study consisted of 1631 consecutive adult HCM patients without a history of SCD events. Extreme gradient boosting (XGBoost) was applied for ML model construction. We compared the predictive performance of the ML model with that of conventional models by calculating C-statistics and interpreted the ML model output using the SHapley Additive exPlanation (SHAP) value. Results: Fifty patients reached SCD endpoints during a median follow-up of 4.6 years. The C-statistic of the ML model was 0.745 [95% confidence interval (CI), 0.723-0.766], which was significantly higher than that of the model recommended in the 2014 European Society of Cardiology guidelines (C-statistics =0.609; 95% CI 0.585-0.623) and the model recommended in the 2020 American College of Cardiology/American Heart Association guidelines (C-statistics =0.628; 95% CI 0.604-0.652). The ML model incorporated 12 features as predictors, including 5 conventional SCD risk markers (NSVT, quantification of LGE, family history of SCD, LVEF 50%, unexplained syncope), WBC, creatine, uric acid, TBIL and cholesterol, NT-proBNP and family history of HCM. Using SHAP values, we quantified the contribution of each feature within the ML model to the final prediction and visualized the relationship between features and SCD risk. Conclusion: Our study constructed an ML model for the prediction of SCD risk in patients with HCM and provided a clinically intuitive interpretation. The ML model showed better discrimination performance than conventional models, demonstrating the feasibility of ML in SCD risk prediction for patients with HCM.

Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS).Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c.Results: Subjects were divided into quartiles according to baseline DB (μmol/L): Q1 (0–1.6), Q2 (1.61–2.20), Q3 (2.21–2.80), and Q4 (>2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate–high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p < 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829–1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001–1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063–1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction.Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.

The prognostic value of high-sensitivity C-reactive protein (hsCRP) in complex coronary artery disease has not been fully established. We aimed to determine the association between hsCRP and long-term outcomes in elderly patients with 3-vessel disease (TVD). From April 2004 to February 2011, 3069 patients aged ≥65 years with TVD were consecutively enrolled and received medical treatment alone, percutaneous coronary intervention, or coronary artery bypass grafting. The patients were divided into 2 groups according to their hsCRP levels

Background There are relatively limited data regarding real-world outcomes in very old patients with three-vessel disease (3VD) receiving different therapeutic strategies. This study aimed to perform analysis of long-term clinical outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) in this population. Methods We included 711 patients aged ≥ 75 years from a prospective cohort of patients with 3VD. Consecutive enrollment of these patients began from April 2004 to February 2011 at Fu Wai Hospital. Patients were categorized into three groups (MT, n = 296; CABG, n = 129; PCI, n = 286) on the basis of different treatment strategies. Results During a median follow-up of 7.25 years, 262 deaths and 354 major adverse cardiac and cerebrovascular events (MACCE) occurred. Multivariate Cox analysis showed that the risk of cardiac death was significantly lower for CABG compared with PCI (adjusted hazard ratio [HR] = 0.475, 95% confidence interval [CI] 0.232–0.974, P = 0.042). Additionally, MACCE appeared to show a trend towards a better outcome for CABG (adjusted HR = 0.759, 95% CI 0.536–1.074, P = 0.119). Furthermore, CABG was significantly superior in terms of unplanned revascularization (adjusted HR = 0.279, 95% CI 0.079–0.982, P = 0.047) and myocardial infarction (adjusted HR = 0.196, 95% CI 0.043–0.892, P = 0.035). No significant difference in all-cause death between CABG and PCI was observed. MT had a higher risk of cardiac death than PCI (adjusted HR = 1.636, 95% CI 1.092–2.449, P = 0.017). Subgroup analysis showed that there was a significant interaction between treatment strategy (PCI vs. CABG) and sex for MACCE (P = 0.026), with a lower risk in men for CABG compared with that of PCI, but not in women. Conclusions CABG can be performed with reasonable results in very old patients with 3VD. Sex should be taken into consideration in therapeutic decision-making in this population.

Aims Risk assessment and treatment stratification for three-vessel disease (3VD) remain challenging. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for prognostication and treatment in heart failure. The present study aimed to evaluate the prognostic value of NT-proBNP beyond the SYNTAX score II (SSII), and its association with long-term outcome after three strategies [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT)] in a cohort of patients with 3VD. Methods and results A total of 6597 patients with available baseline NT-proBNP data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. During a median follow-up of 7.0 years, higher NT-proBNP levels were strongly associated with increased risks of all-cause death, cardiac death, and MACCE (all adjusted P Conclusion N-terminal pro-BNP is a potential biomarker for risk stratification and therapeutic decision-making in patients with 3VD. Further randomized studies are needed to confirm these findings.

With the advancements of percutaneous coronary interventions (PCI), it is not clear whether unprotected left main (ULM) coronary artery disease (CAD) remains an independent predictor of adverse outcomes after PCI therapy. We have therefore carried out a large cohort study to investigate the impact of ULM disease on 2-year clinical outcomes in Chinese patients undergoing contemporary PCI treatment.From January 2013 to December 2013, 10 724 consecutive patients undergoing PCI were prospectively collected. Two-year clinical outcomes were compared for patients undergoing ULM PCI and non-ULM PCI. Among the 10 724 patients, 272 (2.5%) patients underwent ULM PCI. Overall, these patients had higher baseline clinical risks of CAD and more extensive CAD compared with non-ULM PCI patients. During the 2-year follow-up, patients who underwent ULM PCI experienced higher incidence of cardiac death (2.2 vs. 0.7%; log-rank P=0.002), myocardial infarction (7.0 vs. 1.9%; log-rank P0.001), stroke (2.9 vs. 1.3%; log-rank P=0.02), and definite and probable stent thrombosis (3.3 vs. 0.5%; log-rank P0.001), than patients who underwent non-ULM PCI. However, the rates of revascularization (7.4 vs. 8.7%; log-rank P=0.48), target vessel revascularization (5.5 vs. 5.0%; log-rank P=0.66), and major adverse cardiac and cerebrovascular events (15.1 vs. 12.0%; log-rank P=0.11) were not significantly different between the groups. When performing adjusted Cox regression after propensity score matching, ULM PCI was not an independent risk factor of any clinical events (all P0.05).In this large cohort of patients who underwent modern PCI, ULM PCI patients had higher baseline clinical risks and poorer prognosis during 2-year follow-up. However, after multivariate analysis, ULM PCI was not an independent risk factor of any clinical adverse events.

Hyperuricemia has been associated with mortality in patients with coronary artery disease (CAD). However, its prognostic value remains unknown in the context of severe CAD with heavy atherosclerotic burden in all 3 vessels. We used data from a large cohort of consecutive patients with severe CAD. The primary end point was all-cause death. Propensity score matching was used to identify 2 cohorts of patients with similar baseline characteristics. A total of 8,529 patients with available serum uric acid data were included in the study. Hyperuricemia was present in 1,207 (14.2%) patients. At baseline, hyperuricemic patients had more co-morbidities, and more often received medical therapy alone. During the median follow-up of 7.5 years, significantly more deaths occurred in hyperuricemic patients compared with normouricemic patients (22.5% vs 13.7%; p0.001). Multivariable analyses showed that hyperuricemia was associated with an increased risk of mortality (hazard ratio 1.33; 95% confidence interval 1.15 to 1.53; p0.001). Propensity score matching yielded similar results (hazard ratio 1.33; 95% confidence interval 1.11 to 1.61; p = 0.003). The association was relatively consistent across subgroups, except for an interaction between age and hyperuricemia. Addition of uric acid to SYNTAX score II provided significant improvements of reclassification and discrimination for mortality prediction. In conclusion, hyperuricemia is relatively common among patients with severe CAD and is independently associated with mortality. Moreover, uric acid can improve the predictability of a well-established risk score.

Three-vessel disease (TVD) is a severe coronary heart disease (CHD) with poor prognosis. Niemann-Pick C1-like 1 (

Background Patients with diabetes and triple-vessel disease (TVD) are associated with a high risk of events. The choice of treatment strategies remains a subject of discussion. In the real-world, we aim to compare the outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) treatment strategies in patients with diabetes and TVD. Methods A total of 3117 consecutive patients with diabetes and TVD were enrolled. The primary endpoint was all-cause death and the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE, composite of all-cause death, myocardial infarction, or stroke). Results During the mean follow-up of 6.3 ± 2.6 years, 573 (18.4%) deaths and 1094 (35.1%) MACCE occurred. Multivariate analysis showed that PCI (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.32–0.51) and CABG (HR 0.33, 95% CI 0.26–0.44) were associated with a lower risk of death compared with MT, with no difference between the PCI and CABG groups. When MACCE was the endpoint, PCI (HR 0.71, 95% CI 0.60–0.84) and CABG (HR 0.48, 95% CI 0.39–0.57) had a lower risk than MT. CABG was associated with a significantly lower risk of MACCE compared with PCI (HR 0.67, 95% CI 0.55–0.81), which was mainly attributed a lower risk in myocardial infarction, but a higher risk of stroke. Conclusions In this big real-world data and intermediate-term follow-up study, for patients with diabetes and TVD, PCI and CABG were associated with a lower risk of death and MACCE more than MT. The results suggest the importance of appropriate revascularization for diabetic patients with TVD. However, CABG was not associated with a lower risk of death, but with a lower risk of MACCE, compared with PCI. In the future, we perhaps should strengthen comprehensive treatment in addition to PCI or CABG.

BACKGROUND The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P

Aims/Introduction Whether detection of prediabetes by routinely testing hemoglobin A1c and fasting plasma glucose in three‐vessel disease patients could identify individuals at high risk of future cardiovascular disease events remains unclear. This study evaluated the relationship between different glycemic status and clinical outcomes in this specific population. Materials and Methods This study included 8,891 Chinese patients with three‐vessel disease. Patients were categorized according to their glycemic status (normoglycemia [NG], n = 3,195; prediabetes, n = 1,978; diabetes mellitus, n = 3,718). Results The median follow‐up time was 7.5 years, during which 1,354 deaths and 2,340 major adverse cardiac and cerebrovascular events occurred. Compared with the NG group, patients in the prediabetes and diabetes mellitus groups had more comorbidities. After adjusting for confounders, the diabetes mellitus group had a higher risk of all‐cause death (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.20–1.53; P, We evaluated the association between different glycemic status and long‐term outcomes in Chinese patients with three‐vessel disease, and that found three‐vessel disease patients with prediabetes have comparable long‐term outcome in terms of all‐cause death, cardiac death and major adverse cardiac and cerebrovascular events to those with normoglycemia. Routine screening of glycemic metabolism based on hemoglobin A1c and fasting plasma glucose might be valuable to identify individuals with diabetes mellitus who are at high risk of future cardiovascular disease events and individuals with prediabetes who are at high risk of progressing to diabetes mellitus.

Aim. Based on optical coherence tomography (OCT), we aimed to determine the diagnosis, clinical characteristics, and interventions of braid-like coronary arteries, which are rare and tend to be diagnosed as a woven coronary artery (WCA) anomaly. Methods and Results. We identified braid-like lesions on coronary angiography (CAG) in 7 patients (6 men; median age 47 years; age range 26 to 57 years). All patients were heavy smokers. Four patients were diagnosed with an old myocardial infarction and the other 3 with unstable angina. The braid-like lesions were located in the left anterior descending arteries in 2 patients and in the right coronary arteries in the other 5. TIMI grade 2 flow was observed in all involved vessels. OCT findings of all lesions were consistent with recanalization of organized thrombi, which consisted of septa that divided the lumen into multiple small cavities communicating with each other. No separate three-layered structure could be defined. Based on the significance of the stenosis and its related symptoms, drug-eluting stents were implanted in all of the lesions. All patients experienced symptomatic improvement after the intervention and were followed up event-free for 12 months. Conclusions. Braid-like coronary arteries are likely to undergo recanalization of organized thrombi rather than WCA according to our OCT findings. The majority of cases affect men who smoke heavily. Percutaneous stent implantation may be beneficial in selected patients when feasible.

Background and aims It is still controversial whether obesity and overweight increase the risk of mortality for patients with coronary artery disease. The current study aimed to investigate the relationship between body mass index (BMI) and mortality in patients with triple-vessel disease (TVD). Methods and results From April 2004 to February 2011, 8943 patients with angiographically confirmed TVD were consecutively enrolled. Patients were divided into five groups according to BMI: underweight ( Conclusion There is a U-shape relationship between BMI and all-cause death in patients with TVD, with increased risks among both underweight and severely obese patients. This relationship may be influenced by treatment strategies.

Background: Risk stratification for three-vessel coronary artery disease (3VD) remains an important clinical challenge. In this study, we utilized machine learning (ML), which can address the limitations of traditional regression-based models, to develop a novel model to assess mortality risk in patients with 3VD. Methods: This study was based on a prospective cohort of 8943 participants with 3VD consecutively enrolled between 2004 and 2011. A ML-derived random forest model was trained and tested to predict 4-year mortality. The predictability of the model was compared with that of an established model, the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score II (SSII), among 3VD patients undergoing percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT) alone. Findings: The all-cause mortality was 7.5% (667 patients) over the 4-year follow-up period. The correlation-based feature selection algorithm selected 18 of the 94 features to develop the ML model. In the testing dataset, the ML-derived model achieved an area under the curve of 0.81 for 4-year mortality prediction. Its predictability was significantly better than that of the SSII among patients undergoing PCI (0.80 vs 0.70, respectively P < 0.001) or CABG (0.80 vs. 0.67, respectively, P < 0.001). The model also outperformed the SSII in patients receiving MT alone (ML: 0.75 vs. SSII for PCI: 0.70 or SSII for CABG: 0.66, P < 0.001). Interpretation: This ML-based approach exhibited better performance in risk stratification for 3VD compared with the conventional method, indicating its potential utility in clinical practice. Funding Statement: Chinese Academy of Medical Sciences, Beijing Municipal Natural Science Foundation. Declaration of Interests: None declared. Ethics Approval Statement: The study complied with the principles of the Declaration of Helsinki and was approved by the Review Board of Fuwai Hospital. All participants provided written informed consent.

INTRODUCTION Current guidelines recommend coronary artery bypass grafting (CABG) for patients with multivessel coronary disease and left ventricular (LV) dysfunction. However, some patients undergo percutaneous coronary intervention (PCI) or solely medical therapy (MT) in actual practice. The comparison of long-term outcomes of these three treatment strategies in real world is unclear. METHODS A total of 699 consecutive patients in a single centre from 2004 to 2011 who had TVD and LV ejection fraction ≤40%, no prior PCI or CABG and had completed a median 6.2-year follow-up were evaluated. The primary endpoint was all-cause death. The secondary endpoints included cardiac death, major adverse cardiovascular and cerebrovascular events (MACCE; composite of all-cause death, myocardial infarction, repeat revascularization, or stroke), and the individual components of the composite endpoint. RESULTS One hundred forty-two patients (20.3%) underwent PCI, 201 (28.8%) underwent CABG while 356 (50.9%) received MT alone. MT alone was associated with the worst survival (P

Background: There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients. Methods: We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria. Results: During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529–0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529–0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531–0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544–0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup. Conclusions: CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.

Background Hypoalbuminemia was reported to be associated with poor prognosis in severe diseases. Triple-vessel coronary artery disease (TVD) has high risk of death. We aimed to evaluate the predictive value of hypoalbuminemia in TVD patients. Methods A total of 8,943 consecutive TVD patients were enrolled from April 2004 to February 2011. The primary endpoint was all-cause death and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction or stroke). Patients were divided into two groups according to normal serum albumin level ( Results During the median of follow-up 7.5 years, 1365 deaths and 2354 MACCE occurred. Multivariate Cox regression indicated that hypoalbuminaemia ( Predictive value for all-cause death using the AUC, NRI and IDI AUC (95% CI) P value NRI (95% CI) P value IDI (95% CI) P value SYNTAX 0.585 (0.568–0.602) Ref. Ref. – Ref. – SYNTAX + albumin 0.602 (0.586–0.619) 0.002 0.205 (0.145–0.264) Multi-factor adjusted KM analysis in TVD Conclusions For TVD patients, hypoalbuminaemia was a strong independent prognostic factor for long-term outcomes of death and MACCE. Albumin improved the prediction of death with the SYNTAX score and the SYNTAX II score. Acknowledgement/Funding CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002), Beijing Natural Science Foundation (7181008)

The aim of the cohort study was to investigate the relation between plasma lipoprotein(a) (Lp[a]) and long-term clinical outcomes in patients with three-vessel disease (TVD) after the following treatment strategies, including medical therapy alone, percutaneous coronary intervention, and coronary artery bypass grafting. A total of 6,175 consecutive patients with angiographically confirmed TVD and available baseline Lp(a) data were included in this study. Based on the median level of Lp(a) at admission, the patient was divided into 2 subgroups. Primary endpoint was major adverse cardiovascular events (MACE), of which all-cause death, myocardial infarction, and unplanned revascularization were all included. In general, the median value of Lp(a) reached 13.76 mg/dl for all patients. The median follow-up time of all patients was 6.2 years. For MACE, a total of 1,433 cases were generated, accounting for 23.2%, including 804 (13.0%) all-cause death, 302 (4.9 %) myocardial infarction, and 494 (8.0%) unplanned revascularization. For the incidence of MACE, the high Lp (a) and low Lp (a) groups were 24.3% to 22.1% (p = 0.015), respectively. When the risk factors were adjusted, the multivariate analysis showed that high Lp(a) levels was an independent predictor of primary outcome (adjusted hazard ratio 1.169, 95% confidence interval 1.046 to 1.306, p = 0.006). Except for gender group, there is a relatively consistent correlation in the various subgroups. In conclusion, plasma Lp(a) is a potential biomarker for risk stratification and prognosis in patients diagnosed with TVD.

Aims The predictive value of white blood cells in triple-vessel coronary artery disease (TVD) remains unclear. This study aimed to examine the relationship between WBC counts and long-term prognosis of TVD. Methods A total of 8943 consecutive patients with triple-vessel coronary artery disease were enrolled from April 2004 to February 2011. The primary endpoint was all-cause death and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs; a composite of all-cause death, myocardial infarction or stroke). Results After a median of 7.5 years of follow-up, 7678 patients were included in the final analysis. Multivariable analysis showed that the white blood cell count was an independent predictor of death (hazard ratio: 1.04, p Conclusion Total and differential white blood cell counts are independent prognostic factors of long-term mortality and MACCE in triple-vessel coronary artery disease. A combination of monocyte, lymphocyte and eosinophil counts improved the predictive value for mortality with the SYNTAX score, and improved it slightly with SYNTAX score II.

Aim: To evaluate the prognostic value of plasma big endothelin-1 level in the context of three-vessel disease (TVD) with heavy atherosclerotic burden. Methods: A total of 6,150 patients with TVD and available big endothelin-1 data were included in the study. Participants were divided into two groups according to the optimal cutoff value of big endothelin-1 for mortality prediction. The primary endpoint was all-cause death. C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the added prognostic value of plasma big endothelin-1 level beyond the SYNTAX score II. Results: On the basis of the optimal cutoff value of 0.79 pmol/L, 1,984 patients were assigned to the high big endothelin-1 group. During a median follow-up of 6.8 years, 818 patients experienced all-cause death. Plasma big endothelin-1 level was significantly higher in patients who died than in patients who survived. Multivariable analysis found that high big endothelin-1 level was independently associated with an increased risk of mortality (hazard ratio: 1.36, 95% confidence interval: 1.18–1.57, P < 0.001). The association of big endothelin-1 with all-cause death was relatively consistent across subgroups with no significant interactions. The predictive ability of the SYNTAX score II was significantly enhanced by addition of plasma big endothelin-1 level (C-index: 0.723 vs. 0.715, P = 0.029; NRI: 0.304, P < 0.001; IDI: 0.009, P < 0.001). Conclusions: Plasma big endothelin-1 level is an independent predictor of long-term mortality in patients with TVD. It can improve the discrimination and reclassification of the SYNTAX score II for mortality prediction.

Objective.To describe a large cohort of patients with Takayasu arteritis in China.Methods.We retrospectively analyzed 566 patients hospitalized in Fuwai Hospital between 2002 and 2013. Data collected were clinical characteristics, laboratory findings, angiographic features, treatment, and longterm outcome.Results.The female to male ratio was 3.8 to 1, and the mean age of onset was 28.9 ± 12.0 years. The most common inflammatory symptom, initial symptom, and coexisting disease were fever (52, 9.2%), dizziness (214, 37.8%), and hypertension (HTN; 392, 69.3%), respectively. Pulmonary artery, coronary artery involvement, and aortic regurgitation were found in 83 (14.7%), 66 (11.7%), and 181 (36.7%) patients, respectively. Elevation of the erythrocyte sedimentation rate was observed in 131 patients (23.1%). Treatment included drugs, interventional therapy, autologous blood vessel transplant, artificial blood vessel transplant, and aortic valve replacement. During a mean followup of 5.0 ± 0.2 years, 32 patients died, including 1 patient who died suddenly during coronary angiography. HTN, major complications, and a progressive disease course were significant prognostic markers.Conclusion.HTN, rather than fever, is the leading reason for patients with Takayasu arteritis to see a doctor in China. HTN, major complications, and a progressive disease course are statistically significant predictors of survival. Because of cardiovascular events associated with the disease, early diagnosis and treatment are urgent to improve prognosis.

Purpose: Neosquamous epithelium (NSE) can arise within Barrett's esophagus as a consequence of medical or surgical acid reduction therapy, as well as after endoscopic ablation. Morphologic studies have suggested that NSE can develop from adjacent squamous epithelium, submucosal gland ducts, or multipotent progenitor cell(s) that can give rise to either squamous or Barrett's epithelium, depending on the luminal environment. The cells responsible for Barrett's epithelium self-renewal are frequently mutated during neoplastic progression. If NSE arises from the same cells that self-renew the Barrett's epithelium, the two tissues should be clonally related and share genetic alterations; if NSE does not originate in the self-renewing Barrett's, NSE and Barrett's esophagus should be genetically independent. Experimental Design: We isolated islands of NSE and the surrounding Barrett's epithelium from 20 patients by microdissection and evaluated each tissue for genetic alterations in exon 2 of CDKN2A or exons 5 to 9 of the TP53 gene. Nine patients had p16 mutations and 11 had TP53 mutations within the Barrett's epithelium. Results: In 1 of 20 patients, a focus of NSE had a 146 bp deletion in p16 identical to that found in surrounding Barrett's epithelium. The NSE in the remaining 19 patients was wild-type for p16 or TP53. Conclusion: Our mutational data support the hypothesis that, in most circumstances, NSE originates in cells different from those responsible for self-renewal of Barrett's epithelium. However, in one case, NSE and Barrett's epithelium seem to have arisen from a progenitor cell that was capable of differentiating into either intestinal metaplasia or NSE.

The optimal treatment strategy for triple–vessel coronary disease (TVD) remains a critical and uncertain issue. This study aimed to determine the long-term outcome of patients undergoing either percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medication therapy (

The human gene encoding alpha1-antitrypsin (alpha1AT, gene symbol PI) resides in a cluster of serine protease inhibitor (serpin) genes on chromosome 14q32.1. alpha1AT is highly expressed in the liver and in cultured hepatoma cells. We recently reported the chromatin structure of a >100 kb region around the gene, as defined by DNase I-hypersensitive sites (DHSs) and matrix-attachment regions, in expressing and non-expressing cells. Transfer of human chromosome 14 by microcell fusion from non-expressing fibroblasts to rat hepatoma cells resulted in activation of alpha1AT transcription and chromatin reorganization of the entire region. In the present study, we stably introduced cosmids containing alpha1AT with various amounts of flanking sequence and a linked neo selectable marker into rat hepatoma cells. All single-copy transfectants with >14 kb of 5' flanking sequence expressed wild-type levels of alpha1AT mRNA in a position-independent manner. In contrast, expression of transgenes containing only approximately 1.5-4 kb of flanking sequence was highly variable. Long-term culture of transfectant clones in the absence of selection resulted in gradual loss of neo expression, but expression of the linked alpha1AT gene remained constant. DHS mapping of cosmid transgenes integrated at ectopic sites revealed a hepatoma-specific chromatin structure in each transfectant clone. The implications of these findings are discussed.

The genes encoding alpha 1-antitrypsin (alpha 1AT, gene symbol P I) and corticosteroid-binding globulin (CBG) are part of a cluster of serine protease inhibitor (serpin) genes on human chromosome 14q32.1. Both genes are highly expressed in the liver and in cultured hepatoma cells, and the approximately 100-kb region around these genes contains an extensive array of expression-associated DNase I-hypersensitive sites (DHSs). Activation of human alpha 1AT and CBG transcription occurred when human chromosome 14 was transferred from nonexpressing cells to rat hepatoma cells. This activation event was accompanied by long-range chromatin reorganization of the entire region and the de novo formation of 17 expression-associated DHSs. Both gene activation and chromatin remodeling in hepatic cells required the liver-enriched transactivators hepatocyte nuclear factors-1 alpha and -4 (HNF-1 alpha and HNF-4). In this study, we tested whether ectopic expression of HNF-1 alpha and HNF-4 in nonexpressing cells could activate alpha 1AT and/or CBG transcription, and we monitored the chromatin structure of the locus in stably transfected fibroblasts. We report that both alpha 1AT and CBG mRNAs were expressed in fibroblast transfectants that stably expressed HNF-1 alpha and HNF-4, but expression was only approximately 1-10% of that observed in hepatic cells. Gene activation in these cells was accompanied by partial chromatin remodeling, as 6 of 17 expression-associated DHSs were formed. The potential implications of these results are discussed.

Background Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett's esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions The results of this study suggest the environment of the esophagus in BE patients can both generate and select for clones with p16 mutations.