Association between plasma HDL-C levels and coronary artery severity and impact on outcomes of patients underwent percutaneous coronary intervention / 中华心血管病杂志

Objective: To analyze the association between plasma high-density lipoprotein cholesterol (HDL-C) levels and the severity of coronary artery disease, and to evaluate the impact of HDL-C levels on long-term outcomes in patients underwent percutaneous coronary intervention (PCI). Methods: A total of 10 458 consecutive patients underwent PCI from January 2013 to December 2013 at Fuwai hospital were enrolled in this study. Patients were divided into three groups according to HDL-C tertiles: low HDL-C group (HDL-C≤0.89 mmol/L, n=3 525), median HDL-C group (HDL-C>0.89-1.11 mmol/L, n=3 570) and high HDL-C group (HDL-C>1.11 mmol/L, n=3 363). SYNTAX score was used to evaluate the severity of coronary artery disease, linear regression was used to analyze the relationship of HDL-C and SYNTAX score. Kaplan-Meier survival analysis was used to compare the outcomes among the three groups. Multivariate Cox regression was used to define the potential associations of HDL-C and outcomes. Results: The HDL-C level was (1.03±0.28) mmol/L and the SYNTAX score was 11.7±8.1. Patients were older, proportion of female, stable angina pectoris, successful PCI and left ventricular eject fraction value were higher, while incidence of diabetes mellitus was lower, hyperlipidemia, old myocardial infraction, smoking history and left main and three vessels disease were lower in high HDL-C group (all P<0.05). Patients in high HDL-C group also had the lowest SYNTAX score (12.2±8.4 vs. 11.7±8.1 vs. 11.2±7.8, P<0.001). Both univariate and multivariate linear regression analysis showed that HDL-C was negatively associated with SYNTAX score, e.g. Univariate analysis: β=-0.046, P<0.001; Multivariate analysis: β=-0.058, P=0.001. And 10 400 (99.4%) patients completed 2-year follow up. At 2-year follow-up, there were no difference in all-cause death, cardiac death, myocardial infarction, revascularization, stroke, major adverse cardiovascular and cerebral events (MACCE) and stent thrombosis among three groups (P for trend>0.05), while patient in high HDL-C group experienced the highest BARC type 2 bleeding events (P for trend=0.018). Multivariate Cox regression analysis showed that HDL-C level was not an independent risk factor of 2-year adverse ischemia events (P>0.05) and 2-year bleeding events (P>0.05). Conclusion: In patients underwent PCI, plasma HDL-C level is negatively associated with SYNTAX score, but not an independent risk factor of ischemic and bleeding events post PCI.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease / 生物医学与环境科学（英文）

OBJECTIVE@#Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD.@*METHODS@#We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients.@*RESULTS@#A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score.@*CONCLUSION@#Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.

Comparison of Long-term Outcomes in Patients with Premature Triple-vessel Coronary Disease Undergoing Three Different Treatment Strategies: A Prospective Cohort Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with premature triple-vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long-term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients.</p><p><b>METHODS</b>One thousand seven hundred and ninety-two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization.</p><p><b>RESULTS</b>PCI, CABG, and MT alone were performed in 933 (52.1%), 459 (25.6%), and 400 (22.3%) patients. Both PCI and CABG were associated with lower all-cause death (4.6% vs. 4.1% vs. 15.5%, respectively, P < 0.01) and cardiac death (2.8% vs. 2.0% vs. 9.8%, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone (all-cause death: hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23-0.53, P < 0.01 and HR: 0.35, 95% CI: 0.18-0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95% CI: 0.19-0.54, P < 0.01 and HR: 0.36, 95% CI: 0.14-0.93, P = 0.03, respectively).</p><p><b>CONCLUSIONS</b>PCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov; Identifier: NCT02634086. https://www.clinicaltrials.gov/ct2/show/record/NCT02634086?term=NCT02634086&rank=1.</p>

Association of CDKN2B-AS1 Polymorphisms with Premature Triple-vessel Coronary Disease and Their Sex Specificity in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to establish whether cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms are associated with premature triple-vessel disease (PTVD).@*METHODS@#Nine single-nucleotide polymorphisms (rs1063192, rs10757274, rs1333042, rs1333049, rs2285327, rs3217986, rs3217992, rs4977574, and rs9632884) were genotyped in 884 PTVD patients and 907 control subjects (males ⪕ 50 years old and females ⪕ 60 years old) using the improved multiplex ligase detection reaction method.@*RESULTS@#The allele frequencies of rs10757274 G, rs1333049 C, rs4977574 G (all P < 0.001), and rs3217986 G (P = 0.040) were significantly higher in the PTVD group than in the control group, but those of rs1063192 A, rs1333042 G, and rs9632884 C (all P < 0.001) were significantly lower in the former than in the latter. Logistic regression analysis revealed that homozygote AA of rs1333042 is associated with decreased risk for PTVD (OR = 0.42, 95% CI: 0.22-0.82, P = 0.011). In addition, the allele frequencies observed differed between genders. The G allele of rs3217986 was associated with increased risk for PTVD in male patients only (OR = 2.94, 95% CI: 1.27-6.80, P = 0.012) in the dominant model, and no positively mutated allele was found in female patients.@*CONCLUSION@#Polymorphisms of the CDKN2B-AS1 gene are associated with the incidence of PTVD in the Chinese population. Furthermore, the frequencies of mutated alleles differed between genders.

Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of-Hospital Bleeding after Percutaneous Coronary Interventions / 中华医学杂志(英文版)

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 0.05). 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.

Inhibitory effect of iron on in vitro proliferation of smooth muscle cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Iron is a biocorrodible metal that might be used in bioabsorbable stents. This study investigated the effects at the cellular and protein levels of soluble divalent iron (ferrous gluconate) and soluble trivalent iron (ferric chloride) on the proliferation of human aortic smooth muscle cell (HASMC) in vitro.</p><p><b>METHODS</b>The water-soluble tetrazolium (WST-1) test was used to evaluate the effect of iron on proliferation of HASMC and Western blotting was used to measure the levels of signaling proteins involved in proliferative and apoptosis pathways.</p><p><b>RESULTS</b>HASMC proliferation was inhibited in a concentration dependent manner after treatment with soluble divalent and trivalent iron at concentrations of 100-500 µmol/L. Western blotting analysis showed that the proliferating cell nuclear antigen (PCNA) expression following treatment with soluble divalent iron and trivalent iron at 100, 300 and 500 µmol/L was reduced compared to the control. The PCNA expression decreased with increasing iron concentration and to a greater extent with the trivalent iron than with the divalent iron treatment group. The p53 expression was markedly increased in a concentration dependent manner in both iron treatment groups.</p><p><b>CONCLUSION</b>The soluble divalent iron and, to a greater degree trivalent iron, inhibited HASMC proliferation in a dosedependent manner, which may be attributed to reduction of PCNA expression and increase of p53 expression.</p>

Dicycloplatin differentially inhibits proliferation of human aortic smooth muscle and endothelial cells: potential for use in drug-eluting stents / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dicycloplatin is a relatively safe third generation platinum-complex anti-cancer drug. The present study focused on the effects of dicycloplatin on in vitro proliferation and apoptosis of human aortic smooth muscle cells (HASMC) and human aortic endothelial cells (HAEC).</p><p><b>METHODS</b>Proliferation of HASMC and HAEC, DNA content, and cellular levels of proliferation- and apoptosis-related proteins were assessed using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, flow cytometry and Western blotting assays, respectively.</p><p><b>RESULTS</b>Dicycloplatin at 10 ng/ml significantly inhibited HASMC proliferation, however, 10 µg/ml were required to significantly inhibit HAEC proliferation. Cell cycle analysis showed that dicycloplatin was a non-specific inhibitor of the cell cycle. Although dicycloplatin significantly decreased proliferating cell nuclear antigen (PCNA) expression in HASMC at all concentrations tested, it did not significantly affect PCNA expression in HAEC; Bax and p53 protein expression was upregulated in dicycloplatin groups.</p><p><b>CONCLUSIONS</b>Dicycloplatin at nanogram concentrations significantly inhibits HASMC proliferation, although the effect is relatively weaker than that of sirolimus. In contrast, the effect of dicycloplatin on inhibition of HAEC proliferation is much less pronounced than that on HASMC. The latter characteristics point to the potential for use of dicycloplatin in drug-eluting stents.</p>