国际多中心临床试验的监查

为贯彻临床试验管理规范，保证多中心临床试验的质量。本文以ADVANCE多中心临床试验为例，简介监查的程序和方法。提出监查员应当具有医药知识和临床试验经验，应当按程序到研究点去核查CRF，研究文件和有关资料。标准化的监查有助于提高多中心临床试验的质量。     

Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease

Background and aimsWhether 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.Methods and resultsThis 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 (Q1>2.58,n = 704; 2.2 ≤ Q2<2.58, n = 706; Q3<2.22, 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).ConclusionLow 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.     

冠心病合并阻塞性睡眠呼吸暂停患者的血液生化指标分析

目的探讨冠心病合并阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)患者的多项血液生化指标的变化,旨在为合并有OSA的冠心病患者的治疗提供依据。方法 178例冠心病患者经多导睡眠监测(polysomnogra-phy,PSG),依据呼吸暂停低通气指数(apnea-hypopnea index,AHI),分为四组:OSA阴性组、轻度OSA组、中度OSA组、重度OSA组;检测各组患者的空腹血糖(FG)、糖化血红蛋白(HBA1c)、高敏C-反应蛋白(hsCRP)、氨基末端B型钠尿肽原(NT-proBNP)、血清甘油三酯(TG)、总胆固醇(TCHO)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)等指标,并将检测结果在各组间做比较。结果 FG在重度OSA组高于OSA阴性组、轻度OSA组和中度OSA组,差异有统计意义(P值分别为0.006、0.000、0.002),且随着OSA的加重而逐步增高;HBA1c在重度OSA组也高于其他三组,差异有统计意义(P值分别为0.004、0.001、0.023),且随着OSA的加重而逐步增高;hsCRP在OSA重度组高于OSA阴性组,差异有统计意义(P=0.040);NT-proBNP、TG、TCHO、HDL-C、LDL-C等各项目组间比较差异均无统计意义(P>0.05)。结论冠心病合并OSA的患者糖代谢紊乱突出;冠心病合并重度OSA的患者存在慢性系统性炎症。对合并有OSA的冠心病患者除常规冠心病、OSA治疗外,应早期筛查糖耐量,采取积极的降糖、抗炎症措施可能对其有益。     

北京房山社区人群心血管病综合防治研究

目的探索我国农村人群心血管病综合防治经验，初步总结一套有推广价值的综合防治方案。方法采用全人群与高危人群结合的防治策略，研究社区范围包括５个乡，１０万以上人口。干预方式和主要措施：（１）在卫生保健服务和社区组织体系基础上建立健全三级防治网。（２）健康教育和健康促进。（３）基层心血管病防治人员的培训。（４）高血压检出、随访和管理。结果基线调查和复查分别于１９９１～１９９２年度和１９９５年完成，通过３年干预，干预区人群知识、态度和行为得分明显高于对照区，干预区人群态度和行为向有利于心血管病防治方向改变。干预区高血压患者血压测量率和管理率分别明显高于对照区（Ｐ＜０．０１）。与对照区相比，干预区人群收缩压净下降１．２ｍｍＨｇ（Ｐ＜０．０５），但体重和体重指数略有升高。干预区脑卒中发病率下降１３．５％（Ｐ＜０．０１）；脑卒中死亡率下降了１２．９％（Ｐ＜０．０１）。对照区正相反，脑卒中发病率和死亡率均有所上升。结论心血管病综合防治方法与措施可行，初步取得预防和降低脑卒中发病和死亡的效果。     

国人缺血性心血管病发病危险的评估方法及简易评估工具的开发研究

目的 研究开发适合我国人群疾病特点且方便临床使用的心血管病发病危险度评估方法和评估工具。方法 依据中美心肺血管疾病流行病学合作研究队列随访资料，采用Cox比例风险模型拟合最优预测模型，并校正人群危险因素长期变化趋势的影响，采用独立人群回代检验和计算ROC曲线下面积来检验模型的预测能力。进一步建立简易预测模型，并据此制定适合我国人群的心血管病综合危险度简易评估工具。结果 中美心肺血管疾病流行病学合作研究1983～1984年基线调查年龄35～59岁，剔除基线患有冠心病、脑卒中及主要危险因素资料不全者后男女共计9903人，截止到2000年平均随访15．1年，共发生冠心病事件105例、缺血性脑卒中266例、缺血性心血管病360例。基线年龄、性别、血压、血清总胆固醇、体重指数、吸烟和糖尿病与冠心病、缺血性脑卒中和缺血性心血管病(ischemic cardiovascular diseases，ICVD)事件发病有互相独立的显著关联，且联系的方向和规律一致。据此建立的分性别ICVD事件10年发病危险预测模型，经过校正人群危险因素的长期变化趋势，证明能够很好地用于1992～1994年新建立队列的ICVD发病预测，其ROC曲线下面积(AUC)男性最优模型为0．799，女性最优模型为0．844。简易模型的AUC与最优模型几乎相同。结论 初步开发的ICVD事件10年发病危险预测模型和简易评估工具具有令人满意的预测能力，也能够较好地反映国人发生心血管病的综合危险。     

UW液对冠状动脉功能影响的实验研究

目的 :探讨UniversityofWisconsin液 (UW液 )对猪冠状动脉功能的影响。方法 :取新鲜猪心外膜下冠状动脉前降支切成 3段 ,长 3mm ,共 2 8条血管环 ,随机分 4组 ,每组 7条。常温下 ,对照Ⅰ组 :在 37℃有氧的器官槽中用重碳酸盐缓冲液 (KH液 )保存 4h ;AⅠ组 :同等条件下用UW液保存 4h。低温下 ,对照Ⅱ组 :在 4℃无氧的冰箱中用KH液保存 4h ;AⅡ组 :同等条件下用UW液保存 4h。采用器官槽法 ,持续监测在 37℃保存过程中血管环张力的变化 ,及在环加氧酶阻断剂消炎痛 (7μmol L)和一氧化氮合成酶阻断剂N 硝基 L 精氨酸 (30 0 μmol L)作用下 ,前列腺素F2α(30nmol L)及非受体介导钙离子载体引发的收缩舒张反应。结果 :与对照Ⅰ组相比 ,AⅠ组血管末张力明显降低 ,AⅠ组预收缩反应程度明显降低。与对照Ⅰ组、对照Ⅱ组相比 ,非受体介导钙离子载体引发的舒张反应 ,AⅠ组、AⅡ组明显下降。结论 :在 37℃条件下UW液对冠状动脉张力的影响主要以舒张为主 ;低温有利于UW液对冠状动脉的收缩功能的保护 ;冠状动脉经UW液保存 4h后 ,内皮源性超极化因子介导血管舒张功能降低     

CREG, a new regulator of ERK1/2 in cardiac hypertrophy

OBJECTIVES: The cellular repressor of E1A-stimulated genes (CREG), a mannose-6-phosphate-containing secreted glycoprotein, enhances differentiation and inhibits proliferation. In this study, our aim was to understand the role of CREG in cardiac hypertrophy. METHODS: Two models of cardiac hypertrophy were used: the in vivo pressure-overloaded rat cardiac hypertrophy and the in vitro stretched neonatal rat cardiomyocyte hypertrophy. CREG's function in cardiac cells was investigated after over-expression or antisense inhibition of CREG. RESULTS: We found reduced CREG expression in rat hearts after the in vivo overload, as shown by Northern blot analysis. CREG over-expression inhibited cardiac cell growth, as demonstrated by reduced protein content, cell area and ERK1/2 level in cultured neonatal rat cardiomyocytes, and by the reduced proliferation of cultured neonatal rat cardiac fibroblasts. Additionally, over-expression of CREG dampened the stretched cardiomyocyte hypertrophy through ERK1/2. On the other hand, the opposite effects were observed when CREG expression was decreased using antisense. This modulation of CREG expression resulted in no changes in the cardiomyocyte expressions of the hypertrophic or apoptotic signaling molecules such as protein kinase C (PKC) epsilon, PKC beta1, PKC alpha, PKC beta2, PKC delta, JNK1/2, p38, p53, Bax, Bcl2 and Fas. CONCLUSIONS: CREG was found to inhibit cardiac cell growth as a novel regulator of ERK1/2 and might participate in the development of cardiac hypertrophy under pressure overload. The insight that CREG inhibited the growth in rat hearts in vivo and in cardiac cells in vitro provides new clues for further investigation of the mechanism of heart remodeling.