【作者】 许如意；

【导师】 叶平；

【作者基本信息】 中国人民解放军军医进修学院 ， 老年医学， 2011， 博士

【摘要】 背景：高敏心肌肌钙蛋白T (high-sensitivity cardiac troponin T, hsTnT)是预测心血管事件的重要指标。在胸痛人群中,低浓度的hsTnT水平即具有重要的诊断和预后价值。在社区人群中,hsTnT水平与心血管危险关系如何尚不清楚。动脉僵硬度是预测心血管事件的另一个有用指标。过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor, PPAR)及过氧化物酶体增殖物激活受体γ协同子la (peroxisome proliferator-activated receptor-γcoactivator-1a, PPARγC1a)在血糖、血脂的代谢中发挥着重要作用。动脉僵硬度是否与PPAR、PPARγC1a基因内部分单核苷酸多态性(single nucleotide polymorphisms, SNPs)相关,至今仍是个谜。方法：用hsTnT试剂盒检测1365位社区中老年人hsTnT水平。用Framingham冠心病(coronary heart disease, CHD)风险和总心血管病(cardiovascular disease, CVD)风险评分公式计算心血管危险评分。用一种新的方法从血凝块提取DNA后,用实时定量聚合酶链反应(polymerase chain reaction, PCR)、TaqMan探针法获得1374人PPARα、PPARδ、PPARγC1a基因的rs1053049、rs1800234和rs8192678等3个SNPs位点基因型。分析hsTnT水平和心血管危险的关系,分析传统心血管危险因素及SNPs位点与动脉僵硬度的关系。结果：在这个中老年社区人群中有719人(占52.7%)能检测到hsTnT (> 3.0pg/ml),150人(占11.0%)hsTnT升高(≥14.0pg/ml)。多变量分析显示男性、血糖、脑钠尿肽前体及肾小球率过滤与hsTnT水平独立相关。调整混杂因素后,高CHD风险(10年风险≥20%)随hsTnT水平增高而增加[OR值(每增加自然对数转化后hsTnT水平—单位)=2.134；95% CI,1.309至3.480；P=0.002],高总CVD风险(10年风险>20% )也随hsTnT水平增高而增加[OR值=2.362；95% CI,1.583至3.524；P<0.001]。hsTnT增高组和中间组与hsTnT水平最低组相比,其心血管风险明显增高。同时发现年龄、高血压、糖尿病等因素是影响动脉僵硬度的主要因素,rs1053049, rs1800234和rs8192678等三个SNPs位点及其组成的单体型和动脉僵硬度未见明确关系。结论：在这个社区人群中,hsTnT水平与心血管危险因素相关,也与预测的心血管风险相关。hsTnT水平检测可能有利于发现心血管事件高风险人员。本研究未发现PPAR、PPARγC1a基因的SNPs位点与动脉僵硬度相关。更多还原

【Abstract】 Background:The levels of high-sensitivity cardiac troponin T (hsTnT) was useful predictor for cardiovascular events. It provided useful information in population with chest pain, even at levels well below the detection limits of previous assays. However, the association between the levels of hsTnT and the predicted cardiovascular risk remains unclear. The arterial stiffness was another useful predictor for cardiovascular events. The peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor-y coactivator-la (PPARγC1a) play an important role in the metabolic process of glucose and lipid. Whether single nucleotide polymorphisms (SNPs) of these gene accout for arterial stiffness, it was still unknown.Methods:The hsTnT levels were measured from 1,365 community-based middle-aged to older adults. The association between cardiovascular risk factors and hsTnT level was examined. The association between hsTnT levels and predicted coronary heart disease (CHD) risk and predicted general cardiovascular disease (CVD) risk were analyzed. After purification of genomic DNA samples from clotted blood by a new method, three valid SNPs, including rs1053049, rs1800234 and rs8192678 in the PPAR and PPARyCla gene were genotyped in 1,374 subjects (530 patients and 844 controls) by TaqMan allelic discrimination assays. The association between cardiovascular risk factors and SNPs with the arterial stiffness were analyzed.Results:The detectable and elevated hsTnT levels were obtained in 719 subjects (52.7%) and 150 subjects (11.0%), respectively. In multivariable analyses, independent associations were found between hsTnT level and male sex, fasting glucose, N-terminal pro B-type natriuretic peptide, and estimated glomerular filtration rate. After adjustment for confounding factors, strong and graded increases in high predicted CHD risk (10-year risk≥20%) (adjusted OR per unit increase in the natural logarithm of the hsTnT levels,2.134; 95% CI,1.309 to 3.480; P=0.002) and high predicted general CVD risk (10-year risk>20%) (adjusted OR,2.362; 95% CI,1.583 to 3.524; P<0.001) were found. The higher predicted cardiovascular risk were found in intermediate and high hsTnT groups too. DNA samples purified from clotted blood were successfully performed through polymerase chain reaction, real time polymerase chain reaction, and melt curve analysis. Age, hypertension and diabetes mellitus were the main factors for increased arterial stiffness. There were no association between SNPs of rs1053049, rs1800234 and rs8192678 and the increased arterial stiffness among this community-based population. Haplotypes were analysed with multiple loci and there were no association between haplotypes and the increased arterial stiffness too.Conclusions:The hsTnT levels were associated with several cardiovascular risk factors in this community-based population, and it coincided with predicted cardiovascular risk. Determining hsTnT levels may aid clinicians in identifying patients with increased cardiovascular risk in the general population. The present study did not find association between SNPs of PPAR and PPARγC1a with the increased arterial stiffness in this community-based population.更多还原