心血管病是居民健康的主要危害，不断探索新的标志物对于心血管病防治意义重大。最近循环miRNA 被认为可能是心血管病新的血清标志物，但多为小样本病例对照研究，结果很不统一，对于循环miRNA的人群分布以及是否具有心血管疾病的预测价值尚无报道。为此，本申请拟在已收集的1.2 万人大样本自然人群中开展前瞻性研究，检测候选循环miRNA分子在我国人群中的分布特点，验证其对冠心病发生发展及相关事件的预后作用。探讨循环miRNA与其他传统危险因素的关系。同时通过前瞻性随访获得5 年后上述人群冠心病事件的发生情况，探索循环miRNA及其与传统危险因素交互作用对冠心病发生发展及预后的预测价值，筛选出对我国居民冠心病有诊断意义的循环miRNA，为心血管病防治提供依据。

Cardiovascular disease is the leading cause of death in China, new markers are needed to explore constantly in order to prevent and control cardiovascular disease. Circulating microRNA (C-miRNA) is considered to be the new cardiovascular disease markers according to some small sample case-control studies, although the results were also inconsistent. It is an urgent need to verify the distribution of C-miRNA and its role in risk and prognosis of coronary heart disease by carrying out a large-scale prospective study in general population. Based on the previous epidemiological investigation of cardiovascular disease conductd in 2010, in which 12,000 participants were recruited and their demographic information and blood specimens were collected, candidate C-miRNAs will be detected in order to describe its distribution in the population and its relations with other traditional risk factors.All the participants will be followed-up to observe the coronary heart disease events after five years. The predictive power of C-miRNAs and its interaction with the traditional risk factors in risk and prognosis of coronary heart disease can be best assessed using long-term prospective follow-up of large numbers of people. Based on the results, the C-miRNAs that can predict risk of coronary heart disease are expected to be screened, this will be helpful to prevent and control cardiovascular disease in China.

MicroRNAs（miRNAs）是一类长度约20-24个核苷酸的单链小分子非编码RNA。循环miRNA作为一种新的心血管疾病的标志物，在人群中与心血管疾病之间的关联尚不清楚。故本研究利用2010年的行业人群的资料，对12个地区中的9个地区进行了冠心病事件随访，其中4个进行了miRNA的测定。结果发现，在开始的小样本的病例对照研究中，挑选了3个能区分病例和对照的循环miRNA在人群中测量，分别为miRNA-423-3p，miRNA-10a，miRNA-92a。之后，进行了稍大样本的巢式病例对照研究，发现miRNA-423-3p与冠心病事件独立相关（OR：0.620, 95%CI：0.545-0.705）。之后又进行了前瞻性随访研究。到2016-2017年，经过了中位随访时间为6.0年的随访，2,838名研究对象中，共发生131例冠心病事件。多因素分析显示，在调整传统危险因素（年龄、性别、吸烟、饮酒、高血压、糖尿病、TC和HDLC）后miRNA-423-3p为冠心病事件的预测因子（HR：0.784，95% CI：0.732-0.839）。通过计算受试者功能曲线（receiver operating characteristic curve，ROC）下面积（AUC），发现在只包含8个传统指标的模型中，AUC为0.752；当分别纳入候选miRNAs进入方程后，只有miRNA-423-3p可使方程的诊断价值提高 （AUC=0.781）；当将候选miRNAs（miRNA-423-3p，miRNA-10a和miRNA-92a）的交互项放入方程中时，方程的AUC最大，为0.800。此外，在以上传统因素得到的模型基础上，分别将3种miRNA纳入模型中，发现只有纳入miRNA-423-3p的模型，净重新分类指数（net reclassification improvement，NRI）为0.222，为正值，且P<0.001，说明纳入miRNA-423-3p的新模型诊断准确率提高，增加了诊断效能；而将三者的交互项放入方程中时，模型的诊断正确率更高（NRI=0.304，P<0.001）。研究结果提示，miRNA-423-3p为冠心病事件的预测因子，为了方程的有效性和正确性考虑建议将候选miRNAs（miRNA-423-3p，miRNA-10a和miRNA-92a）放入到更大的人群去验证。