HDL 颗粒与冠心病患者心血管事件及炎症的相关研究

Dyslipidemia is a causal risk factor for coronary heart disease(CHD),which is a indisputable fact demonstrated by the medical therapy (especially statins) during the past few decades. However,the clinical trials have showed at the same time that cardiovascular events(CVEs) still occur in patients who attain the recommended low density lipoprotein cholesterol target level with statins administration, which is termed as residual risk. And also, drugs for raising high density lipoprotein -cholesterol （HDL-C） levels could not reduce CVEs in recent clinical trials. These results could partly be explaied by the changes in HDL particle size. A few newly published studies indicated that measurement of HDL particle size could predict future CVEs more precisely compared with traditional HDL-C assay. Besides, a growing body of evidence,including data provided by our research group, has also implicated that atherosclerosis is a inflammatory disease,and the relation between HDL particle size, inflammation and CVEs deserves further investigations. Hence,we will fous on HDL particle in the study and investigate the distribution of HDL particle size in healthy population and patients with new onset CHD, its prediction of CVEs as well as its response to statins therapy on the basis of combining the clinic and basic methods. The possible relationship between HDL particle and inflammation will also be investigated by means of cell culture and animal model. Consequently, our study may has an important scientific as well as clinical implications for the purpose of developing a new strategy for the preventing and controlling of dyslipidemia and CHD.

血脂异常为冠心病（CHD）的致病性危险因素。多年来的他汀类药物临床研究进一步佐证了这一不争的事实。然而，研究结果同时显示，在接受他汀类药物治疗的患者中，即使血清低密度脂蛋白胆固醇水平已经达标，但心血管事件（CVEs）仍有发生并谓之剩余风险。旨在升高高密度脂蛋白（HDL）胆固醇（HDL-C）之药物临床研究也未见改善，究其原因与HDL颗粒变化不无关系。新近研究提示，与传统的HDL-C水平测定相比，HDL颗粒检测似可更好地预测CVEs风险。此外，大量证据包括我们的研究结果提示，动脉粥样硬化确为炎症性疾病，但HDL颗粒改变与CVEs及炎症之关系尚待探讨。本研究拟以HDL颗粒为切入点，从临床和基础两个层面，全面探讨HDL颗粒在健康、初发冠心病人群中的分布及对CVEs的影响和他汀干预后其可能变化；采用细胞和动物研究等方法，揭示HDL颗粒与炎症的关系，其科学意义旨在为血脂异常与CHD临床防治提供新思路。

本研究立足于课题组前期冠心病患者数据库与生物样本库的建立及系列相关研究成果，目前已购置美国Quantimetrix 公司生产的脂蛋白印迹仪（ lipoprint system Quantimetrix corporation）并建立了高密度脂蛋白（HDL）颗粒检测方法与技术。健康人群和未服用他汀及其他降脂药治疗的初发冠心病患者的入选与检测工作继续进行，相应病例资料及生物标本对应收集与保存无误。HDL颗粒的检测由于仪器每次检测的标本数所限（为12份），已完成500余例患者生物学样本和基础资料的收集及400余例血标本的检测及数据统计。本研究初步的数据分析已提示：大颗粒HDL减少与冠心病明显相关，大颗粒HDL减少及小颗粒HDL浓度百分比增加与冠心病冠脉病变程度显著相关。相关成果已发表中文核心期刊（中国循环杂志 2013;28(5):352-355.），相关英文文稿正在撰写中。