Li Sha, Zhao Xi, Zhang Yan, Zhu Cheng-Gang, Guo Yuan-Lin, Wu Na-Qiong, Xu Rui-Xia, Qing Ping, Gao Ying, Sun Jing, Liu Geng, Dong Qian, Li Jian-Jun
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Oncotarget. 2017 Feb 14;8(7):12333-12341. doi: 10.18632/oncotarget.12471.
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 μg/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.
前蛋白转化酶枯草溶菌素/克新9型（PCSK9）、载脂蛋白C-III（apoC3）和小而密低密度脂蛋白胆固醇（sdLDL-C）的血浆水平，最近已被视为与动脉粥样硬化相关的循环脂质指标。我们旨在阐明它们与当前血脂异常的关联，并确定它们在血脂异常风险增加时的水平。对总共1605例连续接受诊断性/介入性冠状动脉造影的未治疗患者进行了检查。使用经过验证的酶联免疫吸附测定法测定血浆PCSK9和apoC3水平，并通过Lipoprint LDL系统测量sdLDL-C。PCSK9、apoC3和sdLDL-C的血浆水平与当前血脂异常分类相关（所有p<0.001）。PCSK9在235 ng/ml水平时对高胆固醇血症和混合性高脂血症均有显著预测作用；高甘油三酯血症、高胆固醇血症和混合性高脂血症的apoC3水平分别为80.0、71.5和86.4 μg/ml；高甘油三酯血症、高胆固醇血症、混合性高脂血症和低高密度脂蛋白（HDL）胆固醇血症的sdLDL-C分别为3.5、2.5、4.5和2.5 mg/dl（所有受试者工作特征曲线下面积p<0.001）。在比较LDL-C类别增加的多分类逻辑模型中，与高PCSK9、apoC3和sdLDL-C的相互作用逐渐升高。同样，apoC3和sdLDL-C与甘油三酯类别增加的相互作用升高，只有sdLDL-C与HDL胆固醇（HDL-C）类别降低有相互作用。此外，观察到PCSK9、apoC3和sdLDL-C与当前血脂异常存在不一致。PCSK9、apoC3和sdLDL-C与当前血脂异常存在显著相互作用，在筛查中具有预测性。与当前血脂异常的大量不一致可能为脂质管理和进一步的心血管益处提供新的视角。
