不同人群男性中前蛋白转化酶枯草溶菌素/克新9型（PCSK9）的血液水平及其与不良长期预后的关系
[Blood Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Men from Different Population Groups and Its Relation to Unfavorable Long-Term Prognosis].
作者信息
Ragino Yu I, Astrakova K S, Shakhtshneider E V, Stakhneva E M, Gafarov V V, Bogatyrev S N, Voevoda M I
机构信息
Institute of Internal and Preventive Medicine, Novosibirsk, Russia.
出版信息
Kardiologiia. 2017 Apr;57(4):72-76.
AIM
of the study was to investigate blood levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in men from different population subgroups, their associations with cardiovascular risk factors and with unfavorable 7-years long-term prognosis.
MATERIAL AND METHODS
The study included three subgroups of men from a population sample of residents of Novosibirsk, 44-73 years old, not receiving lipid-lowering drugs: subgroup of population proper (183 men), subgroup with hypercholesterolemia (46 men), and subgroup with hypocholesterolemia (18 men). Blood level of PCSK9 was determined by ELISA using the test-systems "Human Proprotein Convertase 9/PCSK9 Immunoassay". Study endpoints (myocardial infarction, cardiovascular death) were registered during 7 years after baseline examination of subgroups using the data of the Registers of myocardial infarction and cardiovascular mortality.
RESULTS
Distribution of PCSK9 protein in subgroups with hyper- and hypocholesterolemia was normal. In the subgroup of population proper it was abnormal with leftward shift. PCSK9 protein concentration in the subgroup with hypercholesterolemia was 1.2 times higher than in the population subgroup. PCSK9 protein level correlated significantly with blood levels of total cholesterol (CH), low density lipoprotein (LDL) CH, and glucose. Only 15% of PCSK9 variability was due to the influence of other factors (R Square=0.155, p<0.001). Factors with significant influence on blood level of PCSK9 protein were levels of high density lipoprotein CH (=0.238, p=0.023), triglycerides (=0.253, p=0.049) and LDL CH (=0.751, p=0.009). Multivariate regression analysis revealed significant independent association of PCSK9 protein levels with cardiovascular death during period of registration (7-years) (p=0.048, OR=1.01). This result indicates that in men increase of blood level of PCSK9 protein by 1ng/ml independently of other parameters increases relative risk of cardiovascular death during following 7 years by 1%.
目的
本研究旨在调查不同人群亚组男性中前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）的血液水平，及其与心血管危险因素和不良7年长期预后的关联。
材料与方法
本研究纳入了来自新西伯利亚居民人群样本的三个男性亚组，年龄在44至73岁之间，未服用降脂药物：正常人群亚组（183名男性）、高胆固醇血症亚组（46名男性）和低胆固醇血症亚组（18名男性）。使用“人前蛋白转化酶9/PCSK9免疫测定”检测系统通过酶联免疫吸附测定法（ELISA）测定PCSK9的血液水平。使用心肌梗死和心血管死亡率登记数据，在亚组基线检查后的7年内记录研究终点（心肌梗死、心血管死亡）。
结果
高胆固醇血症和低胆固醇血症亚组中PCSK9蛋白的分布正常。在正常人群亚组中其分布异常且向左偏移。高胆固醇血症亚组中的PCSK9蛋白浓度比正常人群亚组高1.2倍。PCSK9蛋白水平与总胆固醇（CH）、低密度脂蛋白（LDL）CH和血糖的血液水平显著相关。PCSK9变异性中只有15%归因于其他因素的影响（决定系数R² = 0.155，p < 0.001）。对PCSK9蛋白血液水平有显著影响的因素是高密度脂蛋白CH水平（β = 0.238，p = 0.023）、甘油三酯水平（β = 0.253，p = 0.049）和LDL CH水平（β = 0.751，p = 0.009）。多变量回归分析显示，在登记期间（7年）PCSK9蛋白水平与心血管死亡存在显著独立关联（p = 0.048，比值比OR = 1.01）。该结果表明，在男性中，PCSK9蛋白血液水平每增加1ng/ml，与其他参数无关，会使随后7年内心血管死亡的相对风险增加1%。
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