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在一般人群中,血清前蛋白转化酶枯草溶菌素 9(PCSK9)与胰岛素抵抗、甘油三酯、脂蛋白(a)水平独立相关,但与低密度脂蛋白胆固醇水平无关。

Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Independently Associated with Insulin Resistance, Triglycerides, Lipoprotein(a) Levels but not Low-Density Lipoprotein Cholesterol Levels in a General Population.

机构信息

Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine.

Department of Community Medicine, Kurume University School of Medicine.

出版信息

J Atheroscler Thromb. 2021 Apr 1;28(4):329-337. doi: 10.5551/jat.56390. Epub 2020 Jul 4.


DOI:10.5551/jat.56390
PMID:32624555
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8147011/
Abstract

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of low-density lipoprotein (LDL) receptor processing. Evolocumab and alirocumab are PCSK9 inhibitors; however, little is known about the association between PCSK9 levels and lipid profiles in a general population. Because PCSK9 inhibitors have LDL-C lowering effects, we investigated whether there is a positive correlation between serum PCSK9 levels and LDL-C or lipoprotein(a) [Lp(a)]. METHODS: In Uku town, 674 residents (mean age; 69.2±8.3 years) received health check-ups. The participants underwent a physical examination and blood tests, including PCSK9 and Lp(a). Serum PCSK9 and Lp(a) were measured by ELISA and Latex methods, respectively. HOMA-IR was calculated by fasting plasma glucose×insulin levels/405. RESULTS: The mean (range) of PCSK9 and Lp(a) were 211.2 (49-601) ng/mL and 60 (1-107) mg/dL, respectively. Because of a skewed distribution, the log-transformed values were used. With univariate linear regression analysis, PCSK9 levels were associated with Lp(a) (p=0.028), triglycerides (p<0.001), and HOMA-IR (p<0.001), but not with LDL-C (p=0.138) levels. Multiple stepwise regression analysis revealed that serum PCSK9 levels were independently associated with triglycerides (p<0.001), Lp(a) (p=0.033) and HOMA-IR (p=0.041). CONCLUSIONS: PCSK-9 is independently associated with triglycerides, Lp(a) levels, and HOMA-IR, but not LDL-C, in a relatively large general population sample.

摘要

目的:前蛋白转化酶枯草溶菌素/胰凝乳蛋白酶 9(PCSK9)已被确定为调节低密度脂蛋白(LDL)受体加工的重要调控因子。依洛尤单抗和阿利西尤单抗是 PCSK9 抑制剂;然而,对于一般人群中 PCSK9 水平与血脂谱之间的关联知之甚少。由于 PCSK9 抑制剂具有降低 LDL-C 的作用,我们研究了血清 PCSK9 水平与 LDL-C 或脂蛋白(a)[Lp(a)]之间是否存在正相关。

方法:在 Ukutown,有 674 名居民(平均年龄;69.2±8.3 岁)接受了健康检查。参与者接受了体格检查和血液检查,包括 PCSK9 和 Lp(a)。通过 ELISA 和乳胶方法分别测量血清 PCSK9 和 Lp(a)。通过空腹血浆葡萄糖×胰岛素水平/405 计算 HOMA-IR。

结果:PCSK9 和 Lp(a)的平均值(范围)分别为 211.2(49-601)ng/mL 和 60(1-107)mg/dL。由于分布偏态,使用了对数转换值。单变量线性回归分析显示,PCSK9 水平与 Lp(a)(p=0.028)、甘油三酯(p<0.001)和 HOMA-IR(p<0.001)相关,但与 LDL-C(p=0.138)水平无关。多步逐步回归分析显示,血清 PCSK9 水平与甘油三酯(p<0.001)、Lp(a)(p=0.033)和 HOMA-IR(p=0.041)独立相关。

结论:在相对较大的一般人群样本中,PCSK-9 与甘油三酯、Lp(a)水平和 HOMA-IR 独立相关,但与 LDL-C 无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/8147011/e032b8ecde90/jat-28-329-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/8147011/3435b691582a/jat-28-329-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/8147011/e032b8ecde90/jat-28-329-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/8147011/3435b691582a/jat-28-329-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63ca/8147011/e032b8ecde90/jat-28-329-g002.jpg

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本文引用的文献

[1]
Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis.

Clin Biochem. 2020-1-20

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Evolocumab vs. Ezetimibe in Statin-Intolerant Hyperlipidemic Japanese Patients: Phase 3 GAUSS-4 Trial.

J Atheroscler Thromb. 2020-5-1

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J Atheroscler Thromb. 2018-8-1

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Prevention of cardiovascular disease in patients with familial hypercholesterolaemia: The role of PCSK9 inhibitors.

Eur J Prev Cardiol. 2017-6-23

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome components among young adult females.

Diabetes Metab Syndr. 2017-11

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Correlation between serum levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and atherogenic lipoproteins in patients with coronary artery disease.

Lipids Health Dis. 2016-9-22

[9]
Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease.

JAMA. 2016-8-16

[10]
Circulating PCSK9 levels and CETP plasma activity are independently associated in patients with metabolic diseases.

Cardiovasc Diabetol. 2016-8-4

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