The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naïve patients with acute ST elevation myocardial infarction

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Atherosclerosis plus Pub Date : 2022-12-01 DOI:10.1016/j.athplu.2022.09.002
Jun Sawaguchi , Yasuhiko Saeki , Minako Oda , Taka-aki Takamura , Kosuke Fujibayashi , Minoru Wakasa , Hironobu Akao , Michihiko Kitayama , Yasuyuki Kawai , Kouji Kajinami
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引用次数: 2

Abstract

Background and aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI).

Methods

We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level.

Results

One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both p < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan–Meier analysis (p = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06–3.45, p = 0.03) on events than other known atherosclerosis risk factors.

Conclusions

The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words)

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急性ST段抬高型心肌梗死statin-naïve患者循环中游离/成熟PCSK9比值具有潜在的预后意义
背景与目的枯草素/酶解蛋白9型(PCSK9)蛋白转化酶以成熟的和卵磷脂裂解的形式存在,但其生物学功能尚不清楚。我们研究了它们的水平是否与急性ST段抬高型心肌梗死(STEMI)患者的预后相关。方法选取160例statin-naïve急性STEMI患者,随访3年。在紧急冠状动脉介入治疗前和48小时后的5个时间点,通过酶联免疫吸附试验检测PCSK9亚型水平。比较按PCSK9水平分层的受试者之间冠状动脉和心脏事件的发生情况。结果126例患者完成3年随访。在急性期,两种PCSK9亚型水平均下降,随后从6 - 48 h升高(成熟期:从198±67到334±116 ng/mL,氟裂解期:从20±7到39±16 ng/mL, p和lt;0.01)。46例患者发生重大心脏事件。冠状动脉介入治疗后48 h糠蛋白裂解/成熟PCSK9比值预测事件发生的可能性;Kaplan-Meier分析显示,第三组患者的无事件生存率低于第一组和第二组患者(p = 0.004)。多因素Cox回归分析显示,该比值有较大的影响(HR: 1.92;95% CI: 1.06-3.45, p = 0.03)。结论氟化蛋白裂解/成熟PCSK9比值与statin-naïve急性STEMI患者3年心血管事件相关,提示PCSK9的氟化蛋白裂解过程与其对预后的影响存在潜在联系。(249字)
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来源期刊
Atherosclerosis plus
Atherosclerosis plus Cardiology and Cardiovascular Medicine
CiteScore
2.60
自引率
0.00%
发文量
0
审稿时长
66 days
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