Bucci Tommaso, Ames Paul Rj, Cammisotto Vittoria, Bartimoccia Simona, Triggiani Massimo, Parente Roberta, Ciampa Antonio, Pignatelli Pasquale, Carnevale Roberto, Pastori Daniele
Department of General Surgery and Surgical Specialties "Paride Stefanini", Sapienza University of Rome, Rome, Italy.
Immune Response and Vascular Disease Unit, CEDOC, Nova University Lisbon, Rua Camara Pestana, Lisbon, Portugal; Department of Haematology, Dumfries Royal Infirmary, Cargenbridge, Dumfries, UK.
J Autoimmun. 2022 May;129:102832. doi: 10.1016/j.jaut.2022.102832. Epub 2022 May 2.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) is emerging as a novel cardiovascular risk factor. Levels of PCSK9 in thrombotic primary antiphospholipid syndrome (PAPS) have never been investigated.
Cross sectional comparison of baseline characteristics of 91 PAPS patients enrolled in the multicenter prospective ATHERO-APS cohort study. PCSK9 levels were categorized into tertiles and the association with arterial and recurrent thrombosis were assessed by univariable and multivariable logistic regression analysis.
Median age was 51 years and 71.4% (n = 65) were women. Overall, 33% (n = 30) experienced an arterial event while 31% (n = 28) had recurrent thrombotic events. Median PCSK9 levels were 1243 (1100-1650) pg/ml. Patients in the third PCSK9 tertile (>1458 pg/ml) showed a higher prevalence of dyslipidemia, lupus anticoagulant positivity and a history of previous arterial and recurrent thrombosis than patients in the first and second tertile. PCSK9 levels were higher in arterial than venous thrombosis (1502 vs. 1180 pg/ml, p = 0.002), and in patients with recurrent vs isolated thrombosis (1680 vs. 1150 pg/m, p < 0.001). High plasma PCSK9 levels were associated with a 4-fold increase risk for arterial events and with a 10-fold increase risk for recurrent thrombosis after adjustment for confounding factors.
These preliminary data suggest that PCSK9 levels are increased in PAPS patients with arterial and recurrent thrombosis. Its role as a possible therapeutic target in PAPS needs further studies.
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）正成为一种新的心血管危险因素。血栓形成性原发性抗磷脂综合征（PAPS）患者的PCSK9水平从未被研究过。
对纳入多中心前瞻性动脉粥样硬化抗磷脂综合征（ATHERO-APS）队列研究的91例PAPS患者的基线特征进行横断面比较。将PCSK9水平分为三分位数，并通过单变量和多变量逻辑回归分析评估其与动脉血栓形成和复发性血栓形成的关联。
中位年龄为51岁，71.4%（n = 65）为女性。总体而言，33%（n = 30）发生了动脉事件，31%（n = 28）有复发性血栓形成事件。PCSK9水平中位数为1243（1100 - 1650）pg/ml。PCSK9三分位数最高组（>1458 pg/ml）的患者与第一和第二三分位数组的患者相比，血脂异常、狼疮抗凝物阳性以及既往动脉血栓形成和复发性血栓形成病史的患病率更高。动脉血栓形成患者的PCSK9水平高于静脉血栓形成患者（1502 vs. 1180 pg/ml，p = 0.002），复发性血栓形成患者的PCSK9水平高于孤立性血栓形成患者（1680 vs. 1150 pg/m，p < 0.001）。校正混杂因素后，血浆PCSK9水平高与动脉事件风险增加4倍以及复发性血栓形成风险增加10倍相关。
这些初步数据表明，动脉血栓形成和复发性血栓形成的PAPS患者PCSK9水平升高。其作为PAPS可能治疗靶点的作用需要进一步研究。
