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蛋白水解酶枯草溶菌素 9 在伴脊柱关节炎的血脂异常患者中与疾病活动度相关。

Proprotein convertase subtilisin/kexin type 9 in the dyslipidaemia of patients with axial spondyloarthritis is related to disease activity.

机构信息

Divison of Health Sciences, Universidad Europea de Canarias, Tenerife, Spain.

Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.

出版信息

Rheumatology (Oxford). 2021 May 14;60(5):2296-2306. doi: 10.1093/rheumatology/keaa590.

Abstract

OBJECTIVE

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism and has been linked to cardiovascular (CV) risk. The purpose of the present study was to examine whether PCSK9 levels are related to abnormalities in the lipid profile and the development of atherosclerosis that occurs in patients with axial SpA (axSpA).

METHODS

We performed a cross-sectional study that encompassed 545 individuals; 299 patients with axSpA and 246 statin use-matched controls. PCSK9 and standard lipid profiles were analysed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the influence of PCSK9 on axSpA-related dyslipidaemia and subclinical carotid atherosclerosis.

RESULTS

Total cholesterol, high-density lipoprotein and low density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein A1 were significantly lower in axSpA patients than controls. PCSK9 serum levels [β coefficient -44 ng/dl (95% CI -60, -27), P = 0.000] were also downregulated in axSpA patients after fully multivariable adjustment. ASDAS-CRP was found to be independently and significantly related to PCSK9 [β coefficient 10 ng/dl (95% CI 1, 18), P = 0.023] after analysing fully adjusted models that took age, sex and the rest of the lipid profile molecules into account. Whereas patients taking prednisone showed higher serum levels of PCSK9 [55 ng/ml (95% CI 24, 8), P = 0.001], those under anti-TNF-α therapies exhibited lower levels [β coefficient -26 ng/ml (95% CI -43, -9], P = 0.003].

CONCLUSION

PCSK9 is downregulated in patients with axSpA. Disease activity is positive and significantly related to PSCK9. Anti-TNF-therapy yields a reduction in PCSK9 serum levels.

摘要

目的

前蛋白转化酶枯草溶菌素 9(PCSK9)是一种丝氨酸蛋白酶,可调节胆固醇代谢,与心血管(CV)风险相关。本研究旨在探讨 PCSK9 水平与发生在中轴型脊柱关节炎(axSpA)患者中的血脂异常和动脉粥样硬化发展的关系。

方法

我们进行了一项横断面研究,纳入了 545 名参与者,包括 299 名 axSpA 患者和 246 名他汀类药物匹配的对照者。对患者和对照者进行了 PCSK9 和标准血脂谱分析。对患者进行了颈动脉内膜中层厚度(cIMT)和颈动脉斑块评估。进行了多变量分析,调整了标准 CV 危险因素,以评估 PCSK9 对 axSpA 相关血脂异常和亚临床颈动脉粥样硬化的影响。

结果

axSpA 患者的总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)和载脂蛋白 A1 明显低于对照组。经过充分的多变量调整后,axSpA 患者的 PCSK9 血清水平[β系数-44ng/dl(95%CI-60,-27),P=0.000]也降低。在分析充分调整的模型,考虑年龄、性别和其余血脂谱分子后,ASDAS-CRP 被发现与 PCSK9 独立显著相关[β系数 10ng/dl(95%CI1,18),P=0.023]。虽然接受泼尼松治疗的患者 PCSK9 血清水平较高[55ng/ml(95%CI24,8),P=0.001],但接受抗 TNF-α治疗的患者 PCSK9 水平较低[β系数-26ng/ml(95%CI-43,-9),P=0.003]。

结论

axSpA 患者的 PCSK9 水平下调。疾病活动度呈阳性,与 PSCK9 显著相关。抗 TNF-α治疗可降低 PCSK9 血清水平。

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