Section of Inflammation and Cardiometabolic Diseases National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda MD USA.
Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal, and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gaithersburg MD USA.
J Am Heart Assoc. 2023 Nov 21;12(22):e031227. doi: 10.1161/JAHA.123.031227. Epub 2023 Nov 20.
Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low-density lipoprotein by the lectin-like low-density lipoprotein receptor-1 triggers release of the soluble extracellular domain of the receptor (sLOX-1). We sought to characterize the relationship between sLOX-1, inflammation, and coronary plaque progression in psoriasis.
A total of 327 patients with psoriasis had serum sLOX-1 levels measured at baseline by an ELISA-based assay. Stratification by high-sensitivity C-reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high-sensitivity C-reactive protein quartile 4 were middle-aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30-13.40]). In the study cohort, participants with sLOX-1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX-1 was associated with total burden (rho=0.296; =0.01), noncalcified burden (rho=0.286; =0.02), fibro-fatty burden (rho=0.346; =0.004), and necrotic burden (rho=0.394; =0.002). A strong relationship between sLOX-1, noncalcified burden (=0.19; =0.03), and fibro-fatty burden (=0.29; =0.003) was found in fully adjusted models at baseline and 1- and 4-year follow-up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX-1.
Patients with psoriasis with both high sLOX-1 and high-sensitivity C-reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX-1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.
银屑病是一种与冠状动脉疾病风险相关的慢性炎症性疾病。凝集素样低密度脂蛋白受体-1 摄取氧化型低密度脂蛋白会触发受体的可溶性细胞外结构域（sLOX-1）的释放。我们旨在描述银屑病患者中 sLOX-1、炎症与冠状动脉斑块进展之间的关系。
共纳入 327 例银屑病患者，采用 ELISA 法检测其基线血清 sLOX-1 水平。根据高敏 C 反应蛋白（hs-CRP）≥4.0mg/L（四分位 4）进行分层，确定了 81 名基线时具有冠状动脉斑块表型的患者，并通过冠状动脉计算机断层扫描血管造影进行纵向随访。hs-CRP 四分位 4 中的受试者年龄为 51.47±12.62 岁，主要为男性（54.3%），银屑病疾病严重程度中等（6.60[四分位间距，3.30-13.40]）。在研究队列中，sLOX-1 高于中位数的患者显示出更易发生脆弱的冠状动脉斑块特征。基线时，sLOX-1 与总负荷（rho=0.296；=0.01）、非钙化负荷（rho=0.286；=0.02）、纤维脂肪负荷（rho=0.346；=0.004）和坏死负荷（rho=0.394；=0.002）相关。在基线和 1 年及 4 年随访时的完全调整模型中，sLOX-1 与非钙化负荷（=0.19；=0.03）和纤维脂肪负荷（=0.29；=0.003）之间存在很强的关系。无论接受生物制剂或系统治疗，高 sLOX-1 患者的冠状动脉斑块特征在 1 年内均有进展。
高 sLOX-1 合并高 hs-CRP 的银屑病患者，其冠状动脉斑块负担增加，与动脉粥样硬化斑块进展相关，与生物制剂和系统治疗无关。因此，sLOX-1 可能被视为除传统危险因素外，预测冠状动脉疾病风险的一个很有前景的标志物。
