First Department of Propaedeutic Internal Medicine, Joint Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Laiko Hospital, Athens, Greece.
Department of Clinical Biochemistry, 'Aghia Sophia' Children's Hospital.
Rheumatology (Oxford). 2021 Dec 24;61(1):394-399. doi: 10.1093/rheumatology/keab277.
An interplay between thrombo-inflammatory and atherogenic mechanisms is recognized in cardiovascular disease (CVD) pathogenesis in APS. Herein, we examine associations of growth differentiation factor-15 (GDF-15), a pro-inflammatory cytokine identified as a potent CVD risk biomarker in the general population, with subclinical atherosclerosis in APS.
We measured plasma GDF-15 levels by an electrochemiluminescence immunoassay (cut-off 1200 pg/ml) and we examined carotid intima-media thickness (IMT) and the presence of carotid and femoral plaques using vascular ultrasound in 80 patients with APS (44 primary, 36 SLE/APS) and 40 healthy controls. We calculated the adjusted Global APS Score for cardiovascular disease (aGAPSSCVD), a revised adjusted Global APS Score (aGAPSS) for predicting CVD, including lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein-I antibodies, and hypertension, dyslipidaemia, obesity, diabetes and smoking.
GDF-15 levels were higher in APS patients vs controls, after adjusting for age and gender [absolute difference: 281 (95% CI: 141, 421) pg/ml, P < 0.001]. GDF-15 levels ≥1200 pg/ml were associated with higher mean IMT of the right and left carotid arteries [beta coefficient 0.068 (95% CI: 0.020, 0.116), P = 0.006] compared with GDF-15 levels <1200 pg/ml. GDF-15 was independently associated with mean IMT, after adjusting for gender and aGAPSSCVD [beta coefficient 0.059 (95% CI: 0.008, 0.110), P = 0.024], and additionally for statin (P = 0.025) and HCQ use (P = 0.011). GDF-15 levels ≥1200 pg/ml were associated with 2.4 times higher odds for atherosclerotic plaques (odds ratios = 2.438, 95% CI: 0.906, 6.556, P = 0.078), while this effect was reduced by including more covariates in the model.
GDF-15 is independently associated with subclinical atherosclerosis in APS patients, suggesting its potential role in CVD risk stratification in APS.
在抗磷脂综合征（APS）的心血管疾病（CVD）发病机制中，血栓炎症和动脉粥样硬化机制之间存在相互作用。在此，我们研究了生长分化因子 15（GDF-15）与 APS 患者亚临床动脉粥样硬化之间的相关性。GDF-15 是一种炎症细胞因子，已被确定为普通人群中一种强有力的 CVD 风险生物标志物。
我们通过电化学发光免疫测定法（cut-off 1200 pg/ml）测量了 80 名 APS 患者（44 名原发性 APS，36 名 SLE/APS）和 40 名健康对照者的血浆 GDF-15 水平，并使用血管超声检查颈动脉内膜中层厚度（IMT）以及颈动脉和股动脉斑块的存在情况。我们计算了用于预测 CVD 的改良后的全球 APS 评分（aGAPSS）和心血管疾病的全球 APS 评分（aGAPSSCVD），包括狼疮抗凝物、抗心磷脂抗体和抗β2 糖蛋白 I 抗体、高血压、血脂异常、肥胖、糖尿病和吸烟。
调整年龄和性别后，APS 患者的 GDF-15 水平高于对照组[绝对差值：281（95%CI：141，421）pg/ml，P<0.001]。与 GDF-15 水平<1200 pg/ml 相比，GDF-15 水平≥1200 pg/ml 与右侧和左侧颈动脉的平均 IMT 较高相关[β系数 0.068（95%CI：0.020，0.116），P<0.001]。在调整性别和 aGAPSSCVD 后，GDF-15 与平均 IMT 独立相关[β系数 0.059（95%CI：0.008，0.110），P=0.024]，此外，与他汀类药物（P=0.025）和 HCQ 用药（P=0.011）也相关。GDF-15 水平≥1200 pg/ml 与动脉粥样硬化斑块的发生几率增加 2.4 倍相关（比值比=2.438，95%CI：0.906，6.556，P=0.078），而在模型中纳入更多协变量后，这种作用会降低。
GDF-15 与 APS 患者的亚临床动脉粥样硬化独立相关，提示其在 APS 的 CVD 风险分层中具有潜在作用。
