LAUSR

OBJECTIVE An interplay between thrombo-inflammatory and atherogenic mechanisms is recognized in cardiovascular disease pathogenesis (CVD) in antiphospholipid syndrome (APS). Herein, we examine associations of growth differentiation factor-15 (GDF-15), a pro-inflammatory cytokine identified as potent CVD risk biomarker in the general population, with subclinical atherosclerosis in APS. METHODS We measured plasma GDF-15 levels by an electrochemiluminescence immunoassay (cut-off 1200 pg/mL) and 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 systemic lupus erythematosus (SLE)/APS) and 40 healthy controls. We calculated the aGAPSSCVD, a revised adjusted Global APS Score (aGAPSS) to predict CVD, including lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein-I antibodies, and hypertension, dyslipidemia, obesity, diabetes and smoking. RESULTS GDF-15 levels were higher in APS patients vs. controls 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 right and left carotid (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 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 hydroxychloroquine use (p = 0.011). GDF-15 levels ≥1200 pg/mL were associated with 2.4 higher odds for atherosclerotic plaques (OR = 2.438 (95% CI: 0.906, 6.556), p = 0.078), while this effect reduced adding more covariates in the model. CONCLUSION GDF-15 is independently associated with subclinical atherosclerosis in APS patients suggesting its potential role in CVD risk stratification in APS.