Journal Article

Remnant cholesterol predicts risk of recurrent thrombosis beyond LDL-cholesterol in patients with antiphospholipid syndrome

Huang, Can, Li, Mengtao, Jiang, Hui, Wang, Zhaoqing, Xiao, Qingqing, Tian, Xinping, Zeng, Xiaofeng, Yang, Xinzhuang, Wang, Qian, Cai, Bin, Zhou, Yangzhong, Zhao, Jiuliang, Zhao, Yuan, Li, Guanqiao

2025

Overview

Background Antiphospholipid syndrome (APS) is notably linked to thrombotic events, particularly cardiovascular disease (CVD). The role of remnant cholesterol (RC) in predicting CVD risk is established, yet its relationship with thrombotic risk in APS patients remains to be elucidated. This study aims to assess the association between RC and recurrent thrombotic risk in patients with APS. Methods A prospective analysis was conducted based on a cohort of APS patients who met the 2006 Sydney revised classification criteria. Thrombotic risks associated with varying levels of RC were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Mendelian randomization (MR) was applied to examine the causal link between RC and different types of thrombotic events. Results A total of 325 patients with APS were enrolled in this study. Over a median follow-up of 35 months, 51 patients experienced thrombotic events, including 24 venous, 19 arterial, and 16 microvascular incidents. Patients with RC levels above 0.60 mmol/L exhibited significantly higher risks, with multivariable-adjusted hazard ratio (and 95% confidence interval) for all-cause, venous, arterial thrombosis, and microvascular disease being 5.05 (2.23–11.41), 6.34 (1.71–23.54), 3.79 (1.00–14.32), and 4.36 (1.08–17.58), respectively. Notably, elevated RC remained a significant thrombotic risk factor even in patients with normal conventional lipid profiles. MR analysis revealed a significant causal association between RC and arterial thrombosis, but not venous thrombosis. Conclusions Elevated RC is linked to a substantial increase in the risk of thrombotic events in APS patients. These findings suggest that RC could be a valuable marker for thrombotic risk in this population and a potential target for therapeutic intervention. Highlights A more than 5-fold increase in thrombotic risk, including arterial, venous, and microvascular events, is linked to individuals with RC levels >0.60 mmol/L in APS. Elevated RC remains a significant risk factor even in patients with normal conventional lipid indices (LDL-C, TC, TG, and non-HDL-C). Through MR analysis, there was a significant causal relationship between RC and AT in the general population, but not with VT, suggesting the complexity of the pathogenesis of VT in patients with APS. Patients with APS treated with hydroxychloroquine have lower RC levels, and hydroxychloroquine may have the potential to reduce RC. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Analysis / Analysis and chemistry / Antibodies / Anticoagulants / Antiphospholipid syndrome / Antiphospholipid Syndrome - blood / Antiphospholipid Syndrome - complications / Autoimmune diseases / Autoimmune disorders / Biomedicine / Blood / Blood cholesterol / Blood clot / Body mass index / Cardiovascular disease / Cardiovascular diseases / Care and treatment / Cholesterol / Cholesterol - blood / Cholesterol, LDL - blood / Complications and side effects / Confidence intervals / Development and progression / Diabetes / Diseases / Epidemiology / Female / Genetics / Heart diseases / High density lipoprotein / Humans / Hyperlipidemia / Hypertension / Ischemia / Lipids / Low density lipoprotein / Low density lipoproteins / Low-density lipoprotein cholesterol / Lupus / Male / Medical colleges / Medical prognosis / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Metabolic disorders / Microvasculature / Middle Aged / Patients / Prognosis / Prospective Studies / Recurrence / Regression analysis / Regression models / Relapse / Remnant cholesterol / Risk Factors / Statistical analysis / Thromboembolism / Thrombosis / Thrombosis - blood / Thrombosis - epidemiology / Thrombosis - etiology / Thrombotic risk / Variables / Variance analysis / Veins & arteries