San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; The Heart Transplantation Division, Ospedale Niguarda Ca' Granda, Milan, Italy.
The Department of Medicine, San Raffaele Scientific Institute, Milan, Italy.
Nutr Metab Cardiovasc Dis. 2014 Jul;24(7):751-9. doi: 10.1016/j.numecd.2014.01.006. Epub 2014 Feb 1.
Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear.
Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets.
HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.
与普通人群相比，系统性红斑狼疮（SLE）患者亚临床动脉粥样硬化的患病率更高，发生心血管（CV）事件的风险也更高。CV、免疫和疾病相关危险因素对 SLE 加速动脉粥样硬化形成的相对贡献尚不清楚。
本研究纳入了 50 例 SLE 患者（平均年龄 44±10 岁，86%为女性）和 50 名年龄和性别匹配的对照组。采用颈总动脉内膜中层厚度（CCA-IMT）作为动脉粥样硬化的替代标志物。我们评估了传统和免疫及疾病相关因素，通过 10 色 8 色多色流式细胞术评估了多个 T 细胞亚群，并探讨了药物治疗对 CCA-IMT 的影响。在 SLE 患者中，几种心血管代谢危险因素中，高密度脂蛋白（HDL）及其三磷酸腺苷结合盒转运蛋白 1（ABCA-1）依赖性胆固醇流出能力显著降低（p<0.01），而 CCA-IMT 则显著升高（p=0.03）与对照组相比。CCA-IMT 与收缩压、低密度脂蛋白（LDL）胆固醇和体重指数（BMI）相关，但与疾病活动度和病程无关。SLE 患者中活化的 CD4+HLA-DR+和 CCR5+T 细胞亚群扩张。接受羟氯喹（HCQ）治疗的患者 CCA-IMT 较低（0.62±0.08 与 0.68±0.10 mm；p=0.03），且具有更好的危险因素谱，并表现出循环前炎性效应记忆 T 细胞亚群减少和幼稚 T 细胞亚群增加。
HDL 是 SLE 患者中改变的主要代谢参数。SLE 患者 CCA-IMT 的增加可能代表“经典”CV 危险因素持续贡献的净结果，同时免疫因素（CD4+HLA-DR+T 细胞）可能随时间的推移通过不同程度的活动发作不断贡献。接受 HCQ 治疗的患者表现出代谢谱的改变，T 细胞激活减少与亚临床动脉粥样硬化减少相关。
