Piantoni Silvia, Regola Francesca, Angeli Fabrizio, Caproli Alessia, Trovati Annalisa, Tomasi Cesare, Chiarini Giulia, Rossini Claudia, Rosei Claudia Agabiti, De Ciuceis Carolina, Franceschini Franco, Muiesan Maria Lorenza, Rizzoni Damiano, Airò Paolo
Rheumatology and Clinical immunology Unit, ASST Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Internal Medicine Unit, ASST Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Front Med (Lausanne). 2024 Feb 14;11:1247024. doi: 10.3389/fmed.2024.1247024. eCollection 2024.
The evaluation of microvascular alterations might provide clinically useful information for patients with an increased cardiovascular (CV) risk, such as those with rheumatoid arthritis (RA), being the small artery remodeling the earliest form of target organ damage in primary CV diseases, such as arterial hypertension. The evaluation of retinal arterioles is a non-invasive technique aimed to identify an early microvascular damage, represented by the increase of the wall-to-lumen ratio (WLR) index. Abatacept (ABA), a T-cell co-stimulator blocker, is used to treat RA. A CV protective action was hypothesized for its peculiar mechanism of action in the modulation of T-cells, potentially involved in the pathogenesis of CV comorbidity. The study aimed to non-invasively investigate morphological characteristics of retinal arterioles in a cohort of RA patients treated with ABA.
Seventeen RA patients [median (25th-75thpercentile) age = 58 (48-64) years, baseline 28-joint Disease Activity Score DAS28-C-reactive protein (DAS28-CRP) = 4.4 (3.9-4.6), body mass index (BMI) = 24.2 (23.4-26) kg/m, rheumatoid factor positive:52.9%, anti-citrullinated peptide autoantibodies positive:76.5%] without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by the adaptive optics imaging system of retinal arterioles before and every 6 months of therapy with ABA (T0, T6 and T12). Office blood pressure evaluation, 24-h ambulatory blood pressure monitoring and tissue-doppler echocardiography were also performed.
A progressive significant reduction of the WLR of retinal arterioles was observed [T0 = 0.28 (0.25-0.30), T6 = 0.27 (0.24-0.31), T12 = 0.23 (0.23-0.26); p T0 vs. T6 = 0.414; p T6 vs. T12 = 0.02; p T0 vs. T12 = 0.009], without significant variations in other parameters. The T0-T12 reduction of WLR was correlated with that of DAS28-CRP (r:0.789; = 0.005). Moreover, a significant reduction of diastolic office blood pressure and a trend for reduction of daily pressure measured by ambulatory monitoring were observed.
In a cohort of RA patients without known CV risk factors, a reduction of retinal microvascular alterations was demonstrated after treatment for 12 months with ABA, in parallel with the reduction of disease activity. These results might suggest the possibility of microvascular abnormalities regression induced by the immune system modulation.
微血管改变的评估可能为心血管（CV）风险增加的患者提供临床有用信息，例如类风湿关节炎（RA）患者，小动脉重塑是原发性CV疾病（如动脉高血压）中最早的靶器官损伤形式。视网膜小动脉评估是一种非侵入性技术，旨在识别以壁腔比（WLR）指数增加为代表的早期微血管损伤。阿巴西普（ABA）是一种T细胞共刺激阻滞剂，用于治疗RA。因其在调节T细胞中的独特作用机制，推测其具有CV保护作用，而T细胞可能参与CV合并症的发病机制。本研究旨在对一组接受ABA治疗的RA患者的视网膜小动脉形态特征进行非侵入性研究。
17例RA患者[年龄中位数（第25 - 75百分位数）= 58（48 - 64）岁，基线28关节疾病活动评分DAS28 - C反应蛋白（DAS28 - CRP）= 4.4（3.9 - 4.6），体重指数（BMI）= 24.2（23.4 - 26）kg/m²，类风湿因子阳性：52.9%，抗瓜氨酸化肽自身抗体阳性：76.5%]，无已知CV危险因素（动脉高血压、糖尿病、高胆固醇血症、既往CV事件、吸烟），在接受ABA治疗前及治疗后每6个月（T0、T6和T12）通过视网膜小动脉自适应光学成像系统进行评估。还进行了诊室血压评估、24小时动态血压监测和组织多普勒超声心动图检查。
观察到视网膜小动脉WLR逐渐显著降低[T0 = 0.28（0.25 - 0.30），T6 = 0.27（0.24 - 0.31），T12 = 0.23（0.23 - 0.26）；p T0与T6 = 0.414；p T6与T12 = 0.02；p T0与T12 = 0.009]，其他参数无显著变化。WLR从T0到T12的降低与DAS28 - CRP的降低相关（r：0.789；p = 0.005）。此外，观察到诊室舒张压显著降低，动态监测测得的每日血压有降低趋势。
在一组无已知CV危险因素的RA患者中，接受ABA治疗12个月后，视网膜微血管改变减少，同时疾病活动度降低。这些结果可能提示免疫系统调节诱导微血管异常消退的可能性。
