Akuka Aviram, Ben-Shabat Niv, Watad Abdulla, Tsur Avishai M, Ehrenberg Scott, McGonagle Dennis, Comaneshter Doron, Beinart Roy, Cohen Arnon D, Amital Howard
Department of Medicine 'B', Sheba Medical Center, Tel-Hashomer 5262100, Israel.
Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Ramat-Aviv 69978, Israel.
Eur Heart J. 2022 Dec 14;43(47):4912-4919. doi: 10.1093/eurheartj/ehac516.
Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances.
This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25-1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11-1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses.
Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease.
抗Ro/La自身抗体在自身免疫性疾病中尤为常见，但在健康成年人中也相对较为频繁。其对未成熟心脏传导系统的致心律失常作用已得到充分证实，大量证据表明血清反应阳性母亲所生新生儿患先天性房室传导阻滞的风险增加。尽管它们分布广泛且有致心律失常的潜在作用，但尚未对血清反应阳性的成年人进行大规模的人群研究。因此，这是第一项基于大规模人群的研究，旨在探讨抗Ro/La血清反应阳性与心律及传导障碍之间的关联。
这项横断面设计研究涉及以色列最大的健康维护组织的电子健康记录。纳入了2002年至2019年间抗Ro/抗La抗体检测呈阳性的所有受试者，并按年龄、性别和居住地点与对照组进行匹配。比较了两组之间不同心律和传导障碍的发生率。使用倾向得分匹配进行敏感性分析。研究人群包括17231名抗Ro/La血清反应阳性受试者和84368名对照组。抗Ro血清反应阳性患者的传导障碍发生率更高（3.0%对1.7%，P<0.001），心律紊乱发生率也更高（10.5%对7.0%，P<0.001）。仅抗La检测呈阳性的患者与心律失常无显著关联。在控制了可能的混杂因素后进行的多变量逻辑回归分析显示，抗Ro血清反应阳性患者发生心脏传导障碍的风险增加[比值比（OR）1.44，95%置信区间（CI）1.25 - 1.66，P<0.001]，发生心律紊乱的风险也增加（OR 1.21，95%CI 1.11 - 1.31，P<0.001）。然而，在某些亚组分析中，与心律紊乱的关联更为显著。
抗Ro血清反应阳性与成人心脏传导障碍呈正相关，在较小程度上与心律紊乱也呈正相关，无论是否存在并发的自身免疫性疾病。
