Risk of QTc Interval Prolongation Associated With Circulating Anti‐Ro/SSA Antibodies Among US Veterans: An Observational Cohort Study

Abstract

Background Anti‐Sjögren's syndrome‐related antigen A‐antibodies (anti‐Ro/SSA‐antibodies) are responsible for a novel form of acquired long‐QT syndrome, owing to autoimmune‐mediated inhibition of cardiac human ether‐a‐go‐go‐related gene‐potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample‐size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti‐Ro/SSA‐antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti‐Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate‐corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti‐Ro/SSA‐positive (8.3%). Subjects who were anti‐Ro/SSA‐positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26–2.21] for QTc >470/480 ms; 2.32 [1.54–3.49] for QTc >490 ms; 2.77 [1.66–4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT‐prolonging drugs were added to the model. Nevertheless, stepwise‐fully adjusted OR for the higher cutoffs remained significantly increased in anti‐Ro/SSA‐positive subjects, particularly for QTc >500 ms (2.27 [1.34–3.87]). Conclusions Anti‐Ro/SSA‐antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti‐Ro/SSA‐positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.

Keywords

• anti‐Ro/SSA
• connective tissue diseases
• general population
• QTc prolongation
• sudden death risk