4. Discussion
To the best of our knowledge, this is the first study to investigate and observe a significant association between the QTc interval and symptomatic indices of RA. Specifically, CDAI, SDAI, and DAS28-ESR were independently associated with the QTc interval, in addition to the associations with ESR and CRP.
Systemic inflammation is one of the important features of RA; meanwhile, inflammatory parameters are also risk factors contributing to QTc interval prolongation. Prolongation of the QTc interval is an important finding because it has been reported to be associated with cardiovascular death as a result of fatal ventricular tachycardia15. As demonstrated in this study, CRP and ESR levels were significantly associated with the duration of the QTc interval. Additionally, our results aligned with those of existing studies. In the cohort study by Lazzerini et al.7, in which a significant correlation was observed between high sensitivity CRP (hsCRP) and the QTc interval, patients whose high-sensitivity CRP levels were higher than 0.5 mg/dL had a significantly prolonged QTc interval than those with lower hsCRP levels (424.3 ± 21.7 ms vs. 409.6 ± 19.9 ms, p < 0.005).
Our data demonstrated significant and independent associations between the symptomatic indices of RA and QTc intervals. SDAI constitutes counting of SJC28 and TJC28, VAS by patient, VAS by clinician, and CRP value. CDAI was developed to provide a simplified and comprehensive means of assessing RA activity14,16. The CRP level was not included in the CDAI; unlike SDAI, however, it can be calculated immediately in the absence of laboratory tests, allowing for simple and rapid disease activity assessment of RA patients during follow-up14,17. The association between CVDs and CDAI has also been reported previously. Cui et al. found that the presence of ≥1 CVD risk factor was independently associated with higher CDAI18; Fabio et al. used the Expanded Risk Score in patients with RA to evaluate the cardiovascular risks among those who underwent biological treatment16. As a result, they observed a significant decrease of estimated CVD risk in those with persistent CDAI ≤10. Our results indicate that RA-associated symptoms may be used as a predictor of QTc interval, which further support previous findings.
In a cohort study by Chauhan et al.5, the incidence of QTc prolongation (defined as QTc ≥500 ms) during follow-up was significantly higher in patients with RA than in patients without RA. It has been reported that RA can directly affect cardiac electrophysiology by inflammatory cytokines during myocardial electrical instability19,20. Autonomic nervous system dysfunction was more prevalent in patients with RA, thus inducing sympathetic overactivation of stimulated β1-adrenergic receptors, increasing heart rate, and affecting calcium and potassium conductance. Consequently, the action potential duration and QTc interval were affected21. Chronic inflammation in RA can indirectly cause a series of structural changes, such as atherosclerosis, hypertrophy, necrosis, or fibrosis, and also increase the risk of coronary heart disease and heart failure19,22,23. Coronary atherosclerotic burden significantly increased in RA patients, and as Karpouzas et al. reported24, more coronary plaques were found in RA patients than in matched controls. In addition, RA patients had a higher score for segment stenosis and plaque size, and the trend was independent of cardiovascular risk factors24. Puntmann et al.25compared the magnetic resonance data of RA patients and healthy individuals and found that the RA group showed significantly increased end-diastolic volumes and reduced ejection fraction, indicating myocardial alterations in RA patients.
In terms of the medications used for RA patients in this study, prednisolone treatment was associated with a prolonged QTc interval compared with other medications; however, no difference was observed in the comparison of MTX or biologic agents. As prednisolone treatment was likely to be selected for patients with more severe systemic inflammation, it might reflect higher disease activity. As mentioned above, inflammation plays an important role in an abnormal QTc interval. Thus, medications that modulate systemic inflammation may lead to such changes1. In a cohort evaluated by Kobayashi et al.6, patients receiving the IL-6 inhibitor tocilizumab showed a significant reduction in QTc interval. They also found that the CRP level was independently associated with the QTc interval.