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.