Association between corrected QT interval and inflammatory cytokines in rheumatoid arthritis
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Objective.: Corrected QT (QTc) interval predicts all-cause and cardiovascular mortality and may contribute to the increased mortality risk in rheumatoid arthritis (RA). Animal experiments have shown that proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 1 (IL-1)] can prolong cardiomyocyte action potential. We sought to determine whether elevations in circulating inflammatory cytokines were independently associated with QTc prolongation in patients with RA. Methods.: One hundred twelve patients [median age 62 (interquartile range 17) yrs; 80 women (71%)] from a well-characterized RA cohort underwent baseline 12-lead electrocardiograms for QT interval measurement and contemporary blood sampling to assess concentrations of inflammatory markers including C-reactive protein (CRP), TNF-α, and interleukins (IL-1α, IL-1β, IL-6, IL-10). QTc was calculated using the Bazett (QT BAZ= QT ÷ √RR) and Framingham Heart Study (QT FHS= QT + 0.154 × [1 – RR]) heart rate correction formulas. Results.: Inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10) were positively correlated with QT BAZ(Spearman rank correlation coefficient rho = 0.199, 0.210, 0.222, 0.333; all p < 0.05). In multivariable regression analysis, these associations were all confounded by age except IL-10, where higher tertile groups were independently and positively associated with QT BAZ(β = 0.202, p = 0.023) and QT FHS(β = 0.223, p = 0.009) when compared to the lower tertile. CRP (per unit increase) was independently associated with QT BAZ(β = 0.278, p = 0.001), but not QT FHS. Conclusion.: To our knowledge, ours is the first study demonstrating a contemporary link between inflammatory cytokines and QT interval in humans. Our results suggest that a lower inflammatory burden may protect against QTc prolongation in patients with RA. However, further studies are required to confirm the effects of pro- and antiinflammatory cytokines on QTc interval.
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Increased IL-6 levels are associated with prolonged QTc in patients with inflammatory conditions such as rheumatoid arthritis and infections including HIV and SARS-CoV-2.
“Increased levels of IL-6 are associated with prolonged QTc in patients with inflammatory conditions such as rheumatoid arthritis and infections including HIV and SARS-CoV-2 (30–33).”
From Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial (2025) · cites this paper as [30]
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- Authors
- Adlan, A. M., Panoulas, V. F., Smith, J. P., Fisher, J. P., & Kitas, G. D.
- Affiliations
- National Health Service (GB)
- Venue
- The Journal of Rheumatology
- Publisher
- The Journal of Rheumatology
- Published
- 2015-01-15
- Volume
- 42
- Issue
- 3
- Pages
- 421-428
- ISSN
- 0315-162X (ISSN-L)
- 1499-2752
- OpenAlex
- W2327614829
- Cited by
- 71
- References
- 52
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 10 · 2023: 4 · 2022: 8 · 2021: 3 · 2020: 9 · 2019: 4 · 2018: 11 · 2017: 5 · 2016: 7 · 2015: 2
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Versus Arthritis (19633)
- Medical Research Council (MR/K00414X/1)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- rheumatoid arthritis, QTc interval, QTc prolongation, inflammatory cytokines, TNF-α, interleukin-1, interleukin-6, IL-10, C-reactive protein, Bazett correction, cardiovascular risk, inflammatory burden
- MeSH terms
- Cardiac Conduction System Disease, Adult, Aged, Arrhythmias, Cardiac, Arthritis, Rheumatoid, Electrocardiography, Female, Heart Conduction System, Heart Rate, Humans, Male, Middle Aged, Cytokines, Brugada Syndrome
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