Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

Abstract

Background We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. Methods All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as >440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes – involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes–was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. Results After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). Conclusion The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

Autoimmune and inflammatory K+ channelopathies in cardiac arrhythmias: Clinical evidence and molecular mechanisms

“…25 More generally, we demonstrated that regardless of the specific disease involved,QTc prolongation was commonly observed in subjects with elevated C-reactive protein (CRP) levels from different inflammatory conditions (infective, immuno-mediated, other), also robustly correlating with IL-6 serum concentrations. 65 In addition, in a large study performed on 1716 subjects of the general population, Medenwald et al 66 found that after covariate adjustment soluble TNF-receptor-1 levels were associated with QTc duration in women, while Kertai et al 67 reported that high IL-1β expressing gene variants were independent predictors of postoperative QTc prolongation among 957 patients undergoing cardiac surgery.…”

Correlation of inflammatory cytokines on corrected QT interval in rifampicin-resistant tuberculosis patients

“…This was different from a cohort study in the UK, which suggested a lower inflammatory burden may protect against QTc prolongation in patients with rheumatoid arthritis (RA) [ 6 ]. Another study also reported the possible contribution of IL-1β in modulating susceptibility to QTc prolongation after cardiac surgery [ 26 ].…”

Intraoperative transfusion is a risk factor for cerebral injury after cardiac surgery in children: a prospective observational study

“…Описанными характеристиками и обусловлена та его динамика, которую можно наблюдать из наших данныхпик концентрации маркера отмечался после завершения ИК, т. е. после наибольшего среди в сей операции патологического воздействия. В дальнейшем наблюдалось снижение концентрации и возращение к дооперационному уровню, что соотносится с результатами других аналогичных исследований [33]. IL-6 является маркером СВО c двой ным -про-и противовоспалительным действием и отличается разнообразием клеток, продуцирующих его (кардиомиоциты, фибробласты, эндотелиоциты) [34,35].…”