Elevated plasma levels of Th17-related cytokines are associated with increased risk of atrial fibrillation

Abstract

We performed a matched case-control study using a propensity score matching, to assess the association of Th17-related cytokines, including interleukin (IL) 17A (IL-17A), IL-17F, IL-21, IL-22 and IL-6, along with interferon-γ (IFN-γ), IL-10, IL-9, and IL-4, with the risk of AF. A total of 336 patients with AF were matched 1:1 with patients without AF. Plasma levels of cytokines were measured using Luminex xMAP assays. The plasma levels of all examined cytokines were significantly higher in AF patients than controls (P < 0.05), and these cytokines were highly correlated with each other (P < 0.01). A multivariate conditional logistic regression analysis showed that elevated plasma levels of IL-17A, IL-17F, IL-21, IL-22, IFN-γ, IL-10, IL-9 and IL-6 were significantly associated with AF risk independently of potential confounders. There were no significant differences in plasma levels of examined cytokines between paroxysmal and chronic AF patients. IL-17A, IL-21, IL-10 and IL-6 levels were positively correlated with left atrial diameter; IL-17F level was negatively correlated with left ventricle ejection fraction among AF patients (P < 0.05). Elevated plasma levels of Th17-related cytokines were independently associated with increased an risk of AF; hence, Th17-related cytokines may be involved in the pathogenesis of AF.

Hypertension and incident cardiovascular events following ibrutinib initiation

“…39,43 With increasing data-linking alterations in inflammatory pathways with cardiac incident events, including HTN, arrhythmia, and other MACEs, it may be reasonable to postulate that the systemic inflammatory alterations seen among ibrutinib users factors into these events by an as yet unexplored mechanism. [44][45][46][47] It is also plausible that the reduction in MACE among those treated with antihypertensives may have been linked to the suppressive nature of many antihypertensives in arrhythmia treatment. This notion is supported by the loss of statistical significance, after accounting for atrioventricular node blockade use (ie, beta-blockers and calcium channel blockers).…”

Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation

“…Recent evidence indicates that activated macrophages secrete other cytokines such as TNF-a and IL-1b, which can be involved in AF onset through the modifications of Ca 2+ currents and subsequent arrhythmia [43]. Moreover, increased levels of IL-1b, IL-2, IL-8, IL-9, IL-10, IL-15, IL-17A, IL-17F, IL-21, IL-22, interferong, and transforming growth factor-b1 [44][45][46][47][48] were also associated with AF onset. All these studies support the idea that a general proinflammatory status rather than the increased level of a single inflammation marker is responsible for the occurrence of post-operative AF.…”

Elevated Peripheral T Helper Cells Are Associated With Atrial Fibrillation in Patients With Rheumatoid Arthritis

“…The proportion of IL-17-positive CD4+ T cells (Th17 cells) is higher in peripheral blood mononuclear cells from patients with RA compared with healthy controls, and their proportion correlates with systemic disease activity at both the onset and during the progression of RA (24,25). Th17 cells might be involved in the pathogenesis of AF, as elevated plasma levels of Th17-associated cytokines were independently associated with the increased risk of AF, further suggesting that Th17 cells are involved in the pathogenesis of AF (26). Interleukin-17A contributes to the development of AF by promoting inflammation and cardiac fibrosis (27) and affecting protein kinase C (PKC)-b and Erk 1/2 phosphorylation, as well as nuclear factor (NF)-kB activation in fibroblasts from model mice (28).…”