Interleukin-1 beta is associated with diastolic dysfunction in patients with sleep disordered breathing

Philipp Hegner (Regensburg)1, M. Wester (Regensburg)1, M. Tafelmeier (Regensburg)1, S. Klatt (Regensburg)1, Z. Provaznik (Regensburg)2, C. Schmid (Regensburg)2, L. S. Maier (Regensburg)1, M. Arzt (Regensburg)1, S. Wagner (Regensburg)1, S. Lebek (Regensburg)1

1Universitätsklinikum Regensburg Klinik und Poliklinik für Innere Med. II, Kardiologie Regensburg, Deutschland; 2Universitätsklinikum Regensburg Herz-, Thorax- und herznahe Gefäßchirurgie Regensburg, Deutschland


Objective: Diastolic dysfunction is a hallmark of heart failure with preserved ejection fraction (HFpEF) and affects up to 80% of high-risk cardiovascular patients undergoing cardiac surgery. Even without overt HFpEF, echocardiographic diastolic dysfunction is independently associated with increased mortality. One of the most important associated comorbidities is sleep-disordered breathing (SDB). Interestingly, SDB patients frequently exhibit diastolic dysfunction, but the underlying mechanisms remain elusive, although previous studies have suggested the role of inflammation. 


Purpose: We evaluated diastolic dysfunction and expression of circulating interleukin 1β (IL1β) levels in peripheral blood mononuclear cells (PBMCs) of patients with and without SDB.


Methods and Results: 

234 patients with preserved left-ventricular ejection fraction undergoing coronary artery bypass grafting were pre-operatively tested for SDB using polygraphy. SDB was defined as an apnea-hypopnea index (AHI) ≥ 15/h. Diastolic dysfunction was graded (none, grade I, II, or III) by standard echocardiography. PBMCs were isolated from patient blood samples, and IL1β mRNA expression was quantified using real-time-qPCR. Plasma levels of pro-collagen III C-terminal pro-peptide (PIIICP) were measured by ELISA. 

The severity of SDB (AHI) was positively correlated with plasma C-reactive protein (CRP) values (Figure A). Average SpO2 during nocturnal plethysmography was negatively correlated with CRP values (Figure B). Multivariate regression analysis revealed that this observation was independent of important clinical covariates (i.e., age, body-mass index, heart failure, history of stroke, glomerular filtration rate) (p=0.034, r2=0.081). In patients with diastolic dysfunction, IL1β mRNA levels were higher in patients with SDB than in those without (Figure C). Furthermore, IL1β mRNA values in SDB patients were ~3.5-fold higher when diastolic dysfunction was present. 

IL1β mRNA levels in PBMCs were positively correlated with ascending severity grade of diastolic dysfunction (Figure D), but this effect was only present in SDB patients (Figure E+F), which was independent of potential confounders (p=0.003, r2=0.489). The pro-fibrotic blood marker PIIICP was also positively correlated with the severity of diastolic dysfunction (Figure G). This effect was mainly driven by the subgroup of patients without SDB, where PIIICP was positively correlated with the grade of diastolic dysfunction (Figure H+I), independent of potential confounders (p=0.025, r2=0.308).



Inflammation might be an important mechanism promoting diastolic dysfunction in patients with SDB. Patient-individualized anti-inflammatory strategies may be a new approach in improving therapy for patients with SDB and diastolic dysfunction.

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